Clinical Pharmacology Book 2018

Pharmacyprep.
com Clinical Pharmacology & Pharmacy Practice
Clinical Pharmacology &

Pharmacy Practice
Module 1. Autonomic Nervous System
• Chapter 1: Functions of Autonomic Nervous System
• Chapter 2: Adrenergic Drugs
• Chapter 3: Cholinergic Drugs
Module 2. Cardiovascular Drugs

• Chapter 4: Antihypertensive Drugs
• Chapter 5: Antihyperlipidemic
• Chapter 6: Nitrates and Nitroglycerin
• Chapter 7: Cardiac Glycoside Digoxin
• Chapter 8: Anti Arrhythmic Drugs
• Chapter 9: Anticoagulants
• Chapter 10: Antiplatelets Drugs
• Chapter 11: Thrombolytic Drugs
Module 3. Central Nervous System Drugs

• Chapter 12: Antidepressants and Lithium
• Chapter 13: Benzodiazepines and Barbiturates
• Chapter 14: CNS Stimulants
• Chapter 15: Antipsychotics
• Chapter 16: Antiepilepsy Drugs
• Chapter 17: Alzheimer’s and Dementia Drugs
• Chapter 18: Anti-Parkinson’s Drugs
• Chapter 19: Local and general anesthetics
Module 4. Anti-inflammatory Drugs and Autacoids

• Chapter 20: Opioid Analgesics
• Chapter 21: Non-Steroidal Anti-inflammatory Drugs
• Chapter 22: Autocoids Analogs and Antagonists
Module 5. Endocrine Pharmacology

• Chapter 23: Insulin and Anti Diabetics Drugs
• Chapter 24: Thyroids Drugs
• Chapter 25: Gonadal Hormone
• Chapter 26: Adrenal corticosteroids
• Chapter 27: Oral Contraceptives
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is
illegal to reproduce without permission. This manual is being used during review sessions conducted by
PharmacyPrep.
Pharmacyprep.com Clinical Pharmacology & Pharmacy Practice
Module 6. Drugs to Treat Musculoskeletal Disorders

• Chapter 28: Osteoarthritis
• Chapter 29: Disease Modifying Antirheumatic Drugs
• Chapter 30: Gout Arthritis and Hyperuricemia
• Chapter 31: Osteoporosis
Module 7: Drugs to Treat other Diseases

• Chapter 32: Asthma and COPD
• Chapter 33: Anticancer Drugs and Chemotherapy
• Chapter 34: Gastrointestinal Drugs
• Chapter 35: Drug in Renal Disease
• Chapter 36: Immunomodulators
• Chapter 37: Ophthalmic Medications
Module 8: Antimicrobial Pharmacology

• Chapter 38: Antibacterial
• Chapter 39: Antifungals
• Chapter 40: Anti-Mycobacterial Drugs
• Chapter 41: Anti-Viral Drugs
• Chapter 42: Anti-Malarial Drugs
• Chapter 43: Anti-Helminthes Drugs
PharmacyPrep.
Pharmacyprep.com Autonomic Nervous System
1
Autonomic Nervous System
Nervous System
Central Nervous System (CNS) Peripheral Nervous System (PNS)

Spinal cord and brain
Sensory Somatic Nervous System

Autonomic Nervous System (ANS) 12 pairs of cranial nerves
31 pairs of spinal nerves
Cholinergic Adrenergic
Functions of ANS
· The autonomic nervous system controls involuntary body functions. The ANS is composed
of two divisions.
· Sympathetic (adregenic) system
· Parasympathetic (cholinergic) system
Types of Neurons in ANS

· Efferent neurons (motor neurons): deliver
message from brain to organs
· Afferent neurons. Collects message from
organs to the brain
· Efferent neurons divided into the
Sympathetic (adrenergic) nervous system
· Parasympathetic (cholinergic) nervous
system
ANS is responsible for regulation of

· Internal metabolic activity
· Myocardium
· Smooth muscle of the viscera
· Glandular activity
1-1
PharmacyPrep.
· Hormonal activity
· Ensure that the body operates in optimum range
Parasympathetic Sympathetic (adrenergic)

(cholinergic)
Originate in sacral Originate in the thoracic and
and cranial region lumbar region
Post ganglionic Post ganglionic nerve fibre
nerve fibre very very long
short
Preganglionic Preganglionic nerve fibre
nerve fibre very very short
long
Ganglia is near Ganglia is near spinal cord
innervated organs
Neurotransmitters Neurotransmitters
Acetyl choline · Norepinephrine
(ACh) (NE)
· Epinephrine (epi)
· Dopamine (D)
· ACh
Parasympathetic Symptathetic receptors
Receptors · Norepinephrine
ACh; M 1 , M 2 , a 1 ,a 2 , b 1 (Not on
M 3 , M 4 and b2)
M 5 , N 1 and N 2 · Epinephrine
a1 , a2 , b 1 , b 2
· Dopamine D 1 >b>a
· ACh N 1
Parasympathetic Functions Sympathetic Functions
↓ Heart rate Increase ↑ heart rate
↓ Blood pressure Increase ↑ blood pressure
Constriction of pupil (MIOSIS) (i=inch) Increase ↑ blood flow to skeletal muscle and heart
Constrict lungs Dilation of ↑ pupil (MYDRIOSIS) and bronchioles (y =yard)
Maintains essential body functions (Digestive, waste Adjust in response to stressful situation (trauma, cold, fear,
elimination). hypoglycemia, exercise)
Oppose or balance the action of sympathetic. Changes in emergencies (Fight or flight response).
Dominant over sympathetic in rest and digest ↓ Saliva (DRY MOUTH)
situation ↓ peristalis movements (CONSTIPATION)
↑ saliva (SIALLORIA)
↑ peristalis movements
Both the sympathetic and parasympathetic nerves innervate the same structures. Their actions are opposing but
not equal in scope.
1-2
PharmacyPrep.
AUTONOMIC SOMATIC
Sympathetic innervation Sympathetic Parasympathetic
of adrenal medulla
Preganglionic
neuron
Ganglionic
transmitter
Acetycholine Acetycholine Acetycholine (no ganglia)
Nicotinic Nicotinic Nicotinic

receptor receptor receptor
Adrenal medulla
Postganglionic
neurons
Neuroeffector Epinephrine (released

transmitter into the blood)
Norepinephrine Acetycholine Acetycholine
Adrenergic
Adrenergic Muscarinic
receptor Nicotinic
receptor receptor
receptor
Effector organs Striated Muscle
1-3
PharmacyPrep.
Effector Organ Sympathetic Parasympathetic

Adipose ↑ Lipolysis (β 3 )
Metabolise fatty acids
Arterioles
Skin and mucosa Constriction (a 1 ) Some relaxation (M)
Skeletal muscle Usually relaxation (β 2, M) Some relaxation (M)
Bladder
Detrusor Relaxation (β 2 ) Contraction (M 3 )
Sphincter Contraction (a 1 ) Relaxation (M)
Eye
Radial muscle, iris Mydriasis (a 1 ) -
Sphincter muscle, iris - Miosis (M)
Ciliary muscle Accommodation Contraction for near vision (M)
(Relaxation, β 2 )
Heart
Sinoatrial node ↑Heart rate (β 1 )àChronotropic ↓ Heart rate (M 2 )
Atrioventricular node ↑ Conduction (β 1 )àDromotropic ↓ Conduction (M)
Atria ↑ Contractility (β 1 )àInotropic ↓ Contractility (M)
Ventricles ? ?
Kidney Renin secretion (β 1 ) -
Lacrimal glands - ↑ Tear secretion (M)
Liver Glycogen breakdown (β 2 ) Glycogen synthesis (M)
Lung (bronchial muscle) Relaxation (β 2 ) Contraction (M 2 )
Male sex organs Ejaculation (a 2 ) Erection (M)
Nasopharyngeal glands - Mucus secretion
Pancreas ↓ Insulin secretion (a 2 ) ↑ Fluid secretion (M)
↑ Insulin secretion (b 2 )
Salivary Glands Viscous secretion (a 1 ) Marked water secretion (M)
Stomach & intestine
Motility Decrease (β 2 ) à Peristalisis Increase (M)
Sphincters Contraction (a 1 )àSpincter Relaxation (M)
Secretion - Stimulation (M)
Sweat glands ↑ Secretion (M) ↑ Secretion (M)
Uterus ↑ Contraction (a 1 ) -
detrusor muscles
Relaxation (β 2 )
Veins (systemic) ↑ Dilation (β 2 ) -
Spleen Contraction (a 1 ) -
Abbreviation and Terminology

ANS Autonomic Nervous System M Cholinergic –Muscarinic
CNS Central Nervous System D Dopamine
EPI Epinephrine ACh Acetylcholine
1-4
PharmacyPrep.
www.PharmacyPrep.Com Adrenergic Drugs
2
Adrenergic (Sympathetic
System) Drugs
There are four types of adrenergic receptors. These are alpha1 and alpha2 and βeta1 and
βeta2. Alpha receptors are located mainly in the blood vessels (Vascular system) and pupils
(eye) radial muscle of iris and bladder sphincter. Βeta1 receptors are in the heart and βeta2
receptors are mainly in the lungs, celiary muscle, skeletal muscles and uterus.
Adrenergic Drugs
Adrenergic agonist Adrenergic antagonist
Alpha agonist Beta agonist Mixed agonist
Alpha antagonist Beta antagonist
a1 antagonist a2, antagonist a1,b2, mixed antagonist
Non-selective Cardioselective Partial alpha & Partial agonist &

Beta antagonist Beta antagonist Beta antagonist antagonist
2-1
PharmacyPrep.
Adrenergic receptors (Sympathetic receptors ᾳ 1, ᾳ 2, beta 1 and beta2 )

ᾳ 1 Receptors ᾳ 2 Receptors
Located on vascular smooth muscle of the Located in presynaptic nerve terminals (CNS), platelets, fat cells
skin and splanchnic regions, the and the walls of the GI tract
gastrointestinal (GI) and bladder sphincters, Often produce inhibition (eg. Relaxation or dilation).
and the radial muscle of the iris (MYDRIOSIS) Mechanism of action inhibition of adenylate cyclase and
produce excitation (e.g. Contraction or decrease in cyclic adenosine Monophosphate (c AMP). Produce
constriction). inhibitory action.
Equally sensitive to norepinephrine and
epinephrine, but only norepinephrine is CNS (NE & EPINEPHRINE RELEASE INHIBITS ALPHA 2 RECEPTORS)
Present in concentrations that are high Pancreas ((¯ INSULIN SECRETION)
enough to activate ᾳ receptors. GASTRONINTESTINAL TRACT
Mechanism of action: formation of inositol
1,4,5-triphosphate (IP 3 ) and increase in
Intracellular (Ca2+).
SMOOT MUSCLE VASCULAR (ARTERIES &
VEINS) CONSTRICTION.
Sphincter of bladder (CONTRACTION,
URINARY RETENTION)
Salivary gland (¯SALIVA)
GI-spincter
Spleen
Skin (CONSTRICTION)
ẞ 1 Receptors ẞ 2 Receptors
Located in the sinoatrial (SA) node -HR Located on vascular smooth muscle of skeletal muscle,
atrioventricular (AV) node - CONDUCTION (vasodilatation, ¯TPR = ¯ AFTER LOAD).
Ventricular muscle of the heart produce Bronchial smooth muscle DILATION
excitation (eg. Increase heart rate, increase In the walls of the GI tract and bladder.
conduction velocity, increase Contractility). Produce relaxation (eg. Dilation of vascular smooth muscle,
Sensitive to both norepinephrine and dilation of bronchioles,
epinephrine and more sensitive than the ᾳ 1 Relaxation of the bladder wall).
Receptors. More sensitive to epinephrine than to norepinephrine.
Uterus
Mechanism of action. Activation of Pancrease: - INSULIN SECRETION
adenylate cyclase and production of cAMP. - GLYCOGENOLYSIS,
Kidney à - RENIN SECRETION - GLUCONEOGENESIS
Celiary epithelial; - aqeous humor - GLUCOGENESIS
production - LIPOLYSIS
HEART
KIDNEY LUNGS
UTERUS GI TRACT
STOMACH ADIPOSE TISSUE
SALIVARY GLAND
2-2
PharmacyPrep.
ADRENERGIC AGONIST. Increase heart rate, vascular constriction, branchodilatation

· Alpha 1 : peripheral vascular constrictors (blood vessels)
· Alpha 2 . inhibitory receptor act on norepinephrine in brain
· Beta 1 . Increase HR, Conduction, Contraction on heart, ↑Renin secretion
· Beta 2 . Branchodilators in lung, relaxation of bladder detrussors, vasodilator in skeletol
muscles.
Alpha 1 agonist Phenylephrine, Clinical outcomes
Alpha pseudoephedrine, ephedrine ALPHA1 act locally as
agonist methoxamine, xylometazoline. vasoconstrictor. - BP, -
glaucoma, BPH,
HYPERTHYROIDISM
Alpha 2 agonists Methyldopa, clonidine, ¯NE, ¯ EPINEPHRINE
guanabenz
Beta agonist non- Dobutamine, isoproterenol - HR
Beta selective (Beta 1 &
agonist Beta 2)
Beta 2 agonist SABA. Salbutamol, terbutaline, - BRONCHIAL
LABA: Salmeterol, formoterol DILATATION
Mixed alpha and Dopamine, epinephrine, - HR, - CO

beta norepinephrine
ADRENERGIC ANTAGONIST. decrease heart rate, vascular dilatation, branchoconstriction
Alpha Alpha 1 antagonist Prazosin, terazosin, doxazosin, - VASCULAR DILATOR,
blockers tamsulosin, and alfuzosin RELAX SPHINCTOR
MUSCLES
Alpha 2 antagonists Yohimbine, MIRTAZEPINE - NE
Alpha 1 and 2 Phentolamine,
antagonists phenoxybenzamine
beta Beta antagonist
blockers Nons-selective Propanolol, pindolol, nadolol, ¯HR, ¯ CO AND ¯
blockers timolol, and levobutalol CONDUCTION
(beta 1 and beta 2)
Cardioselective b- Esmolol, metoprolol,
blockers acebutolol, atenolol, bisoprolol
(beta 1 selective)
Partial alpha and Acebutolol, pindolol, oxprenolol
beta blockers
a1 antagonist a2 agonist
Indication Hypertension, Benign Prostatic Hypertension and Treat withdrawal
2-3
PharmacyPrep.
Hypertrophy (BPH or enlarged symptoms in recovering drug and alcohol

prostate). abusers (clonidine)
Contraindic Orthostatic hypotension Orthostatic hypotension and liver disease

ation
Side Effects Orthostatic hypotension, Decrease lipolysis
Fainting (syncope) Decrease insulin secretion
Reflex tachycardia Sexual dysfunction
Vertigo Rebound hypertension with clonidine
Sexual dysfunction
a 1 agonists
· Phenylephrine
· Pseudoephedrine
· Ephedrine
· Methoxamine
· Xylometazoline
Question Alerts!
1) Who should avoid oral pseudoephedrine or
ephedrine?
2) Rebound congestion can occurs if it is used
prolong time.
Pharmacological · LOCALLY Constrict dilated arterioles in the nasal mucosa ¯ BLOOD

actions FLOW and reduce airway resistance. (Vasoconstriction). NO EFFECT
HISTAMINE MEDIATED ALLERGY.
↑ Blood pressure ↑ Peripheral resistance (precaution in
hypertension).
· ↑ Closure sphincter muscles in bladder cause urinary retention,
precaution in prostatic hyperplasia.
· Alpha1 constriction of radial muscle in eye cause mydriasis.
Therapeutic use · Decongestant because constrict dilated arteries in the nasal mucosa
and reduce airway resistance.
Side effects · Tachycardia, palpitation and tremor, diabetes, hyperthyroidism
(more sensitive to sympathomimetics), BPH, glaucoma.
Drug therapy · Hypertension generally accepted with mild or well controlled
problem (DTP) hypertension. AVOID use with UNCONTROLLED HYPERTENSION
2-4
PharmacyPrep.
a2 agonist, centrally acting antihypertensive
a2 agonists · Methyldopa, Clonidine, Brimonidine

Mechanism · Decrease central adrenergic outflow. a 2 receptors located on
perineuronal membrane. a 2 receptors have inhibitory action
Question Alerts! on epinephrine and norepinephrine.
Rebound · Increase a2 receptors increase inhibitory action on
hypertension in epinephrine and norepinephrine.
clonidine is · ↓ Blood pressure
possible. · ↓ Release of insulin - a2 = ↓ NE & ↓EPI
· ↓ Norepinephrine
· Bradycardia
Therapeutic use · Centrally acting antihypertensive. Hypertension with renal
disease (no decrease blood flow to kidney), and methyldopa
is the drug of choice in pregnancy.
Common side · Rebound hypertension in clonidine. Clonidine is used for
effects opioid withdrawal symptoms like flushing.
b agonists
b agonists non Dobutamine (b 1>b 2 ) and isoproterenol (b 1 = b 2)

selective
Mechanism · Increase heart rate
· Increase cardiac output
· +ve inotropic effect (increase force of contraction of heart).
Tachycardia
· Increase lipolysis
· Bronchodilation
Therapeutic use Dobutamine used in treatment of adults with cardiac
decompensation due to depressed contractility resulting from
organic heart disease or following cardiac surgical procedures in
which parenteral therapy is necessary for inotropic support.
Contraindication Tachycardia and ventricular fibrillation.
b 2 agonist
b 2 agonist Mechanism
· Bronchodilation
2-5
PharmacyPrep.
· vasodilation due to slightly decrease peripheral resistance

· Increase muscle and liver glycogenolysis
· Relax uterine muscles
· Increase release of glucagon and increase insulin secretions.
· Beta2 agonist drugs have no anti-inflammatory effect and act as branchodilators
Short acting beta 2 agonist Long acting beta 2 agonist

Salbutamol (Albuterol), Terbutaline Salmeterol, Formeterol (full agonist, short onset)
Rapid 3-5 min onset of action and provide · Formeterol rapid onset 1-3 minutes of action
relief for 4 to 6 hours. and long duration. Some cases used as rescue
Indicated in symptomatic treatments medication.
(QUICK RELIEF), rescue agents, combat · Salmeterol has long duration of action,
acute providing bronchodilation for at least 12 hours,
Salbutamol 2 puffs Q4-6 hrs PRN max 8 and slow onset of action.
puff/day. · Indicated in maintenance treatment in
Overdose cause tachycardia, tremors, and combination with corticosteroids especially for
QTc prolongation. nocturnal asthma, and COPD.
· Not indicated in acute asthmatic attacks.
· SABA always used as PRN and · LABA always used as daily dose.
tolerance can occur with regular use · LABA has synergistic effect with
and also mask the symptoms of corticosteroids. (Products available:
inflammation. Fluticosone + Salmeterol = Advair).
· SABA has additive effect with · Budosenide + Formeterol = Symbicort
anticholinergic drugs (Ipratropium)
Mixed a and b agonist
Mixed a and b · Dopamine, Epinephrine, Norepinephrine

agonist
Norepinephrine · a 1, a 2 , b 1 agonist
· Alpha receptor effect causes rise in peripheral resistance due
to intense vasoconstriction of vascular beds (including
kidney).
· Baroreceptor stimulates cardiac contractility.
Major affects · Vasoconstriction

· ↑ Cardiac contractility
· ↑ Systolic blood pressure (SBP)
· ↑ Diastolic blood pressure (DBP)
· ↑ Peripheral resistance (PR)
· Reflex bradycardia
2-6
PharmacyPrep.
· Vasoconstriction à causes peripheral resistance

· Baroreceptor reflex à stimulates cardiac contractility
Epinephrine (adrenaline)
Action a1, a2 at higher doses at lower doses b 1 and b 2

Cardiovascular · a b = low dose
· a= b = intermediate dose
· a> b = high dose
· ↑ oxygen demand
· ↑ the rate of contraction (+ve chronotropic effect, b 1 action)
· ↑ The contractility of myocardium (+ve inotropic effect, b 1 action).
· ↑ Systolic (SBP) and slight decrease diastolic (DBP), reflex bradycardia.
· Epinephrine strengthens the contractility of the myocardium (positive inotropic) and incre
Respiratory · Intense bronchodilator is used for allergic and histamine induced bronchoconstriction.
Hyperglycemia · Has significant hyperglycemic effect (↑glycogenolysis)

· ↓ Release of insulin and causes lipolysis.
Therapeutic · Acute asthma, anaphylactic shock (type1 hypersensitivity)
use · Glaucoma (2% epinephrine solution).
· In local anesthesia (1:100,000) due to vasoconstrictor (alpha 1 agonist)
Side effects · CNS: Anxiety, fear, tension, headache, and tremor.
· Hemorrhage: Elevation of BP may cause hemorrhage.
· Arrhythmias: Can trigger arrhythmias in patient using digitoxin
· Can cause pulmonary edema.
Question Alert!
Epinephrine used in local anesthetic? Vasoconstriction effect
increase local effect anesthesia.
Epinephrine
Alpha1 ↑ vasoconstriction In anaphylaxis shock caused by severe vasodilation, thus lead to
↑ BP, ↑ vascular tone severe hypotension. Epinephrine vasoconstriction effect ↑ blood
pressure and helps to treat hypotension.
↑ heart O 2 demand
Alpha 2 ¯ NE
Beta 1 ↑ HR, conduction, CO, Epinephrine reverse hypotension
Beta 2 branchodilatation Reverse branchial constriction thus prevent shock.
2-7
PharmacyPrep.
Dopamine
Mechanism: Act on D 1 , D 2 , D 3 , D 4 , D 5 , and mixed a1 and a2 , b 1 , b 2 agonist. Activate alpha and

beta-adrenergic receptor. At higher doses it causes vasoconstriction by activating alpha
receptor, whereas at lower dose, it stimulates beta receptor. In addition, D 1 and D 2
dopaminergic receptor, occur in the mesenteric and renal vascular beds where binding of
dopamine produces vasodilation.
Major affects
· Has +ve inotropic and +ve chronotropic effects.
· Dilates renal arterioles by increasing blood flow to kidney
· Dopamine is drug of choice for shock given by continuous infusion.
· Metabolizes to homovanillic acid.
DOPAMINE DOBUTAMINE
The first line agent for cardiac shock Increase heart rate, CHF
To treat cardiac shock, renal diseases Used for +ionotropic effect when vasoconstriction
undesirable, reduces preload & after load.
Natural cateholamine D2>B1>B2>alpha Synthetic drenergic affect B1>B2>alpha
Dopamine à Norephinephrine.
1-3 mcg/kg/min à renal, coronary, A synthetic catecholamine
cerebral vasodilation Strong B1 agonist
3-10 mcg/kg/min à beta1 stimulation
>10 mcg/kg/min à alpha 1 stimulation
Adrenergic Antagonist
Adrenergic antagonist
alpha antagonist Beta antagonist
a1 antagonist a2 antagonist
Non-selective Cardioselective Partial alpha & Partial agonist &

Beta antagonist Beta antagonist Beta antagonist antagonist
2-8
PharmacyPrep.
a1 antagonists
a1 antagonists · Prazosin, Terazosin, Doxazosin, Tamsulosin (a1A ) and Alfuzosin (a1A).
Mechanism · ↓Peripheral vasodilation ↓ peripheral vascular resistance and lower
aterial blood pressure by causing relaxation of both arterial and venous
smooth muscle. In otherwords ↓total peripheral resistance.
· Internal bladder sphincter muscle relaxation in bladder helps to treat
urinary flow in BPH. (Note: drug oxybutynin relaxes detrusor muscle
enhance bladder storage).
Therapeutics · Antihypertensive and symptomatic benign prostate hyperplasia by blocks
use post synaptic alpha1 located on prostate capsule, causing relaxation and
decrease resistance to urinary flow.
Side effects · Orthostatic hypotension thus first dose effect (syncope). Fainting, reflex
tachycardia, headache, drowsiness, palpitation, and miosis.
Comments · Starting dose for doxazocin 1 mg once daily and titrate slowly.
· Tamsulosin and alfuzosin are a selective a 1A receptor blocker and has no
postural hypotension.
QAlerts!
1) Alpha1 blockers cause syncope or orthostatic hypotension or first dose effect.
2) Alpha1 blockers relaxation of spincter muscles decrease bladder pressure.
a2 antagonist
Yohimbine Yocon and odan

Pharmacological actions · Blocks presynaptic a2
· ↑HR and ↑BP
Therapeutic use · For impotency treatment
Side effects · Postural hypotension?
Contraindications · Renal and hepatic diseases
· Cardiovascular disease
Mirtazepine · Used as antidepressant
· ANTAGONISM OF presynaptic a 2, CUASE ↑ NE and
serotonergic (5HT) activity.
a1 & a2 antagonists
a1 & a2 antagonist
2-9
PharmacyPrep.
Phentolamine · Competitive, short acting agent

(Reversible) · a blockade
· ↓BP
· ↓total peripheral resistance, reflex tachycardia.
Therapeutic use · Used occasionally in patients to ↓BP (antihypertensive).

· Pheochromocytoma is catecholamine induced
vasoconstriction
Phenoxybenzamine · Non-competitive long acting blocker
(Irreversible) · NE release is enhanced due to blockade of presynaptic a
receptors cause’s excessive response.
· Used occasionally in patients to ↓blood pressure.
Beta Blockers
Beta Blockers
Nonselective CardioSelective Beta & Alpha Partial agonist

(b1 & b2) (b 1 only) blockers & antagonist
Nonselective (b 1 & Cardioselective b 1 , b 2 & a1 blockers Partial agonist &

b2) (b 1 only) antagonist
· Propranolol · Esmolol · Labetalol · Acebutolol
· Pindolol · Metoprolol · Carvedilol · Pindolol
· Nadolol · Acebutolol · Oxprenolol
· Timolol · Atenolol
· Levobutolol · Bisoprolol
Vasoconstriction Vasoconstriction a receptors produce Intrinsic
Reduce intra ocular without vasodilation sympathomimetic
pressure. ¯ Secretion of bronchoconstriction.
activity (ISA)
aqueous humor and Caution: Peripheral b blocker cause
bradycardia. Peripheral
Minimized
vascular diseases.
Caution: Peripheral vasoconstriction disturbances of lipid
vascular diseases (DVT). Does not alter serum and carbohydrate
lipid levels. metabolism.
None selective beta blockers: " ProPiNaTionaLE" and selective EMAAB
Mixed beta1 & beta2

Antagonist (non-selective): Propanolol, Pindolol, Nadolol, Timolol
Mechanism:
· Ptopanolol. Diminishes cardiac output, having both (-) ve inotropic and chronotropic effect
bradycardia.
· Blocks b 2 receptor in lungs causes contraction of bronchiolar smooth muscle.
2-10
PharmacyPrep.
· Timolol. reduce intraocular pressure: decrease secretion of aqueous humor

· Bradycardia, bronchoconstriction (bronchospasm). Decrease in contractility of heart and
decrease in oxygen consumption.
Beta 1 blockers (Cardioselective)

· Esmolol
Selective "EMAA B"
Cardioselective beta · Metoprolol
blockers · Acebutolol
· Atenolol
· Bisoprolol
Mixed alpha & beta antagonist
· Labetalol
· Carrveidilol
Mechanism
· Produce vasodilation-decrease in blood pressure.

· Peripheral vasoconstriction.
· Does not alter serum lipid levels
Partial agonist and antagonist
· Acebutolol
· Pindolol
· Oxprenolol
Mechanism
· Intrinsic sympathomimetic activity
· Minimized disturbances of lipid and carbohydrate metabolism
ISA: Intrinsic Sympathomimetic Activity
The partial agonist stimulates the beta receptors to which they are bound; yet inhibit
stimulation by the more potent endogenous catecholamines, epinephrine and norepinephrine.
The result of opposing actions is much diminished effect on cardiac rate and cardiac output
compared to beta blockers without intrinsic sympathomimetic activity
Side effects
· Bradycardia, heart blockage (AV blockade)
· Bronchospasm (avoid non-selective in asthma and COPD)
· Cuases vascular constriction, thus avoid beta blockers in peripheral vascular disease such as
Raynaud’s phenomenon and intermittent claudication however carvedilol and labetalol can
be tried.
· CAUTION in congestive heart failure and left ventricular dysfunction.
· CNS: lipid soluble BBs propranolol cause drowsiness, headache, depression, sexual
dysfunction.
Pharmacokinetics
2-11
PharmacyPrep.
· Propanolol is the best absorbed with food but consistency is the most important factor.
· Metoprolol is best taken with meals
· These drugs shoukd be taken at about same time everyday.
· Beta blockers that have first pass metabolism propanolol and timolol
· Beta blockers that have no biotransformation atenolol.
· Beta blockers that have alpha blockade effect labetalol and carvedilol
· Beta blockers that acts as membrane stabilizer is propanolol.
Beta-blockers therapeutic uses:

· Propranolol is used for hypertension, angina, post MI, migraine, essential tremor,
performance anxiety, Hyperthyroidism (acute-thyroid storm).
· Timolol is used for chronic treatment of open angle glaucoma. Hypertension, post MI, and
migraine.
· Pindolol used for hypertension.
· Cardioselective, metaprolol, atenolol, esmolol and acebutolol used to treat for
hypertension, angina and tachycardias.
· Beta-blockers are drug of choice for uncomplicated hypertension in patient age under 65
years old.
· Beta-blockers are used cautiously in asthma, CHF, diabetes and sever peripheral vascular
diseases.
· Beta-blockers do NOT cause orthostatic hypotension.
· What adrenergic blockers are useful in treating Tachycardia? Beta blockers (Propranolol)
· The longest acting beta-blockers is? Nadolol
· Diabetic patient taking beta-blockers monitor? Blood sugar levels
Beta blockers therapeutic Mechanism

Migraine prophylaxis (propranolol, nadolol) Vasoconstriction effects of beta blockers
hypertension Decrease HR, CO and Conduction
Hyperthyroidism Decrease HR,
Glaucoma
Anxiety (stage fear)
Supraventricular tachycardia
Congestive heart failure (carvedilol,
metoprolol, bisoprolol)
2-12
PharmacyPrep.
Tips
· Epinephrine (Epipen) is used for anaphylactic reaction or hypersensitive reactions.
· Epinephrine act on alpha1, alpha2, beta1 and beta2 agonist
· Example of irreversible and noncompetitive alpha1 and alpha2 blocker is à
Phenoxybenzamine
· Examples of drugs that reverse effect of epinephrine associated vasocontriction à alpha1
blockers.
· Examples of sympathomimetic that should be avoided in Glaucoma à Phenylephrine,
pseudoephedrines.
· Xylometazoline action is on alpha-adrenergic receptors.
ABBREVIATION AND TERMINOLOGY

NE Norepinephrine SABA Short Acting Beta Agonist
ProPiNaTionaLE Proparanolol, Pindalol, Nadilol, Timolol, LABA Long Acting Beta Agonist
Esmalol
CO Cardiac output BP Blood Pressure
COMT Cathecol Amine O- Methyl Transferase EMAA Esmolol, Metoprolol, Acebutolol,
Atenolol
ISA Intrinsic Sympathommimetic Activity HR Heart rate
EIA Exercise induce asthma TPR Total Peripheral Resiistance
SBP Systolic Blood Pressure PR Peripheral Resiistance
DBP Diastolic Blood Pressure IOP Intra Ocular Pressure
GENERIC and BRAND

Xylometazoline Otrivin
Fluticasone + Salmeterol Advair
2-13
PharmacyPrep.
2-14
PharmacyPrep.
www.PharmacyPrep.Com Cholinergic Drugs
3
Cholinergic Drugs
The parasympathetic (cholinergic) system slows the heart, constricts the pupil, and stimulates
the GI tract and aids in digestion and elimination. Drugs with a cholinergic effect will produce
similar effects. A cholinergic effect may be direct acting drugs occupy the cholinergic receptor.
Indirect acting drugs inhibit the activity of cholinesterase, an enzyme that breaks down
acetylcholine. By preventing the breakdown of acetylcholine, there is an accumulation of
acetylcholine allowing increased parasympathetic effects.
Cholinergic
Cholinergic Agonist Muscarinic Antagonist
Direct cholinergic agonist Indirect cholinergic Tertiary amines Quaternary amine

agonist Atropine Ipratropium
Scopolamine Tiotropium
Acetylcholine agonist anticholinesterase Benztropine Glycopyrrolate
Trihexyphenidyl
Choline ester Pilocarpine

Bethanachol
Carbachol Reversible Reversible Organophosphate
Methanacol Quaternary alcohols Carbamate (Irreversible cholinesterase inh.)
Donepezil Physostigmine Echothiophate, Malathion
Neostigmine Parathion, Sarin
Rivastigmine
Pyridostigmine
GALANTAMINE
Cholinesterase
Acetylcholine -------------> Acetyl + Choline
3-1
PharmacyPrep.
Summary of cholinergic receptors effects

Muscarinic Rec Muscarinic Effect Anti-muscarinic
ept
or
Eye –sphincter muscle M3 causes miosis MYDRIOSIS
Heart – SA node M2 Decrease HR (-ve chronotropy), vagal arrest TACHYCARDIA
AV node M2 Decrease conduction velocity (-ve dromotrophy)
Lung- branchioles M3 Branchospasm (contraction) BRANCHODILATION
Glands M3 Increase secretions
GI tract M3 Stomach-increase motility causes cramps ¯STOMACH MOTILITY
Intestine-increase motility causes diarrhea CONSTIPATION
M1 Glands – secretion of HCl ¯ HCL SECRETION
Blood vessels M3 Vasodilation but no innervation (to stimulate for
action)
Nicotinic N
Adrenal medulla N Increase secretion of epi and norepinephrine
Ganglia
Neuromuscular Stimulation causes muscle hyperactivity
junction
Cholinergic receptors (cholinorecetors)

Nicotine receptors Muscarinic receptos
Located in the autonomic ganglia of Located in the heart, smooth muscle (except vascular smooth
the sympathetic and muscle) and glands.
parasympathetic nervous Activated by Ach and muscarine
systems, at the neuromuscular Inhibitory in the heart (eg. Decreased heart rate, decreased
junction, and in the adrenal conduction velocity in AV Node).
medulla. The receptors at these Excitatory in smooth muscle and glands (e.g. Increased GI
locations are similar, but not motility, increased secretion).
identical. Muscarine receptors for Ach are blocked by atropine.
Activated by Ach or nicotine. Mechanism of action:
Produce excitation. 1. Heart SA node inhibition of adenylate cyclase, which leads to
opening of K+ channels. Slowing of the rate if spontaneous
Ganglionic blockers depolarization and decreased heart rate.
(eg.hexamethonium, trimethaphan) 2. Smooth muscle and glands: formation of IP 3 and increase in
block the nicotinic receptors. intracellular (Ca2).
ACh receptors are also ion channels for Na+ and K+.
Drugs act on
M1
M2
M3
3-2
PharmacyPrep.
Side effects of cholinergic drugs Side effects of anticholinergic

Cholinergic!
Bradycardia Tachycardia
D = diarrhea
Salivation Dry mouth, Dry eye, Dry skin
U= urination
Lacrimation Blurred vision and mydriasis
M= myopic
Flushing Constipation
B = bradycardia
Diarrhea Urinary retention
E = Excessive sweat
Hypotension Dizziness and drowsiness
L = lacrimation
Tremors Hyper optic accommodation
S = Salivation
Myopic accommodation Increased intraocular pressure
WATERY DRY
Direct acting cholinergic drugs
Direct acting · Acetylcholine
Cholinergics · Pilocarpine
· Bethanechol
· Carbachol
· Methacholine
Pharmacological · ↓ Heart rate
actions · ↓ Cardiac output
· ↓ Blood pressure
· ↑ saliva secretion
· Miosis
Bethanecol: Used clinically for its therapeutic effects in
postoperative atony of the bowel, for abdominal distention and
urinary retention. Other drugs in this group are pilocarpine and
carbachol, used in the eye to treat glaucoma.
Pilocarpine
Mechanism: The cholinergic agent most often used to treat
glaucoma since it produces a reduction in intraocular pressure.
Side effects: Cramps, diarrhea, and increased gastric acid. May
cause bradycardia, flushing and a fall in blood pressure,
bronchoconstriction causing difficulty in breathing, sweating and
salivation.
Indirect acting cholinergic drugs

Indirect acting cholinergic drugs further categorized as indirect acting reversible or
anticholinesterases and indirect irreversible or organophosphates.
3-3
PharmacyPrep.
Indirect acting · Physostigmine, Neostigmine, Rivastigmine, Donepezil

reversible
anticholinesterases
Pharmacological · Effects on muscarinic and nicotinic receptors and on NMJ and brain.
action
Therapeutic use · Physostigmine antidote of atropine, can get into brain (3o amine).
· Neostigmine is used to treat myasthenia gravis. Does NOT get into
brain (quaternary amine salt).
· Edrophonium is not clinically used.
· Donepezil is the drug of choice for the treatment of Alzheimers, and it
is lipid soluble (enter CNS).
Side effects · Diarrhea, cramps, increased salivation, increased bronchial secretions,
miosis, sweating and muscle cramps.
Indirect irreversible · Insecticides, parathion, malathion, and echothiophate.
or
organophosphates
Question Alerts!
Antidote of Atropine?
Antidote of organophosphates?
Tertiary Quaternary
Atropine Ipratropium
Scopalamine Tiotropium
Benzotropine Glycopyrrolate
Trihexyphenidyl ACLIDINIUM
UMECELIDINIUM
Anticholinergic effect Branchodilators
CNS effect dizziness, drowsiness, anxiety,
headach No CNS effect
Dry mouth, constipation, urinary retention, Dry mouth, constipation, urinary

blurred vision. retention, blurred vision
Muscarinic antagonists
Anticholinergic · Atropine, ipratropium, tiotropium, scopolamine, benztropine
drugs · tropicamide, glycopyrrolate, and trihexyphenidyl.
Pharmacological · ↓ in salivation cause dry mouth (xerostomia).
actions · ↓ intestinal secretion cause constipation
· Increase HR cause tachycardia
· Mydriasis cause pupil dilatation
· Relaxation of detrussor muscle cause urinary retention.
3-4
PharmacyPrep.
Anticholinergic · Dry mouth, blurred vision, tachycardia, constipation and urinary

side effects retention.
Therapeutic use · Atropine is antidote of organophosphates.
· Ipratropium is used as rescue for asthma and COPD
· Tiotropium is in maintenance therapy of COPD
· Scopolamine is used for prevention of motion sickness.
· Benztropine is used to treat Parkinsons disease associated with
antipsychotic drug side effects.
· Tropicamide is used in ophthalmic exams (topical).
· Glycopyrrolate is used as antispasmodic, antisecretory.
· Trihexyphenidyl is used to treat drug induced extrapyramidal
symptoms caused by antipsycotic drugs.
Nicotinic Blockers (Ganglionic blockers)

Nicotine: Depolarizes ganglia, resulting first in stimulation and followed by paralysis of all
ganglia, increase in BP, HR, increased peristalsis, and secretion.
a-Bungarotoxin and botulinum toxin. a Bungarotoxin (a-BgTx) is a postsynaptic neurotoxin
found in the venom of the braided Krait snake (Bungarus multictus). Like other neurotoxins it
blocks neuromuscular transmission.
NMJ blockers
These agents are used for surgical patients to relax the muscles during surgery.
Pharmacological actions. Blocks the cholinergic
transmission between motor nerve and nicotinic
Question Alerts!
receptors. Antagonizes (non-depolarizing type)
1) Mechanism of succinyl choline?
and agonist (polarizing) the effect of
Depolarizing non-competitive NMJ blockers.
acetycholine.
2) Pancuronium is?
Non-depolarizing Competetive NMJ blocker
Classified as two categories of NMJ blockers
Depolarizing NMJ Blockers
Depolarizing Non- · Succinylcholine
competitive
Mechanism · Blocks the cholinergic transmission between motor nerve and
nicotinic receptors.
· Antagonizes (non-depolarizing type) effect of acetylcholine.
Therapeutic use · Clinically used in surgery to produce complete muscle
relaxation.
Side effect · Malignent hyperthermia, hyperkalemia and myalgia
3-5
PharmacyPrep.
Non-depolarizing NMJ Blockers

Non Depolarizing · Atracurium
competitive · Tubocurarine
· Doxacurium
· Pancuronium
· Vecuronium
· Mivacurium
Mechanism · Prevents the binding of acetylcholine, inhibits muscular contraction.
At higher doses, these (non-depolarizing) drugs block the ion
channels of end plate and reduced the ability of antagonists.
Therapeutic uses · Indicated in anesthesia during surgery to relax skeletal muscles.
Side effects · Decrease BP, paralysis of diaphragm
Antagonist for non · Neostigmine, edrophonium (cholinesterase inhibitors)
depolarizing agents
Myastenia gravis: This disease is a disorder of skeletal (voluntary striated) muscle due to
excessive cholinesterase or lack of acetylcholine (ACh). It is characterized by increasing fatigue
and muscle weakness; some cases are mild, some are severe. Death usually occurs due to
respiratory depression.
GENERIC AND BRAND

Pilocarpine Isotocarpine Succinylcholine Anctine, Quelicin, Sucostrin
Atropine Atrezat, AtroPen, Physostigmine Mestinon, Regonol
Ipratropium Atrovent, Atrovent HFA Neostigmine Prostigmine
Scoopolamine IsoptoHyoscine, Pyridostigmine Pyridostigmine
Benztropine Congentin Edrophonium Enlon, Reversol, Tensilon
Tropicamide Mydriacyl Donepezil Aricept, Aricept ODT
Glycopyrrolate Robinul, Robinul forte Tacrine Cognex
Trihexyphenidyl Artane Malathion Ovide
Atracurium Tacrium Echothiophate Phospholine Iodide
Tubocurarium Tubarine, Metubine, Jex Neostigmine Prostigmin
Doxacurium Nuromax Edrophonium Enlon, Reversol, Tensilon
Pancuronium Pavulon Pilocarpine IsotoCarpine
Vecuronium Norcuron Mivacurium Mivacron
3-6
PharmacyPrep.
www.PharmacyPrep.Com Antihypertensive Drugs
4
Antihypertensive Drugs
This chapter review antihypertensive drugs such as an Angiotensin converting enzyme
inhibitors (ACEi), Angiotensin receptor blockers (ARBs), beta blockers, alpha1 blockers, calcium
channel blockers (CCBs) and vasodilators mechanism of action, major therapeutic use, side
effects, pharmacokinetics, dosage forms and instructions for counseling.
Regulation of arterial blood pressure: The renin angiotensin aldosterone system (blood
volume). Renin is a proteolytic enzyme and also called angiotensinogen’s and it is produced in
kidney Juxtaglomerular cells. Angiotensinogen is plasma protein produced by liver in to blood.
ACE is produced from lungs and kidney.
Angiotensinogen Sympathetic action ANGIOTENSIN II
(alpha globulin in blood)
VASOCONSTRICTOR
Renin
Vasodilation
- Na & H2O
(kidney) SYMPATHOMIMETIC ACTIVITY
BP
- SECRETION OF K+
Angiotensin I Angiotensin II
Bradykinin
ACE I
Na & H2O levels
Baroreceptor reflex: Four effects that increase arterial blood pressure to normal.
· Increase heart rate
· Increase contractility
· Increase vasoconstriction of arterioles (TPR will increase)
· Increase vasoconstriction of veins
ACE Inhibitors
Angiotensin II is the body’s most potent circulating vasoconstrictor causing increases blood
pressure. Angiotensin II stimulates aldosterone secretion to increase the kidney sodium
reabsorption and increase in blood volume, which contribute to increase in BP. The ACE
inhibitors are used to treat hypertension and congestive heart failure. The
PharmacyPrep.
4-1
ACEi also tend to protect the kidneys of diabetics from developing renal failure when used in
the early stages of diabetic nephropathy.
Generic Name (PRIL) Side effects Drug Interactions Tips

Benazepril (Lotensin) 5mg, 10 mg, Dry cough (BECAUSE - ↑Li levels & can cause Can precipitate renal failure in
20mg, 40mg tab BRADYKININ), lithium toxicity. renovascular disease, volume
+
↑K (INH. NSAIDs ↓ hypotensive depletion and those receiving
ALDOSTERONE, ¯ K+ effect. NSAIDs.
Captopril(Capoten generics) 12.5mg, SECRETION FROM Taken empty stomach 6.25-50 mg TID
25mg, 50 mg, 100mg tab COLLECTING DUCT), Prodrug
Cilazapril (Inhibace) Oral tablet Hypotension.
Enalapril (Vasotec) Minor: GI, vertigo, Once daily or 2.5-20 mg bid
2.5mg, 5mg, 10mg, 20mg headache, fatigue, first
tab,1.25mg/ml inj dose hypotension.
1 mg/ml susp Rare; angioedema
Fosinopril (Monopril) 10 mg, 20 mg, Does NOT require renal 50:50 renal hepatic elimination
40 mg qd tab dose adjustment
Lisinopril (Zestril, generics) 2.5mg, 5 Once daily, 2.5-40 mg qd
mg, 10 mg, 20 mg, 30 mg, 40 mg tab
Perindopril (Coversyl) 10-40 mg
Quinapril (Accupril)
Ramipril (Altace) 2.5, 5. 10 mg Usual Once daily or divided bid
dose 10 mg/day
Max 20 mg/day
Trandolapril (Mavik) 0.5-4 mg qd
ANGIOEDEMA: Symptoms of swelling of the lips, mouth, or face.
Pharmacological actions: ACE inhibitors block the angiotensin converting enzyme that cleaves
angiotensin I to form, angiotensin II. The angiotensin II is potent vasoconstrictor. It also
decreases the secretion of aldosterone resulting in decreased sodium and water retention.
Therapeutic use: 1ST line to treat heart failure (by reducing preload and after load), diabetes
nephropathy, post MI, uncomplicated hypertension, and pre-hypertensive patient, LVH (left
ventricular heart failure) and prior CVA/TIA (cardiovascular attacks/transient ischemic attacks)
& in renal disease.
Preload is ↑ stroke volume and improve ejection fraction.
After load is↓ systemic congestion and edema.
Therapeutic use Mechanism

Hypertension ↓angiotensin à ↓sympathetic activity, ↓aldosterone, ↓ vasoconstriction, ↓ ADH.
THE OUTCOME ↓ TPR
Congestive heart ↓ preload and after load, ↓ mortality and morbidity
failure (CHF)
Diabetic nephropathy ↓Prostaglandin à ↓ protein secretion, ↓Na & water retention
Pre-hypertensive Low dose sympathetic activity and prevention of nephropathies
PharmacyPrep.
4-2
Side effects: Dry cough (5 to 15%), ORTHOSTATIC hypotension, hyperkalemia, renal

insufficiencies (For the most ACEi renal elimination (except fosinopril) is the primary route of
elimination, therefore dosage of ACEi should be reduced in renal impairment).
Angioedema (rare), reversible neutropenia, proteinuria (some patient with pre-existing renal
disease) and fatigue.
COUGH
ACE
Bradykinin --------------> Inactivates
The increased levels of both bradykinin and prostaglandin are responsible for cough. The
bradykinins stimulate prostaglandin synthesis.
Angioedema is an allergic response of ACEi and ARBs produce symptoms of fluid retention in
blood vessels of throat, tongue, lower lips.
Contraindications: Pregnancy (absolute) because can produce hypotension in the fetus leading
renal failure and death, skull hypoplasia and death. Documented angioedema secondary,
bilateral renal artery stenosis.
Question Alerts!
1) Dry cough side effect of ACEi, is treated by? Change to ARBs
2) Angioedema is allergic reaction of? ACEi. and ARBs.
3) Hyperkalemia is SEs of? ACEi, ARBs, and K+. Sparing diuretics.
4) ACEi are the DOC to treat BP in DM patient because? Prevent nephropathy
associated with DM.
Pharmacokinetics
· High fat meals may reduce absorption of quinapril. Food does not affect the other drugs in
this class.
· Captopril should be taken one hour before meals. Dosage captopril is taken BID or TID due
to short half life.
Angiotensin-Converting Enzyme Inhibitors (ACEi).

Elimination Food Creatinine
Benazepril renal +
Captopril bid renal empty + Food has high effect on bioavailability
or tid NOT a prodrug (no biotransformation
required)
Cilazapril renal empty +
Enalapril renal +
Maleate
PharmacyPrep.
4-3
Enalaprilat (i.v) renal +

Fosinopril Renal/Feca + No dosage adjustment in renal. NOT a
l prodrug
Lisinopril renal +
Perindopril renal Empty + Food has high effect on bioavailability
Quinapril renal +
Ramipril renal +
Trandolapril renal + High potency
· Breast feeding and pregnant mothers should not take ACE inhibitor. If they become
pregnant while on medication, they should contact their physician immediately.
· Call doctor ASAP if you experience swelling of the face, eyes, lips, tongue, arms, or legs, or if
you have difficulty breathing or swallowing (symptoms of angioedema). In case of cause
cough symptoms contact doctor to change the medication to ARBs.
· Drug interactions: NSAID’s can reduce the effect of captopril. Diuretics can cause rapid fall
of blood pressure with captopril.
ARB Inhibitors (AT1 receptor blockers)

Ends with “SARTAN”
Generic /Brand Name Side Effects Drug Interactions Tips
Candesartan (Atacand) ↑K+ (pt. receiving K+ ↑Li levels & can Can precipitate renal failure in
Oral tablet4-32mg qd suppl. or K+sparing cause lithium renovascular disease, volume depletion
Combination available diuretics) toxicity. and those receiving NSAIDs.
Rare; angioedema NSAIDs ↓ Hyperkalemia usually occurs only those
↑ creatinine levels hypotensive effect. on K+ supplements or K+ sparing agents.
ORTHOSTATIC HYPERKALEMIA, Contraindicated in pregnancy
HYPOTENSION AVOID ORAL
POTASSIUM SALTS.
Eprosartan (Teveten) Oral NSAID ↑ Na & water retention, thus ↑
tablet blood volume.
Irbesartan (Avapro)
75mg, 150mg, 300 mg tab
Losartan (Cozaar) Losartan has moderate uricosuric
25mg, 50mg tab effects and may be useful in patients
with gout or hyperuricemia who require
antihypertensive therapy.
Telmisartan (Micardis)
40mg, 80mg tab
Valsartan(Diovan) 20-160 mg bid
40mg, 80mg, 160mg tab
The angiotensin II receptor exist in at least two subtypes type 1 (AT1) and type 2 (AT2).
ACE
Angiotensin I -----------> Angiotensin II (AT-1 and AT-2).
PharmacyPrep.
4-4
AT 1 receptors are located in brain, neuronal, vascular, renal, hepatic, adrenal, myocardial
tissues and mediate the cardiovascular, renal and CNS effects of angiotensin II.
ARBs bind to AT 1 receptors and prevent formation of angiotensin II, a naturally occurring
PROTEIN that causes blood vessels to narrow (constrict). When these drugs are administered,
blood vessels dilate, thereby lowering blood pressure and decreasing the workload of the heart.
These drugs appear to have the same benefits as ACEi, without or less producing the common
side effect of a dry cough.
Pharmacological actions: Angiotensin binds to its own receptors are found on vascular muscle
and in the adrenals. Stimulation leads to vasoconstriction and release of aldosterone in the
adrenal gland. It blocks aldosterone secretion.
Losartan has moderate uricosuric effects and may be useful in patients with gout or
hyperuricemia who require antihypertensive therapy.
Side effects: Less dry cough (cough associated with ACEi does not appear with these drugs),
bradykinin causes vasodilation of arterioles and venules results ↓TPR, less dry cough. Dizziness,
hypotension (syncope), renal dysfunction (reversible renal failure), hyperkalemia and
angioedema.
Contraindications. Pregnancy (renal fetal toxicity), and bilateral renal artery stenosis (stenosis,
abnormal narrowing of passage or opening, such blood vessels or heart valve).
Pharmacokinetics: Losartan may increase the effects of potassium supplements, potassium

sparing diuretics, and cyclosporine, leading to raise of potassium in the blood.
Direct Renin inhibitors: Aliskiren 150 mg once ACEi ARBs

daily. Takes 4 weeks to 6 wks realize maximum
antihypertensive effect. cardio protection Yes No
Aliskiren is an analogue of the natural substrate (cardiac remodeling)
of renin: angiotensinogen. Competes with Cough Yes No
angiotensinogen for access to the active site of Hypotension Yes Yes
the renin enzyme. This drug reduces plasma Microalbuminuria Yes Yes
activity by about 75% and thus decrease
angiotensin 1 and II. Hyperkalemia Yes Yes
Side effects: Diarrhea, the incidence of dry cough, Angioedema Yes yes
and hyperkalemia is low compared with ACEi.
Avoid use in pregnancy.
PharmacyPrep.
4-5
b-blockers
Beta-blockers are used to treat hypertension and angina. These drugs act by slowing the
heartbeat, which results in lowered blood pressure since blood pressure is affected by the heart
rate and peripheral resistance. Beta-blockers are categorized into 4 types based on their
action on sympathetic receptors beta1, beta2, alpha1, and alpha2 action.
Beta Blockers
Nonselective CardioSelective Beta & alpha Partial agonist &

(b1 & b2) (b 1 only) blockers antagonist
Nonselective (b 1 & b 2 ) Cardio selective (b 1 b 2 & a1 Partial agonist &
(b 1 only) blockers antagonist
· Propranolol · Esmolol · Labetalol · Acebutolol
· Pindolol · Metoprolol · Carvedilol · Pindolol
· Nadolol · Acebutolol · Oxprenolol
· Timolol · Atenolol
· Levobutolol · Bisoprolol
Betaxolol
Propranolol · BP, angina, MI, · CHF · BP, dysarrthymia
BP, anxiety, CHF,
hyperthyroidism, dysrhythmia. INTRINSIC
migraine, dysarrthymia. SYMPATHOMIMETICS
Pindolol. CHF (ISA): DRUGS HAVE
Timolol. Glaucoma LESS BRADYCARDIA
Pharmacological actions of beta blockers

· b 1 decrease heart rate
· b 2 bronchoconstriction
· Peripheral vasoconstriction (Increase TPR)—b 2
· ↓ Na/water retention Question Alerts!
· b 2 ↓ glycogenolysis (glycogen à glucose) and 1) Watch for combination with ABCD!
gluconeogenesis. A= amiodarone
· ↓ glucagon secretions B= BB
· Blocks the effect of isoproterenol C= non-dihydropyridine CCB (verapamil
& diltiazem)
With ISA Without ISA D= digoxin
Acebutolol
Pindolol
Oxprenolol
PharmacyPrep.
4-6
Therapeutic use.
· Beta-blockers are used to treat hypertension and angina. Because of its action on the lining
of arteries, propranolol is also used migraines and it highest lipid soluble beta blocker.
· Abrupt discontinuation may cause rebound hypertension.
· Labetalol & carvedilol may cause orthostatic hypotension due to partial alpha blockade.
Therapy Beta blockers

Hypertension ¯HR, CO, conduction,
CHF (carvedilol) ¯ Mortality and ¯ cardiac load
Migraine prophylaxis vasoconstriction
Anxiety (stage fear) ¯ increase blood flow to brain
Hyperthyroidism ¯HR
Tachycardia ¯HR
Glaucoma Inhibit aqueous humor formation
on ciliary muscle with beta 1
receptors.
Angina ¯HR, decrease work load.
Side effects: Fatigue, bradycardia, decreased exercise capacity, headache,
impotence, vivid dreams. Less common hyperglycemia, depression, CHF, and heart
blockade.
Mechanism of action of beta-blockers

Effect of B receptor Cardiac output
on heart
Renin Angiotensin II Preripheral

BP
resistant
Aldosterones
Blood volume
Na, H2O levels
Cardiac output
Beta blockers
Monitored BP HR RFT LFT Blood QTc Mg

glucose
Acebutolol + + + + Only DM
Atenolol + + + + in DM
Bisoprolol + + + + in DM Beta1 antagonist, orthostatic hypotension
Carvedilol + + + + in DM Alpha blockade helps in treatment of CHF.
Esmolol + + + + in DM Only iv
Labetelol + + + + in DM Alpha blockade effect
Metoprolol + + + + in DM Cardio selective
Nadolol + + + + in DM Long acting
Nabivolol + + + + in DM
Pindolol + + + + in DM
PharmacyPrep.
4-7
Propranolol + + + + in DM CNS side effects (depression, dizzy, vivid

dreams), and sexual dys.
Sotalol + + + + in DM + + Prevention of recurrence of atrial fibrillation.
Timolol + + + + in DM Open angle glaucoma
· CHF patients should weigh themselves daily if possible every morning after urinating. If the patient gains more
than one pound a day or 3 to 5 pounds in a week should contact physician. In CHF patients may cause fluid
retention or worsening of heart failure with initiation of therapy or an increase in dose.
· Report any cases of dizziness, light-headedness, or blurred vision. These may be caused of too low blood
pressure or from bradycardia or heart attack.
Beta blocker effect on blood glucose: Beta blockers can mask signs and symptoms of
hypoglycemia (except sweating); also some inhibition of glycogenolysis and insulin secretion;
cardio selective agents such as acebutolol, atenolol, bisoprolol, or metoprolol may be safer.
a1 blockers
Generic Name Trade Name Generic Name Trade Name
Doxazosin Cardura Alfuzosin Xatral
Prazosin Minipress Tamsulosin Flomax
Terazosin Hytrin
End with "sin"
Alpha1 blockers dilate both arteries and veins Question Alert!

because both are innervated by sympathetic Alpha blockers cause orthostatic
system. However alpha 1 blocker effect is more hypotension or syncope and often
pronounced on arteries. They are more effective associated with first dose.
under condition under stress because more
sympathetic activity.
In addition to being used for hypertension these drugs cause the muscles (sphincter) of the
bladder neck and prostate to relax, thereby making it easier for patients to urinate thus also
used for benign prostatic hyperplasia.
Pharmacological actions: Primary action is due to peripheral vasodilation by inhibiting post

synaptic alpha1 receptors in vascular smooth muscles. Alpha1 also abundant in smooth muscles
of bladder and prostate. Alpha 1a blockade can cause relaxation of bladder muscle (sphincter)
and increase urinary flow.
· ↓ Blood pressure by ↓ total peripheral resistance, reflex tachycardia, and vasodilatations.
· First dose effect (syncope) slow titration of dose can minimize the syncope. and miosis.
Therapeutic use: Hypertension, benign prostatic hyperplasia and prazosin is used to insomnia
due nightmare in post traumatic stress disorder.
PharmacyPrep.
4-8
Side effects: Orthostatic hypotension, tachycardia (reflex tachycardia), headache, vertigo, sexual
dysfunction to avoid the first dose effect of hypotension and occasional syncope, the starting doses
should be small and given at bedtime.
Alpha 1 blockers
¯ TPR
VASODILATATION
ORTHOSTATIC HYPOTENSION
- URINE FLOW
a2 agonist – Centrallyacting antihypertensive

Generic Name Trade Name
Clonidine Catapres
Methyldopa Aldomet
Alpha 2 agonist used to treat hypertension are centrally acting agents, which act directly in the
brain to change the signals send to the heart and blood vessels.
Pharmacological actions
· Decrease central adrenergic outflow. a 2 receptors have inhibitory action on epinephrine
and NE.
· Increase alpha 2 receptors increase inhibitory action on epi
and norepinephrine.
· ↓ Blood pressure, ↓ insulin secretions, ↓ norepinephrine
Question Alerts!
1) Methyldopa is the drug of choice to treat hypertension
in pregnancy.
2) Clonidine gives rebound hypertension. Not used in
treatment of hypertension.
· Bradycardia (little).
Methyldopa optimum blood pressure response occurs in 12-24 hrs in most patients. After
withdrawal of the drug blood pressure returns to pretreatment levels within 24-48 hrs.
Therapeutic use: These drugs are not commonly used as it is difficult to achieve the proper dose
with these agents. They are generally reserved for people who fail to respond to other
therapies. Clonidine is sometimes used to treat withdrawal symptoms in recovering drug and
alcohol and opioid abusers.
Clonidine an alpha2 agonist that decrease the neuronal output of norepinephrine (¯

sympathetic activity), can be used to blunt the noradrenergic signs/symptoms of opioids
PharmacyPrep.
4-9
withdrawal such as chills and flushing. Clonidine used adjunctively with opioid can reduce
length of hospital stay, decrease seizures and decrease treatment failure.
Sudden stop using clonidine can cause withdrawal symptoms, nervousness, agitation,
headache, and rapid increase blood pressure and orthostatic hypotension.
Clonidine: Don’t discontinue abruptly, reduce dose over 2 to 3 days to reduce sever
hypertension.
Clonidine comes as transdermal patch TT1 (release 0.1 mg/24 h), TT2 (0.2 mg 24/h). TT3 (0.3
mg/24 h). Pruritus and rash at the site of transdermal patch.
Methyldopa is the drug of choice to treat hypertension in pregnancy due to no side effects on
fetus. Methyldopa also can be used pregnancy induced hypertension (pre-eclampsia).
Side effects: Clonidine may cause severe rebound hypertension, decrease lipolysis, decrease
insulin secretions, and sexual dysfunction. Methyldopa has cardiovascular, bradycardia,
orthostatic hypotension, blood related hemolytic anemia, thrombocytopenia and bone marrow
depression. The GI related include dry mouth, nausea, and diarrhea.
Pharmacokinetics: Methyldopa is prodrugs. Active product methyldopa is alpha methyl

norepinephrine in CNS reduce blood pressure and alpha2 agonist. Decrease TPR with little
change in HR and CO by stimulation of alpha 2 receptors in brain.
Methyldopa is contraindicated in patient taking MAOi.
DIURETICS
Diuretics also known as water pills.
Thiazide Loop diuretics K-sparing diuretics Carbonic Osmotic diuretic

diuretics acid inhibitor
Mannitol
Distal convoluted "Ascending Collecting duct"
Urea
tubule" loop" Spironolactone "proximal"
Triamterene
Chlorothiazide Furosemide Acetazolamide
Amiloride
Hydrochlorothiazide Ethacrynic acid Dorzolamide
Chlothalidone Bemetanide
PharmacyPrep.
4-10
Serum Electrolyte of Diuretics. In general, the opposite findings of serum electrolytes are
seen in urine
Type of Ca Mg N K Uric Blood Lipids Metabolic Disturbances
diuretic a acid sugar
Thiazide - ¯ ¯ ¯ - - - Hypokalemic metabolic alkalosis (HPERGLUC)
Loop ¯ ¯ ¯ ¯ - - _ Hypokalemic metabolic alkalosis (Loop lose calcium)
K-sparing _ - ¯ - - _ _ Hyperchloremic metabolic acidosis (↑CO 2 ), and
intracellular alkalosis
CAi _ _ _ ¯ - - _ Hyperchloremic metabolic acidosis
Osmotic ¯
Thiazide Diuretics
Generic Name Trade Name Generic Name
Hydrochlorothiazide Generics Chlorothiazide
Indapamide Generics Metolazone
Pharmacological · It increases Na+ and water excretion causing a decrease in extra cellular
actions volume, resulting in a decrease cardiac output and renal blood flow.
· ↑ H 2 O, Na+, Cl, K, excretions (↓ levels in body), retain Ca
· May cause alkaline urinary pH by effecting on carbonic anhydrase.
· Metabolic alkalosis (hypochloremia alkalosis).
Therapeutic uses · Especially useful in elderly ↓ blood pressure.
· Counteract Na/H 2 O retention caused by other antihypertensive such as
hydralazine and b-blockers
and African populations and with chronic renal diseases.
· Not effective in patient renal clearance less than 50 ml/min
· Not preferable in diabetic because hyperglycemia and hyperlipidemic
patient.
Side effects · Hypokalemia (↑ risk of digoxin toxicity, monitor K levels),
hypomagnesia, hyponatremia, hypercalcemia, hyperuricemia (thiazides
exacerbate gout), hyperglycemia and hyperlipidemia (did NOT translate
into CV events), metabolic alkalosis. Photosensitivity rashes, acute
pancreatitis, libido, difficulty with erection and ejaculation (long term in
2% in men).
Thiazide diuretics Na and H2O retention
Thiazide cause HYPERGLUC

Blood Volume Hyperglycemia
Hyperlipidemia
Hyperuricemia
Cardiac output
Hypercalcemia
Peripheral resistant
B.P.
PharmacyPrep.
4-11
Loop Diuretics
Drug Name
Furosemide (Lasix) “OH DANG” reversible Ototoxicity, hypokalemia, dehydration, Allergy (sulfa
allergy), Nephritis intestinal. Safe in renal disease.
Bumetanide
Ethacrynic acid IRREVERSIBLE OTOTOXICITY. Permanent hearing loss risk (hear tinnitus) and No
sulfa allergy.
Mechanism Act at site ascending loop.

Therapeutic uses Edema related diseases such as CHF, pulmonary edema, cirrhosis,
nephrotic syndrome, hypertension and hypercalcemia.
Side effects [OH DANG]! Ototoxicity (temporary hearing loss risk), hypokalemia,
dehydration, allergy (sulfa), Nephritis (intestinal), gout. Do not use if
patient has renal stones (loop loose calcium) hypocalcemia.
Pharmacokinetics Can be used in renal diseases (CrCl <30 ml/min). Oral solution, tablets,
and taken by mouth only.
Stability. Exposure to light may cause discoloration.
Dose Store at 15 to 30 ºC in a well closed container. Protect from light. Protect
from freezing. Do not dispense discolored tablets, store in amber color
bottle. Counsel patient to take medication early in the morning to avoid
nocturia.
Potassiumsparing
Generic Name
Spironolactone
Trade Name
Aldactone
Generic Name
Triamterene
- K+
COLLECTING DUCT
Amiloride EPLERENONE ¯ ALDOSTERONE
HCTZ/amiloride (50/5) Moduret HCTZ/Triamterene (25/50)
HCTZ/spironolactone (25/25) Aldectazide
PharmacyPrep.
4-12
Potassium sparing The K+ STAys: Spironolactone, Triamterene, Amiloride, Eplerenone
Potassium sparing Spironolactone, Triamterene, Amiloride

Pharmacological · Act in the early collecting duct to inhibit the electrogenic
actions reabsorption of Na+ by blocking the Na channels and hence the
exchange of sodium for potassium.
· After administration ↑ Na+, Cl- elimination, ↓K+, Ca++ (amiloride).
· Increase Na, H 2 O, HCO 3 excretion (decrease levels in body)
· Decrease K+, H+ excretion.
· Alkaline urinary pH and increase excretion of HCO 3
Aldosterone Spironolactone
antagonist
Pharmacological Competitive inhibits aldosterone at minor aldocorticoid receptors.
actions Decreases potassium excretion.
Side effects Sulfa drug like allergy.
Endocrine: Gynecomastia, menstrual irregularities.
Electrolytes. Hyperkalemia (monitor K+ levels)
CNS. Mental confusion.
Metabolic acidosis and intracellular alkalosis
Therapeutics use Drug of choice in ascites (aldosterone is responsible for fluid retention).
Pharmacokinetics Take drug with food to enhance absorption.
Adverse reactions usually disappear after drug is discontinued. However,
gynecomastia may continue. For children dose crush tablets and mix in
cherry soup as an oral suspension.
Dose Adults. 25 mg to 200 mg PO daily in divided doses
Spironolactone is antiandrogenic and has been used to treat hirsutism in
doses of 200 mg/day.
Protect drug from light. (store in amber color bottle)
Non aldosterone Amiloride and triamterene

antagonist
Pharmacological Act directly on late distal tubule and collecting duct. They disrupt
actions sodium exchange with potassium and hydrogen by blocking
sodium channel. Decrease in the driving force for secretion of
potassium and hydrogen.
Therapeutic use Amiloride. Used in nephrogenic diabetic insipidus
Pharmacokinetics Amiloride. 15 to 30 ºC in a well-closed container and take with
meals or milk.
Triamterene. 15 to 30 ºC in a tight, light-resistant container, Take
with meals or milk, Avoid exposure to sun or sunlamp. Turns
urine into blue color.
PharmacyPrep.
4-13
Osmotic Diuretics
Osmotic · Mannitol and Urea

Pharmacological · Increases the osmotic pressure of the glomerular filtrate and thus
actions increase excretion of H 2 O, Na+, Cl- and HCO3+ (decrease levels in body).
· Increase alkaline urinary pH, increase excretion of HCO 3
· Increase tubular osmolarity, and increase urine flow.
Therapeutic use Mannitol: Shock, or drug overdose, decrease intracranial or intraocular
pressure (cerebral edema).
Side effects Pulmonary edema (absorbs water from extracellular compartment), and
dehydration.
Contra Indications: CHF and anuria (renal failure).
Question Alerts!
1) Pulmonary edema is SEs of? Osmotic DUs
2) Pulmonary edema is treated by Loop DUs.
2) Mannitol is used for treatment of cerebral edema.
Carbonic anhydrase Inhibitors
CA Inhibitors · Acetazolamide and Dorzolamide

Pharmacological · Inhibition of carbonic anhydrase in the ciliary process of the eye
actions results in a decrease in production of bicarbonate and aqueous
humor, thus reducing intraocular pressure in patients with
glaucoma. Noncompetitive inhibition of carbonic anhydrase enzyme
Increase excretion of H 2 O, Na, K, and HCO 3 (decrease levels in body).
· Cause alkaline urinary pH, increase alkaline pH inc. exc HCO 3
Therapeutic use · Glaucoma (not chronically). Acute mountain sickness (respiratory
alkalosis), high altitude sickness (mountain sickness). Because of the
alkaline diuresis it produces, acetazolamide has been used for the
treatment of overdoses of acidic drugs.
Side effects Electrolytes: Acetazolamide may cause metabolic acidosis (ACIDzolamide).
Hyperchloremic metabolic acidosis (loss of HCO 3 -), hypokalemia. Both
drugs have sulfa allergy.
· Formation of renal stones (phosphaturia & hypercalciuria).
· CNS. Depression, drowsiness, sedation, fatigue, disorientation.
· GI: Nausea, vomiting, and constipation.
· Blood related. Bone marrow depression, thrombocytopenia .
PharmacyPrep.
4-14
(reduction of number of platelets in blood), hemolytic anemia,

leucopenia (reduction in number of WBC), agranulocytosis (acute
deficiency of neutrophils).
· Hyperchloremic metabolic acidosis and sulfa allergies
Vasodilators
Vasodilators
Direct Vasodilators Indirect Vasodilators

· Hydralazine · ACE inhibitors
· Sodium nitroprusside · Calcium channel blockers
· Minoxidil
· Diazoxide
¯Preload & ¯ after load
Vasodilators cause the smooth muscle in blood vessels to relax. Relaxed or dilated blood
vessels allow more blood to flow through, causing a reduction in blood pressure by decreasing
peripheral resistance. As vasodilators work, the blood vessels become dilated causing a drop-in
pressure because there is less blood volume to fill the vessel. The body can compensate for this
by retaining enough fluid to fill the blood vessel sufficiently to raise the blood pressure again.
Hydralazine and minoxidil are direct vasodilators not usually used a sole therapy for high blood
pressure, as their effect is usually short lived when administered alone.
Side effects: flushing and headache
Pharmacological action
· Vasodilators reduce excessive preload and after load.
· Elevated after load causes the heart to work harder to pump blood into arterial system.
· Dilation of venous blood vessels leads to decrease in cardiac preload by increasing venous
capacitance.
· In arteries dilators reduce systemic arteriole resistance and decrease after load.
Minoxidil
· A prodrug, which must be conjugated with a sulfate to form the
active drug.
Mechanism · Minoxidil is potent renal vasodilator and stimulator of renin
release. Minoxidil activate the ATP modulated K+ channel in
smooth muscle and thus relaxation of blood vessels.
Therapeutic · Hypertension and alopecia treatment.
use
Side effects · Salt and water retention (use a diuretic). Reflex tachycardia.
· Pulmonary hypertension and blurred vision. (Avoid retinoid, and
PharmacyPrep.
4-15
corticosteroids). Hypertrichosis.
· Hypertrichosis: Topical 2% & 5% SOLUTION and Foam is 5%. Can
be use men (2 to 5%) & women (only 5%).
For alopecia · Each mL of clear, colorless to slightly yellow solution contains.
minoxidil 20 mg (2%), in alcohol (63%), propylene glycol (20%)
and water. For external use only. Store at controlled room
temperature (15 to 30°C).
· Hypertrichosis (excessive hair growth) occurs continued
treatment over 4 weeks.
Question Alerts!
Cyanide toxicity of nitroprusside is treated by?
Sodium Nitroprusside
Mechanism · Dilates both resistance and capacitance vessels. More active on
veins than on arteries, but this selectivity is less than nitroglycerine.
· Nitroprusside when come in contact with red blood cells produces
nitric oxide (NO), which then stimulates guanylate cyclase.
Therapeutic Drug of choice for hypertensive crisis.
use
Side effects · Short term-excessive vasodilatation and hypotension. Long term-
accumulation of cyanide and thiocyanate (24 hours). Nitroprusside
is metabolized by combination with hemoglobin to produce
cyanmethemoglobin.
· Concomitant administration of sodium thiosulfate decreases cyanide
accumulation by changing into thiocyanate.
Thiocyanate · Nausea, disorientation and toxic psychoses.
toxicity
Diazoxide
Mechanism · Dilates arterial smooth muscle.

· Used IV for the treatment of hypertensive emergencies.
Therapeutic use
Side effects · Salt and water retention
· Hyperglycemia (↓ release of insulin) and hypertrichosis
Hydralazine
Mechanism Acts directly relaxing arteriolar smooth muscle.
PharmacyPrep.
4-16
Therapeutic use · Indicated in pregnancy induced hypertension (PIH) AND

HYPERTENSION CRISIS.
· This drug causes direct vasodilatation, acting primarily on the arteries
and arterioles, resulting in decreased peripheral resistance which in
turn prompts a reflex elevation in heart and cardiac output.
Side effects · Salt and water retention, which may lead to CHF (use a diuretic).
· Hematologic-neutropenia, Leucopenia, and agranulocytosis.
· Muscle cramps
· Orthostatic hypotension, and tachycardia
· Lupus like syndrome. (Long term therapy likely >6 mo) butterfly
reaction on face.
Ca2+CHANNEL BLOCKERS
These agents are used to treat hypertension and are effective in treating angina as well. All
muscles, including the smooth muscle of the blood vessels, require calcium in order to contract.
If the CCB block the entrance of the calcium into the muscle, the muscle will not contract. This
will allow the muscle to relax and subsequently reduce the blood pressure. Other therapeutic
uses angina, migraine, and antiarrhythmic.
Nondihydropyridine
· Diltiazem hydrochloride
· Verapamil hydrochloride
Mechanism
· Verapamil similar to beta blockers in effect
· Verapamil can
cause
bradycardia
· The effect on
heart is graded
from higher to
lower.
Verapamil>Diltiazem>Nifedipine
· Verapamil-avoid using in CHF (cause -ve inotropic effect) and
constipation
Dihydropyridine
· Nifedipine
· Felodipine
PharmacyPrep.
4-17
· Amlodipine
· Nicardipine
Side effects
· Flushing, headache
· Profound low blood pressure
· Swelling of legs and feet.
· constipation and stomach upset.
· If ankle edema (swelling) of legs and feet occurs, a diuretic may be
added to the regimen.
Nifedipine is similar to nitrate in effect (peripheral, decrease after load, dihydropyridine can
cause tachycardia.
Dihydropyridine relax and dilating arteries. The effect on vascular smooth muscles is high with
dihydropyridine Nifedipine>Diltiazem>Verapamil.
Dihydropyridine (DHP) Non-Dihydropyridines (NDHP)
“DIPINE” Phenylalkylamine Benzothiazepines
Nifedipine, Amlodipine, Verapamil Diltiazem hydrochloride
Nicardipine, Felodipine
¯ Peripheral vascular ¯ Myocardial oxygen Have both cardiac depress and vasodilator.
resistance. Vasodilation and demand and reverse Decrease arterial pressure without producing
hypotension may lead to coronary vasospasm severe degree of reflex cardiac stimulations caused
reflex tachycardia. by dihydropyridines
Reflex tachycardia bradycardia bradycardia
No heart blockade Peripheral Cause heart blockade Cause heart blockade
vasodilatation. Myocardial Myocardial vasodilatation
Peripheral edema (ankle vasodilatation Negative (-ve) inotropic effect (worsening CHF)
edema or pitting edema). Negative (-ve)
inotropic effect
Headache, and flushing (worsening CHF)
Constipation
Avoid CYP3A4 Inhibitors/Inducers
Duration of action ranges 4-8 hrs. Verapamil 4hr (TID to QID)

Nifedipine 4-8hrs (TID to QID) Diltiazem 6-8hrs (TID to QID)
Nicardipine 6-8hrs (TID to QID)
Amlodipine 24hr once Daily
Similar to nitrates. Similar to beta Similar to beta blockers because

blockers ¯HR, ¯ CO AND ¯ CONDUCTION
Therapeutic use:
Hypertension: Vascular smooth muscle relaxation (↓TPR).
PharmacyPrep.
4-18
Angina: vasodilator and cardiodepressent effect.

Dysarrhtymia: Class IV antiarrhythmic drug
Peripheral vascular disease (DVT, Raynaud's, and intermittent claudication). AND vasodilator
The most common SEs dizziness, hypotension, headache, peripheral and pulmonary edema.
Dihydropyridines
Nifedipine, 1st gen
Nicardipine, Felodipine – 2nd gen
Amlodipine - 3rd gen
Mechanism A calcium blocker which interfere with conduction of signals in
the muscles of the heart and vessels.
Therapeutic use Given regularly to prevent angina attacks. Reduce high blood
pressure and is often helpful in improving circulation to the limbs
in disorders such as Raynaud’s disease.
Side Effects Blood pressure will fall too low and sometimes causes heart
rhythm. Tachycardia, flushing, headache, dizziness, orthostatic
hypotension, and edema. Gingival hyperplasia.
Amlodipine
Mechanism A calcium blocker which interfere with the conduction of signals
in the muscles of heart and vessels.
Therapeutic use Angina and chest pain. Can be safely used by asthmatic and non-
insulin-dependent diabetic.
Side Effects May cause mild to moderate leg and ankle swelling (arterial), and
hypotension.
Non dihydropyridines
Verapamil and Diltiazem

DILTIAZEM Cardizem CD once daily, Tiazac XC once daily and IR formulation
TID or QID
Mechanism ¯HR, ¯ contraction and ¯ conduction.

A calcium blocker that interferes with the conduction of signals
Therapeutic use in the muscles of heart and blood vessels.
Angina: Longer acting formulations are used to treat high blood
pressure.
Side Effects Usually well tolerated, occasional hypotension or orthostatic
hypotension, flushing, arrhythmia, and bradycardia. Use with
caution in patient with CHF.
PharmacyPrep.
4-19
Tips
· Diuretics that cause metabolic alkalosis: (thiazide, loop diuretics)

· Diuretics that cause intracellular alkalosis: (spironolactone)
· Diuretics that act on distal convoluted tubule: (thiazides)
· Diuretic that cause metabolic acidosis: (CAIs, potassium sparing)
· Diuretics that have greater vasodilatation effect (thiazides)
· What diuretics disturb the electrolyte balance, the most? (loop diuretics)
· Patient taking hydrochlorothiazide should be monitored (BP, glucose and potassium)
· Hypertension + pheochromocytoma which antihypertensive is used phentolamine and beta
blockers.
· Isolated systolic hypertension (e.g. 170/80), the drug of choice is? CCBs
· Cardio selective beta-blockers are EMAA.B
· The most beta 1 selective blockers that has been studied in lung dysfunction = bisoprolol.
· What percent of patients diagnosed with high blood pressure have essential hypertension
90%.
· Name the cation most prevalent in the extracellular fluid of the body --> Na
· Why is bedtime the best time to dose terazosin? orthostatic hypotension (syncope)
· Antihypertensive Lowers blood pressure through reducing the PR or CO.
· Propranolol is best absorbed with food but consistency is the most important factor
· Metoprolol is best taken with meals
· Beta blockers that have first pass metabolism; propranolol, timolol
· Beta blockers that have no biotransformation; atenolol
· Beta blockers that have a blockade effect: labetalol, carvedilol
· Beta blockers that act as membrane stabilizer; propranolol
· Central a 2 -sympathomimetics cause negative sympathetic outflow and lowering peripheral
resistance.
· The following beta-blockers are used in treatment of angina:
· Beta-blockers with selective intrinsic sympathomimetics activity (ISA): Acebutolol
· Beta blockers with Non-ISA: Atenolol and metoprolol tartrate can be used.
· Beta blockers with Nonselective, ISA: Pindolol
· Beta blockers with Nonselective, Non-ISA: Nadolol, Propranolol hydrochloride, Timolol
maleate
· The following Calcium Channel Blockers are used in treatment of angina:
· Amlodipine besylate, Diltiazem hydrochloride, Nifedipine, Verapamil hydrochloride
· Drugs that have +ve inotropic and +ve chronotropic effect is dopamine and epinephrine
· Inotropic is force of contraction (+ve increase in force of contraction)
· Chronotropic is heart rate (+ve increase in heart rate)
· Drugs that have +ve inotropic and –ve chronotropic is digoxin
· Drugs that have +ve inotropic are ACE Inhibitors.
PharmacyPrep.
4-20
Antihypertensive drug Therapeutics uses Mechanism of therapy

ACEI
ARBs
Beta blockers
Diuretics
Calcium channel blockers
Vasodilators
TPR Total Peripheral Resistance DHP Dihydropyridine

DBP Diastolic Blood Pressure NDHP Non Dihydropyridine
SBP Systolic Blood Pressure GFJ Grapefruit juice
Hyper HyperGlycemia, Lipidemia, Uricemia, CA Calcium
GLUC Calcemia
GFR Glomerular filtration rate
CO Cardiac output ARB Angiotensin Receptor Blocker
ADH Antidiuretic hormone NO Nitric oxide
BPH Benign Prostate Hyperplasia RBC Red Blood Cell
ACE Angiotensin converting enzyme PIH Pregnancy Induced Hypertension
HR Heart rate SV Stroke Volume
ISA Intrinsic Sympathomimetics Activity LVH Left Ventricular Heart Failure
EMMA Esmolol, Metoprolol, Acebutolol, Atenolol CVA Cardiovascular attacks
NE Norepinephrine CAIs Carbonic anhydrase inhibitors
PharmacyPrep.
4-21
PharmacyPrep.
4-22
www.PharmacyPrep.Com Antihyperlipedemic Drugs
5
Antihyperlipedemic Drugs
Classification of antihyperlipidemic drugs
HMG-CoA reductase inh. Nicotinic acid Bile acid Fibric acid Cholesterol
sequesterants derivatives Absorption
inhibitors
Lovastatin Niacin
Simvastatin Act at liver Cholestyramine Gemfibrozil
Pravastatin Cholestipol Clofibrate
Ezetimibe
Fluvastatin Act at GIT Fenofibrate
Atorvastatin Compete with bile salts
Rosuvastatin prevents reabsorption
LOW DENSITY LIPOPROTEINS (LDL) is composed of TG 4-8%, free cholesterol 4-8%, cholesterol
esters 45-50%, phospholipids 18-24% and apoproteins 18-22%. The LDL receptors contain
apoB-100 and apoE.
Increased intracellular cholestrol results from LDL catabolism inhibits the activity of 3-hydroxy-
3-methyl glutaryl-coenzyme A (HMG-CoA) reductase, the rate limiting enzyme for intracellular
cholesterol biosynthesis.
Target LDL-C TG HDL Total INITIATE

levels cholesterol TREATMENT
Normal <2.5 mmol/L <3.3 mmol/L > 0.9 mmol/L 5 >5 mmol/L
CAD <2 mmol/L <1.7 >1 for men <5 - >4.5 >4.5
> 1.3 for women
Target Apolipoprotein B<0.8 g/L. The apo B levels ¯ with any condition that effect lipoproteins
productions. The - ratio of Apo B to Apo A may indicate higher risk of developing CVD.
FRAMINGHAM RISK CALCULATOR: Estimates the 10-year risk of total cardiovascular disease.
10-year risk ?
FRS <10% LOW RISK
FRS >10-19% MODERATE RISK
FRS >20% HIGH RISK
Statins
PharmacyPrep.
5-1
Generic Trade Generic Trade Name Generic Trade

Name Name Name Name Name
Atorvastatin LIPITOR Fluvastatin LESCOL Simvastatin ZOCOR
Lovastatin MEVACOR Pravastatin PRAVACHOL Rosuvastatin CRESTOR
Mechanism Liver Cell
Acetyl CoA
HMG CoA
HMG CoA STATINS
Reductase
Mevalonic acid
Cholesterol
Therapeutic use: Lower LDL (normal levels <2.5 mmol/L)
Side effects: (HMG = Hepatotoxicity, Myopathy, GI side effect)
GI: Mild upper GI disturbance (Constipation, dyspepsia, flatulance, diarrhea, nausea and
vomiting). Myalgia or arthralgia, sleep disturbances.
HEPATOTOXICITY: Increases liver enzymes AST and ALT (transaminases).
Myopathy (CK-MM), and rarely this may lead to rhabdomyolysis. The rhabdomyolysis is
disintegration and dissociation of muscles. It is common high doses, old age, and in renal
insufficiency patients.
Patient presentation of myalgia is fever, muscle ache, or cramps, unusual tiredness or
weakness.
Rhabdomyolysis is massive muscle necrosis which secondary to acute renal failure.
Drug Interactions: Extreme precaution if combine the medication such as cyclosporine,

itraconazole, erythromycin, clarithromycin, gemfibrozil, niacin, fibrates and grapefruit juice
increase myopathies/myositis and hepatotoxicity, due to inhibition of CYP 3A4 enzyme, which is
essential for metabolism of statin niacin.
CYP3A4;CYP2C9, CYP2C19
STATIN -----------------------------à METABOLITES
Pharmacokinetics: Fluvastatin, lovastatin and simvastatin should be taking at nighttime. Rest

other drugs anytime of the day.
PharmacyPrep.
5-2
· Lovastatin should be always administered with food to increase bioavailability, otherwise it

can decrease 30% bioavailability.
· Atorvastatin can be taken anytime of the day, because has long half-life.
· The best agent for renal disease patient is atorvastatin, because it has minimal renal
elimination, thus do not require dose adjustments.
Statin
Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin
Metabolizing CYP3A4 CYP2C9 CYP3A4 Not known CYP2C9 CYP3A4
Enzyme (s)
Grapefruit juice Avoid Avoid Avoid
Take Anytime At night At night HS Anytime At night
Food With or With or after With or With or With or without With or without
without after without
(↑50%)
HALF LIFE LONG LONG
Statins (A= atorvastatin, L=lovasatin, F=fluvastatin, S = simvastatin, P = pravastatin); FLS = take
at bed time (night); ALS = avoid grapefruit juice (because grape fruit juice inhibit CYP 3A4); ALS
= avoid grapefruit juice (substrate CYP3A4); FLS = take at bedtime; FL = take with food; A = any
time of the day; PF = can taken with grapefruit juice; P = least drug interaction
Pregnacy: All statins are contraindicated to use in pregnancy, breast feeding, and children.
Monitoring: LFT, evaluate liver function and measure serum transaminases and creatin kinase
CK-MM (monitored for myopathy).
Niacin (Nicotinic acid)

Mechanism · Niacin also known as vitamin B 3
· Participation in tissue respiration oxidation, reduction reactions, which
decreases hepatic LDL and VLDL production
· Inhibits tubular secretion of uric acid, causes gout or hyperuricemia.
Therapeutic use · TG reduction 20 to 50% (higher dosage). HDL increase 15 to 35% (greatest
HDL raising effect AND as good as fibrates).
Side Effects · The most common and often dose limiting side effect Intense cutaneous
flushing accompanied by uncomfortable feeling warm and pruritic, dry
skin. Hyperglycemia, hyperuricemia, GI distress like reactivation of peptic
ulcer, flatulance, nausea and diarrhea can be minimized by taking with
food or immediately after food. Hepatotoxicity (if combine with statin can
potentiate hepatotoxicity and myopathy).
Management · Administration of ASA 325 mg prior to taking niacin decrease flushing side
effect. Take with food. Tolerance develops in 1 to 2 weeks.
· Higher dose 2 g/day may produce hepatic damage.
PharmacyPrep.
5-3
· Niacin IR have high flushing, Niacin SR more frequent hepatotoxicity.

· No-flush prep contains Inositol + niacin.
Fibrates
Bezafibrate BEZALIP Fenofibrate LIPIDIL
Gemfibrozil LOPID
Mechanism: Activate peroxysome profilator activating receptors alpha (PPAR alpha) and
alteration of gene expression, resulting in decrease LDL, TG and Increase HDL.
Therapeutic use: Decrease TG levels, LDL levels and
increase HDL levels (moderately). Very useful in treatment
Question Alerts!
of hypertriglyceridemia in diabetic patients. Prophylaxis for
CholeLithiasis predispose
coronary heart disease and cerebrovascular diseases.
gallstone formation.
Side effects: Mild GI disturbances. Drug may cause
accelerate excretion of cholesterol into the bile leading to
cholelithiasis. Lithiasis predispose gallstone formation. If tested discontinue the drug.
Drug Interactions: Combination with statins may lead to myopathies, or rhabdomyolysis.
Contrainidcations. Sever hepatic and renal dysfunction, potentiates warfarin activity.
Preexisting gall bladder disease.
Monitoring: At 3, 6 and 12 mo, and yearly liver function test. Creatinin kinase complete blood
count, and renal function test.
Pharmacokinetics: Fibrates renally eliminated. Thus, no hepatotoxicity. Need dose adjustment

in renal disease.
Fenofibrates decrease serum uric acid levels (uricosuric effect) in normal patients and
hyperuricemic patients.
Antihyperlipidemics Elimination Food LFT CK-MM Uric acid Tips

Atorvastatin Biliary + Long half life; Parent drug 14h, metabolite
(feces) 20-30 hr
Fluvastatin Biliary + Half life <3 hr
(feces)
Lovastatin Biliary With + Half life 1.1-1.7 hrs
(feces) food
Pravastatin Biliary + Long Half life 1.8 hrs, take at bedtime
(feces)
Rosuvastatin Biliary + Long half life 19 hrs
(feces)
Simvastatin Biliary + Half-life 3 hrs
(feces)
Niacin Biliary + + Avoid in uncontrolled diabetics
(feces) Least likely used combination niacin +
statin (increase risk myopathy), - URIC
ACID.
PharmacyPrep.
5-4
Fibrates Renal/Biliar LFT Good for lowering TG

y (feces) / Monitor CK, CBC, liver and renal function
RFT Fenofibrate is uricosuric
Ezetamibe Statin+ezetamibe
Fibrate+ezetamibe
Resins hepatic LFT Monitor LFT and TG
· Pravastatin not extensively metabolized by CYP450. Can be taken with grapefruit juice.
· Should not be used in patients with active liver disease. (Statins & niacin).
Resins(Bile acid sequestrant)

Resins · Cholestyramine and colestipol.
Pharmacological · Anion-exchange resins bind with the enzymes in intestine and inhibit
action the synthesis of cholesterol. Bile acids are synthesized from
cholesterol. Decrease LDL 15 to 30% and increase HDL 3 to 10%.
· No change or increase in TG (disadvantage), avoid in patient with
high triglycerides.
Therapeutic use · Drug of choice in pregnancy.
· Cholestyramine also relieves pruritis caused by accumulation of bile
acids in patients with biliary obstruction in cholestasis.
Side Effects · Decrease absorption of ADEK fat soluble vitamins. Some recommend
concurrent supplementation with fat solube vitamin. High doses of
folic acid and ascorbic acid absorption is reduced. Most common GI
problem constipation, flatulance, stomach fulness, ↑ TG and
transaminase (reversible).
Drug-Drug · These, drug interfere with intestinal absorption of many drugs
interactions (tetracycline, phenobarbital, warfarin, pravastatin, fluvastatin,
aspirin, and thiazide diuretics).
Pharmacokinetics · Urge patient to comply with blood testing, and special diet.
· Urge patient to control weight and stop smoking.
· Recommend high fiber diet to reduce constipation
· Tell patient not to take powder in dry form. Teach patient to mix
drugs with fluids or pulpy fruits.
Dose · 4 to 24 g/day.
Ezetimibe
Mechanism · Selectively inhibit the intestinal absorption of cholesterol and
related phytosterol. (DIETARY CHOLESTEROL)
Therapeutic · Used in combination with statins (increasing dose of statins only
use does not decrease LDL levels; hence combination ezetimibe is
recommended).
Side Effects · GI effects. Abdominal cramps, liver problems, sexual dysfunction
and weight loss.
PharmacyPrep.
5-5
When it used · Muscle pain, chest pains, upper respiratory infections, angioedema,
with statins and skin rash.
Advantage · Does not affects fatsoluble vitamins. Low potential for drug
interactions.
Tips
· FLS: only taken at night (at bedtime), for maximum effect.
· Pravastatin and rosuvastatin have least drug interactions (T/F)
· Statins increase risk of arrhythmias at night (T/F)
· HMG Co A inhibitors are mainly metabolized by àCYP 3A4
· HMG Co A inhibitors side effect rhabdomyolysis patient may notice by àmuscle pain and
CK-MM.
· Which antihyperlipedemic have no effect or increase triglyceride levels à Resins
· Which antihyperlipidemics have equal proportion effect on LDL, HDL and TG --> niacin
· Resins act what part of GI àsmall intestine
· Lovastatin is given with food because àIncrease bioavailability
· Drug of choice against cholesterol in DM patients à Fibrates
· Drug that inhibit intestinal absorption cholesterol --> ezetamibe
· Statins only taken at night (at bedtime), for maximum effect. ( FLSP )
· Statins that have have the least drug interactions (PRAVASTATIN)
· HMG Co A inhibitors side effect rhabdomyolysis patient may notice by (Muscle pain)
· Which antihyperlipedemic have no effect or increase triglyceride levels (cholestyramine )
· Which antihyperlipidemics have equal proportion effect on LDL, HDL and TG (NIACIN )
· What part of GI, resins act (small intestine)
· ANTIHYPERTESNSIVE DRUGS THAT Increase LDL, Decrease HDL and Increase TG (thiazides
AND BETA BLOCKERS)
· Lovastatin given with food because (increase bioavailability)
· Cholesterol lowering drug that should not be used diabetes mellitus patients (niacin, cause
hyperglycemia SE).
· The rate-limiting step in cholesterol biosynthesis is (HMG Co A reductase)
· Lovastatin should be taken with food to (elevate 33% bioavailability)
· HMG Co A inhibitors are mainly metabolized by CYP 3A4 are (ALS)
· A patient taking statins monitor LFT and at CK at 3, 6, 12 months then yearly (true)
ABBREVIATION and TERMINOLOGY
TG Triglycerides DM Diabetes Milletus

CBC Complete Blood Count VLDL Very Low- Density Lipoprotein
HMG 3-hydroxy, 3-methyl glutaric acid LDL Low- density Lipoprotein
LFT Liver Function Test HDL High-Density Lipoprotein
CK Creatinine Kinase FLS Fluvastatin Lovastatin Simvastatin
ADEK Vitamine A, D, E, K ALS Atorvastatin Lovastatin Simvastatin
PharmacyPrep.
5-6
www.PharmacyPrep.Com Nitrates
6
Nitrates
Nitrates are antianginal agents. The most common complications associated with coronary
artery disease includes angina pectoris, MI, post MI, ischemic stroke. Insuficient supply of
oxygen to heart can lead to ischemic conditions.
Nitrates
Short duration Intermediate duration Long duration

Sublingual Oral regular or sustained Transdermal
Nitroglycerin release Isosorbide dinitrite Nitroglycerin patch
Isosorbide dinitrite
Inhaled amyl nitrite
Generic Name Brand Name Generic Name Brand Name

Isosorbide dinitrate Cedocard SR Nitroglycerin SL Nitrolingual
(generics) spray Spray
Isosorbide mononitrate Imdure Nitroglycerin SL
tab,
Nitroglycerin injections, Nitrostat
ointment, patch
Nitrates
Pharmacological action
Nitrate Increase nitrite Increase nitric oxide (NO) Increase cGMP

+ Endothelial cell
Vascular smooth muscle relaxation - Dephosphorylation of myosin light chain
Nitrate reductase Nitrite reductase

Nitrate (NO 3 ) ----------------------àNitrite (NO 2 )------------------------àNitric oxide (NO)
6-1
PharmacyPrep.
Organic nitrates act primarily by vasodilation (especially venodilation). The dilatation of

coronary vasculature, provides increased blood supply to the heart muscles. which reduces
myocardial preload and therefore myocardial oxygen demand. Nitrates also promote
redistribution of blood flow to relative ischemic areas. Effects of nitrates and nitrites on smooth
muscle.
Nitrate produce two major effects "dilation of the large veins (resulting of pooling blood in
veins this reduces preload and decrease work of heart).
NITRATES
¯CARDIAC PRELOAD
¯ MYOCARDIAL OXYGEN REQUIREMENT
Therapeutic use: Coronary vasodilators nitrates are used in treatment of angina and myocardial
infarctions.
Side effects: The most common side effect is headache. Higher doses, postural hypotension,
facial flushing and tachycardia. Long acting nitrate preparations frequently cause headache.
Tolerance to anti-anginal effects of nitrates develops unless a nitrate-free period of 10-12 hours
is used each day.
Drug Interactions: Additive hypotension effect cause severe hypotension with sildenafil,
tadalafil, and verdanafil. Concomitant use of alpha blockers can cause hypotension, thus
require precaution.
Phosphodiesterase V (PDE5)
Endogenous Nitric oxide à Guanylate cyclase à -cGMP-----------------àInactivation
-cGMP - Vasodilation
Relief of agina
Large postural Hypotension
Short acting nitrates

· Nitroglycerin SL spray 0.4 mg for acute (do not shake but prime). Onset <5min. More stable
then SL tab.
· Nitroglycerin SL tablets 0.3 and 0.6 mg for acute CHEST PAIN ASSOCIATED WITH ANGINA OR
MYOCARDIAL INFARCTION. Onset <5min
· Storage Conditions: Amber color, glass and metal capped.
· Dispense in original container. Light sensitive, and hygroscopic.
· Discard cotton present on tablets in bottle.
· Drug expires after 6 months from the day bottle open.
6-2
PharmacyPrep.
Intermediate Nitrates
Isosrobide dinitrate: Oral tablet and SL Onset <10 min
Long acting nitrates: Nitroglycerin transdermal patch 0.2-0.8 mg/hr for 12-14 hr for
maintenance. Onset 30-60 min.
Tolerance develops rapidly. This can be overcome by using “nitrate free period” 10-12 hr and
restore sensitivity to drug.
Nitroglycerin iv for acute. Onset <10 min
Inorganic nitrates: Nitroprusside

Therapeutic use: Drug of choice for hypertensive crisis.
Side effects: Cyanide toxicity (releases CN). Sodium thiosulfite is an antidote (Cyanide
Intermediate) + sodium thiosulfite à sodium thiocyanate (water soluble).
Photosensitive.
Detoxification of cyanide with thiosulfate and rhodenase
Nitroprusside Thiocyanate
Cyanide (toxic) (nontoxic)
Thiosulfate
Tips
· Insufficient supply of oxygen to heart can lead to ischemic conditions à angina, MI
· Nitroglycerine spray storage and administrationà room temperature
· Nitroglycerine SL storage condition requireà room temperature
· Nitrates should be avoid taking with à sildenafil
· What is active moiety of nitrates à nitric oxide
· Nitroglycerine is chemically classified as ànitrates
· Nitroglycerine patch can cause tolerance, to avoid tolerance use nitrate free period.
· Nitroglycerin SL spray storage and administration (room temp)
· Nitrates should be avoided taking with (sildenafil, TADALAFIL, VERDANAFIL)
· What is active moiety of nitrates ( NO )
· Nitroglycerin is chemically classified as (nitrates)
· What drugs effective in MI prevention and treatment (nitroglycerine)
· What nitrates can cause tolerance, to avoid tolerance use nitrate free period. (nitroglycerin
patches)
· What is used for only 6 months after opening bottle: Light sensitive à amber glass and
metal cap: Hygroscopic: dispense in same container; discard cotton (nitroglycerin SL)
· What nitrates can be used until expiry, do not shake, prime it. (nitroglycerin SL spray pump)
6-3
PharmacyPrep.
Select True/False statement

· Nitroglycerine + seldanafil can cause hypotension and this due to vasodilatation contributed
by nitroglycerine and sildanafil (T/F)
· The most common side effect of nitroglycerine is headache; therefore, nitroglycerine should
be taken while sitting position (T/F)
· Nitrates à Increase nitrites àIncrease nitric oxide (NO) à vascular smooth muscle
relaxation

LDL Low density lipoprotein STEMI ST-Segment Elevation MI
SL Sublingual NSTEMI NON ST-Segment Elevation MI
CCB Calcium channel blockers ASA Acetyl salicylic acid
MI Myocarddial infarction
ACE Angiotensin converting enzyme
6-4
PharmacyPrep.
Pharmacyprep.com Cardiac Glycosides: Digoxin
7
Cardiac Glycosides: Digoxin
Cardiac glycosides • Digoxin, and digitoxin
Mechanism • Cardiac glycoside increases myocardial contractility and efficiency
• Improve systemic circulations and improve renal perfusion and reduce
edema.
Positive inotropic • Inhibit the membrane bound Na+/K+ activated ATPase.
effect • Increase intracellular sodium concentration and reduce calcium
transport form cell thus facilitate calcium entry via voltage gated
membrane channel.
Negative • Increased vagal tone of the sinoatrial (SA) node
chronotropic effect • Reduced CNS sympathetic out flow. Systemic arteriolar and venous
constriction.
Vagomimetic effect
Side effects Early stages of toxicity GI, anorexia, nausea & vomiting and diarrhea. CNS
headache, visual disturbances (green and yellow vision) confusion,
neuralgia, and delirium. Bradycardia.
Digoxin Digoxin is the most widely used cardiac glycoside but digoxin has
lowest therapeutic index. INDIVIDUALIZE THE DOSE BASED ON
AGE, WEIGHT, RENAL FUNCTION, AND CONCOMITANT USE OF
DRUGS. THE USUAL DOSE RANGE FROM 0.00625 TO 0.25 mg
DAILY. (6.25 mcg – 250 mcg).
Therapeutic use CHF (↑ SYMPTOMS RELIEF & ↓HOSPITALIZATION BUT NO AFFECT
ON MORTALITY). Atrial fibrillation, protects ventricles (CONTROL
VENTRICULAR RATE). Used to treat atrial fibrillation. However
NOT used to treat ventricular tachycardia.
Side effects 1st sign: GI effects: Nausea, vomiting, diarrhea, blurry yellow
vision, and scotoma. CVS: Arrhythmias, ventricular tachycardia.
CNS: visual disturbances (blurred vision).
Bioavailability • 75% bioavailability, 20-40% protein bound.
• Half life T1/2 = 26 hr to 45 hr
• Urinary excretion
Monitor • Patient should understand the importance of follow up
7-1
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is illegal to
reproduce without permission. This manual is being used during review sessions conducted by PharmacyPrep.
laboratory test for this medication.

• Pulse, ECG and Adjust the dose with renal failure patients.
Digitalis toxicity
Digitalis toxicity Toxicities of digoxin increased by renal failure (decrease excretion)
hypokalemia, or hyperkalemia (potentiates drug effect)
Predisposing Hypothyroidism, hypoxia, renal failure and myocarditis also predisposing factors
factors for digitalis toxicities.
Digitalis toxicity Digitalis toxicity can be managed by discontinue digoxin, monitor blood
Management potassium levels. Sever tachycardia may require the use of Fractionated
antibodies (FAB antibodies). Which bind to inactive digoxin.
Antidote Digifab
Drugs that may cause digitalis toxicity

Drugs that ↑ digoxin levels Drugs that ↓K+ levels
Amiodarone Thiazides
Verapamil Loop diuretics
Erythromycin Corticosteroids
Tetracycline
Quinidine
Digitalis toxicity symptoms are severe nausea vomiting, anorexia, muscular weakness, bradycardia, and
ventricular premature contractions. Severe toxic symptoms include blurred vision, disorientation,
diarrhea, ventricular tachycardia, AV blockade which progress to ventricular fibrillation.
MANAGEMENT OF DIGITALIS TOXICITY: Measure the serum concentration once daily until steady state
accomplished, particularly in elderly and renal disease patients. Measure trough concentration at least
8 hours after digoxin administration and adjust the dose to maintain the serum concentration 0.6 to 1
nm/L.
7-2
Comparison of digoxin and digitoxin

Digoxin Digitoxin
Digoxin has advantage of a relatively short Binds strongly to proteins extravascular space,
half-life compared to digitoxin, which allows resulting in large volume of distribution.
better treatment of toxic reactions.
Rapid onset of action. Slow onset of action
Digoxin eliminated largely unchanged in urine Extensively metabolized by liver before it
excretes in feces.
Avoid in ventricular arrhythmia. Where as
used in supra ventricular (atrial arrhythmias).
Tips
• Natural source (genus and species) of digoxin Digitalis lanata.

• Digoxin pharmacological action include  positive inotropic, negative chronotropic and
vagomimetic effect
• Comparison of digoxin and digitoxin, which is short acting and why digoxin is more water soluble,
and excrete faster
• Digoxin antidote digifab
• Symptoms of digoxin toxicity  severe nausea vomiting, anorexia, muscular weakness,
bradycardia, and ventricular premature contractions. Severe toxic symptoms include: blurred
vision, disorientation, diarrhea, ventricular tachycardia, AV blockade which progress to ventricular
fibrillation.
• Drugs that cause digitolis toxicity include --> thiazides, loop diuretics, corticosteroids, erythromycin,
verapamil, and quinidine.
• Digoxin antidote (digifab).
• Pharmacological action of digoxin includes +ve inotropic, -ve chronotropic and vagomimetics
(digoxin).
• Signs of toxicity are nausea and vomiting, palpitation (digitalis toxicity).
• Drugs that can cause digoxin toxicity (hypokalemic drugs, AMIODARONE, quinidine, verapamil,
tetracycline, ERYTHROMYCIN, CLARITHROMYCIN).
ABBREVIATION and TERMINOLOGY

CHF Congestive heart failure SA Sinoatrial
ACE Angiotensin converting enzyme ECG Electroencephalograph
CCB Calcium channel blockers CVS Cardiovascular system
CNS Central nervous system
7-3
7-4
www.PharmacyPrep.Com Antiarrhythmic drugs
8
Anti Arrhythmic Drugs
ANTIARRHYTHMIC DRUGS CLASSIFICATION
+
Class I Na Class II Class III Class IV Miscellaneous
+ 2+
channel b-blockers K channel Ca channel
blockers blockers
Ia- Esmolol blockers Verapamil Adenosine
Quinidine Propranolol Amiodarone Diltiazem Magnesium
Procainamide Atenolol Dronedarone
Disopyramide Metoprolol Bretylium RATE
Nadolol Dofetilide CONTROL
Ib: Lidocaine RATE CONTROL Sotolol
Mexiletine DRUGS
Tocainide RHYTHM
Ic: Flecainide CONTROL DRUG
Propafenone
RHYTHM
CONTROL DRUG
Arrhythmias: Arrhythmias develop because of abnormal impulse generation, propagation or

both. Cardiac arrhythmias are related to abnormal electrical activity of the heart resulting in
either altered rhythm or impulse conduction.
Supraventricular (atrial) SVA Ventricular arrhythmias (VA)
Premature atrial contraction Premature ventricular contraction (PVC)
Atrial flutter Ventricular tachycardia (VT)
Atrial fibrillation (left atrium) Ventricular fibrillation (VF)
· Paroxysmal supraventricular
tachycardia (PSVT)
· Sinus tachycardia
· Sinus bradycardia
*ATRIAL FIBRILLATION: PWAVE IS INVISIBLE (HIGHER RISK OF THROMBUS)
*ATRIAL FLUTTER: PWAVE IS VISIBLE BUT ATRIAL RATE HIGHER THAN VENTRICULAR
RATE.
8-1
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and
it is illegal to reproduce without permission. This manual is being used during review sessions
conducted by PharmacyPrep.
Antiarrhythmic drugs act on 4 ion channels in cardiac muscles;Voltage activated Na+

channel; Voltage activated Ca 2 + channel; Voltage activated K+ channel (Ikr)
ANTIARRHYTHMIC DRUG ACTIONS
CHANNELS RECEPTORS Clinical Effects
DRUG
Vaughn-
Ca2 N K+ ᾳ ẞ A Ade Pro- Extra LV Heart
Williams ECG +-
a+ C nosi Arrhy Cardi func Rate
Class Chang
h ne QT ac tion
e
prolongatio
n
Quinidine M M L M H M
A Procainami M M M M H ↓↓
de M M L M
I Disopyrami
de
B
Lidocaine L M L M ↓↓ ↓
Mexiletine L L M ↓↓
Profafenon M L
C e M L
Flecainide
II ẞ-blockers H L L ↓ ↓↓
Dronedaro L L H M M M L H ↓ ↓
III ne L L H M M M L H ↓ ↓
Amiodaron H H H L ↓
e ∆ H H L
Sotalol H H L
Ibutilide
Dofetilide
IV Verapamil M L L ↓↓ ↓
Diltiazem M L L ↓ ↓
Misc Adenosine ∆ L L
Antagonist relative potency ∆ = Agonist
L = Low ECG Changes related to Ca ++ channel block
M= Moderate ECG Changes related to Na + channel block
H= High ECG Changes related to K+ channel block
Ach – Acetylcholine
Antiarrhmic Drug Classes
ANTIARRHYTHMIC DRUG CLASSES
1a Quinidine Phase 0 Slows depolarization
Procainamide Na+ In
Disopyramide
1b Lidocaine Phase 3 Shortens repolarization (shortens duration of
+
K Out refractory period)
1c Flecanide, phase 0 Significantly slow depolarization (slow conduction)
+
Propafenone Na In
II Propranolol phase 4 Decrease depolarization (beta 1 blocker action)
III Amiodarone phase 3 Prolong repolarization (increase refractory period)
Dronadarone
8-2
sotalol
IV Verapamil Phase 2 Shortens action potential (increase refractory period
Ca 2 In
+ AV node)
Myocardial action potential curve reflects action potential, which describes electrical
activity of five phases. This occurs in atrial and ventricular myocytes and purkinje fibers.
Phase 0: Rapid depolarization Na+ enters the

cell.All class 1a drugs
Phase 1: Early rapid repolarization: K+ leaves the
cell
Phase 2: Plateau: Ca+ enters the cell
Phase 3: Final rapid repolarization: K+ pumped out
of the cell
Phase 4: Slow depolarization: K+ inside the cell and
Na+ outside the cell
Phase 1 to starting phase 3 is ABSOLUTE

REFRACTORY PERIOD or Effective Refractory
Period, the cell cannot respond to any stimuli.
During phase 3 is Ansolute refractory period the
cell ability to respond stimuli increases or cell can
respond to strong stimuli.
Drugs and diseases that can lead to Q-T

prolongation. Phenothiazine and haloperidol-
anyipsychotics. Type III antiarrhythmic drugs.
In patients with renal failure
Electrocardiograph Wave Forms. The electrical activity occurs during depolarization and
repolarization transmitted through electrode attached to the body and transformed by
an electrocardiograph into series of waveforms.
· P Wave: indicated atrial depolarization.
· PR INTERVAL: indicates the spread of impulse from the atria to the purkinje fibers.
· QRS Complex. indicates ventricular depolarization
· ST Segments. Indicates phase 2 of the action potential, the absolute refractory
period.
· T Wave: shows phase 3 of the action potential ventricular repolarization.
· Q-T Interval. Mechanical contraction of the ventricles (Torse de pointes).
· U wave. Caused by hypokalemia.
8-3
Clinical indicationsofantiarrhythmic drugs
Na+ channel blockers Clinical indications

1a Quinidine Used primarily for malaria, but not for arrhythmias due to its side effects,
proarrhythmia & better drug options being available
Procainamide Most atrial and ventricular arrhythmias in patients without a history of
ischemic heart disease
Drug of 2nd or 3rd choice in the CCU for the treatment of sustained
ventricular arrhythmias following an MI (amiodarone & lidocaine are
preferred)
Disopyramide
1b Lidocaine Drug of 2nd choice (vs amiodarone) to terminate VTach and prevent VFib after DC
cardioversion
Used only in a hospital setting (not effective orally)
Ineffective against atrial arrhythmia
1c Flecanide, Supraventricular arrhythmias in patients without a history of ischemic

heart diseas
Propafenone
Beta blockers
Propranolol Rate control drugs for tachycardia.
II Atenolol
Carvedilol
Class III K+ channel Blockers

III Amiodarone The most commonly used Class III drug is amiodarone. It is also
one of the most commonly used drugs for chronic treatment of
arrhythmias. It is effective against both ventricular and atrial arrhythmias
Dronadarone
sotalol Adjuvant drug to reduce ICD (implantable cardioverter-defibrillator)
shocks in patients with an ICD
Drug of 2nd choice to prevent the re-occurrence of atrial fibrillation
(rhythm contro
Calcium Ca2+ Channel Blockers

IV Verapamil Prevent re-occurrence (prophylaxis) of AVN reentry (by ↑AVN ERP)
Diltiazem e.g. Paroxysmal SupraVentricular Tachycardia
Control ventricular rate in patients with atrial tachyarrhythmias, such
as atrial fibrillation (by ↑AVN ERP)
Digoxin
Digoxin is often used in the treatment of patients with systolic heart failure
8-4
Digoxin who have atrial fibrillation, to slow ventricular rate to <90/min. Most other
drugs that can be used to achieve the same goal have undesirable negative
inotropic side effects (e.g. beta blockers and calcium channel blockers), which
could be potentially harmful in a patient having a low ejection fraction. Hence
this remains a primary indication for the use of digoxin,
MAJOR SIDE EFFECTS OF ANTIARRHYTHMIC DRUGS

Na+ channel MAJOR SIDE EFFECTS
blockers
1a Quinidine Produce anticholinergic effects on the heart due to their ability to block m2
receptors.
Partially block L-type Ca channels cause negative inotropic effect
Procainamide Procainamide: Lupus erythematosus-like syndrome that occurs in 20-
25% of all patients on drug therapy for more than 1 year
Disopyramide
CNS excitation and/or depression (drowsiness, dissociation), nausea,
1b Lidocaine tremor, vertigo, metallic taste, numb lips, visual and hearing
disturbances. Class Ia & most Class III drugs produce Torsede pointes.
1c Flecanide, Quinidine “syncope”(fainting) is typically caused by this Torse de pointes
arrhythmia.
Propafenone Procainamide is converted to N-acetylprocainamide (NAPA) which has
Class III actions (including proarrhythmia) and has a longer half-life than
procainamide. NAPA levels accumulate with chronic therapy
Propafenone: proarrhythmia in patients with ischemic heart disease
potentially life-threatening situation of dangerous acceleration of ventricular rate can
also occur when attempting to treat atrial flutter or fibrillation with a Class Ia drug alone
Beta blockers MAJOR SIDE EFFECTS

Propronolol bradycardia, hypotension, left ventricular failure, AVN block, bronchospasm
Class III K+ Blockers

K+ Blockers MAJOR SIDE EFFECTS
Amiodarone corneal microdeposits in most patients
Dronedarone: peripheral neuropathy
PULMONARY FIBROSIS (rare with normal therapeutic doses, but
Sotolol potentially fatal)
disturbed thyroid function (hypo- or hyper-thyroidism)
photosensitivity with blue-gray discoloration
may precipitate heart failure
very rare incidence of Torsade de Pointes (compared to other drugs)
Dronedrone: structurally related to amiodarone but without the iodine
component so it does not posse’s amiodarone's iodine related organ
toxicity (NO hypothyroidism, pneumonitis, corneal toxicity, and
pigmentation).
Sotolol: non-selective beta blockade (one enantiomer is a beta-blocker, the
other blocks IKr). Torsade de pointes
8-5
Tips
· What drug cause severe QT prolongation (torse des pointes)à Class 1a and class III
· Digoxin is contraindicated in what type of arrhthmiasàventricular arrhythmias
· Amiodarone side effects are photosensitive reactions, skin pigmentation, blurred
vision. Pulmonary toxicity (pneumonitis) and inhibit peripheral conversion of T 4 to
T3 .
· What drug cause QT prolongation (torse des pointes)à Class I and mainly Sotolol
class III (K+ channel blockers)
· Amiodarone mechanism à Amiodarone blocks both Na+, K+ channels and has a and
b antagonist action. iv dosage gives effect on K+ channels
· Amiodarone oral dosage gives effect on à all (Na+, K+, a and b)
· Amiodarone side effects are: (4Ps) Photosensitive reactions (skin pigmentation),
Blurred vision. Pulmonary toxicity (Pneumonitis), Inhibits peripheral conversion of T 4
to T 3 . can cause hypo or hyper thyroids.
8-6
PharmacyPREP.Com Anticoagulants
9
Anticoagulants
Anticoagulants
LMWH
Heparin Vit K antagonist Factor10:2 Factor 10a Inh Others
Enoxaparin
Catalyzes the Warfarin Fandaparinaux Direct thrombin (IIa)
Dalteparin
inhibition of (indirect) Dabigatran (Pradaxa)
Tinzaparin
thrombin 3 Rivaroxaban
Nadroparin
(direct)
Apixaban
Heparin sodium
Warfarin act on extrinsic

Blood clot initiates by two pathways.
9-1
PharmacyPrep.
Heparin (Unfractionated Heparin)

Mechanism · High molecular weight mucopolysaccharide. Heparin directly
deactivates clotting factor II and X. Heparin therapy is monitored by
aPTT assay because aPTT monitors factor II and X as well as other
factors.
· Binds to the antithrombin III (also known as heparin cofactor) to
cause a rapid anticoagulation effect. Heparin catalyzes the factor
(thrombin activation factor) 2a, 9a, 10a, 11a, 12a, and 13a.
Therapeutic use · Major antithrombotic drug for prophylaxis DVT and pulmonary
embolism. To prevent postoperative venous thrombosis in patient
undergoing surgery. Maximum effect occurs within minutes.
Drug-Drug · Do not take ASA, which may increase the anticoagulant effect of this
interaction drug and the risk of bleeding in the intestines or joints.
Side Effects · Hypersensitivity reaction (chills, fever, urticaria etc), bleeding,
heparin induce thrombocytopenia (HIT).
Contraindications · Alcoholics, bleeding disorders, brain, eye, spinal chord surgeries.
Monitoring · Periodic blood and liver test will be required aPTT (activated partial
thromboplastin time) after 6 hours of initiating heparin.
Advantage · Can be used in pregnancy
Dosage · iv and SC
Heparin Anticoagulation Mechanism
With Heparin Without Heparin

Active clotting factors Active clotting factors
IIa, IXa, Xa, XIa, XIIa, XIIIa IIa, IXa, Xa, XIa, XIIa, XIIIa
Anti Thrombin III Anti-thrombin III

Rapid Slow
& Heparin
Inactive factors Inactive

2, 9, 10, 11, 12, 13
Question Alerts!
1) Heparin dosage forms?
2) Antidote of heparin?
3) Heparin is monitored by? aPTT
4) sc dose of heparin is given based on body weight.
1) What is laboratory test monitored for LMWH?
2) What symptoms are monitored in patient using LMWH?
9-2
PharmacyPrep.
LowMolecular WeightHeparin
LMWH · Enoxaparin, Dalteparin, Tinzaparin and Nadaroparin

Mechanism Higher effect on factor Xa than heparin. More specific to factor X and
less against factor II (thrombin).
Therapeutic · The drug of choice for the prevention (prophylaxis) and treatment of
DVT or PE, NSTEMI and unstable angina.
Monitoring · Does not change prothrombin levels. Act longer and do not require
close blood monitoring as heparin does. LMWH have predictable
response. Highly predictable dose response relationship.
Side effects · Hypersensitivity reaction (chills, fever, urticaria etc), bleeding.
· Heparin induce thrombocytopenia (HIT) is significantly low LMWH.
· Heparin induced osteoporosis is significant in low in LMWH.
Dosage · SC and iv available.
· These administered parenterally as sodium salt. Because poorly
absorbed from GI tract LMWH are not interchangeable with heparin in
their actions and use. Because these highly acidic.
Warfarin Question Alerts!

Vitamin K-dependant proteins or clotting factors. "01972"
Mechanism · Vitamin K antagonist producing their anticoagulant effect by interfering

with cyclic interconversion of vitamin K and it 2,3-epoxide (vitamin K
epoxide) in LIVER.
· Inhibition of vitamin K-dependent proteins or clotting factors 2, 7, 9
and 10.
Therapeutic · Anticoagulant used to prevent blood clots, mainly in areas where blood
flow is slowest, particularly in the leg and pelvic veins.
Side Effects · Bleeding, purple toe syndrome, and skin necrosis

Monitoring · Prothrombin time (PT) ratio and international normalized ratio (INR)
are performed daily upon starting warfarin.
· Oral anticoagulant therapy warfarin INR should be between 2 to 3
Antidote · Vitamin K
9-3
PharmacyPrep.
Warfarin
Chronic alcohol
Vitamin K epoxide reductase Barbiturates
Rifampin
Vitamin K VitaminK epoxide Vitamin K
Polypeptides Dark green vegetables
Spinach
O COO- Cheddar cheese
O
HOOC NH2 CO2 HOOC NH2 Cabbage
Ginseng
Active Clotting Factors
Precursor of clotting Factors Sulfonylureas
II, VII, IX, X
II, VII, IX, X Edema
Hypothyroidism
↓INR Cholestyramine
Penicillin (high doses)
Warfarin Nafcillin
Oral contraceptives
Decrease intestinal flora

Acute alcohol
Cotrimoxazole
Metronidazole
Phenylbutazone
Due to decrease synthesis of
clotting factor Cefamindole
Cefaprazone
Warfarin Cefatetan
Cefametazole
INR
Due to additive effects
Heparin
LMWH
Thrombolytic agents
Comparison of heparin, LMWH and warfarin
HEPARIN LMWH WARFARIN
(UNFRACTIONATED) Enoxaparin, Dalteparin, Tinzaparin,
Nadroparin
Source Natural Unfractionated FRACTIONATED Synthetic
MUCOPOLYSACCHARIDES MUCOPOLYSACCHARIDES
Route Parenteral (SC and IV) SC and IV Oral
Mech Enhances the serum More specific to factor Xa and Inhibits the hepatic
protease antithrombin III less to factor II. synthesis of vit K
results in dependent factors II, VII,
Inactivation of fators IIa, IX, and X.
IXa, Xa, XIa, XIIa, XIIIa.
Antidote Protamin sulfate. This Protamine sulfate Vitamin K,
works by acid base K 1 = phytanadione
neutralization.
9-4
PharmacyPrep.
Site of action In vitro, In vivo In vivo only (liver) or

Intrinsic and extrinsic extrinsic pathway only.
Onset of action Faster (minutes) Longer half life long half life 6 to 8 hours
Pregnancy Yes LMWH do not cross placenta NO (Terotogenic)

alternate to heparin
Renal Can be use in <30 ml/min Renally cleared and first order Safe in renal
CrCl kinestics. Avoid <30 ml/min CrCl.
monitor aPTT No monitoring. Predictable dose INR 2-3
response relationship.
KINETICS DOSE AJUSTED TO MORE PREDICTABLE THAN COMMON CAUSE OF
PROLONG aPTT TO A HEPARIN. POOR ANTI-COAGULANT
TIME HEPARIN anti-XA CONTROL IS DUE TO
levels 0.3 to 0.7 (aPTT DRUG INTERACTIONS.
1.5-2.5 TIMES)
New oral anticoagulant comparison

NOAC WARFARIN Dabigatran Apixaban Rivaroxaban
MOA Vitamin K Direct Thrombin Factor Xa inh. Factor Xa inh.
antagonist inh.
Dosing Once daily Twice daily Twice daily Once daily
Prodrug No Yes No No
Bioavailability 100% 6% 60% 80-100%
15, 20 mg
taken with food
Time to peak 4-5d 1-3 h 1-2h 2-4h
affect RAPID ONSET RAPID ONSET RAPID ONSET
Half life 40 h 11 h 12 h 5-13 h
INR 2-3 NO MONINTORING OF ANTICOAGULANT EFFECT IS REQUIRED
BECAUSE THEY ARE GIVEN FIXED DOSE.
Renal clearance None 80% 25% 33
Safe. No dose CrCl <30 ml/min CrCl <15 ml/min CrCl <30 ml/min
AVOID adjustment
require
CrCl/dose 110 mg; 30-49, >25 ml/min, check (30-49) 15 mg od
>65yo,↑risk factor age, weight, SrCr (>50), 20 mg od
for bleeding.
AF, DVT, prevention and prevention and prevention and

prevention and reoccurrence of AF reoccurrence of AF reoccurrence of AF
reoccurrence of AF
D-D Interaction CYP 2C9, 2C19, P-gp CYP3A4, P-gp* CYP3A4, P-gp
3A4
D-L interaction PT and INR aPTT, Thrombin PT, INR and aPTT PT, aPTT, Heptest.
effective to assess Time (TT), Ecarin are little affection. influenced but none is
anticoagulant clotting time (ECT). Not useful in used to assess. PT (not
effect. If necessary test assessing INR) may be used
are used to assess anticoagulant excess anticoagulant
anticoagulant. *** effect activity.
Antidote Vitamin K NO available NOT available Not available
9-5
PharmacyPrep.
· St. John wort strong induce of both CPY3A4, P-gp (p-glycoproteins) may lead to reduced
drug plasma concentration.
· Grapefruit juice is only a moderate CYP3A4 inhibitor, therefore grapefruit juice
consumption is not expected to be clinically relevant.
· To assess dabigatran anticoagulant activity PT (INR is NOT useful and should not be used for
this purpose.
Tips
· Prothrombin time (extrinsic pathway) à warfarin
· Partial thromboplastin time (instrinsic pathway) à heparin
· Heparin antidote à protamine sulphate
· Patient taking heparin monitored for àaPTT
· Heparin action include àfactor 2a,9a, 10a,11a, 12a and 13a
· What is the safest anticoagulant in pregnancy àheparin
· What are the factors heparin inhibits à factor 2a,9a, 10a,11a, 12a and 13a
· Monitor warfarin through àPT, INR
· What do you monitor in low molecular weight heparin (LMWH) ànone
· Vitamin K supplements and green vegetable effect on INR by à decrease
· Increase in INR can increase risk of --> bleeding
· Heparin + protamine sulfate antidote mechanism of action àneutralization
· ASA and NSAIDs interaction with warfarin à increase risk of bleeding
· Warfarin act on what factors vitamin K à 2,7, 9, and 10
· Recurrance of heparin induced thrombocytopenia syndrome can be prevented by usingà
Fondaparinux (Monitor platelet count every other day for 14 days until heparin therapy is
stopped and use other anticoagulants or antithrombotics)
· Warfarin blocks epoxide reductase preventing gamma craboxylation of 2, 7, 9. 10 so PT, and
PTT are prolonged
· Direct acting thrombin inhibitor is --> Dabigatran
· Clotting factor Xa inhibitor --> Fondaperinaux
9-6
PharmacyPrep.
www.PharmacyPrep.Com Antiplatelet Drugs
10
Antiplatelet Drugs
Antiplatelet drugs
COX inhibitor or ADP receptor TxA2 Inh Glycoprotein IIb/IIIa

irreversible platelet inh. antagonists Dipyridamole receptor antagonists
ASA Clopidogrel Abciximab

Prasugrel Eptifibatide
ticagrelor Tirofiban
Ticlopidine
Platelets are the elements of blood cells, tend to clump together. The antiplatelet drugs
interfere with the coagulation by inhibiting platelet aggregation. Heart attacks and strokes
occur when a blood clot that forms in a narrowed portion of an artery blood flow and cuts off
the supply of oxygen and nutrients to the tissue that lies beyond the site of the clot.
Antiplatelets drugs works by one of the 3 mechanisms
1) Formation of ligands example ASA decrease TxA 2 formation (irreversible platelet aggregation
inhibitor). The minimum dose required ASA to produce antiplatelet effect is 60 to 80 mg acts as
antiplatelets. ASA 81 mg (enteric coated), and ASA 80 mg (chewable).
The cyclooxygenase (COX) enzyme is present in platelets, which is precursor of Thromboxane

A 2 , and TXA 2 are potent vasoconstrictor and labile platelet aggregation inducer.
2) Thrombin production releases adenosine diphosphate (ADP): The ADP is potent inducer of
platelet aggregation and stimulates prostaglandin synthesis from arachidonic acid in
platelet membrane.
Blocking interaction of ligands binding with ADP receptor on platelets.
Example Clopidogrel, Prasugrel, ticagrelor and ticlopidine
PharmacyPrep.
10-1
Clopidogrel and ticlopidine given those who do not tolerate ASA. Interact with glycoprotein
IIb/IIIa (a fibrinogen receptor) resulting in an inhibition of the fibrinogen to form aggregated
plug.
3) Interfere with intracellular signaling (Glycoprotein IIb/IIIa inhibitor). Example Abciximab,

Eptifibatide, and Tirofiban.
Acetyl Salicylic Acid (ASA)

The enzyme cyclooxygenase is present in
platelets. The cyclooxygenase catalyzes the
production of prostaglandin and then Question Alerts!
thromboxane A 2 . 1) What dose ASA is used as
antiplatelets agent? 80-325 mg
· Thromboxane A 2 is potent vasoconstrictor
2) Does enteric coated ASA have GI
and platelet aggregation inducers.
bleeding?
· The production of thromboxane’s is
effectively inhibited by ASA, which
permanently inactivates COX through covalent acetylation of COX enzyme.
· ASA antiplatelets action occurs at minimum 60 to 80 mg. Available strengths. ASA 81 mg
enteric coated and ASA 80 mg chewable.
ASA 80-325 mg once daily. SEs. GI bleeding (serious GI bleeding less common with lower doses
(80-160 mg daily). Bleeding risk increase if combined with other antiplatelets or anticoagulants.
Question Alerts!
1) Mechanism of clopidogrel?
2) Ticlopidine SEs and monitoring? Agranulocytosis and CBC or WBC
3) If patient is allergic to Ibuprofen, can a low dose ASA is used? ASA is not used if patient
allergic to any of NSAIDs.
Adenosinediphosphate(ADP)receptor blockers
Clopidogrel, Prasugrel, ticagrelor and ticlopidine

Pharmacological Thrombin production releases ADP. It is potent inducers of platelet
action aggregation and stimulates prostaglandin synthesis from arachidonic
acid in the platelet membranes.
Therapeutic use · Reduce thrombotic risk in patient usually cannot tolerate ASA or
the drug of choice in patient with allergic to ASA.
Side effects · Ticlopidine: hemorrhagic complications such as bruising or
ecchymosis, epistaxis, this can cause severe neutropenia 2.5%
(agranulocytosis). Rash and diarrhea. Monitor. CBC weekly.
PharmacyPrep.
10-2
Contraindications · Presence or history of hematopoietic disorders (such as

neutropenia, thrombocytopenia or agranulocytosis).
· Hemorrhagic diathesis or presence of hemostatic disorder
· Conditions associated with active bleeding, such as bleeding
peptic ulcer or intracranial bleeding, severe liver dysfunction.
Storage conditions · Store at room temperature. Dispense in light-resistant containers.
Blister packs should not be exposed to light.
Dosage · The recommended dose is 250 mg twice daily with food.
Pharmacokinetics · Ticlopidine should be taken with meals to minimize GI
intolerance. Clopidogrel hepatic elimination, renal dose
adjustment is not necessary.
Glycoprotein IIb/IIIareceptor antagonists
Abciximab, Eptifibatide and Tirofiban

The final common pathway in platelet aggregation is the expression of functional glycoprotein
IIb/IIIa (also known as integrin alpha, beta) receptors. These proteins help fibrinogen molecules
to bind with platelet cell surfaces receptor sites.
Eptifibatide and tirofiban: Indicated for unstable angina, NSTEMI and cutaneous coronary
procedure. mainly used during and after coronary artery procedures like angioplasty to prevent
platelet aggregation.
Side effects: bleeding (risk of serious bleeding is low). Primarily at puncture sites.
Thrombocytopenia.
Miscellaneous: Epoprostenol is prostacyclin, PGI2, PGX, a bicyclic oxidative prostaglandin

metabolites of arachidonic acid with potent vasodilatory and antiplatelet aggregation
properties.
Tips
· Life of platelets is --> 7 to 10 days

· What is the usual dose of ASA is used as antiplatelet to prevent cardiovascular death à
80-325 mg
· What is the mechanism of ASA antiplatelets action --> irreversible inhibition of platelets
· What is the effect of ASA on warfarin à increase risk of bleeding
· Mechanism of action of clopidogrel --> ADP inhibitor
PharmacyPrep.
10-3
· Abciximab and Eptifibatide are examples of --> glycoprotein IIb & IIIa inhibitors.
· A prescription for combination of ASA 325 mg and Clopidogrel 75 mg is used for? Post
MI in patient with stent.
· What is the drug of choice antiplatelet in patient allergic to ibuprofen? Clopidogrel
PharmacyPrep.
10-4
www.PharmacyPrep.Com Thrombolytic Drugs
11
Thrombolytic Drugs
Thrombolytic are also known as fibrinolytic used to dissolve already been formed thrombus, as
in conditions such as deep vein thrombosis, acute stroke, acute pulmonary embolism and acute
myocardial infarction.
Thrombolytic Drugs
Streptokinase Anistreptase (Aminase) Urokinase

t-pa
(Strepto protein from Prodrug of streptokinase (Abbokinase)
(tissue type
Group C-B-hemplytic plasminogen activator)
steptococci bacteria
Directly degrade Alteplase (activase)
fibrin and Reteplase (Retevase)
fibrinogen very high affinity to
plasminogen, bound to
thrombus

Alteplase Activase Urokinase Abbokinase
Reteplase Retevase Anistreplase Aminase
Streptokinase Tenecteplase
Thrombolytics also known as fibrinolytics. Tissue plasminogen activator tPA are alteplase and
reteplase.
Pharmacological action: Blood clots are dissolved by the action of the fibrinolytic system.
· Facilitate conversion of plasminogen to plasmin that subsequently hydrolyzes fibrin to
dissolve clots.
· Recombinant DNA derivatives of tissue plasminogen activator (tPA).
· They contain 527 and 355 amino acids of natural tPA.
· tPA catalyzes the conversion of plasminogen to plasmin.
11-1
PharmacyPrep.
VIIa
Blood
IX X
Xa X
Prothrombin (II) Thrombin IIa
Thrombolytics:
Streptokinase XII
Urokinase
Alteplase
Fibrinogen
Catalyzation
Plasminogen Plasmin Fibrin (Soluble)
XIIa
Fibrin degradation product Fibrin (insoluble)

Site of injury
Tissue plasminogen activators (tPAs)

Alteplase and Reteplase
· These drugs have low affinity for free plasminogen but a very high affinity for plasminogen
bound to fibrin in a thrombus. Both streptokinase and urokinase lack this specificity and act
on free plasminogen inducing generalized thrombolytic state.
· Alteplase has greater specificity to older clots than newer clots.
Contraindications: cerebral bleeding (hemorrhagic), high blood pressure, acute stroke > 3.5 and
MI > 6 hr.
Streptokinase ------------> plasminogen
Streptokinase
Mechanism · An enzyme produces by streptococcus bacteria.
· Dissolve the fibrin of blood clots, especially those in the arteries of the heart
and lungs.
Therapeutic use · Acute coronary syndrome, deep vein thrombosis, pulmonary embolism and
cerebrovascular stroke.
Drug-Drug · There is an increase bleeding when anticoagulants are taken at the same
interactions time as streptokinase.
11-2
PharmacyPrep.
Side Effects · Can produce allergic reactions (urticaria). Give antihistamine before starting
the treatment. Because allergic reactions are more common with
streptokinase urokinase.
· Excessive bleeding
· Bronchospasm
· Angioneurotic edema
· Headache
Monitoring · Don’t give second streptokinase within 6 months of the first treatment.
Urokinase
Mechanism It is an enzyme with the ability to directly degrade fibrin and
fibrinogen.
Two-chain serine protease obtained from cultured human kidney cell.
Therapeutic use Coronary artery thrombosis, Pulmonary embolism (PE).
Side effects Allergic reactions may lead to bronchospasm and skin rash
Anistreplase
It is prodrug of streptokinase, It is used to improve streptokinase

pharmacokinetic profile.
APSAC (Anisoylated plasminogen streptokinase activator complex)
Mechanism It is a complex of human lys-plasminogen and streptokinase with
anisoyl group blocking catalyst site.
Therapeutic Acute MI, coronary artery emboli lysis.
use
Tips
· Thrombolytic drug dissolve blood clot by activating? Plasminogen

· Plasmin is a proteolytic enzyme that is capable of dissolving? Fibrin molecules.
· t-PAs are à Alteplase, and reteplase.
· Thrombolytic therapeutic use is àAcute stroke, Acute coronary syndrome (MI or heart
attack) and some cases deep vein thrombosis and pulmonary embolism.
· Streptokinase is produced by? Streptococci (hemolytic bacteria).
· The most common side effect of thrombolytics? Hemorrhage or bleeding
11-3
PharmacyPrep.
11-4
PharmacyPrep.
www.PharmacyPrep.Com Antidepressants
12
Antidepressants
Classification of Antidepressants
Monoamine Oxidase (MAO) INH Amine reuptake a2 receptor inhibitors + 5HT2 INH.
IRREVERSIBLE non-selective MAOi inhibitors drugs Mirtazapine (SARI)
Phenelzine
Tranylcypromine
REVERSIBLE selective MAO-A (RIMA).
Moclobemide
Non-selective 5HT only
5HT, NE, D Selective serotonin
reuptake inhibitors
Fluoxetine
Fluvoxamine
Tricyclics (TCA’s); 5HT, NE DUAL ACTING
Paroxetine
Tertiary amine type (5HT & NE) SNRI Sertraline
Amitriptyline Venlafaxine Citalopram
Imipramine Desvenlafaxine Escitalopram
Secondary amine type Duloxetine Vortioxetine
(5HT<NE) Trazodone
Desipramine
sNDRI 1st line therapy for major
Nortriptyline
Bupropion depression
1st line therapy for
major depression
Abbreviations: 5HT = 5-hydroxy tryptamine (Serotonin), NE = Norepinephrine; SNRI =
Serotonin Norepinephrine Reuptake Inhibitors, NDRI = Norepinephrine Dopamine
Reuptake Inhibitor; RIMAs = reversible inhibitors of monoamine oxidase. TCA = Tricyclic
Antidepressants.
Serotonin has variety of central and peripheral physiological actions such as

vasoconstriction, regulation of body temperature, mood, sleep and hormonal
regulations.
Depression occurs due dysregulation in the production, uptake or reuptake

(presynaptic) of 5HT, NE, D, neurotransmitter.
LOW MOOD OR DEPRESSION ANTIDEPRESSANTS SEROTONIN SYNDROME
¯5HT, NE, D NORMAL 5HT, NE, D -5HT, NE, D
12-1
Serotonin targets:
Serotonin receptors (peripheral effects)
Serotonin reuptake process (central)
Serotonin degradation by MAO. (Central)
Signs and symptoms of depression. “SADIFACES”

S = Sad feeling
A = Loss of Appetite
D = Depressed Mood
I = inability to feel pleasure
F = Fatigue
A = Anxiety
C = Concentration (difficulty in concentration)
E = Esteem (feeling of worthless)
S = Suicidal (self-harming)
Sadness, tearfulness, dejection, self-criticism, loss of ability to experience pleasure, loss
of appetite, inability to sleep and loss of libido.
5HT NE Dopamine
Mood Alertness REWARD
Cognitive function Energy PLEASURE
Compulsive & obsessive EUPHORIA
Anxiety MOTOR FUNCTION
PROCESSING SLEEP MOTIVATION
MEMORY
Selective Serotonin Reuptake Inhibitors (SSRI)

The SSRIs are selective in blocking the reabsorption of serotonin by nerve cells by acting
at the 5HT receptors, and therefore, increasing the amount of serotonin available in the
brain. This class of antidepressants has fewer side effects than MAOi’s or TCA’s. They
are also used for bulimia, obsessive-compulsive disorder and panic attacks.
Mechanism: SSRI selectively block the prejunctional neuronal reuptake pumps in the
CNS that terminate serotonin transmission thus increase activity on serotonin receptors.
SSRIs optimal effect is 4 to 6 wks for the treatment of depression symptoms.
Side effects
· GI: Nausea (most common), dry mouth, somnolence and sweating. ↑ risk of GI
bleeding and constipation.
· CNS. Headache, insomnia, nervousness, and fatigue. Sexual dysfunction (orgasmic
delay).
12-2
Serotonin syndrome: The serotonin syndrome may occur if the SSRI are combined with
MAOi, SSRI and TCA.
MAO Inhibitors Serotonin symptoms

SSRI · Hyperpyrexia (fever)
TCA · Agitation
· Neuromuscular pains, myoclonus hyper
reflexia
· Hypertension or hypotension
· Tremors, shivering
Tramadol
· Seizure
Meperidine, fentanyl
Amphetamine · Coma, and death
Dopamine
Cocaine
Methyldopa
Dextromethorphan
Caffeine
Lithium
SSRI
MAO Inhibitors
TCAs
St. John wort
ONDANSETRON
SUMATRIPTAN
Serotonin syndrome is an acute condition due to increase serotonin levels and develops
within minutes to hours (typically within 6 hours) after starting a medication, increasing
the dose of a medication, or overdosing.
Signs and symptoms of Serotonin syndrome

Neurobehavioral confusion, agitation, seizures, coma,
Autonomic Hyperthermia (fever), diaphoresis (sweating), tachycardia,
hypertension, diarrhea
Neuromuscular Myoclonus, rigidity, tremor (shivering), ataxia, shivering, and
nystagmus
Serotonin syndrome management: Management of the serotonin syndrome involves

discontinuation of the serotoninergic agent and supportive therapy. Most cases are mild
and resolve spontaneously within 24 to 72 hours. Cardiac arrest, coma, and multiorgan
system failure have been reported as consequences of serotonin syndrome.
Symptoms resolve quickly as soon as offending drug is discontinued. Pharmacist has to
contact the physician and tell the patient to withhold the serotoninergic agent.
12-3
Benzodiazepines, propranolol, and cyproheptadine, a serotonin antagonist, have been

used successfully.
Serotonin syndrome occurs with the following agents: All SSRIs, mirtazapine,
venlafaxine and moclobemide. The syndrome is possible when these agents are
combined with each other, MAOi, lithium, meperidine, pentazocine, and
dextromethorphan.
Discontinued syndrome (FINISH) Question Alerts!

· Flu like syndrome 1) Serotonin syndrome?
· Insomnia 2) Discontinued symptoms. "FINISH"
· Nausea
· Imbalance
· Sensory disturbances
· Hyper activity
Wash out period: (FIVE HALF LIFE)

Two SSRI’s or SSRI with TCA or MAOi should not combine. If switch from one SSRI to
other (SSRI, TCA or MAOi), waiting period required (washout period). All SSRIs have
washout period for 2 weeks, except fluoxetine (require 5 weeks). Moclebamide 5 days.
Tricyclic Antidepressants (TCA): Amitriptyline, Clomipramine, Desipramine, Doxepin,

Imipramine, Maprotiline, Nortriptyline, Trimipramine.
Tertiary amine type TCAs Secondary amine TCAs

Dibenzocycloheptadiene (e.g. Amitriptyline), Dibenzocycloheptadiene
Darenzepine (e.g. Imipramine). (e.g.Nortriptyline) dibenzapine (e.g.
Desipramine).
Higher anticholinergic SEs Less anticholinergic SEs than tertiary
NE&5HT NE>5HT
Mechanism: NE and 5HT reuptake inhibitor

Therapeutic use: Antidepressant, neuropathy pain, enuresis in children (bedwetting)
imipramine, and anxiety disorder.
Amitriptyline: Therapeutics uses: Major depression, migraine prophylaxis, neuralgia,

fibromyalgia and insomnia.
Migraine PROPHYLAXIS
neuralgia
Insomnia
ENURESIS
ANXIETY
12-4
Side effects: (Block M receptors, H 1 receptors, alpha1 receptor)

· Anticholinergic side effects constipation, blurred vision, urinary retention dry mouth,
confusion, and delirium.
· Antihistaminic effect. Sedation, weight gain.
· CVD effects. Orthostatic hypotension, tachycardia (AV blockade)
· Sexual dysfunction
· Bone marrow depression
· Mania with manic depressive illnesses, lower seizure threshold
Overdose symptoms.
Question Alerts!
· Mydriasis
1) Amitriptyline is proarrhythmic (AV node)
· Nausea 2) Amitriptyline overdose symptoms?
· Constipation
· Confusion, sedation
· Sleepiness
· Palpitation (tachycardia)
· Dizziness
· Dry mouth
· Blurred vision
· Fever
· Overdose treatment: Contact physician immediately if any over dose symptoms
appears.
Contraindications. Avoid combining with MAOi and SSRI.
MonoaminooxidaseInhibitors
The major route of metabolism of serotonin is oxidative deamination by MAO-A to the

unstable 5-hydroxyindole-3-acetaldehyde.
MAO (oxidative deamination)
Serotonin----------------> 5-hydroxyindole-3-acetic acid
The monoamine oxidase inhibitors (MAOis) were the first class of compounds used to
treat depression. Patients, taking these drugs, must monitor their diet for tyramine, an
amino acid present in many foods that are fermented, aged or smoked. There is a
number of foods containing tyramine and MAOi must be avoided. Monoamine oxidase
is an enzyme, which inactivates the neurotransmitters, epinephrine, norepinephrine and
dopamine. These drugs inhibit the destruction of these brain chemicals, which leads to
increased concentrations of these neurotransmitters, which may account for their
antidepressant activity.
NON-SELECTIVE Phenelzine and tranylcypromine
12-5
MAOI
Mechanism Irreversibly nonselective Monoamine oxidase inhibitors,
permitting neurotransmitter to escape degradation and therefore
to both accumulate within. Inhibit both MAO A and MAO B . Blocks
deamination in brain biogenic amines.
Therapeutic use Antidepressant, anti anxiety and narcolepsy

Side effects CVS. Orthostatic hypotension, tachycardia, arrhythmias, and
stroke.
CNS. Insomnia, CNS stimulations
Weight gain
Sexual dysfunction
Anticholinergic SEs less than TCA
Drug interactions Avoid concomitant use of meperidine, Amphetamine, SSRI
TCA
Serotoninergic Dopamine
syndrome Cocaine
Methyldopa
Dextromethorphan, caffeine and lithium
Use washout period for 2 weeks before administering SSRI.

Hypertensive crisis Inhibitions of MAOi in brain causes catalyze oxidative
deamination of toxic substances such as tyramine. The tyramine
is present in foods such as fermented food cheese, wine etc.
Food to avoid Aged cheese (cheddar, blue and swiss), yogurt, smoked meats,
wine, liquor, yeast, raisins, chocolate, dry salami, pepperoni,
sausage, bananas, figs, tea and coffee.
Drugs sympathomimetics, ephedrine, and pseudoephedrine.
Question Alerts!
MAO Hypertension crisis with tyramine and
Tyramine -------------> Inactivated sympathomimetics
Reversible Inhibitors of Monoamine Oxidase (RIMAs)

Moclobemide is short acting, reversible selective inhibitors of monoamine oxidase type
A, the enzyme, which inactivates the neurotransmitters, epinephrine, norepinephrine
and dopamine.
Side effects. Headache, abdominal fullness, GI upset, dry mouth. Insomnia and dizziness.
Question Alerts!
Moclobemide is? Reversible MAOi-A
12-6
Dual action antidepressants:

Bupropion, Venlafaxine, desvenlafaxine, duloxetine, Mirtazapine and Trazodone.
Bupropion: Serotonin (very little), dopamine and norepinephrine reuptake inhibitor

(sNDRI).
Therapeutic use: 1st line treatment for major depression and also used for smoking
cessation (Zyban).
Side effects: Stimulant affect (tachycardia, agitation), aggravation of psychosis,
aggravation of seizure (reduce seizure threshold). Least weight gain and the lease
sexual dysfunction.
Venlafaxine, duloxetine and desvenlafaxine:
Therapeutic use: Depression + pain neuropathic pain, or fibromyalgia.

VENLAFAXINE: Side effects: dose dependent hypertension (>225 mg).
Desvenlafaxine is active metabolite of venlafaxine.

Side effects: Common SEs insomnia, somnolence, dizziness & nausea.
Mirtazapine (SARI)
· Alpha 2 antagonist and potent 5HT 2 5HT 3 receptor antagonist, H 1 RECEPTOR
ANTAGONIST
· Increases release of norepinephrine and serotonins.
· Side effects: Increase appetite (weight gain), sedation DUE TO H 1 RECEPTOR
ANTAGONISM.
· Increase serum cholesterol levels.
Trazodone: 5HT 2 antagonist with some serotonin reuptake inhibitor properties.

Side effects: Sedation, drowsiness, N&V, headache, dry mouth, priapism.
Rarely associated with serotonin syndrome. May be combine with SSRIs.
Excessive sedation (rarely prescribed therapeutic antidepressant doses 300-400 mg
daily because of excessive sedation) ®as a hypnotic (50-100 mg) with other
antidepressants. Trazodone is alternate hypnotics over BZD (lack of tolerance and
potential antidepressant enhancement).
ANTIDEPRESSANTS 5HT NE D M1 H1 Alpha1 5HT 2a

reuptake antagonist
SSRI +
Dual acting + + +
12-7
Venlafaxine, + +
desvenlafaxine,
duloxetine
Bupropion + + +
Trazodone + + + + +
Atomoxetine +
TCA + + ++ ++
MIRTAZEPINE + ++ +
Bipolar depression: Hallmark symptoms. Feeling excessive happiness (manic) and low
mood (hypomanic) and almost always includes episodes of clinical depression.
Lithium
· Mood stabilizer lithium is the drug of choice to treat manic

depressions.
· Lithium act on multiple levels of signaling in the brain, restore the
balance among aberrant signaling pathways.
Therapeutic · Used prophylactically in treating manic depressive patient and to
use treat manic episodes. Bipolar depression (disorder) or mood
swings.
Pharmacokin · Steady state reached in 5 days. Narrow therapeutic window
etics · Renal excretion. Onset of lithium 3 weeks.
Therapeutic · Acute mania 1 to 1.5 mEq/liter. Maintenance bipolar disorder 0.6

levels to 1.2 mEq/liter. Increasing dose 300 mg/day raises level 0.2
mEq/liter.
Dose · Start 300 mg PO bid, effective dose 900 to 1800 mg per bid
Side effects · Tremor
· Polydipsia
· Hypothermia or hyperthermia
· Weight gain and weight loss
· Nausea or vomiting
· Diarrhea
· Hypothyroidism and hyperthyroidism
Monitoring · Lithium serum levels
· Renal function tests
· Thyroid function tests
Drug · Diuretics, NSAID’s, and ACE Inhibitors
interactions
12-8
Lithium toxicity
Lithium is narrow therapeutic index. Drug serum levels >1.5 mEq/L associated with
lithium toxicity. These symptoms include cerebral symptoms. Drowsiness, in
coordination, dizziness, blurred vision, confusion. Autonomic symptoms. Tremors,
Change in heart rate or rhythm, fluid retention and CNS like seizures.
Initial Onset SEs Lithium Long term SEs Lithium Toxicity (Serum > 1.5 mEq/L)
N&V, GI upset, Dry Fine hand tremors Coarse hand tremor
mouth, Fine hand Weight gain Muscle twitching
tremor, sedation Hypothyroidism Vomiting, severe drowsiness, confusion,
Muscle weakness acne, psoriasis nystagmus, seizure, Ataxia (irregular
Polydipsia rash, alopecia walking or widening of legs while
Polyuria Decreased libido walking), cogwheel rigidity, coma, death
Nocturia Arrhythmia: Non-specific
T-wave changes,
Nephrotoxicity
Nephrogenic
Monitor. Li, Na, Serum TSH, CBC, weight, CrCl (No LFT)
Antidepressant Summary
· Most anorexic: Fluoxetine
· Most nauseating: Fluvoxamine
· Most weight gain: Mirtazapine
SSRIs
· Citalopram side effects: Somnolence

· All SSRIs have common side effects: Nausea and diarrhea
· Antidepressants with Less sexual dysfunction are Bupropion, Mirtazapine, moclobemide
· Less hypotensive TCA; Nortriptyline
· Most Anticholinergic and sedative TCA; Amitriptyline
· Least sedative of TCA –Nortriptyline
· Less anticholinergic TCA—Nortriptyline
TCAs
· Take medication daily

· Antidepressants must be taken for two to four weeks for a noticeable effect
· Continue to take medication even if you are feeling better
· Do not stop taking the antidepressant without checking with the physician
Tips
· SSRI onset of action begin in? → 2 to 4 weeks (optimal effect 4 to 6 weeks).

· Fluoxetine washout period →5 weeks
· Depression with sexual dysfunction → Bupropion, mirtazapine, moclobemide
· To treat Depression in patient with insomnia →trazodone
· To treat Depression in patient with diabetes → SSRI, SNRI
· Higher dose of venlafaxine (225 mg/day) have effect on → 5HT and NE
12-9
· TCA onset of action is → 2 to 4 weeks

· A substance found commonly in fermented foods which can be toxic when MAO
inhibitors are used→ Tyramine
· MAO is classified as → Enzyme
· Renal dysfunction and dehydration → Increase lithium toxicity
· Lithium toxicity symptoms --> drowsiness, dizziness, confusion, blurred vision
changes in heart rate.
Select TRUE OR FALSE

· Normal blood levels of lithium in adult is <1.5 mEq/L (true/false)
· Lithium concentration varies with Na+ ions (true/false)
· Li+ conc. increases with decrease Na+ (true/false)
· Li+ conc. decreases with Increase in Na+(true/false)
· NSAID decrease Na+ renal perfusion is less (true/false)
· Thiazides deplete Na+ (true/false)
· SSRI Paroxetine and fluoxetine inhibit cytochrome CYP2D6 (T/F)
· FLUVOXAMINE inhibits CYP1A2 AND CYP2C19 (T/F)
· FLUVOXAMINE AND FLUOXETINE INHIBITS CYP3A4 (T/F)
· Mirtazapine may cause higher weight gain (T/F)
· Avoid cheese with Phenelzine, tranylcypromine (T/F)
· Milk + MAOI ok take it (T/F)
· St. John's wort have antidepressant effect (T/F)
· Serotoninergic symptoms: fever, hypo or hypertension, agitation, diarrhea
neuromuscular pain, seizure, tremors.
· Drug of choice in bipolar disorders and manic depression --> Lithium
· Normal blood levels of lithium in adult is <1.5 mEq/L (T/F)
· Lithium concentration varies with Na+ ions (T/F)
· ACEi (decrease Na+)can increase lithium serum concentrations in patients on lithium
therapy. (T/F)
· NSAID decrease Na+ renal perfusion is less (T/F) à Decrease lithium
·
Concurrent administration of thiazide diuretics (deplete Na+) may result in increase
lithium serum concentration. (T/F)
· Fluoxetine (SSRI) increase Li+ toxicity (T/F)
· Patient on antidepressants and shows with dilated pupil, may be due to TCA
overdose symptoms
· Take SSRI in the preferably morning (T/F)
· Take TCAs in preferably evening or bedtime (T/F)
· Bupropion, trazodone and mirtazapine have least sexual dysfunction (T/F)
12-10
www.PharmacyPrep.Com Sedative, Hypnotics and anxiolytics
13
Benzodiazepine and Barbiturates
Benzodiazepines
Benzodiazepines (suffix "am") are minor tranquilizers are used to treat insomnia (sleeping pill),
epilepsy and anxiety.
Short acting Half- life Intermediate Half- life Long acting Half-life
(Hrs) acting (Hrs) (Hrs)
Midazolam 1.8 Alprazolam 12 Diazepam 100
Xanax (generics) Valium (generics)
Triazolam 2 Lorazepam 15 Flurazepam 100
Halcion (generics) Ativan (generics) Dalmane (generics)
Oxazepam 8 Clonazepam 34
Generics
Temazepam 11 Chlordiazepoxide 100
Restoril (generics)
Nitrazepam
INSOMNIA INSOMNIA & ANXIETY SEIZURES

↑ REM SLEEP ↑ REM SLEEP
IMMEDIATE withdrawal WITHDRAWAL SYMPTOMS Slower and longer duration
symptoms Low hangover 2 TO 4 DAYS withdrawal symptoms (5 TO
effect 10 DAYS).
High hangover effect
TO FALL IN SLEEP TO MAINTAIN SLEEP
Benzodiazepine pharmacokinetics
Long acting benzodiazepines includes diazepam (longest half life), flurazepam, clonazepam,
chlordiazepoxide.
Intermediate acting. Alprazolam, Lorazepam, Oxazepam, temazepam and nitrazepam.
13-1
PharmacyPrep.
Short acting. Triazolam, midazolam (shortest half-life). Short acing benzodiazepine. have no
phase I metabolism, or extra hepatic metabolism.
Benzodiazepine withdrawal symptoms: Insomnia, agitation, anxiety, seizure.
Benzodiazepines bind to specific, high affinity site in cell

membrane, BZ1 AND BZ2 RECEPTORS which are
separate from but adjacent to the receptor for GABA.
The benzodiazepine receptor found only in the CNS and
their location parallels that of GABA neurons. The
binding of benzodiazepines enhances the affinity of
GABA receptor for this neurotransmitter and resulting in
BZD Therapeutic Reduce anxiety, insomnia, sedative and hypnotic action, anticonvulsant action,
use and muscle relaxant action.
opening of adjacent chloride channel, in turn results in hyperpolarization and inhibition
neuronal firing.
Zopiclone, Zaleplon, Zolpidem

Mechanism: Acts on subset of benzodiazepine receptors however these drugs are not
benzodiazepine.
Zaleplon
• Short half life 1 hours. Headache. most common
• Reduce sleep latency, used in initial treatment.
• Act on benzodiazepine receptors. No anticonvulsant and muscle relaxant activity.
Zopiclone (Immovane)
BZD Dependence Physical and psychological dependence (at high doses). Withdrawal symptoms
upon abrupt discontinuation.
Long acting withdrawal symptoms occurs after number of days.
Short acting benzodiazepine associated with immediate withdrawal symptoms
if it is stopped abruptly.
BZD Withdrawal Psychological: Confusion, anxiety, agitation, restlessness, insomnia, and
symptoms tension. Physical: tremors, seizures, Autonomic: tachycardia and hypertension.
Short and intermediate have severe withdrawal symptoms than long acting.
Rapid development of tolerance and withdrawal symptoms occurs with short
acting.
13-2
PharmacyPrep.
• No anticonvulsant and muscle relaxant activity. Short half life 5 hours. Bitter metallic taste
and bad breath.
• Confusion is most common in elderly, do not accumulate, may cause less withdrawal effects
and less rebound insomnia. Less tolerance, minimal additive effect with alcohol.
Zolpidem (Ambien)
• It is not a benzodiazepine. It is having no anticonvulsant properties.
• Elimination half life is 3 hours
• SEs. NIGHTmares, Dizziness Agitation, GI upset, Headache.
Barbiturates
Barbiturates are used much less commonly than before. They are effective only for a few
weeks since they alter the length of time spent in R.E.M. sleep. They should only be used for
short-term therapy as sedative or hypnotics. Phenobarbital is used to control seizure disorders,
often in combination with primidone and/or phenytoin.
Short acting
Amobarbital Long action
Ultra-short action
Secobarbital Phenobarbital
Thiopental
Pentobarbital
• Phenobarbitals: Long acting
• Amobarbital: short acting
• Butabarbital : short acting
• Pentobarbital : short acting
• Secobarbital: short acting
• Thiopental.shortest acting (acts within second)
• Primidone: active drug is phenobarbital (metabolite)
Mechanism • Potentiate GABAA action on Cl- entry by increasing the duration of

chloride ion channel opening.
• Do not bind to BZ1 and BZ2 receptors
Actions • Sedation (calming effect, reduce excitement), respiratory depression
Metabolic • Barbiturates induce CYP450 in liver, reduces the effect of several drugs
Enzymes that depends on CYP450.
Therapeutic • Anesthesia, anti seizure, anxiety
use
Withdrawal • Addiction potential.
symptoms • Abrupt withdrawal of barbiturates may cause: Tremors, Anxiety,
Weakness, Restlessness, Nausea, Vomiting, Seizures, Delirium, Cardiac
arrest
13-3
PharmacyPrep.
• Withdrawal symptoms are more severe than opioids, can cause death.
Overdose • Severe depression of respiration
Poisoning • Cardiovascular depression
• Shock like condition shallow and infrequent breathing
Poisoning • Artificial respiration, Purging stomach content and Hemodialysis.
management Alkalinization of urine for phenobarbital
Barbiturates • Aminophylline
antagonist
Miscellaneous
Non-barbiturate Chloralhydrate, ethanol, antihistamine and buspirone.

sedatives
Chloralhydrate Tri chlorinated derivative of acetaldehyde
Antihistamine Doxylamine and other antihistamine are used as OTC treatment of sleep
disorders
Hydroxyzine
Mechanism H1 antihistamine with antiemetic activity
Therapeutic use Antihistamine, Antiemetic, Anxiety, Sedation prior to dental procedure, and
Insomnia.
Advantages Low tendency of habituation thus it is useful for anxiety in-patient who a
history of drug abuses.
Buspirone Buspirone acts on 5HT1a receptors and D2 receptors causes’ minimal sedation,
least addiction liability.
Disadvantage. slow onset of action
Advantage: Less interference with motor functions (helpful in elderly).
Ethanol Ethanol is metabolized in liver, first to acetaldehyde by alcohol
dehydrogenase and acetate by aldehyde dehydrogenase. Ethanol has
sedative and antianxiety effect.
13-4
PharmacyPrep.
Ethanol
Question Alerts!
Alcohol dehydrogenase 1) Chronic use of alcohol can
cause deficiency of?
2) Alcohol metabolizing
Nausea and vomiting
enzymes?
Acetaldehyde headache
Hypotension
Thiamine decrease
bioavailability
Acetaldehyde dehydrogenase
Acetic acid
Tips
• Long acting benzodiazepine include →diazepam, chlordiazepoxide, clonazepam
• Intermediate acting benzodiazepine oxazepam, temazepam, alprazolam, and nitrazepam
• Short acting benzodiazepines → triazolam, midazolam
• Least addiction potential sedative drugs are non- benzodiazepines
• Least hangover hypnotic benzodiazepine → triazolam, midazolam
• Zaleplon and zopiclone act → benzodiazepine receptors
• Ethanol metabolizes to acetaldehyde by enzyme called? alcohol dehydrogenase
SELECT TRUE OR FALSE
• Drug induced delirium caused by alcohol, benzodiazepines and barbiturates withdrawal
(T/F)
• Alcohol withdrawal symptom delirium is treated by long acting benzodiazepines
• Benzodiazepine has high tolerance, addiction potential and dependency. (T/F)
• Valerian is used for insomnia (T/F)
• Ginko biloba is used for memory enhancer (T/F)
• Disulfiram inhibit aldehyde dehyrogenase(T/F)
• Overdose of benzodiazepine is treated by flumazenil (T/F)
• Barbiturate antidote is aminophylline (T/F)
• Elderly + BDZ  decrease clearance significantly (true/false)
• Liver disease +BDZ  decrease clearance significantly (true/false)
• Pregnancy + BDZ  neonates may develop withdrawal symptoms (true/false)
13-5
PharmacyPrep.
13-6
PharmacyPrep.
Pharmacyprep.com CNS stimulants
14
CNS Stimulants
These drugs have a stimulating effect on the CNS. Psychomotor stimulants are used to treat
children hyperactivity and attention deficit disorder. As a side effect, they decrease appetite
and for many years were used as appetite suppressants. Addiction and abuse were side effects
of taking these drugs.
These drugs are also used to treat narcolepsy, a condition where the patient lapses into
momentary sleep while sitting. This may occur as many as 20 times a day and is dangerous if it
were to happen while the patient is driving or operating machinery.
CNS Stimulants
Psychomotor Psychomimetic stimulants/

Hallucinogenic "higher"
· Methyl xanthines; Theophylline, tea, coffee

· Cocaine · Phencyclidine (PCP)
· Nicotine · Lysergic acid (LSD)
· Amphetamines · Tetrahydrocannabinol (THC) or dronabinol
· Methylphenidate (Marijuana) (POT)
· Sativex (pain reliever spray)
Psychomotor Stimulants
Methylphenidate, amphetamine, dextroamphetamine methyl xanthine
Mechanism: Psychological. Increase alertness & attention span, insomnia.
Physical: Decrease appetite, weight loss. Bring changes in thought patterns and mood pattern.
Excitement, euphoria, decrease feeling of fatigue. Increase motor activity. Little effect on
brainstem and spinal cord.
Psychological and physical dependency and addiction potential development of tolerance to
euphoric and anorectic effects of chronic use.
Cocaine Ester type local anesthetic. Blockade of voltage sodium ion activated channel.
Side effects. Anxiety, depression, seizures, and cardiac arrhythmias.
14-1
PharmacyPrep.
Pharmacyprep.com CNS stimulants
Therapeutic use Methylphenidate, amphetamines are the drug of choice for attention deficit
hyperactivity disorders (ADHD).
Side Effects · Decrease appetite, insomnia and nervousness, abdominal pain, headache,
fatigue, palpitations and chest pain. Less tolerant to convulsions and toxic
CNS effect. All CNS stimulants including Amphetamine is classified as
controlled drugs.
Drug-drug · Anticoagulants, anticonvulsants, and tricyclic antidepressants ↑its effects
interaction with methylphenidate.
· Antihypertensive will reverse its effects with methylphenidate
· Sympathomimetics and MAOis may cause severe hypertension when used
with methylphenidate.
Contraindication · Not recommended to children under 6 yrs.
Monitoring · Physician will assess growth and blood pressure at regular intervals.
Call physician · Palpitation and chest pain
NOW
Psychomimetic stimulants
Hallucinogens Phencyclidine (PCP), Lysergic acid diethylamide (LSD).
Tetrahydrocannabinol (THC) or dronabinol (marijuana).
Tips
· Hallucinogens are à (MARIJUANA, LYSERGIC ACID, CANNABINOIDS)
· Amphetamines should not be used with (OTHER STIMULANTS)
· What OTC drug cause opposite effect of Euphoria? à dimenhydrinate,
· What are the characteristics of cocaine overdose à dilatation of pupil, euphoria,
tachycardia, peripheral vasoconstriction, and hallucinations.
TRUE OR FALSE
· All CNS stimulants have addiction potential, physical dependency (True/False)
· In ADHD treatment it is important to emphasize non-pharmacological recommendations
such as taking breakfast every day and good sleep in night, counsel parents and teachers.
(True/False)
· Hallucinogens are psychomimetic drugs (True/False)
· CNS stimulants have been used as an anorexic agent (True/False)
· Theophylline is chemically related to methyl xanthine (True/False)
14-2
PharmacyPrep.
Pharmacyprep.com Antipsychotic Drugs
15
Anti Psychotic Drugs
The antipsychotic agents are classed as major tranquilizers and are used to help people with
schizophrenia and other psychoses (major mental disorders). Psychotics symptoms can be
categorized as positive and negative symptoms. Positive. hallucination, delusions, agitation,
disorganized behavior. Negative. social withdrawal or isolation. Cognitive: memory, judgment,
and thinking.
The mesolimbic pathway in brain involved in integration of emotions, behaviors and higher
thought process. Increased dopamine neurotransmission in limbic pathway results in +ve
symptoms but not necessarily -ve symptoms, and cognitive symptoms.
Typical antipsychotics inhibits D 2 present in mesolimbic and extrapyramidal pathway.
Mechanism: Inhibition of dopamine action in the mesocortical and mesolimbic dopaminergic

pathways of the CNS or block post junction dopamine D 2 receptors.
PharmacyPrep.
15-1
Atypical
nd
(2 generation)
Clozapine
Antipsychotics Risperidone
Olanzapine
D 2 & 5HT 2 inh. Quetiapine
Typical (1st generation) Paliperidone
Aripiprazole
D 2 inhibitors Ziprasidone
Low Potency Intermediate Potency High Potency

Chlorpromazine Loxapine Haloperidol
Methotrimeprazine Perphenazine Fluphenazine
Zuclopenthixol Trifluoperazine
Flupenthixol
Pimozide
Thiothixene
Psychotropic (neuroleptic) agents or Antipsychotic drugs or anti-schizophrenia drugs. Potency

(low, intermediate, high) as determined by dopamine D 2 -receptor binding affinity.
LOW POTENCY
Low potency (Chlorpromazine, Methotrimeprazine): Most commonly associated with sedation.
The risk of tardive dyskinesia when initiating treatment for typical.
MECHANISM Side effects THERAPEUTIC USE
Chlorpromazine antiemetics QT c prolongation,
cholestatic jaundice
<1%, ~Seizures <1%
INTERMEDIATE POTENCY
Intermediate potency (Loxapine, Perphenazine, Zuclopenthixol): Zuclopenthixol injectable FGA, long
T 1/2. Not used in antipsychotic naive patients.
Generic Name Mechanism of Action Side effects Therapeutic use
Loxapine
perphenazine ¯D 2 EPS, TD
prochlorperazine
PharmacyPrep.
15-2
HIGH POTENCY:
High potency drugs like haloperidol, fluphenazine have high EPS and prolactinemia and these
drugs least sedation and weight gain.
MECHANISM Side effects THERAPEUTIC USE
Haloperidol
Fluphenazine +ve schizophrenic
symptoms
Trifluoperazine
Flupentixol
Pimozide
Thiothixene
Side effects
· CNS: Extra pyramidal symptoms such as akathisia, tardive dyskinesia, acute dystonia and
Parkinsonism. Alteration of temperature regulating mechanism (poikilothermy).
· CVS. Postural hypotension, and reflex tachycardia.
· Other. Sexual dysfunction and anticholinergic.
· Haloperidol with lorazepam im for acute phase, SEs EPS, QT c prolongation. DOC for +ve
symptoms delirium.
· Pimozide: SEs QT c prolongation with dose 8 mg/day (avoid use with sertraline).
· Haloperidol and phenothiazines have high tardive dyskinesia, due to high effect on D 2 -
receptors.
2nd generation antipsychotics (SGAs): Risperidone, olanzapine, quetiapine and clozapine,

paliperidone, ziprasidone, and aripiprazole. The 2nd gen. antipsychotics are strong inhibitors of
serotonin and dopamine. Due to serotonin receptor inhibition these drugs have less extra
pyramidal side effects, and more effective treatment of negative symptoms.
trifluoperazine
generics
Second generation antipsychotics
Quetiapine ¯D 2 ¯5HT2, ¯H 1 , ¯M, QT PROLONGATION Usual: 600 mg/day
Seroquel ALPHA1
Olanzapine ¯D 2 ¯5HT 2 , ¯H 1 , ¯M, Usual: 10 mg im. If
Zyprexa, Oral ¯ALPHA1 necessary 2nd dose of 5–10
tab, Zyprexa im mg im may be given 2 h
injection, after first injection
Zyprexa Zydis
OD is rapid
dissolving tab.
Clozapine ¯D 2 ¯5HT 2 , ¯H1, ¯M, Usual: 300–600 mg/day po
Clozaril, ALPHA1-2 Max: 900 mg/day, Divided
generics in 1–3 doses/day
PharmacyPrep.
15-3
Risperidone ¯D 2 ¯5HT2, ¯H1, ¯M, Usual: 2–6 mg/day, Max: 8

Risperdal ALPHA1 mg/day
Risperdal M Frequency: one dose/day,
(rapid preferably HS. Injection
dissolving oral usual: 25–37.5 mg IM
tab), Risperdal every 2 wk.
IM slow
release
injection
Ziprasidone ¯D 2 ¯5HT 1A , ¯H1, ¯M, QT PROLONGATION
ALPHA1
Paliperidone METABOLITE OF
RISPERIDONE
Aripiprazole ¯D 2 ¯5HT 1A , ¯H1, ¯M,
ALPHA1
Side effects: Significantly reduced risk of EPS (acute dystonia, parkinsonism, akathisia and
tardive dyskinesia) than typical. Weight gain (greatest), hyperlipidemia, - glucose abnormalities
(diabetes).
Comparison of anti psychotic drug side effects.

Typical (1st generation) Atypical (2nd generation)
High sedation (except Haloperidol, Fluphenazine) Low sedation (risperidone)
Low weight gain High weight gain (clozapine)
High tardive dyskinesia (↓D 2 ) Low tardive dyskinesia – clozapine
anticholinergic side effects anticholinergic side effects
High sexual dysfunction Low sexual dysfunction (quetiapine)
High EPS (↓↓D 2 ) Low EPS
Neuroleptic malignant syndrome Neuroleptic malignant syndrome
Clozapine: Only antipsychotic with proven efficacy in treatment resistant schizophrenia.

Mechanism: Inhibit D2, 5HT2, D1-5, and H1, M (low affinity), alpha1-2. High affinity to 5HT2 and D2
receptors may produce atypical antipsychotic effect.
Side effects: agranulocytosis (1-2%), need for regular (weekly for first 6 mo) blood monitoring
WBC). Weight gain (greatest), and hyperlipidemia. Hyper salivation.
Drug of choice for resistance type of psychosis only.
· Improves –ve and +ve symptoms
· Advantage no EPS or TD.
Risperidone
· Mechanism: Inhibits D 2 and 5HT 2 , also has relatively high affinity at histamine H 1 and
adrenergic alpha 1 and alpha 2
PharmacyPrep.
15-4
· Improves –ve symptoms and + ve symptoms

· Side effects: Hyperprolactinemia (dose related), EPS, weight gain, dizziness, diabetes
(hyperglycemia) but least likely dyslipidemia.
· NO WBC is monitored.
Olanzapine (Tab and RD tab)

Therapeutics use: Olanzapine orally disintegrating (Zyprexa zidis). Approved for acute
treatment of mania. Use for acute phase. Do not combine with parenteral BDZs (cardiac &
respiratory problems).
Inhibit D 2 , 5HT 2 , D 1-5 , and H 1 , M, alpha 1-2 . High affinity to 5HT 2 and D 2 receptors may produce
atypical antipsychotic effect.
Side effects: Sedation, restless, Weight gain (greatest), hyperlipidemia, EPS (especially
akathisia), diabetes.
Quetiapine
Mechanism: Most effectively binds 5HT 2a , H 1 , alpha 1 . alpha 2 in brain and has low affinity to D 2
receptors.
Side effects: Hyperlipidemia, ↑triglycerides (17%), ↑ cholesterol (11%), hypothyroidism,
akathisia>2%, and diabetes. Least EPS.
Paliperidone: Active metabolites of risperidone. This is not metabolized in liver thus have low
drug interactions. Available as PO daily dose (taken in morning due to insomnia SE), and
prolong released injectable suspension.
Ziprasidone: Agonist of 5HT 1A and moderate inhibition of synaptic reuptake of 5HT and NE.
Thus ziprasidone has potential efficacy in –ve symptoms and depression.
Aripiprazole: partial agonist at 5HT 1a and D 2 receptors. Thus, has potential efficacy in –ve
symptoms and depression. Available oral single daily dose. Taken with or without food.
· D 2 inhibitory effect effective produce more pharmacological benefit to treat positive
symptoms.
· 5HT 2A inhibitory effect effective in producing more pharmacological benefit to treat
negative symptoms.
Pharmacological D2 5HT 2 M1 H1 Alpha 1 Alpha 2 5HT 1A QT pro

effects
Clozapine + (low) +++ +/- (low) + + +

Olanzapine + +++ + + + +
PharmacyPrep.
15-5
Risperidone + +++ + + + +
Quetiapine + (low) +++ Low + + + +
Paliperidone + +++ + + + +
Ziprasidone + +
Aripiprazole + +
Ziprasidone: moderate 5HT and NE reuptake inh.
Extra pyramidal symptoms (EPS). "PATD"

· Parkinson’s like symptoms: Tremors, Rigidity, Akinesia, Postural instability.
· Akathisia: motor restlessness (cannot sit still)
· Tardive dyskinesia: Inappropriate postures of neck, trunk and limbs.
· Dystonia: Involuntary contraction of muscles (spasm).
Neuroleptic malignant syndrome (NMS): This can occur within first few weeks of therapy. It is
characterized by the acute onset of hyperthermia (fever), muscle rigidity, tremor, tachycardia,
mental status changes and diaphoresis. NMS can occur frequently in patient receiving FGAs,
injectable or depot and patient are dehydrated, with physical exhaustion.
Antipsychotics Bp/ BG LFT BMI WBC TG/ QT others

pulse TC
Clozapine + ++ + +++ + + Cardio toxicity, Sedation, weight gain,
hypersalivation. (least anticholinergic)
Risperidone + + +++ + + Akathisia, Mild sedation
Olanzapine ++ + +++ + Sedation, weight gain
Quetiapine + + + +++ ECG Sedation
Ziprasidone ++ Sedation, insomnia, nausea
ECG Weight neutral
Paliperidone Insomnia
Aripiprazole + Insomnia & sedation, dose dependant somnolence,
weight neutral
Haloperidol +
Tips
· 2nd gen increase risk of lipids? Quetiapine, olanzapine and clozapine

· A patient experiencing social withdrawal --> olanzapine, risperidone
· Clozapine mechanism of action --> act on 5HT, D, M, H 1 , and a
· Clozapine side effects -->Agranulocytosis
· Clozapine monitoring -->CBC or WBC
· Risperidone monitoring include --> BP, BLOOD GLUCOSE, cholesterol, LFT (No CBC)
· A patient has social withdrawal, what is the drug of choice --> 2nd gen antipsychotics.
· What is the treatment of extra pyramidal symptoms --> benztropine, and trihexyphenidyl
· 1st generation 4 to 8 weeks no response, change to 2nd generation. For 2 episodes, continue
for 2 to 5 yrs
PharmacyPrep.
15-6
TRUE OR FALSE
· Least extra pyramidal symptoms clozapine, quetiapine (True/False)
· Highest EPS haloperidol, fluphenazine (True/False)
· A patient experiencing hallucination high potency haloperidol, fluphenazine (True/False)
· 1st generation 4 to 8 weeks no response, change to 2nd generation. (true/false)
· Schizophrenia is characterized by à long standing paranoid delusion. (true/false)
· 2nd generation drugs treatments cover +ve and -ve symptoms (True/False)
· Schizophrenia is characterized by hallucination, social withdrawal etc. (True/False)
· Metoclopramide and chlorpromazine is low potency 1st generation antipsychotic
(True/False)
· Tardive dyskinesia is caused by antipsychotic drugs side effects (True/False)
· Tardive dyskinesia symptoms involuntary movement trunk, neck, and jaws (True/False)
· For resistance schizophrenia drug of choice clozapine (True/False)
· Orthostatic hypotension is side effect of antipsychotics cause due to alpha1 receptors
blockade (can cause additive effects with other antihypertensive drugs) (True/False)
PharmacyPrep.
15-7
PharmacyPrep.
15-8
www.PharmacyPrep.Com Antiepileptic Drugs
16
Antiepileptic Drugs
Antiepileptic drugs by mechanism of action
Reduces NMDA Potentiate Reduce Na+ Reduce Ca2+ current

Receptor activation GABA receptors conductance in through T- channels
hyperactive
neurons
Felbamate
Phenobarbital Carbamazepine Ethosuccimide
Topiramate
Primidone Phenytoin
Fosphenytoin
Diazepam Lamotrigine
Vigabatrin
Topiramate Valproate
Tiagabine Valproic acid
Gabapentin?
After each depolarization, Na+ channel adopt an inactive state and remain refractory
to reopening for a period of time. While channels are unable to open rapid repetitive
firing is diminished and spread of electrical seizure to adjacent cells is suppressed.

Carbamazepine Tegretol (generics) clobazam Frisium (generics)
Phenytoin Dilantin clonazepam Rivotril (generics)
Gabapentin Neurontin (generics) diazepam Valium (generics)
vigabatrin Sabril lorazepam Ativan (generics)
phenobarbital Generics primidone Mysoline (generics)
divalproex Epival (generics) lamotrigine Lamictal (generics)
valproic acid Depakene (generics)
Seizure: Abnormal or burst electrical discharge from local areas and spread around the brain
adjacent areas. Condition like hypoxia, uremia, bacterial meningitis, genetic predisposition and
drugs such as cocaine, penicillin G, and anticholinergics can produce seizure. Withdrawal from
16-1
PharmacyPrep.
chronic use of alcohol, barbiturates, benzodiazepines and most anti seizure medication can also
lead to seizures.
Epilepsy. Epilepsy is a disorder of the brain characterized by recurrent and spontaneous

seizures, which are self-limiting. Which usually recur unpredictably.
Convulsions. Involuntary contractions (abrupt) of voluntary muscles.
Seizures can be characterized by clinical symptoms and Electroencephalography (EEG),

computerized tomography (CT), and magnetic resonance imaging (MRI).
Carbamazepine
Mechanism By blocking Na channels reduces abnormal impulses in brain.

Therapeutic To treat partial seizures and tonic-clonic seizures, trigeminal neuralgia
use and bipolar disorder. Avoid in absence seizure (petit-mal), because it
can exacerbate or precipitate.
Side effects • Rash, ↑ liver enzymes, neutropenia, aplastic anemia
16-2
PharmacyPrep.
• Chronic. drowsiness, vertigo (the sensation of dizziness and a

confused, disoriented state of mind).
• Idiosyncratic. Rash, aplastic anemia, Stevens Johnson syndrome
(skin hypersensitivity reactions).
• Acute intoxication. Coma, hyperirritability, convulsions and
respiratory depression.
Management • Start low and increase gradually. CR may be better tolerated,
improve compliance. May upset stomach, if so take with food or
milk.
Question Alerts!
1) Used for treatment of partial seizure and contraindicated in absence (petit-mal).
2) Dose independent SE of CBZ? Rash and fever (SJS)
CYP3A4 inhibitors: Diltiazem, erythromycin, ↑ clearance of OCPs, Warfarin, Risperidone,

Isoniazid, propoxyphene, and cimetidine TCAs
Carbamazepine clearance is ↓ by CYP3A4 Inh Carbamazepine induce

thus increase plasma levels 1A2, 2C9, 2C19, 3A4
CBZ is principally metabolized by CYP3A4 and also induce CYP3A4 (auto inducer).
ANTIEPILEPTIC DRUGS CLASS TOXICITIES:
HEPATOTOXICITIES; NEUROTOXICITIES, GI TOXICITIES, DERMATOLOGICAL
AND HEMATOLOGICAL.
Phenytoin
Phenytoin decreases the sodium content of nerve in the brain and thereby decreases the
hyperexcitability of the cells that are involved in initiating seizures.
Mechanism • Stabilizes neuronal membranes to depolarization by decreasing flux

of Na+ ions into neurons in the resting state or during repolarization.
Therapeutic use • Partial seizures and tonic-clonic seizures or generalized seizure.
Status epilepticus caused by recurrent tonic-clonic seizures.
• NOT effective for absence (petit-mal) seizures.
Side effects • Idiosyncratic: Skin rash and Steven Johnsons syndrome
• Gingival hyperplasia (reversible), encephalopathy, blood dyscrasias,
Nystagmus, hirsutism and birth defects like cleft palate.
Pharmacokinetics • Non-linear pharmacokinetics (toxic concentration of are between
16-3
PharmacyPrep.
(7.5 mcg/ml to 20 mcg/ml). Oral absorption is slow (extended release

phenytoin sodium). Chronic administration is always oral. The
elimination half life for phenytoin in children increases with age due
to age dependant decrease rate of metabolism.
• Metabolized by hydroxylation in liver. At low doses half life is 24
hours. As dose increase hydroxylation becomes saturated, and can
produce large in increase plasma concentration, resulting in drug
induced toxicity.
• Phenytoin accelerates metabolism of folic acid CAUSE
MEGALOBLASTIC ANEMIA.
Dosages • Chewable tablets (100%), suspension (100%) capsules (92%), and
i.v/im (92%).
Phenytoin metabolism is inhibited by sulfonamide, Isoniazid, Chloramphenicol, Dicumarol.

Phenytoin metabolism is stimulated by Carbamazepine.
Question Alert!
1) Non-linear pharmacokinetics? over 20 mg/ml can saturate.
2) SEs: gingival hyperplasia, nystagmus.
Carbamazepine Phenytoin
Linear kinetic High dose can cause non- linear and toxicity
Lymphadenopathy (nystagmus and ataxias), induce CYP450,
gingival hyperplasia, hirsutism, (LIGHT)
Gingival hyperplasia
CYP3A4 inh and inducer CYP 2C9, Induce CYP2C9, 2C19, 3A4, 2B6, 2C8
2C19, 1A2, 2D6, 2C8, 3A4
Drug of choice in pregnancy (given Birth defects cleft palate, megaloblastic anemia.
with folic acid 5 mg)
Decrease folic acid levels
↓ efficacy of OCP ↓ efficacy of Oral contraceptive pills (OCP)
OVERDOSE: NEUROTOXICITY
0-10 mg/ml  subtherapeutic
10-20 mg/ml  therapeutic
20-30 mg/ml  mild toxicities: nystagmus, mild ataxia
30-40 mg/ml  moderate toxicity: ataxia prominent
>40 mg/ml severe toxicity: ataxia, consciousness,
encephalopathies.
16-4
PharmacyPrep.
Phenobarbital
Primidone Metabolite of phenobarbital

Mechanism
Question Alerts!
Antiepileptic drugs that do NOT decrease efficacy of OCP?
Gabapentin, valproic acid
Therapeutic use Epilepsy, insomnia, and anxiety. Sedative drug when combined with
other drugs it is used in anxiety associated with menopausal symptoms.
Side Effects Unwanted sedation, Skin rash (Phenobarbital), Depression and libido
(Primidone).
Advantage Long t1/2
Disadvantage Metabolism inhibited by valproic acid. STRONG INDUCER OF CYP3A4
Tips Declining use because of side effects
Clobazam Question Alerts!

Drugs that cause tolerance?
Clobazam, diazepam, phenobarbital
Mechanism Benzodiazepines effects gamma aminobutyric acid (GABA) receptors,

high-affinity benzodiazepine receptors and chloride channels.
Therapeutic use Useful as “add on” for patients nearly seizure free.
Side effects Ataxia
CNS. Insomnia, depression, dizziness, drowsiness, lightheadedness.
Tolerance to therapeutic effects.
Management Advantage. Very safe, rapid onset.
Disadvantage. Tolerance (initially good response then no control for
seizures). Not recommended for use in patients with major
depressive disorder or psychosis in which anxiety is not a prominent
feature.
Abrupt withdrawal may lead to symptoms such as anxiety, insomnia,
psychomotor agitation, and GI discomfort.
Dose 5 to 15 mg/day.
Ethosuccimide
Mechanism Inhibit Na+ and K+ adenosine triphosphate system (Na+, K+ ATPase).
CALCIUM ION CHANNEL BLOCKER.
16-5
PharmacyPrep.
Therapeutic The drug of choice to treat petit mal (absence seizure).

use
Side effects GI: nausea, anorexia, vomiting, CNS. drowsiness
Management Advantage: Few drug interaction
Disadvantage: For absence seizure only, no protection for generalized
tonic clonic.
Gabapentin
Mechanism Analog of GABA, however, this do not act as GABA mimetic and does not
block Na ion channel. May encourage production of or discourage
degradation of GABA.
Therapeutic use Partial seizures, and trigeminal neuralgia and neuropathic pain.
Side effects When initiating therapy CNS. somnolence, sedation, fatigue, dizziness
vision problems and ataxia.
Advantage Safe, well tolerated, not metabolized, can be used in liver failure.
No interaction with oral contraceptives pills.
Disadvantage Not for generalized seizure. Administration with aluminum, magnesium
antacid may ↓ bioavailability. INCOMPLETE ABSORPTION IN GI THUS
GIVEN BID TO TID.
Tips Very expensive at high doses, best used as “add on drug”.
Lamotrigine
Mechanism Inhibit glutamate and aspartate release and blocks sodium channels and
prevents repetitive firing.
Therapeutic The drug of choice for generalized seizure.
use
Side effects Dose dependent rash (rapid dose increased can cause rash). CNS: Somnolence,
dizziness, insomnia. Adding valproic acid increase the risk of serious rash
WITHIN 4-6 WKS.
Advantage Broad spectrum, no enzyme induction, some patients more “alert”.
Disadvantage Metabolism inhibited by valproic acid can increase risk of rash.
Only available in oral form.
Topiramate
Mechanism Enhances GABA activity antagonizes excitatory amino acid
(glutamate).
Side Effects Cognitive dysfunction, headache, kidney stones and weight loss.
Management Topiramate also used as weight loss therapy and migraine
prophylaxis.
16-6
PharmacyPrep.
Advantage Broad spectrum, safe, few drug interaction, weight loss

Disadvantage ↓ efficacy of OCPs, and expensive.
Valproic Acid
Valproic acid and divalproex are related chemicals. Divalproex is a mixture of valproic acid and
sodium valproate. In the body they are metabolized to separate compounds, and both exert
anticonvulsant effects.
Mechanism It may enhance GABA action at inhibitory synapses.

Therapeutic Drug of choice for generalized seizures. Most effective in treatment of
use myoclonic seizures.
Side Effects Most common GI: Nausea, anorexia, indigestion, tremor,
hair loss (alopecia), and edema. Menstrual irregularities and teratogenicity.
VA
HEPATOTOXICITY Photosensitivity.
TERATOGENICITY Idiosyncratic. skin rash, Steven Johnson’s Syndrome, hepatotoxicity, blood
PANCREATITIS dyscrasias.
Pregnancy: Neural tube defects (avoid in pregnancy).
Monitoring Liver function test, complete blood count.
Advantages: Low incidence of rash.
No interactions with oral contraceptives.
Disadvantage. high drug interaction ( but do not reduce OC’s efficacy).
Drug of choice for patients with mixed generalized seizures, absence,
myoclonus, tonic seizure, and not for partial seizure.
Vigabatrin
Mechanism Inhibits GABA-Aminotransferase, the enzyme responsible or
degrading GABA in the synapse. It does prolongs the sojourn of GABA
molecules and promotes binding in this way.
Side Effects Low incidence of psychosis
Depression
Visual problems
Comment: Limited use because of visual defects
Advantage Well tolerated, few drug interactions, does not cause skin, blood, liver
adverse effect
Disadvantages May worsen absence seizures, myoclonus. Expensive when using high
doses.
16-7
PharmacyPrep.
Pregnancy
Patient taking antiepileptic drugs phenytoin, CBZ, and valproic acid should take folic acid 1 to 5
mg/day supplements.
Antiepileptic Serum Elimination LFT Rash Fever BMI Folic acid

Drugs level
Carbamazepine + hepatic + + + ↓absorption
Phenytoin + hepatic + + + ↓absorption NEUROTOXICIT
Y
Valproic acid + hepatic +++ + + PANCREATITIS
Lamotrigine 90% hepatic +++ SERIOUS RASH
INITIAL DOSE % excreted WITH RAPID
50 MG ONCE unchanged TITRATION
DAILY
Ethosuccimide hepatic
Clobazam hepatic
Gabapentin >90%renal
eliminated
Pregabalin
Topiramate 5-70% renal red eye,
glaucoma
(↑IOP), kidney
stones.
Vigabatrin 90% renal
Phenobarbital ↓absorption
• Folic acid ↓absorption can cause deficiency. In pregnancy this can lead to spina bifida.
Vitamin K is routinely given to all new born at delivery to prevent hemorrhagic disease.
• If skin rashes occur contact your physician immediately.
Tips
• Drug that interferes with thyroid function test. (valproic acid )
• Stimulates hepatic microsomal enzymes (HME). (CBZ, Phenytoin, Phenobarbital)
• What drug should be avoided in petit-mal (absence seizures)? ( CBZ, Phenytoin)
• Overdose of this drug has zero order (saturated) kinetic. (Phenytoin)
• Gingival hyperplasia associated with phenytoin is treated by mouth hygiene and…
• A mouth rinse used for the treatment of gingivitis, stomatitis and mucositis. (Chlorhexidine)
• These drugs decrease efficacy of oral contraceptives. ( CBZ, Phenytoin )
• Drugs with no interaction with oral contraceptives. (gabapentin & valproic acid)
• Drug that cause weight loss, and kidney stones. (Topiramate)
16-8
PharmacyPrep.
• Antiepileptic drugs that have least drug interactions with OCP. (gabapentin, valproic acid )
• What antiepileptic drug is available as suspension, iv, chewable tablets and capsule.
(Phenytoin)
• What antiepileptic drug is available as chewable tablets and suspension (CBZ )
• A drug that has a high tolerance. (clonazepam, clobazam, diazepam, phenobarbital)
• These drugs have low teratogenic effect (ethosuximide).
• Dryness of mouth. (xerostomia )
• Excessive saliva outside the mouth. (sialorrhea)
• Vigabatrin + carbamazepine+ phenytoin? (worsen absence seizures)
TRUE OR FALSE
• Valproic acid interferes with thyroid function test (True/False)
• Phenobarbital and phenytoin stimulates CYP 3A4 (True/False)
• Avoid phenytoin and carbamazepine in absences seizure (True/False)
• Phenytoin have gingival hyperplasia and nystagmus side effects (True/False)
• Gingival hyperplasia associated with phenytoin is treated by mouth hygiene and
chlorohexidine oral rinse. (True/False)
• Chlorhexidine is used for treatment of gingival hyperplasia (True/False)
• Carbamazepine, phenytoin, clonazepam is used for partial seizures (True/False)
• Gabapentin, and valproic acid, have no interaction with oral contraceptives (True/False)
• Topiramate cause weight loss (True/False)
• Gabapentin has least drug interactions, especially with oral contraceptive pills (True/False)
• Phenytoin available as iv (92%), capsules (92%), suspension (100%) and chewable (100%)
(True/False)
• Carbamazepine available as IR tabs and SR tabs, chewable (True/False)
• Clobazam is a benzodiazepine has high tolerance (True/False)
• Gabapentin and lamotrigine GABA analogs (True/False)
• Xerostomia is dry mouth (True/False)
• Sialorrhea excessive saliva (True/False)
• Vigabatrin + carbamazepine and phenytoin are used for partial seizures (True/False)
• Phenytoin blood levels monitored for 10 to 20 mcg/ml (True/False)
• List the monitoring parameters for phenytoin-->blood levels
• Nystagmus is rapid eye movement (True/False)

CR Control release LFT Liver Function Test
GAB Gamma-Aminobutyric OCP Oral contraceptive pills
A Acid
CBC Complete Blood Count
16-9
PharmacyPrep.
16-10
PharmacyPrep.
www.PharmacyPrep.Com Dementia
17
Dementia
Dementia is a declined in mental ability that usually progresses slowly, in which memory,
thinking, judgment, and ability to pay attention and learn is impaired, and personality may
deteriorate.
Alzheimer's dementia: The most common form of dementia.

Levy body dementia: Associated with psychosis symptoms (hallucination, delusion etc).
Vascular dementia: Vascular constriction.
· Risk factors of Alzheimer’s disease family history, age, and CVD.

· Symptoms of Alzheimer’s disease? Slurred speech, reduced cognitive functions, reduce
sexual function, and decrease in judgment and skills.
STAGES of dementia
· Mild: Forgetting daily activities. Example taking medicines, tel. phone number, finances,
paying bills and directions.
· Moderate: Forgetting personal activities bathing, dressing, eating (remember upon
reminders).
· Severe: Forgetting personal activities but cannot recall upon reminders.
· Terminal: Patient must be fed, immobile and mute.
CHOLINERGIC AGOINIST ANTICHOLINERGIC ????

THE DRUG OF CHOICE AVOID
SIDE EFFECTS: DUMBELS
Reversible acetyl cholinesterase inhibitor
Galantamine, Donepezil, Rivastigmine
PharmacyPrep.
17-1
Donepezil
Mechanism Donepezil is a piperidine-based, reversible inhibitor of the enzyme

acetylcholinesterase (AChE)
It selective and have greater affinity for AchEi in brain than periphery. Little or no
hepatotoxicity.
Reduces the hydrolysis of acetylcholine, increasing the amount available in the
synaptic cleft.
Side effects GI effects. Nausea, vomiting and diarrhea.
· CNS effects. Fatigue, insomnia, headache
· Other effects. Muscle cramps, anorexia, and difficulty in passing urine.
Dosage · Daily one dose in the morning or evening
· Initial 5 mg/day, target 10 mg/day adjust dose after 4 wk
Advantage · Toxicity may be ↑ by inhibitors of CYP2D6 or CYP3A4 (e.g. paroxetine,
erythromycin, prednisone, grapefruit juice, nefazodone).
Drug and · Effectiveness may be ↓ by inducers of CYP2D6 or CYP3A4 (e.g.
Drug carbamazepine, phenytoin, rifampin).
Interactions
Monitor · Periodic checks may be performed to see benefit of drug.
Rivastigmine
Mechanism Rivastigmine, a reversible cholinesterase inhibitor of the carbamate-type

· It has short half life of 2 hours, but able to inhibit AchEi up to 10
hours. Because of slow dissociation of carbamate enzyme, it is
referred as pseudo-irreversible AchEi.
Side effects · Weight loss due to reduced appetite. Nausea, abdominal pain
· Depression, agitation, confusion, drowsiness, dizziness.
· Weakness, trembling, sweating, malaise, convulsions (rare).
Therapeutic · The drug of choice to treat Lewy body dementia.
use · Avoid antipsychotics
Dosage · For rivastigmine, the initial dose is 1.5 mg PO BID, and can be
doubled to 3 mg PO BID after 30 days. Transdermal patch for 24 hr.
Galantamine
Mechanism Competitive, reversible acetylcholinesterase inhibitor.

Therapeutic Effective in Alzheimer’s and vascular dementia.
use
PharmacyPrep.
17-2
Side effects Nausea, vomiting, abdominal pain, diarrhea, indigestion, decreased appetite and
weight loss, headache, dizziness, tiredness, sleepiness or sleeplessness,
confusion, runny nose, urinary tract infection, falls.
Dosage 16- 32 mg bid. Available as extended release once daily.
DUMBEL
DIARRHEA, URINATION, MIOSIS, BRADYCARDIA, EXESSIVE
SALIVATION, LACRIMATIN, SWEATING
Tips
· Alzheimer's dementia occurs due to --> decrease in acetylcholine

· Amnesia à Short time loss of memory
· Donepezil and rivastigmine and galantamine all have anorexia SEs.
· Drug of choice for Alzheimer's is --> donepezil.
· Memantine --> N-methyl D-aspartate (NMDA) receptor antagonist.
· Selective reversible acetylcholinesterase inhibitor (donepezil and rivastigmine)
· Non-selective reversible acetylcholinesterase inhibitor. (Galantamine)
· N-methyl D-aspartate (NMDA) blockers (non-competitive) (memantine)
SELECT TRUE OR FALSE

· Donepezil and rivastigmine and galantamine all have anorexia SE. (True/False)
· Delirium is short time agitation, and lack of judgment and memory loss (True/False)
· Amnesia is short time memory loss (True/False)
· Galantamine is classified as non-selective acetyl cholinesterase inhibitor (True/False)
PharmacyPrep.
17-3
PharmacyPrep.
17-4
www.PharmacyPrep.Com Anti-Parkinson's Drugs
18
Anti-Parkinson’s Drugs
Parkinson's is a condition, which is characterized by muscle tremors at rest, muscle weakness,
emotionless facial expressions, increased sweating and salivation, disturbances of motion and
increased postural balance difficulty. These patients have a deficiency of the neurotransmitter,
dopamine, allowing acetylcholine to dominate.
DA COMT DA MAOi- B Anticholinergic Anti-viral

precursor inhibitors agonist inhibitor drug
Benztropine
Peripheral dopa Selegiline Trihexphenidyl
Entacapone Amantadine
decarboxylase Rasagiline
Tolcapone
inhibitor
Levodopa Carbidopa D1D2 Non selective

D2 selective
Pramipexole Ergots. Bromocriptine
Ropinirole
Combination
*Sinemet

Levodopa Sinemet Levodopa/carbidopa Sinemet CR
Bromocriptine Parlodel Levodopa/benserazide
Pergolide Permax Selegline Deprenyl
Pramipexole Mirapex Entracapone Comtan
Benztropine Benztropine Tolcapone Tasmar
Domperidone Motilium Amantadine Symmetrel
PharmacyPrep.
18-1
Anti-Parkinson’s drugs pharmacology

Brain
GIT Peripheral tissues
3-O-Methyldopa 3-O-Methyldopa
Tolcapone
Entacapone COMT
Tolcapone
Striatal neuron
Levodopa Levodopa Levodopa
Carbidopa
Dopamine
Dopamine
D1 and D2 Dopamine
Bromocriptine and
receptors
Pramipexole
Ropinirole
MAO-B
Selegiline
Rasagiline
Dihydroxyphenylacetic
Acid (DOPAC) + H2O2
Levodopa preparations
Mechanism: Levodopa, a dopamine precursor that is converted to dopamine in the brain by
with enzyme dopa-decarboxylase, appears to correct akinesia, rigidity and tremors of
Parkinson’s disease by the formation of dopamine
at the nigro striatial dopaminergic site.
Concept!
1) Wearing off (end dose effect)
Side effects: The most common SEs of levodopa
2) On-off motor fluctuation
therapy is gastric upset Nausea, vomiting,
orthostatic hypotension, dyskinesia,
hallucinations, confusion Long term use of Levodopa/carbidopa therapy can produce mydriasis
& precipitation of glaucoma, melanoma.
Pharmacokinetics. High protein content meals interfere with transport of levodopa into CNS.
Levodopa should be taken on an empty stomach, typically 45 min before a meal.
Wearing off: Short duration response or "end dose" effect. The motor complications include
"off periods" of immobility or greater severity of the other parkinsonism symptoms and various
PharmacyPrep.
18-2
abnormal movements. This is due to decrease synthesis and storage of dopamine generated
from endogenous or exogenous levodopa.
On-off fluctuations: Most severe form of wearing off effect (abruptly freezes).
ALL ANTIPARKINSON’S DRUGS SIDE EFFECT:

HALLUCINATIONS (DUE TO -D2)
ORTHOSTATIC HYPOTENSION
DYSKINESIA (INVOLUNTARY MOVEMENT OF LIMBS)
Anticholinergic drugs: Benztropine mesylate AND trihexyphenidyl HCl.

SEs. Anticholinergic, avoid in elderly can cause aggravation of glaucoma, memory impairment.
Benztropine
Therapeutic use Direct acting D 2 agonist, antimuscarinic with some DA reuptake

inhibitor. The drug of choice to treat drug induced Parkinsonism.
Side effects Anticholinergic side effects, avoid in elderly, aggravation of
glaucoma, memory impairment. Drowsiness, Dizziness, dyskinesia,
hallucinations and confusion.
Contraindications Pregnancy, inhibits the lactation, should not be used in breast-
feeding mothers, hypertension.
Counseling Take drug with food, snacks, milk to reduce GI side effects
Antiviral Agent
Antiviral agent with anti-Parkinson properties. Indicated in drug induced PD because levodopa
will reverse the beneficial effect of the drug.
Side effects: anticholinergic side effects, hallucinations, edema of feet & ankles.
Amantadine (Symmetrel)
Mechanism Prevent damage to dopaminergic neurons acting as (NMDA) N-

Methyl-D-Aspartate receptor antagonist.
Therapeutic use Indicated in Parkinson's disease and also for prevention and
treatment of influenza A viral infections.
Drug-Drug Amantadine may add to the effects of anticholinergic drugs.
interaction
Side Effects Anticholinergic side effects, hallucinations, edema of feet &
ankles.
COMT inhibitor (Catecholamine O-Methyl transferase): Entacapone and Tolcapone.
PharmacyPrep.
18-3
Prolong the action of levodopa by inhibiting the methylation and subsequent inactivation of
dopamine.
Side effects: Dyskinesia, nausea, sleep disorders, anorexia, severe diarrhea, hallucinations
COMT inhibitors are used as an adjunct to levodopa and carbidopa to reduce response
fluctuation.
The dyskinesia or induction of hallucination can be managed by reducing the dose of levodopa.
Entacapone
Mechanism Prevent the conversion of levodopa to homovallinic acid in the

peripherally, allowing more levodopa to cross the blood-brain
barrier and resulting in greater production of dopamine in the
brain.
Side Effects Dyskinesia, sleep disorders, hallucinations, nausea, diarrhea, and
anorexia.
Entacapone is preferred over tolcapone which is associated with hepatotoxicity.
Direct acting dopamine agonist: (Bromocriptine, Pramipexole, Ropinirole)

SEs. Nausea, vomiting, orthostatic hypotension, psychosis, pleural fibrosis (chest x ray before
initiating therapy). Ergot alkaloids are bromocriptine and pergolide.
Bromocriptine
Mechanism · Direct acting non-selective D 1 and D 2 agonist. Inhibiting the

secretion of the hormone prolactin from pituitary gland.
Therapeutic use
Question Alerts!
1) Non selective dopamine agonist cause pulmonary fibrosis.
· Relieving symptoms of parkinsonism.

· Treatment of conditions associated with prolactin production
such as female infertility and male infertility and impotence.
· Treat benign breast condition and some menstrual disorder.
Drug-Drug · Antipsychotics oppose the action of bromocriptine and increase
interaction the risk of parkinsonism.
· Using bromocriptine with ephedrine, pseudoephedrine, and
phenothiazines, erythromycin and other macrolide antibiotics
may lead to severe adverse effects.
PharmacyPrep.
18-4
Contraindication · Pregnancy, hypertension.

Side Effects · Drowsiness, dizziness, dyskinesia, hallucinations and confusion.
· Pleural fibrosis (do chest X-ray before initiating).
· Erythromelalgia (painful red swelling of the legs).
· Q. Used for the treatment of neuroleptic malignant syndrome
and is approved for hyperprolactinemia.
· Inhibits the lactation, should not be used in breast-feeding
mothers.
· Take drug with food, snacks, milk to reduce GI side effects.
Pramipexole and ropinirole

Mechanism · Selective D 2 receptor agonist.
Therapeuti · Mild to moderate Parkinson’s disease and to manage motor,
c use
fluctuation. The drug of choice for restless leg syndrome.
Side Effects · Dizziness, insomnia, lightheadedness. Rarely it can cause
hallucinations or dyskinesia. Sudden onset of sleep.
Monitoring · Regular monitoring of your Parkinson's symptoms, and report any
changes to the physician.
MAO-B inhibitor: Selegiline, Rasagiline

· Selective inhibitor of MAO type B at low doses. Indicated in early stages of PD and as an
adjunct to levodopa in patients who exhibit deterioration in their response.
· Side effects: Insomnia, confusion, hallucinations, anorexia, diarrhea, increase dyskinesia,
serotonin syndrome and hypertension crisis.
Summary of anti-Parkinson’s drugs

Drug Role in Parkinson’s disease Common Adverse Effects
Levodopa/Carbidopa or Mainstay of therapy Nausea, hypotension, hallucinations “wearing
Levodopa/benserazide off’, “on-off”, dyskinesia (after 3-5 y).
Dopamine agonists Adjunct to levodopa may be Nausea, headaches, hypotension, sedation
useful as monotherapy to dyskinesia, hallucinations, confusion.
delay initiation of levodopa
Anticholinergic drugs Monotherapy or adjunct to Dry mouth, blurred vision, urinary retention,
levodopa in early stages constipation, confusion, decreased memory,
psychosis, delirium (worsens with age).
Amantadine Monotherapy or adjunct to Dizziness, confusion, nausea, hallucinations,
levodopa in early stages constipation
Selegiline Adjunct to levodopa in mild Nausea, confusion, confusion, depression,
disease insomnia, hypotension
COMT inhibitor
PharmacyPrep.
18-5
Tolcapone
The most common side effects of LEVODOPA are nausea, hypotension, and hallucinations. Domperidone
is useful for managing nausea and hypotension.
After 3-5 years of levodopa therapy, patients begin to develop motor fluctuations (“wearing off”, “on-off”)
and dyskinesias. The exact cause of these late side effects is uncertain. Several strategies can be tried in
an attempt to manage motor fluctuations.
Management of Adverse Effects from Drugs Used in Parkinson’s Disease

Adverse Effect Management Strategies
“on-off” (sudden “freezing” Add a dopamine agonist
unrelated to time and dose Switch to Sinemet CR
“Wearing off” Administer levodopa more frequently
Switch to Sinemet CR. Add or increase dose of a dopamine
agonist.
Switch to a different dopamine agonist.
Dyskinesia Decrease dose of levodopa or dopamine agonist
Switch to a different dopamine agonist
Psychosis, confusion, Decrease dose of levodopa or dopamine agonist. Discontinue
agitation, hallucinations, anticholinergic drugs, amantadine, selegiline
delusions
Orthostatic hypotension Can be caused by anti-Parkinson medications, other medications
and by Parkinson’s disease itself. Lying down and standing blood
pressure should be checked at each visit.
Decrease dose of levodopa or dopamine agonist, increase
gradually
Add salt to diet.
Add domperidone for N&V or fludrocortisone to treat
hypotension. DOMPERIDONE INHIBIT D 2 RECEPTORS AND IT DOES
NOT CROSS BBB, THUS IT HAS NO EPS.
Nausea and vomiting Take levodopa with food. Increase dose of levodopa or dopamine
agonist gradually over several weeks.
AVOID METOCLOPRAMIDE BECAUSE IT CAUSE EPS.
Tips
· Levodopa side effects --> hypotension, nausea, vomiting, hallucination, dyskinesia
· Entacapone and tolcapone are -->COMT Inhibitors
· Entacapone side effect --> have less hepatotoxicity than tolcapone. Gives orange color
urine.
· Parkinson's disease is due to decrease in ( dopamine )
· What does penetrate into brain ( levodopa )
· Abnormal involuntary movements ( dyskinesia )
· What antiemetic drug should be avoided in PD patient (metoclopramide)
· A selective MAO- type B inhibitor (SELEGILINE AND RASIGILINE )
· Decreased voluntary movement is (AKINESIA OR BRADYKINESIA )
PharmacyPrep.
18-6
· Slowness in performing common voluntary movement, including, standing, walking, eating,

writing, and talking. (BRADYKINESIA)
· What is NOT a Parkinson’s disease symptom (TARDIVE DYSKINESIA)
· COMT inhibitor (ENTACAPONE)
· Repetitive involuntary choreiform movement of the tongue, limbs and trunk (TARDIVE
DYSKINESIA)
· The common side effect of levodopa (90%) (NAUSEA AND VOMITING)
TRUE OR FALSE
· All antipsychotic required caution in Parkinson’s disease (True/False)
· Levodopa/carbidopa is drug of choice in Parkinson’s disease in patient over 70 yo (True/False)
· Levodopa does penetrate into brain (True/False)
· Dopamine does not penetrate into brain (True/False)
· Carbidopa does not penetrate into brain (True/False)
· Dyskinesia is repetitive involuntary movement of tongue, limbs, hands, and trunk (True/False)
· Metochlopramide an antinauseating drug should be avoided in PD patient (True/False)
· All antipsychotic required caution in PD (True/False)
· Levodopa/carbidopa is drug of choice in PD (True/False)
· Parkinson's is due to decrease in Dopamine (True/False)
· Selegiline is a selective MAOI type b (True/False)
· Akinesia is decreased voluntary movement (True/False)
· Bradykinesia is slow movement (True/False)
· Over treatment of Parkinsonism drugs can result into schizophrenia (True/False)
· Pramipexole and ropinirole are dopamine agonist (True/False)
· Pulmonary fibrosis is side effect of bromocriptine, pergolide (except pramipexole and ropinirole)
(True/False)

COMT Catecholamine O-Methyl transferase PD Parkinson's Disease
DA Dopamine MAO Monoamine Oxidase
TRAP Tartrate Resistent Acid Phosphatase Kinesia motor movements
PharmacyPrep.
18-7
PharmacyPrep.
18-8
www.PharmacyPrep.Com Anesthetics
19
Anesthetics
Local anesthetics
Esters Type Amides Type
Short duration Long duration Medium

Long duration Bupivacaine
Procaine duration
Tetracaine Ropivacaine Lidocaine
Surface active
Medium duration
Benzocaine
Cocaine
Ester type Amide type

Benzocaine Lidocaine
Procaine Bupivacaine
Tetracain Ropivacaine
PABA intermediate, can cause Very low allergies
frequent allergies.
Metabolism in plasma pseudo- Liver enzyme inducer
cholinesterase
Unstable in solution Very stable in Solution
Inhibit sensory nerves that carry stimuli to CNS and block nerve fiber conduction. Blockade is
reversible, must continue administration of the drug for effects to continue. Ester local
anesthetics produce para amino benzoic acid (PABA) as metabolic product.
Amide local anesthetics metabolized by liver. Most local anesthetic solutions contain the
vasoconstrictor epinephrine. Epinephrine used (1:100000) in local anesthetics act as
vasoconstrictor. Epinephrine in local anesthetic helps to prolong the duration of action on
locally. Reduce systemic absorption thereby decrease systemic toxicity.
PharmacyPrep.
19-1
General Anesthetics
Inhaled Intravenous
Barbiturate Miscellaneous Dissociative

Gas Volatile liquid Thiopental Propofol Ketamine
Halothane
Nitrous oxide
Enflurane
Ether (diethyl ether)
Isoflurane Benzodiazepines
Midazolam
The minimum alveolar concentration (MAC) is the alveolar anesthetic concentration at one
atmosphere (760 mm Hg) preventing movement in 50% of patients exposed to noxious stimuli.
Inhaled anesthetics: Inhaled anesthetic are used to provide general surgical anesthesia
Halothane (Fluothane)
· Halothane is used in pediatric anesthesia. It is infrequently used in adults.
· Side effects: Malignant hyperthermia.
Enflurane
Enflurane is used as an inhalation agent for adults, but is not widely used for pediatric cases.
Isoflurane.
Isoflurane may be the most widely used inhalation agent.
Nitrous Oxide. With a MAC value of 105%, nitrous oxide, by itself is not suitable or safe as a sole
anesthetic agent. Nitrous oxide is an effective analgesic and nitrous oxide in combination with
thiopental for induction, a skeletal muscle relaxant and hyperventilation to reduce CO 2 .Use as
an adjunct to other inhalation agents allows reduction in their dosage.
Ketamine
Congener of phencyclidine. Question Alerts!
· Short acting non-barbiturate anesthetic induces a Ketamine is categorized as narcotic
dissociated state in which the patient appears drug due to abuse potential.
awake but is unconscious and does not feel pain.
· Causes sedation, immobility, amnesia, and nightmares, and causes hypertension and
increases cardiac output-avoid use in stroke and high blood pressure patients.
· Mainly used for short procedures.
PharmacyPrep.
19-2
Intravenous
· Intravenous are indicated to induce drowsiness and provide relaxation before the induction
of inhalational general anesthetics.
Propofol
· Sedative or hypnotic
· Used in induction and maintenance of anesthesia
· Fast onset (40 seconds of administration).
· Poor analgesic.
Fentanyl
· Narcotic
· Available as transdermal patch, but iv fentanyl good analgesic property.
Anesthetic Tips
· Sequence of MAC. Nitrous oxide > Ether > Enflurane >Isoflurane > Halothane
· Isoflurane (Forane), enflurane (Ethrane), sevoflurane (Sevorane, Ultane) and desflurane
(Suprane) are frequently used in adults.
1 Epinephrine 2 Local anesthetics 3 Halothane
4 Chlorpromazine 5 Benzocaine 6 N2 O
7 Butamben 8 Procaine 9 PABA
10 Procainamide 11 Cocaine 12 Local anesthetics
13 Thiopental 14 Tetracaine 15 lidocaine
· Ester type of local anesthetic metabolize to … ( 9 )
· A vasoconstrictor ( 1 )
· Its action is to helps prolong duration of action and decrease systemic SE. ( 1 )
· Topical anesthetic used for canker sores, cold sores, dental pains, and hemorrhoids (5 )
· Ester type local anesthetic include. (5,8,11,14 )
· Antiarrhythmic drug (Class Ia, Na+ channel blocker) shows action similar to quinidine (10)
· Used as an antiarrhythmic drug and it is an amide type local anesthetic (15)
· Classified as rapid acting barbiturates. (13)
· Malignant hyperthermia associated with what anesthetic. (3)
· Inhaling gas general anesthetic also known as laughing gas (N 2 O)
· General anesthetic safe in children. (3)
· Reason for treating infection prior to use of local anesthetic? à infection and inflammation
lower tissue pH, reducing the diffusion of the agent into the nerve, thus reduce
effectiveness.
· Local anesthetics do not produceà loss of consciousness
· Local anesthetics like lidocaine is NOT used for? sunburns
· TRUE OR FALSE
PharmacyPrep.
19-3
· Ester type of local anesthetic metabolize to para aminobenzoic acid (PABA) (True/False)
· Epinephrine in local anesthetics act as a vasoconstriction (True/False)
· Epinephrine helps in prolongs duration of anesthesia (True/False)
· Local anesthetic do not produce loss of consciousness (True/False)
· Benzocaine topical anesthetic is used for aphthous ulcers and cold sore (True/False)
· Ester type local anesthetic include benzocaine, tetracaine, and procaine (True/False)
· Amide type anesthetics include bupivacaine, ropivacaine, and Lidocaine (True/False)
· Procainamide class 1a antiarrhythmic drug (True/False)
· Lidocaine is used for class 1b antiarrhythmic drug and local anesthetic (True/False)
· Thiopental is classified as short acting barbiturates (True/False)
· Malignant hyperthermia is side effect of halothane (True/False)
· Halothane is general anesthetic safe in children (True/False)

MAC Minimum Alveolar Concentration PABA Para Amino Benzoic acid
CNS Central Nervous System
PharmacyPrep.
19-4
www.PharmacyPrep.Com Opioid Analgesics
20
Opioid Analgesics
Mixed agonist–antagonist Antagonists
Pentazocine (m antagonist) Naloxone (Full)
Nalbuphine (m antagonist) Naltrexone (Partial)
Agonists Buprenorphine (m partial agonist)
Butorphenol (m antagonist)
Strong (efficacy &

addiction, abuse) Moderate (efficacy Weak (efficacy &
Morphine & addiction, abuse) addiction, abuse)
Heroin Codeine Propoxyphene
Meperidine Oxycodone
Methadone Hydrocodone
Fentanyl
Levorphanol
Hydromorphone
Drug Name Trade Name Drug Name Trade Name

Nalbuphine Nubain Pentazocine Talwin, Talwin NX
Naloxone Narcan, Narcan Neonatal Naltrexone Depade, ReVia, Vivitrol
Naltrexone Depade, ReVia, Vivitrol Levorphanol Levo-Dromoran
Meperidine Demerol, Meperitab
Methadone Diskets, Dolophine, Methadose
Fentanyl Duragesic Hydrocodone Hycodan, Hydromet, Hydropane,
Oxycodone Endocodone Propoxyphene Darvon, Darvon-N 100, Darvon-N,
Opioids are derived from opium. These are powerful central nervous system drugs that are
used medically to relieve pain. These drugs are used for moderate to severe pain of trauma,
post-surgical pain, pain associated with myocardial infarction and pain of terminal illness.
Physical and psychological dependence (addiction) can occur when opioids are administered for
some time. When tolerance develops, the patient requires increasing amounts of drug to treat
pain. All opioids are habit forming, however, titrated doses to treat pain; the risk of addiction is
slight.
20-1
PharmacyPrep.
Opioid analgesics act primarily on the CNS and the intestines. The perception of and emotional
response to pain are modified when opioid analgesics bind with stereospecific receptors in the
CNS. The most studied subtypes of opioid receptors are mu (μ), delta (δ) and kappa (κ). Pure
opioid agonists such as morphine act primarily at the mu receptor. Mixed agonist-antagonists
such as butorphanol, nalbuphine and pentazocine are most active at the kappa receptor.
Buprenorphine is a partial agonist at the mu receptor and an antagonist at the kappa receptor.
There are three known peptide neurotransmitters that act on mu, delta and kappa receptors.
· Enkephalin mu & delta

Question Alerts!
· Endorphine mu
1) Morphine derivatives analgesic activity is due to?
· Dynorphine kappa
mu agonist (analgesia, respiratory depression and
euphoria caused by mu opioid agonist)
Mu receptor simulation (supraspinal,
spinal) cause
3) Mu receptors are found in supraspinal and spinal
· Analgesia (CNS).
· Respiratory depression 4) analgesia induced by acupuncture results from
· Euphoria biofeedback mechanism thus release endogenous
· Physical dependency endorphins.
· Pupil constriction
Kappa receptor simulation cause (spinal analgesia)

· Analgesia
· Miosis
· Sedation (sedation and dysphoria are kappa agonist effect).
Tolerance: Need to use the high dose of drug to get the same effects.
Physical dependency and psychological dependency (craving, euphoria (feeling good).
Opioid overdose gives three characteristic symptoms such as pinpoint pupil (due to increase in
cholinergic activity), decrease respiration (hypoxia), constipation, coma and somnolence.
Opioid withdrawal symptoms Question Alerts!

· Nausea, vomiting 1) Opioid Induced constipation is treated by?
· Muscle ache A) Docusate sodium (stool softener)
· Lacrimation or rhinorrhea B) Senna (stimulant laxative) or BISACODYL & DOCUSATE
· Diarrhea C) Psyllium
D) Magnesium hydroxide
· Fever and dilated pupil
E) lactulose
· Autonomic hyperactivity
Therapeutic use:
· Analgesics (moderate to severe pain)
20-2
PharmacyPrep.
· Antitussive (dextromethorphan, codeine)

· Antidiarrheal (Loperamide)
Side effects
· N&V very common and tolerance develops in 2-3 days: dimenhydrinate/metoclopramide
PRN.
· Constipation (increase GI tone): Daily laxatives (stool softener & stimulants)
· Sedation, drowsiness, somnolence very common, tolerance develops in 2-3 days.
· Respiratory depression
· Urinary retention, dry mouth; chew gums
· Hypotension
· Pruritus (OPIOID THAT RELEASE H 1 )
Side effects Withdrawal

· Constipation (increase GI tone) · Diarrhea
· Sedation, drowsiness · Nausea, vomiting, Muscle ache
· Miosis · Lacrimation or rhinorrhea
· Respiratory depression · Fever and dilated pupil (mydriasis)
· Urinary retention · Autonomic hyperactivity (palpitation)
· Hypotension · yawning
Opioid analgesic therapeutic effects

Drug Therapeutic Effects
Morphine · Act on Mu receptor agonist and for chronic use
Hydrocodon · Cannot be glucuronidase at 6-position. Used in renal failure
e · Codeine derivative, used for pain cough suppression
· More addictive than codeine.
Codeine · Used for cough suppression (AVOID IN <12 YO) and mild to moderate pain.
· Analgesia does not increase with dose (ceiling effect).
· Additive effect with ASA and acetaminophen
Oxycodone · Codeine derivative, used for pain AND cough suppression.
· More addictive than codeine.
Methadone · Acts on Mu receptor agonist and NMDA antagonist.
· Oral form once daily, long half-life (36-48 HRS). (SLOW WITHDRAWAL SYMPTOMS).
· Used for suppressing opioid withdrawal symptoms and reduction of opioid use.
· Less emetic effect
· Milder withdrawal symptoms.
Meperidine · Mu receptor agonist
· Used during labor (USED FOR LABOR PAIN) because this has least respiratory
depression. Anticholinergic effect. No miosis, Tachycardia (IV), Toxic doses may
20-3
PharmacyPrep.
cause CNS stimulation.

· The least respiratory depression and less constipation
· Normeperidine (metabolite) - hallucinations and convulsions
· Constipation and urinary retention less than for morphine.
Pentazocine · Weak antagonist at mu receptors (1/30 naloxone) and agonist at kappa receptors.
· May precipitate (trigger) withdrawal symptoms when given instead of morphine.
Oral and IM dosing.
Butorphanol · Strong agonist at kappa. The kappa agonist has lower ceiling analgesic; thus, they
are not effective in treating severe pain.
· Same as pentazocine.
· Used for chronic pain only (intranasal, refract headache)
Nalbuphine · Antagonist at mu receptors and agonist at kappa
· Same as for pentazocine.
· Low respiratory depression. Little euphoria (excited state of mind). Analgesia during
labor.
Naloxone · Antidote of mu agonist opioids. Full antagonist at mu receptors.
· Full antagonist. IV only because first pass effect is 98%.
· Short half-life.
Naltrexone · Partial antagonist at mu receptors, long half-life. Is given orally.
· Treat alcoholics decrease craving. Blocks opioid re-addiction and craving.
Naltrexone and buprenorphine have shown promise in treatment of cocaine abuse.
Tramadol · The (+) isomer weak mu agonist (30%) and (-) isomer neurotransmitter 5HT and NE
reuptake inhibitor (70%). Not narcotics and less abuse potential
Fentanyl · mu agonist. Produce short duration of action 1-2hr. It does not cause histamine
release up on iv injection FOR ACUTE PAIN. Fentanyl patch produce analgesia for 72
hrs FOR CHRONIC PAIN.
buprenorph Partial mu agonist and kappa antagonist. Long half-life once daily or alternate day
ine dosing.
SUBOXONE (NALOXONE+ BUPRENORPHINE)
Dextrometh Cough suppressant, D-isomer of morphine, has NO analgesic effect. Has NMDA
orphan antagonist.
Opioids Mu receptor Kappa receptor NMDA receptor

Morphine Agonist
Methadone Agonist antagonist
Fentanyl Agonist
Meperidine
Codeine
Propoxyphene
Pentazocine Antagonist Agonist
Buprenorphine Partial agonist ANTAgonist
20-4
PharmacyPrep.
Butorphanol
Nalbuphine
Naloxone antagonist
Tips
· Avoid opioids in head trauma patients

· Morphine active metabolite → morphine-6-glucoronide
· Analgesic activity of morphine is due to → mu agonist
· Codeine is metabolized by → CYP2D6
· Patient taking Tylenol # 3 + hydromorphone → can cause constipation
· Methadone is used for → opioid withdrawal management
· Morphine over dose symptoms → miosis, respiratory depression, constipation,
· Which opioids has highest addiction potential → morphine, heroin, fentanyl,
hydromorphone.
· In angina pain what opioids is used →morphine
· Drugs used to treat opioids withdrawal symptoms→ methadone and suboxone
· Opioid antagonist→ naloxone
· A patient with chronic renal disease developed seizure after initiating opioids therapy,
which opioids would be responsible→ meperidine toxicity
· Opioids least used in→ head trauma
· Pinpoint pupil is opioids → over dose symptoms
· Avoid opioids with MAOI → meperidine, fentanyl and tramadol
· Opioid induced constipation treated by → Senna and docusate
· Enkephalins are →peptide type opioid neurotransmitters
· A patient is on opioids, having constipation, started taking psyllium laxatives but no
improvement, you advise him→ change to Senna and docusate
· Where to apply fentanyl transdermal patch → shoulders, abdomen, thighs and less hairy
area.
· Allergic to morphine (due to histamine release) can use →fentanyl
· What is the antidote for an oxycodone overdose? →naloxone
· Name the antagonist of choice for an opioid overdose. → naloxone
· Least respiratory depression → meperidine
· If allergic to morphine → use fentanyl
· Highly fat-soluble opioids → fentanyl
· Preferred opioids in labor pain → meperidine
· Sequence of addiction/abuse liability: Fentanyl > Morphine = Meperidine = Methadone >
codeine > Propoxyphene
20-5
PharmacyPrep.
20-6
PharmacyPrep.
www.PharmacyPrep.Com Non–Steroidal Anti-inflammatory Drugs & Analgesics
21
Non–Steroidal Anti-inflammatory
Drugs & Analgesics
Cox-1 protect GI mucosa (high concentration of Cox-1 in GI)
Cox-2 released at site of inflammation.
Cyclooxygenase I (COX1) Cyclooxygenase II (Cox II)

Catalyze prostaglandins Catalyze prostaglandins
· Antipyretic: a drug to reduce fever

· An analgesic: a drug used to relieve pain
· Anti-inflammatory: Drugs that reduce redness and swelling
· Antiplatelet: Prevent platelet aggregation.
Acetyl Salicylic Acid, COX inhibitors, and Acetaminophen
Salicylates Non-selective COX II Acetaminophen

COX inhibitors Inhibitors
ASA NSAIDs:
*Diflunisal
*Flurbiprofen
*Salicylic acid *Ibuprofen *Celecoxib (Celebrex)
*Methylsalicylic *Naproxen *Rofecoxib
*Indomethacin
*Sulindac
*Piroxicam
*Ketorolac
21-1
PharmacyPrep.

acetylsalicyclic acid, Aspirin® diclofenac Voltaren® (generics)
ASA
enteric coated ASA Entrophen®, diflunisal generics
Novasen®
celecoxib Celebrex® floctafenine Idarac® (generics)
flurbiprofen Ansaid® (generics)
ibuprofen Motrin®, Advil® (generics)
indomethacin Indocid® (generics) ketoprofen Orudis® (generics)
ketorolac Toradol® meloxicam Mobicox®
naproxen Anaprox®, Naprosyn® piroxicam Feldene® (generics)
(generics)
sulindac generics tiaprofenic acid Surgam® (generics)
tolmetin Tolectin®
Non Steroidal Anti-inflammatory Drugs (NSAIDS)

Salicylates derivatives
Acetyl salicylic acid (ASA) Antiplatelet, antipyretic, analgesic and anti-inflammatory.
ASA bind irreversibly to COX enzymes, while other NSAIDs bind in a
reversible.
Salicylic acid
Methyl salicylates Wintergreen oil-topical agent, counter irritant
Salsalate, sodium Injectable
thiosalicylate
Choline salicylate Oral liquid
5-Aminosalicylic acid Crohn's disease and ulcerative colitis
Olsalazine
Sulphasalazine Ulcerative colitis and Crohn's disease
Diflunisal Diflurophenyl derivative of salicylic acid
Pyrazolone derivatives
Sulfinpyrazone
Phenylbutazone
Propionic acid derivatives The order of gastric ulcerogenic activity.
indomethacine> Sulindac>naproxen >ASA, indomethacin,
ketoprofen, ibuprofen
Ibuprofen
Ketoprofen
Naproxen
Carprofen
Fenoprofen
21-2
PharmacyPrep.
Acetic acid derivatives

Indomethacin High renal side effects, have high anti-inflammatory
Diclofenac Voltaren
Ketorolac Toradol. NSAID used for acute pain.
Sulindac Clinoril
Etodolac
Anthranilic acid derivatives
Mefenamic acid
Meclofenate
Oxicams derivatives
Piroxicam Feldene
Meloxicam
Pyrazole derivatives.
COXII inhibitors
Celecoxib Celebrex
Only Lumerocoxib has no sulfa allergy, where all other Cox II inhibitors have sulfa allergy.
Chemistry of Salicylates derivatives
Acetyl salicylic acid (ASA)

· Pharmacological actions. ASA exhibits analgesics, antipyretics, anti-inflammatory and
antiplatelet actions. ASA irreversibly inactivates both COX 1 & COX 2 , where as all other
NSAIDs inactive reversible COX 1 &COX 2 .
Analgesic action
· Prostaglandin PGE 2 thought to sensitize the nerve endings to the action of bradykinin,
histamines and other chemical mediators, thus inflammatory process may cause analgesic
action. Decrease of PGE 2 synthesis
represses the sensation of pain. ASA Question Alerts!
analgesic dose 325 mg every 4 to 6 h. 1) What is endogenous pain producing substance?
bradykinin
Antipyretic action 2) What is endogenous fever producing substance?
· Prostaglandin PGE 2 stimulation occurs pyrogen
when pyrogen an endogenous fever 4) What drugs cause Reye's syndrome? ASA
producing agents such as cytokines is 5) NSAIDs that are used as antiplatelets?
released from the white blood cells that
are activated by infection, hypersensitivity, malignancy or inflammation. Salicylates lower
temperature by decreasing PGE 2 synthesis. ASA antipyretics dose 325 to 650 mg q 4 to 6 h
PRN.
· Reye syndrome. Children with flu and viral infection should avoid using ASA, because it may
cause Reye’s syndrome.
21-3
PharmacyPrep.
Antiplatelets action
· Irreversible platelet inhibition and inhibition of Cox-I & Cox-II action gives antiplatelets
action. Antiplatelets 60 to 80 mg.
Anti-inflammatory action
· Cox-I, Cox-II and prostaglandin inhibition. The anti inflammatory dose of ASA 650 mg
Mechanism of action of ASA.
COOH
O OCH3
ASA
O
ASA mechanism of AAAAs!
Analgesic 325 mg Q4 to 6 h
Cyclooxygenenase Active
O
Antipyretic 325 to 650 mg Q4-6h
COX I & II PRN
O C CH3
Cyclooxygenase (inactive) Anti-inflammatory 650-975 mg Q4-
6h
COOH
OH Antiplatelets 81-325 mg daily
Complications associated with NSAID and acetyl salicylic acid.

· Respiratory depression. Toxicity respiratory alkalosis and metabolic acidosis (increase CO2
and decrease pH).
· GI effects. due to inhibition of prostaglandin PGEs. Prostacyclin PGI 2 inhibit gastric

secretion. The most common side effects of salicylate are GI disturbances like nausea,
vomiting, epigastric discomfort, peptic ulcers (dyspepsia, heart burn).
GI complications management: use prophylaxis of PPI with NSAIDs or Misoprostol + NSAIDs.
Oral NSAIDs are given with food to reduce gastrointestinal irritation.
· PGE 2 and PGF 2a stimulates synthesis of protective mucosa in stomach and small intestine.
· Indomethacin has the highest incidence of (35 to 50%) of GI ulcers.
Renal problems: PGE 2 and PGI 2 are responsible for renal blood flow. It can cause acute renal
failure.
All NSAIDs are contraindicated in patient with severe renal impairment CrCl <30 mL/min).
ASA is the only NSAID that removable by hemodialysis. Other NSAID overdose management is
symptomatic and supportive. There is no specific antidote.
Reye's syndrome is an acute syndrome that may follow influenza and chicken pox infections in
children. It is characterized by symptoms of sudden vomiting, violent headache, and unusual
behavior. The Reye's syndrome is associated with only ASA.
NSAID’s induced ulcers: Risk factors for development of upper GI side effects with NSAID:
· Age >65
· Anticoagulants or oral glucocorticoids
21-4
PharmacyPrep.
· History of peptic ulcer disease (past complicated or uncomplicated ulcers)

· History of upper GI conditions
Co-morbid medical conditions
Short acting NSAIDs t 1/2 <6rs Long acting NSAIDS t 1/2 >6hr
Ibuprofen, diclofenac, ketoprofen, Naproxen, celecoxib, meloxicam and
Indomethacin piroxicam
Tips
· Analgesic action of acetaminophen is due to → central prostaglandin inhibition
· If allergic to ASA → can use acetaminophen and avoid all NSAIDS and COX-II
· Rye syndrome is caused by →ASA in children with flu symptoms
· Life span of platelet → 7-10 days
· Sulfasalazine metabolism occurs in → colon by azoreduction
· Acetaminophen least used as → anti-inflammatory drug like Gout arthritis.
· Antiplatelet action of ASA occurs at the minimum? 60-80 mg dose
· Symptoms of salicylism is treated by→NaHCO3
· Misoprostol is → PGE1 analog
· Misoprostol chemically classified as → Ecosonide
· Salicylism generally occurs at what dose of ASA→ > 4 g/day (ASA associated with Tinnitus)
· Mercapturic acid is produced by → glutathione conjugation
· Glutathione contains → glycine-cysteine-glutamic acid
· ASA and acetaminophen interchangeable for → analgesic and antipyretics
· All NSAIDs common complication is →GI, renal, cardiovascular and respiratory toxicities
· ASA toxicity symptoms are → metabolic acidosis and respiratory alkalosis (hyperventilation)
· In alcoholic patient if acetaminophen given in multigram (high doses), which substance is
decreased→ glutathione
· Acetaminophen antidote →N-acetyl cysteine
· Acetaminophen metabolized by → CYP450, sulfate conjugation and glucuronidation
· What are pharmacological action of COXII selective → inflammation and cardiovascular
protection
· Which salicylate cause folic acid deficiency →sulfasalazine
· What is mechanism of N-acetylcysteine →activate of glutathione conjugation.
· The DOC for ASA induced asthma → Montelukast
· Which NSAID has most effect on kidney (CrCl) →Indomethacin
· The primary active component of sulphasalazine → 5ASA
· What kind of metabolic reaction ASA undergoes in stomach→ hydrolysis and glycine
conjugation
· Toxicity of ASA in child will be worse than in adults because → inability of liver metabolism
· Rye syndrome → neurotoxicity associated with encephalopathy
21-5
PharmacyPrep.
· Which is the strongest endogenous pain producer→ bradykinin

· Salicylate toxicity excessive respiration is due to →respiratory alkalosis
· Diclofenac eye drops causes → stinging and burning side effect
· Ketorolac is used to treat →acute pain
· Celecoxib mechanism of action → Cox II inhibitor
· All cause GI side effects, except →acetaminophen

NSAIDS Nonsteroidal Anti-Inflammatory Drugs COX Cyclooxygenase
PGE Prostaglandin MI Myocardial Infarction
ASA Acetyl Salicylate
21-6
PharmacyPrep.
Pharmacyprep.com Autocoids
22
Autocoids
Autocoids (local hormones). Chemical mediators that the body releases as a response to pathogens or
noxious substances. Produced in the body and has profound pharmacological effects.
Autocoids or chemical mediators
Endogenous type
Amine types
Ecosonides
Histamines Prostaglandins
Serotonin Prostacyclin
Thromboxane
Leukotrienes
Bradykinin
Amines. No real clinical application in the treatment of diseases however antihistamines are of great
importance. Amine types of autocoids include histamines and serotonin.
Endogenous Peptides
· Site of production for endogenous peptides are GIT, kidneys, lungs, pancreas and uterus.
· Physiological actions of endogenous peptides are.
· Prostaglandin’s. Pain sensation, development of inflammation
· Thromboxane. Aggregation of platelets
· Prostacyclin. Inhibition of platelet aggregation
· Leukotrienes. Inflammation, chemotactic properties (pull substances to them)
Histamines. The histamine is produced from mast cells. Histamines act on three receptors, of
these H1, H2 receptors are excitatory and H3 receptors.
Physiological functions of H 1 receptor typical

· Allergic and anaphylactic response to histamines.
22-1
PharmacyPrep.
· Gives bronchoconstriction, and vasodilatation.

· Increase capillary permeability.
· Spasmodic contractions of gastrointestinal smooth muscle.
Chemistry of H 1 antihistamine. Usually lipid soluble, and similar in terms of absorption and
distribution.
· Good absorption after oral administration distribution with peak plasma concentration of 1
to 2 hours.
· Allows some to go to the blood-brain-barrier especially structural resemblance to
histamine.
H 1 antihistamine chemical classification
· Ethylene diamines. Pyrilamine, and triplennamine
· Alkylamines. Brompheniramine, chlorpheniramine, and acrivastine.
· Ethanolamines. Diphenhydramine, dimenhydrinate, and doxylamine.
· Piperazines. Meclizine, cyclizine, hydroxyzine, and cetrizine.
· Phenothiazine. Promethazine
· Dibenzocycloheptenes. Cycloheptadienes.
· Pthalazinone. Azelastine.
Piperidine. Terfenadine, astemizole, levocabastine, loratadine, and fexofenadine.
Mechanism. Competitive antagonist of histamine receptors. H 1 receptors are located in the
brain, heart, bronchi, GI tract and vascular smooth muscle. Mast cells and basophiles are
principle histamine containing cells.
H1 Antihistamine
1st Generation (PM) 2nd Generation (AM) 3rd Generation

Ethanol amines. Piperazine derivatives Piperadine Derivatives
Diphenhydramine Cetrizine (Reactine) Desloratadine (Aerius)
Dimenhydrinate Piperidine Derivatives
Doxylamine Fexofenadine (Allegra)
Alkyl amines Loratadine (Claritin)
Chlorpheniramine
Piperidine Derivatives Once daily dose
Azatadine, Cyproheptadine
Piperizines Question Alerts!
Meclizine, Cyclizine 2nd gen antihistamines are less sedative or used at AM.
hydroxyzine
Side effects. Sedation, dizziness, nausea, constipation, diarrhea, loss of appetite and
anticholinergic.
22-2
PharmacyPrep.
Metabolism of antihistamines. Some examples of metabolites of antihistamine, that are used as

drugs.
· Loratadine metabolizes to desloratadine.
· Hydroxyzine metabolizes to Cetrizine
· Terfinadine metabolizes to Fexofenadine.
Histamine H1-receptor blockers
Particularly Particularly Particularly All H1- antihistamines

Diphenhydramine, promethazine cyproheptadine
promethazine
Anti Alpha Dopamine Serotonin Histamine H1 Histamine H2

Cholinergic Adrenergic receptor receptor receptor receptor
(muscarinic) receptor
Pharmacology H1-antihistamines
H 1 antihistamine pharmacological actions (drugs action) takes place by blocking blocks H 1 -histamine
receptor effect. This results in beneficial effect on, Allergic symptoms, seasonal rhinitis, conjunctivitis,
rhino viral infections (common cold) and urticaria.
H 1 -antihistamine therapeutic uses. Antihistamine may bring relief to cold symptoms, runny nose, red
and itchy eyes. Allergic rhinitis symptoms such as nasal allergies. Antihistamine sedative properties are
utilized to treat temporary relief of insomnia. Antihistamines are effective to treat nausea and vomiting.
Used for Question Alerts!

· Allergiesà 2nd gen A person like to go into boat in 45 min. This person has
· Runny noseà motion sickness (sea sickness). What is good choice
Diphenhydramine treatment choice for motion sickness?
· Insomnia à
Diphenhydramine
· Nausea and (motion sickness) à Dimenhydrinate, doxylamine.
· Motion sickness à Dimenhydrinate, Meclazine & scopolamine, Promethazine.
22-3
PharmacyPrep.
Side effects:
Anticholinergic. Dry mouth, constipation, tachycardia, and difficulty voiding urine.
CNS. Dizziness, drowsiness, performance impairment (memory, work performance, visual
motor coordination).
GI. Constipation
Contraindications with mainly first generation anti histamines. Narrow angle glaucoma, bladder
neck obstruction, hyperthyroidism, cardiovascular disease, and benign prostate hyperplasia.
Comparison of 1st and 2nd generation of H 1 antagonist

First generation Second generation
Higher sedation and anticholinergic Less sedation due to less lipid soluble and do not
Tertiary amine (cause sedation) penetrate the BBB.
Lipids soluble, and can cross blood brain barrier NO anticholinergic effect
More central anticholinergic side effect Drug interaction
Anti-serotonin Terfenadine/astemizole. Cardiac arrhythmias
Anti-bradykinin characterized by prolong QT interval (torse de
Usually QID pointes).
Grapefruit juice (apple, orange) reduces oral
bioavailability of fexofenadine.
Dimenhydrinate, Meclizine, cyclizine and Cetrizine have high fatigue and somnolence
promethazine are useful for the prophylaxis of (10%).
motion sickness and vertigo. Loratadine have low fatigue and somnolence.
Promethazine is the most potent antihistamine,
and limits its use due to sedation.
Pregnancy. Bromopheniramine can cause teratogenicity. All 1st gen and 2nd generation antihistamine are
used in pregnancy except bromopheniramine due to its teratogenicity. 1st generation commonly used
due to its wide experience.
In children (less sedative) antihistamines such as loratidine or use sodium chromoglycate. First
generation impairs academic and learning abilities in children. Most antihistamine and nasal cromolyn
considered safe in children over 2 years of age.
There is limited information about fexofenadine Question Alerts!
in under 12-year-old age. Topical antihistamines like levocabastine
eye drops are used allergic conjunctivitis
Topical antihistamines. Olopatadine and available as nasal spray.
(Pantanol), Levocabastine (Livostin),
Emedastine (Emadine), Azelastine (Astelin),
and Kitotifen (Zaditor).
Topical applications of H 1 receptor antagonist to the eye relieves itching, congestion of
conjunctiva and erythema. The density of mast cells are high conjunctiva and tear film.
22-4
PharmacyPrep.
H 2 receptor antagonist (H 2 RA) present on parietal cell, and help to produce HCl secretions. H 2
receptors mediated functions. H 2 receptors responses to histamine such as increased secretion
of gastric acid increase pepsin and intrinsic factor (Castle’s factor).
Ach Histamine Gastrin

Atropine Ranitidine
Muscarinic receptor H 2 receptor
IP 3 C a 2+ cAMP ?
H+ secretion
PPIs
Classification of H 2 antagonist (H 2 RA). Ranitidine, Cimetidine, Famotidine and Nizatidine (drug

names end with "tidine").
H2 antagonist chemistry
H 2 antagonist pharmacology. H 2 receptor antagonist competitively blocks H 2 receptors thus

blocking the effect of histamines on gastric secretions.
H 2 antagonist therapeutic use. To treat heartburn, dyspepsia GERD, GI ulcers, Stress-induced

gastritis.
H 2 antagonist side effects. Cimetidine can cause gynecomastia. Mild diarrhea, or constipation,
headache, myalgia, confusion, hallucination, and excitement.
Administration: all H 2 RA are available oral and cimetidine, famotidine and ranitidine are also
parenteral . Oral have rapid absorption.
Serotonin (5-Hydroxy tryptamine 5HT)
Question Alerts!
1) Serotonergic system modulates mood, emotion, sleep, and appetite.
2) Serotonin contain indole ring.
3) Tryptophan to serotonin is catalysed by? Hydroxylase & decarboxylase
22-5
PharmacyPrep.
Serotonin neurotransmitters involved in vasoconstriction, vasodilation, regulation of body

temperature, sleep, depression and hormonal regulations.
Tryptophan (amino acid) à 5-hydroxy tryptophan à Serotonin (neurotransmitter).

Tryptophan is precursor of serotonin and tryptophan taken up in neuron and converted to
serotonin.
Conversion of tryptophan to serotonin takes place in two reaction, first hydroxylation and
decarboxylation catalyzed by tryptophan hydroxylase and L-amino acid decarboxylase
respectively. Serotonin contain indole ring.
MAO
Serotonin---------------> 5-hydroxy indole acetic acid
Serotonin targets
Serotonin receptors
Serotonin reuptake
Break down of serotonin by MAO.
Physiological functions of serotonin receptors. Serotonin group has several subtypes of

receptors: 5HT 1 , 5HT 2 , and 5HT 3 àDeficiency of 5HT 1 , 5HT 2 and 5HT 3 gives anxiety, depression,
aggression, impulsive and appetite.
· 5HT 1D ; Auto receptors inhibit presynaptic activity in both serotoninergic and adrenergic
neurons in the CNS.
· 5HT 2 . Vasoconstriction, and platelet aggregation
· 5HT 3 . Excessive of 5HT 3 gives nausea, vomiting
· 5HT 4 . Release of acetylcholine in the enteric region
Subtype Clinical significance Drug Clinical Use

5HT 1a CNS Buspirone 5HT 1a agonist Antianxiety,
antidepressant, antiaggressive,
antiemetic.
CNS, vasoconstriction Triptan Migraine attacks
5HT 1b/1d
5HT 1c CNS
Platelets, smooth muscles. Ergotamine Antimigraine (acute)
5HT 2 CNS (-ve schizophrenic Cyproheptadine
symptom).
CNS, gastrointestinal Ondansetron Antiemetic in chemotherapy
5HT 3
5HT 4 CNS, gastrointestinal
22-6
PharmacyPrep.
Serotonin
5HT1a 5HT1b/1d 5HT2 5HT3 5HT4
Agonist Non selective

Agonist Antagonist Agonist
Buspirone Ergotamine (DHE) are
Triptans Ondansetron Cisapride
5HT2 agonist.
Sumatriptan Alosetron
Cyproheptadine affects
Rizatriptan Fabesetron
both 5HT2 and 5HT1
Zolmitriptan Ramosetron
Naratriptan Trazadone is 5HT2
agonist
Antagonist of 5HT2a
atypical
antipsychotic
olanzapine
clozapine
risperidone
Quetiapine
5HT 1 receptor class of drugs

5HT 1B/1D receptor agonist
Mechanism. Contraction of arterial smooth muscles, especially in carotid and cranial
circulations.
Triptans (all are indole derivatives). Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan,
Almotriptan, and Frovatriptan.
5HT 1D/1B receptor agonist therapeutic uses. Triptans are used to treat migraine headache
attacks.
5HT 1D/1B receptors pharmacological actions cause constriction.
5HT 1D receptor agonist side effects. Feeling of warmth, dizziness, tightness or heaviness in the
chest, rarely patient may experience chest pain.
5HT 4 agonist
Cisapride (a benzamide), and tagaseride (indole derivative). Ergotamine serotonin partial
agonist. Ergot alkaloids have agonist and antagonist properties.
Ergot alkaloids and derivatives with antagonist/partial agonist activity include ergonovine,
dihydroergotamine (DHE), methysergide and bromocriptine.
5HT 3 receptor antagonist. Ondansetron (indole derivatives) and Granisetron (benzimidazole

derivative).
22-7
PharmacyPrep.
5HT 3 receptor antagonist pharmacology act on 5HT 3 mixed receptors and can effect on nausea
and vomiting.
5HT 3 receptor therapeutic use ondansetron and granisetron are used to treat chemotherapy
induced or vagal stimulation and surgery nausea and vomiting.
5HT 3 receptor antagonist side effects. Ondansetron side effects. Constipation, headache,
dizziness and granisetron diarrhea.
Prostaglandins, throboxanes, prostacyclins and leukotrienes are synthesized from arachidonic

acid. These four substances are naturally occurring 20-carbon cyclopentanofatty acids
derivative.
Ecosonides
Ecosonides are metabolites of arachidonic acid (a fatty acid). Examples of ecosonides are
prostaglandin analogs, thromboxanes, and prostacyclins. Arachidonic acid is derived from
linoleic acid or taken from diet and esterified to phospholipids (phosphatidylethanolamine). Site
of production of endogenous peptides are GIT, kidney, pancreases and uterus.
Arachidonic acid is derived from dietary linoleic acid (2 double bonds) or is ingested from the
diet and esterified to phospholipids.
Prostaglandin
Prostaglandin has been classified based presence and absence of keto or hydroxyl groups at 9 and 11.
Subscripts relate to the number of double bond present in aliphatic chains.
Corticosteroids Leukotrienes
Lipoxygenase
Membrane phospholoipids Arachidonic acid
Cyclooxygenase
NSAID, ASA, COX-II
Phospholipase A2
Prostaglandins G
Hydroperoxidase
Prostacyclin (PGI2) Thromboxane A2

PGH2
Platelet aggregation Paltelet aggregation
Vascular tone Vascular tone
Bronchial tone Dipyridamole
PGE2 & PGF2
Uterine tone
Uterine tone
Vascular tone
Bronchial tone
22-8
PharmacyPrep.
PHYSIOLOGICAL FUNCTIONS. Platelet aggregation, relaxes bronchial and GI smooth muscles, relax
smooth muscles, and inhibit gastric acid secretion, pain, edema, and inflammation.
Prostaglandin analogs
PGE1 PGE2 PGF2a PGI2 TxA2
Pyrogen elevate Bronchoconstriction Increase Platelets

Protects gastric Decrease platelets
PGE2 contraction contraction of aggregation
mucosa aggregation
of uterus uterus
Misoprostol Dinoprostone Epoprostenol Thromboxane A2

Alprostadil Bronchial & Latano"prost" Blood vessels Dipyridamol
Bronchial & smooth muscle Bronchial & dilatation inhibits
smooth muscle dilatation smooth muscle Inhibit aggregation platelet
dilatation constriction of platelets aggregation
PGE analogs
PGE 1 analogs classification. Misoprostol, and alprostadil.
PGE 1 analogs medicinal chemistry. Misoprostol is chemically belongs to Economides.
Misoprostol structure. Consist of 2-OH and one double bond.
PGE 1 analogs pharmacology. PGE 1 and PGH 1 can be used to produce relatively local
vasodilatation.
PGE 1 analogs therapeutic uses.

· Misoprostol is used for prevention of NSAID induced GI ulcers.
· Combination products. Naproxen + misoprostol, and diclophenac + misoprostol.
· Misoprostol vaginal use is for cervical priming before endometrial procedures.
· Alprostadil. In adults it useful for the treatment of impotence due to erectile dysfunction.
· Alprostadil is used for temporary maintenance of a patent ductus arteriosus when awaiting
corrective surgery for congenital heart defects.
PGE 1 analogs side effects
· Misoprostol. Abortificient side effect. The common side effects is diarrhea.
22-9
PharmacyPrep.
PGE 2 analogs classification

· Dinoprostone derivatives. Dinoprostone
PGE 2 analogs therapeutic uses. Dinoprostone are used for their abortificient effects and to
induce cervical ripening in pregnancy.
PGF 2a analogs classification. LATANOPROST (XALATAN), TRAVOPROST (TRAVATAN),

BIMATOPROST (LUMIGAN), UNOPROSTONE (RESCULA) and Carboprost (Hemabate).
PGF 2a analogs pharmacology. Lowers IOP by increasing uvescleral (aqueous humor) outflow.
PGF 2a analogs therapeutic uses.
· Latanoprost (Xalatan) 0.005% ophthalmic solution. Used topically to lower intra ocular
pressure in OAG, combination products latanoprost + timolol indicated for open and close
angle glaucoma.
· Travoprost (Travatan). Topical ophthalmic drug
· Bimatoprost (Lumigan). Topical ophthalmic drug
· Unoprostone (Rescula). Topical ophthalmic drug
· Carboprost (Hemabate). Abortificient (withdrawn).
PGF 2a analogs side effects. Eye pigmentation, lengthening and thickening eyelashes.
PGI analogs. Epoprostenol (Prostcyclin)
PGI analogs (prostacylcin) chemistry
PGI analogs (prostacylcin) pharmacology

PGI analogs (prostacylcin) therapeutic use. Epoprostenol. Used in the treatment of emergency
pulmonary hypertension. It produces antiplatelets action.
Thromboxanes (TxA2).
· Increase platelet aggregation and potent vasoconstrictors.
· Dipyridamol blocks thromboxane thus produce antiplatelet action.
Leukotrienes
Leukotrienes are produced from arachidonic acid; this reaction is catalyzed by 5-lipoxygenase
enzyme, which oxidize polyunsaturated fatty acids possessing two cis double bonds separated
by a methylene group to produce lipid hydroperoxide. Plays important role in numerous
physiological functions.
· Slow reacting substance of anaphylaxis.
· Heart. Negative inotropic, and smooth muscles chemotaxis.
· GI tract. Neutrophil chemotaxis.
22-10
PharmacyPrep.
· Pulmonary (major). Bronchoconstriction, increase permeability, and increase mucus

secretion.
· Blood. Chemotactic agent for neutrophil, eosinophils, and modify lymphocyte proliferation
and differentiation.
Leukotriene antagonists chemistry. Zafirlukast and montelukast have peptidomimetic

structure and inhibit LTC 4 and LTD 4 receptors.
Leukotrienes antagonists therapeutic uses.

Zafirlukast. For the prophylaxis and chronic treatment of asthma in adults and children 12 years
of age and older. Take empty stomach to enhance it absorption.
Montelukast. Can be used in children over 2 year age, montelukast may be taken without
regard of food. Available as chewable tablet (once daily in the evening) and granules.
Administer granules directly into mouth or mix with teaspoon of cold or room temperature
applesauce, carrot, rice or ice cream. Do not take Aspirin or NSAIDs while on this medication.
Leukotriene inhibitors are drug of choice for the treatment of Aspirin induced asthma and
maintenance.
Side effects. GI upset, abdominal pain, diarrhea, liver dysfunction, and headache.
Drug interactions. Terfenadine significantly reduces the plasma concentration of zafirlukast.

5HT 5-hydroxy tryptamine LTD Leukotriene d
DHE Dihydroergotamine PGI Prostaglandin I
PGF Prostaglandin F OAG Open angle glaucoma
LTC Leukotriene c IOP Intraocular pressure
22-11
PharmacyPrep.
22-12
PharmacyPrep.
Pharmacyprep.com Insulin and Antidiabetic drugs
23
Insulin and Antidiabetic Drugs
There are two types of diabetes mellitus, type I and type II. For type I diabetes, patients need
insulin injections. Type I diabetes is known as insulin dependent diabetes mellitus (IDDM). It
usually begins in young people under 40 and of normal weight.
Hyperglycemia: Polyurea, polydipsia, polyphagia, and fatigue.
Hypoglycemia. (FPG <4 mmol/L)

Autonomic Symptoms. Sweating, shaky, tremor, hungry and palpitation
Neurological symptoms: confuse, disorientation, dizziness.
Normal blood sugar levels (BSL):

• Fasting blood sugar levels 5 to 6 mmol/L (100 mg/dL)
• Random blood sugar levels 11 mmol/L.
• Post prandial 11 mmol/L.
HbA1C normal is 4 to 6%, measures past three months blood sugar levels. Used to determine
antidiabetic drugs compliance of patient.
Treatment of diabetes begin if HbA1c >6.5% and FPG >7 mmol.
Types of insulin are categorized by their onset of action, and these relative positions hold true
for their effectiveness and their duration of action as well. The delayed onset action of insulin is
due to dimmer and hexamer formation, which takes time to dissociate.
Diabetes: Insulin
Iletin® Humulin R,N,U Humalog® Humalog Mix25
Novolin® Mixtures of 30/70; NPH
20/80; 50/50; (intermediate)
40/60
Glargine (long Lantus
acting)
23-1
PharmacyPrep.
Types of Insulin
Ultra rapid Regular Intermediate Long acting
Insulin Lispro Regular NPH Glargine, Detemir

sc, and iv sc and iv sc only, sc only
cloudy do not mix with insulin
Insulin combinations
Insulin Duration Onset Duration of Action
(hours) Peak (hours)
(hours)
Humalog (H) (lispro) Very short 10-15 60-90 min 2-3 h
Synthetic (fastest iv form) min
NovoRapid (Aspart)
Insulin glulisine (Apidra)
Regular (R) Rapid (short) ½ -1 h 2-3 h 5-7h (dose-dependent;
Humalin R, Novolin ge SC or iv (in may be longer)
Toronto, Pork insulin emergencies).
(Suitable for iv dose).
Both human and animal
source
NPH (N). Intermediate 1-2 h 5-8 h 14-18 h

Humalin N, Novolin ge Semilente (30%) not suitable for iv dose
NPH, Pork insulin NPH
Amorphous precipitate
of insulin with zinc ion
acetate buffer.
Detemir Contain a C14 fatty 1.5 h & 6-24h Do not mix with other
SC only acid chain and is Flat insulin
highly bound to
serum albumin
Glargine An acidic solution 1.5h & 24 h Do not mix with other
SC only (pH4), after injection Flat insulin (acid buffer). No iv
(Do not inject im or iv) the solution and im
neutralizes and
micro precipitate
form, from which
drug is slowly
released.
Premixed (Humulin 30/70, Novolin ge 30/70, 40/60, 50/50) Premixed 30/70 means 30% short
acting/70% intermediate acting.
23-2
PharmacyPrep.
Insulin storage conditions: Should be stored in refrigerator. Can be stored at room temperature
28 days. Do not shake vigorously. If you notice turbidity or vapors or precipitation, do not use,
discard it.
Oral antidiabetic drugs
Hypoglycemic drugs Antihyperglycemics

Increase insulin secretion
Meglitinides
Sulfonylureas Repaglinide
nd
2 Generation 3rd Generation
1st Generation
Glyburide Glimepiride
Chlorpropamide
Gliclazide beta and delta extra
Tolbutamide
pancreatic.
Biguanide Thiazolidinedione DPP-4 inhibitors

Metformin Sitagliptin, Saxigliptin, linagliptin
Agonist PPAR-γ
Increase insulin sensitivity Inhibitor of dipeptidyl peptidase enzyme (DPP-
Rosiglitazone
Increase glucose uptake in cell 4) that enhances the incretin hormone.
Pioglitazone
Decrease gluconeogenesis DPP-4 inactivates incretin hormone
Decrease glycogenolysis
α-glucosidase inhibitor GLP-1 (glucagon like peptide) enhancers. or
Acarbose Incretin analog.
Glucosidase breakdown starch Liraglutide: Incretin hormone analog
and disaccharide into glucose.
Starch ----> glucose Increase glucose excretion in urine Sodium-
glucose transport protein 2 (SGLT2) inhibitor
Canagliflozin, dapagliflozin, empagliflozin
Oral Hypoglycemic Agents

acarbose Prandase pioglitazone Actos
metformin Glucophage (generics) rosiglitazone Avandia
repaglinide GlucoNorm chlorpropamide Generics, Diabinase
gliclazide Diamicron, Diamicron MR glimepiride Amaryl
(generics)
glyburide Euglucon, Diaβeta (generics)
23-3
PharmacyPrep.
Sulfonylureas1st Generation
Chlorpropamide Stimulate both basal and meal stimulated insulin release.

and tolbutamide
First gen. is not used due to their pharmacokinetic profile and DIs.
Mechanism • Increased insulin release from beta cells of the pancreas
Therapeutic use • To control hyperglycemia in glyburide-responsive DM of stable, mild,
nonketosis prone, maturity onset or adult type which cannot be
controlled solely by proper dietary management, exercise and weight
reduction or when insulin therapy is not appropriate.
Contraindications • Patients during stress conditions such as severe infection, trauma or
surgery.
• Patients with liver disease or renal impairment or frank jaundice.
• Chlorpropamide not a good choice in elderly (long half life)
Side Effects • Hypoglycemia, GI discomfort, Nausea, weight gain. Chlorpropamide
cause water retention by increasing antidiuretic hormone.
Sulfonylureas2ndGeneration
• Gliclazide, and glyburide.

• Glyburide is associated with a greater risk of hypoglycemia, especially in
elderly or those with renal impairment. (included in BEERS list of
medication).
Mechanism • Stimulates the production and secretion of insulin from the islet cells of
pancreas.
Therapeutic use • 2nd line therapy T2DM, or add on therapy, or if Metformin
contraindicated.
Side Effects • Fainting and confusion. Weakness and tremor, sweating, constipation
and diarrhea. Glyburide has the highest hypoglycemia. Glyburide is an
alternate to insulin for the treatment of gestational diabetes in patient
who cannot tolerate insulin use.
Drug-drug • Corticosteroids, estrogens, diuretics, rifampin, other drugs may reduce
interaction the effect of gliclazide.
Contraindication • Type 1 DM. Not recommended to pregnant, lactating mothers, and
children. AVOID COMBINATION WITH INSULIN.
Monitoring • Regular testing of sugar levels in the blood and urine is required.
• Periodic assessment of the eyes, heart, and kidneys may also be advised.
• Q All sulfonylureas should take with food.
23-4
PharmacyPrep.
Meglitinides
Repaglinide • Stimulate release of endogenous insulin (rapid-acting), but their
actions rapid are much shorter compared with sulfonylureas. better
post-prandial glucose control. Half life is 1 hr
Therapeutic use • Post prandial blood glucose. Can be used in sulfa allergies (NO SULFA
ALLERGY). Need to be taken just prior meals. TAKE WITH FIRST BITE OF
MEALS. IF SKIP THE MEALS, SKIP THE DRUG.
• Can be used in renal disease without dose adjustment. SAFE IN RENAL
DISEASE.
Contraindications • Hypersensitivity, diabetic ketoacidosis (DKA).
Side Effects • Hypoglycemia (less frequent than with sulfonylureas).
Concept!
SEs: RARE AND SERIOUS: Lactic acidosis! Increased with alcohol renal and hepatic
di
Biguanides.Metformin
Mechanism Does not stimulate secretion of insulin like sulfonylureas. EFFECT ONLY WITH
EXISTNG INSULIN. Rather decreases hepatic glucose output by inhibition of
gluconeogenesis. Reduces LDL, VLDL, and cholesterol levels.
Therapeutic use The drug of choice for T2DM. IMPROVES OVULATION BY ↓ ELEVATED
ANDROGEN LEVELS AND INSULIN LEVELS.
Side Effects The most common side effect is stomach upset or diarrhea.
No weight gain because it anorexic and hypoglycemia side effect thus preferred
in obese patients.
Lactic acidosis IS RARE BUT SERIOUS (in hepatic or renal failure patient and
alcohol intake, imaging contrast agent), metallic taste, N, V and anorexia. Long
term therapy can cause vitamin B12 deficiency.
Contraindication Contraindicated in pregnancy, renal and hepatic impairments.
Patient with history of lactic acidosis, irrespective or precipitating factors.
Drug-Drug Alcohol potentiates effects hypoglycemia. Potentiates other oral hypoglycemic
interactions effect.
Thiozolidine diones
Mechanism • Increasing insulin sensitivity in type 2 diabetes. It improves sensitivity
to insulin in muscle and adipose tissue and inhibits hepatic
23-5
PharmacyPrep.
gluconeogenesis.
• PPAR-γ : Peroxisome proliferator-activated receptor activates
nuclear genes involved in glucose & lipid metabolism and adipocyte
differentiation activated. PPAR-γ receptors are located on cell
nucleus, influence gene expression in the cell that increase insulin
sensitivity.
Therapeutic Effects • As monotherapy, in patients not controlled by diet and exercise
alone.
• To reduce insulin resistance and lower elevated blood glucose in
patients with type II DM.
Pioglitazone
• Decreases insulin resistance in the periphery and liver.
• Improves glycemic control while reducing circulating insulin levels.
Contraindications • Contraindicated in patients with serious hepatic impairment, and

acute heart failure.
Side Effects • Weight gain is due to increased subcutaneous fat deposition. Fluid
retention (edema) likely is caused of CHF. Hemodilution, varying
effects on lipids. Increase HDL, Increase LDL, pioglitazone decrease
TG. Pioglitazone is associated with bladder cancer (avoid in those
with active and history of bladder cancer).
Drug-Drug • Increase the risk of pregnancy, recommend adequate contraception
interactions not used.
• Resume ovulation in previously anovulatory (polycystic ovarian
syndrome). TZDs potentiates other hypoglycemic.
• Combination. Rosiglitazone + metformin (Avandamate)
Acarbose
Mechanism • Inhibits alpha glucosidase in intestinal border thus decrease absorption of
starch and disaccharides. (STARCH  GLUCOSE)
Therapeutic • Type II diabetes mellitus in combination with other antidiabetic drugs.
use
Drug-Drug • May decrease metformin bioavailability
interaction • Potentiates other oral hypoglycemic effects
• Diuretics, corticosteroid, estrogen, oral contraceptives, phenytoin, and
sympathomimetics drugs may increase blood glucose level and effect
diabetic control.
Dose • 50 -100 mg TID with each meal, start low and go slow.
Side Effects • Flatulence, diarrhea, abdominal pain, cramps, and nausea
Monitoring • Regular testing of after meal blood sugar level.
23-6
PharmacyPrep.
• In combination oral hypoglycemic therapy always use agents from different

class of oral hypoglycemics.
Orlistat(Xenical)
Mechanism Intestinal lipase inhibitor. Blocks the action of stomach and pancreatic enzymes
(lipases) that digest fats, so fats and other fat-soluble vitamins ADEK are not
absorb in the body but pass through and excreted in the feces.
Therapeutic Reduces fats stores and produce weight loss in patient BMI >30.
use
Drug-Drug Orlistat increases blood levels and toxicity of pravastatin.
interaction
Dose 120 to 360 mg daily
Side Effects Diarrhea (stethorrhea oily leakage), and abdominal discomfort.
Incretin hormones: DPP-4 enzyme inactivates GLP-1. Gliptins inhibits DPP-4 and thus enhances
endogenous incretin hormone like GLP-1 peptides.
INCRETIN:
↓ GLUCAGON
↑ INSULIN
GLP-1 increase glucose dependent insulin release and decrease level of circulating glucagon and
hepatic glucose production.
DPP4 INH.
DPP-4
ACT AS INCRETIN ENHANCER.
GLP-1 -------------> Inactive GLP-1
INCRETIN IS RELEASED IN RESPONSE TO
GLUCOSE IN GI.
↓GLUCOGON FROM ALPHA CELLS
DPP-4 inhibitors: Sitagliptin, Saxigliptin and Linagliptin.
Inhibitor of dipeptidyl peptidase enzyme (DPP-4) that enhances the incretin hormone. DPP-4
inactivates incretin hormone.
Therapeutic use: Linagliptin can be used renal disease patients. (CrCl 15 ml/min), sitagliptin and
saxigliptin can be used if crcl >50 ml/min
23-7
PharmacyPrep.
SIDE EFFECTs: N.V, hypoglycemia, upper respiratory tract infections (URI) (THE MOST COMMON
SE IS NASOPHARYINGITIS), and headache.
weight neutral,
Incretin (GLP-1) analog: Liraglutide. Exenatide, are GLP-1 (glucagon like peptide) enhancers.
Incretin hormone analog.
GLP-1 analog is structurally and functionally same as human GLP-1. When administered
subcutaneously they increase GLP-1 action by five folds.
Liraglutide (Victoza) is once daily SC inj. This has 24-hour duration of action.
Exenatide (Byetta) is bid SC inj.
The highest HbA1c lowering effect.

Side effects: The most common GI disorders, infections and nervous system disorders.
GLP-1; ↓ GLUCAGON RELEASE; ↑ INSULIN (STIMULATES); ↓ APPETITE; ↓

BODY WEIGHT; SLOW GASTRIC EMPTYING TIME.
Sodium Glucose Cotransporter 2 Inhibitor (SGLT2): Canagliflozin, dapagliflozin, empagliflozin.

These drugs
prevent glucose
reabsorption in
the kidney
leading to
increase
excretion of
glucose in urine.
SGLT2 expressed
in the proximal
renal tubules
and responsible
for majority of
reabsorption of
filtered glucose
from tubular
lumen.
SIDE EFFECTS: HYPERKALEMIA, UTI, VAGINAL CANDIDIASIS, RARE BUT SERIOUS
KETOACIDOSIS.
Tips
23-8
PharmacyPrep.
• Examples of hypoglycemic drugs Sulfonylureas, meglitinides

• Examples of antihyperglycemicsBiguanides, Thiazolidines
• pre-prandial glucose concentrations→ insulin lispro
• Lactic acidosis is rare side effect of --> metformin
• Lactic acidosis risk is increased by --> alcohol intake, CHF, renal and hepatic disease
• Diabetic ketoacidosis risk increases when --> uncontrolled type 2 DM
• What major ketones are observed in DKA --> beta hydroxy butyric acid (80%)
• What antidiabetic medications are not given to type 1 --> sulfonylureas, meglitinides
• Example of glucagon like peptide-1 (GLP-1) agonist--> Liraglutide
• Alpha glucosidase inhibitor. ( ACARBOSE )

• Intestinal lipase inhibitor. ( ORLISTAT )
• Antidiabetic drugs taken before or after meals. (REPAGLINIDE )
• Works on cell membrane. ( INSULIN )
• The antidiabetic drug side effect of anorexia. (METFORMIN )
• Anticholesterol drug of choice in diabetic patient. ( STATINS AND FIBRATES )
• Which antidiabetic drugs are not used in type I DM. (sulfonylurea, and meglitinides)
• What antidiabetic drug of choice in pregnancy. ( INSULIN )
• If patient has admitted in surgical ward and her blood glucose levels high, what is drug of
choice? (REGULAR INSULIN)
• Which of the available forms of insulin should be used to treat diabetic ketoacidosis?
(REGULAR IV )
• What substance that when combined with metformin gives lactic acidosis? (alcohol)
• Chlorpropamide + alcohol give what reaction. (disulfiram like reaction)
• 2nd generation sulfonylureas. (glyburide, glimepiride, gliclazide)
• What drug decrease absorption of starch? ( ACARBOSE )
• WHAT DRUG does not decrease absorption of glucose. ( ACARBOSE )
• Difference between glyburide and gliclazide These 2 drugs are 2nd gen sulfonylureas,
however glyburide (2 to 3 hr), has shortest half-life and 100% metabolized in liver and
gliclazide has long half-life.
• What antidiabetic drugs good option for patient with irregular food habits? Gliflozins,
gliptins, and glutides (taken with or without food).
TRUE OR FALSE
• Acarbose mechanism is alpha glucosidase inhibitor (True/False)
• Orlistat mechanism is intestinal lipase inhibitor (True/False)
• Difference between glyburide and glimepiride. glyburide is short acting and glimepiride is
long acting (True/False)
• Antidiabetic drugs taken before or after meals (with meals) are sulfonylurea, repaglinide,
metformin, and acarbose (True/False)
• The most common cause of glaucoma (blindness) is associated with diabetes mellitus
(True/False)
23-9
PharmacyPrep.
• Insulin works on receptors on cell membrane (True/False)

• The antidiabetic drug that cause side effect of anorexia is metformin (True/False)
• Anticholesterol drug of choice in diabetic patient is fibrates (True/False)
• Metformin monitoring are renal function and liver function tests (True/False)
• Antidiabetic drugs that is not used in type I DM are sulfonylureas and meglitinides
(True/False)
• Glucagon gives hyperglycemia and insulin gives hypoglycemia (True/False)
• Insulin is antidiabetic drug of choice in pregnancy (True/False)
• If patient has admitted in surgical ward and her blood glucose levels high, the drug of choice
is insulin (True/False)
• Metformin monitoring BSL, HbA1C, CrCl, CBC. (T/F)
23-10
PharmacyPrep.
Pharmacyprep.com Thyroid disorders
24
Thyroid Drugs
Thyroid Drugs
Hypothyroids
Hyperthyroid
LEVOthyroxine (T4) Triidothyronine (T3)

Synthroid, Eltroxin
131
Thioamides: Lugol's solution (10% KI + 5 %I) I
Methimazole
Propylthiouracil (PTU)

Levothyroxine Eltroxin, Synthroid Methimazole Tapazole
Propylthiouracil Propyl-Thyracil
Levothyroxine
Levothyroxine Eltroxin, Synthroid
Mechanism A major hormone of thyroid gland.
Therapeutic use Hypothyroidism, goiter, thyroid cancer.
Side effects Rare side effects such as anxiety, diarrhea, weight loss, sweating, Insomnia, and muscle
cramps.
Drug-drug Antiepileptic, cholestyramine, and sucralfate, iron, Ca and antacids may reduce the
interaction absorption of levothyroxine. Administer levothyroxine at least four (4) hours apart
from these agents. Levothyroxine may increase the effects of warfarin. Take in the
morning. Take empty stomach. Glycemic control may decline with initiation of
levothyroxine, potentially necessment of antihyperglycemic agents.
Over dose HYPERTHYROID SYMPTOMS: Symptoms of hyperthyroidism if over treated possible
exacerbation of angina. Toxic symptoms are nervousness, palpitation, intolerance to
heat and unexplained weight loss.
Monitoring Periodic tests of thyroid function (normal serum TSH 0.3 mU/L to 6 mU/L). Monitor TSH
24-1
PharmacyPrep.
levels to adjust initial dosage after 6 to 8 weeks then as required or annually adrenal
insufficiency may adrenal insufficiency may have to be increased during pregnancy to
maintain TSH in desired range. Check TSH each trimester and 4 to 6 wk after any dosage
adjustment.
Food and drug May decrease absorption of levothyroxine by iron salts, cholestyramine colestipol, and
interactions sucralfate.
Anti-thyroid drugs (Methimazole and propylthiouracil)

Methimazole
Mechanism · Potent inhibitor of thyroid peroxidase enzyme (TPO). This TPO is

responsible for iodination of tyrosine residues to form
iodotyronine.
· Inhibit the synthesis of T 3 and T 4 by inhibiting the iodination of
tyrosine in the thyroglobulin.
· Blocks the coupling of the iodo thyroxine.
· Do NOT prevent the uptake of iodine by the gland.
· Obvious effects are very slow since it takes 3 to 4 weeks before the
hormone levels show a decrease.
Pharmacokinetics · Well absorbed, slow excretion and t 1/2 is 6 hours. Both drugs
accumulate in the plasma.
· Similarities between Carbimazole and Methimazole Both cross the
placental barrier and can accumulate in the thyroid gland of the
fetus.
Side effects Agranulocytosis is rare but the most serious SEs of thioamide therapy.
This can occur suddenly in first 3 mo of therapy. (it sudden so routine
monitoring of CBC is not done). Lupus like syndrome and arthralgia
can occur after 6 mo.
Hepatotoxicity shows up in first 3 mo of therapy.
Therapeutic use The drug of choice of hyperthyroidism.
Propylthiouracil
Mechanism · Manage the overactive thyroid gland. Inhibits the conversion of T 4
to T 3 . Thus, thyroid hormone synthesis is decreased.
Therapeutic use · Drug of choice in pregnancy for hyperthyroidism. Preferred
because in pregnancy.
Side effects · Reduction in white blood cells leading to the risk of infection
Nausea and vomiting, joint pain, headache, rash and itching,
Jaundice and fever.
24-2
PharmacyPrep.
Pharmacokinetics · Propylthiouracil rapid absorption after oral administration. Peak

serum levels seen after 1 hour t 1/2 is only 2 hours.
· Extensive first pass metabolism. Excreted by the kidneys as
glucuronide (inactive).
· Strongly protein bound. Secreted in breast milk less than
methimazole.
Disadvantage · More agranulocytosis seen than that of methimazole.
Contraindication · Prescribed with caution in pregnant mothers. There is risk of goiter
and hypothyroidism in the newborn infant if too high dose is used.
Reduce dose to infant and children.
Monitoring · Periodic tests of thyroid function and blood cell counts.
Stop taking drug · Jaundice
and call physician · Sore throat and fever (symptoms of agranulocytosis).
NOW
Iodides
Mechanism · Inhibits the uptake of I 2 by a tyrosine
Therapeutic use · Used in the treatment of thyroid storm
Doses · Therapeutic doses (>6mg/day)
· Results observed within 2-7days
Withdrawal · Causes thyrotoxicosis

Contraindications · Should be avoided in pregnancy as it crosses the placental barrier
thus causing fetal goiter
Side effects · Outbreak of acne
· Swollen salivary gland
· Ulceration of the mucous membranes
· Conjunctivitis
· Rhinorrhea
Question Alerts!
· Metallic taste
Lugol's solution is? Oral
· Bleeding disorder
drops of 10% KI + 5% I
· Anaphylactic reaction
Iodide preparations · Lugol's solution (KI + I 2 )
· Oral drops
· May cause stains
RadioactiveIodine(I131isomerofiodine)
Mechanism · Emission of b-rays, gets incorporated into the storage facility
24-3
PharmacyPrep.
Therapeutic use · I131 isomer of iodine is used in the treatment of thyrotoxicosis

Pharmacokinetics · Sodium I131 given orally and well absorbed from the GIT
· t 1/2 is 5 days.
Advantage · East admission
· Cheap
· Very effective
· Absence of pain
Disadvantage · Radiation- induced genetic damage
· Leukemia
· Neoplasia
· Cannot be administered to pregnant and nursing mothers cross
placental barrier secreted into the breast milk
Dose · Stop for 5-7 days then give I131
· Take 12 weeks for the glands to be reduced in size
Complications · Hypothyroidism
Tips
· Why is it beneficial to add propranolol to a drug regimen of a patient diagnosed with
hyperthyroidism? → to decrease heart rate
· What factors changes required dose adjustment in patient using levothyroxine? → age,
weight, heart rate and CVD
1 PTU 2 Serum TSH 3 TSH
4 Hyperthyroidism 5 Deiodinase enzyme 6 Calcitonin
7 Hypothyroidism 8 Lugol’s solution 9 Propranolol
· Stimulated by hypercalcemia. ( 6 )
· Secreted from pituitary gland (anterior) (3)
· Monitoring parameter for hypothyroidism. (2 )
· What the DOC in pregnancy for hyperthyroidism. (1 )
· What condition has the following symptoms; cold intolerance, constipation,
hypertension, bradycardia, and puffy. (7)
· Graves disease, and Plummer disease. (4)
· Myxedema and Hoshimoto. (7)
· T 4 metabolized to T 3 by what enzyme. (5)
· Its symptom is sweating. (4)
· 10% KI +5% I solution. (8)
· Addition of this drug to a drug regimen is beneficial to patient diagnosed with
hyperthyroidism to decrease tachycardia. (9)
· Direct effect of thyroid hormone on heart à increase heart rate, stroke volume
· In treatment of hypothyroidism with T 4 have effect on à fetus
24-4
PharmacyPrep.
SELECT TRUE OR FALSE STATEMENTS

· Calcitonin is stimulated by hypercalcemia (True/False)
· TSH is secreted from anterior pituitary gland (True/False)
· In treatment of hypothyroidism with T 4 have effect on fetus? (True/False)
· Hypothyroidism is monitored by serum TSH (True/False)
· Drug of choice in pregnancy for hyperthyroidism is propylthiouracil (True/False)
· Hypothyroidism symptoms are sensitive to cold, bradycardia, weight gain, constipation,
hypertension (True/False)
· Hyperthyroidism is also called Graves' disease and plummer disease (True/False)
· Hypothyroidism is also called Hoshimoto disease and myxidema (True/False)
· Levothyroxine T 4 metabolized to T 3 in liver by deiodinase enzyme (True/False)
· Discontinue antithyroid if patient notice even a single rash (True/False)
· Sweating is symptom of hyperthyroidism (True/False)
· Lugol's solution is KI +I 2 (True/False)
· Lugol's solution can stain. (True/False)
· Diltiazem has been shown to be comparable to propranolol in lowering heart rate and
blood pressure. (True/False)
Question Alerts!
1) Levothyroxine food, and Ca, Mg, Fe, Al antacids interaction (decrease absorption of T4).
2) Drug taken first thing in the morning? Thyroxin, bisphosphonates, and diuretics.
3) Overdose or over treated symptom? Hyperthyroidism and possible exacerbation of angina.
24-5
PharmacyPrep.
24-6
PharmacyPrep.
www.PharmacyPrep.Com Gonadal Hormones And Antagonists
25
Gonadal Hormones and
Antagonists
Gonadal Hormones
Ovary
Testes
Testosterone
Estrogen Progesterone
Testosterone
17β-Estradiol Norethindrone Anabolic steroids
Estrone Norgestrol
Norethynodrel
Testosterone Antagonist
Desogestrel
Estrogen antagonist Finasteride
Medroxyprogesterone
Tamoxifen Dutasteride
Clomiphene Cyproterone
Estrogen agonist + Progesterone Nonsteroidal
antagonist (SERM) antagonist Flutamide
Raloxifene Mifepristone Bicalutamide
(RU-486) Nilutamide
Physiological activity of Estrogen Progestin

Reproduction and development of female sex Maintenance of Pregnancy
organs Inhibition of follicular maturation and
Role in ovulation and pregnancy ovulation
Role in bone density modulation Prevention of spontaneous uterine
Estrogen platelet aggregation. contractions
Estrogen is carcinogen
25-1
PharmacyPrep.
Estrogen
Estrogens are female sex hormones that are used primarily to decrease bone loss and to treat
the symptoms of menopause. Estrogen is used to reduce or prevent osteoporosis in
susceptible women. Estrogens decrease the frequency and severity of hot flashes as well as the
dryness in the vagina that many post-menopausal women experiences.
Estradiol and Estrone (Exist in body in equilibrium)

Estriol
Ethinyl estradiol; 17 alpha estradiol
Mestranol
Quinestrol; Used for estrogen replacement therapy (HRT)
Diethylstilbestrol; Non- steroidal synthetic estrogen (stilbene derivatives)
Therapeutic use Estrogen is component of all brands of oral contraceptive pills.

Estrogen is used to reduce or prevent osteoporosis in susceptible women.
(Both senile and post-menopausal). HRT (hormone replacement therapy) is
used to treat menopause symptoms such as Vasomotor symptoms:,HOT
FLASHES, NIGHT SWEATS, vaginal atrophy, DYSPAREEUNIA, psychological
disorders. To treat prostate cancer. To treat primary hypogonadism.
Side effects GI: Nausea and vomiting are the most common weight gain, diarrhea
CNS. Headache, breast tenderness.
CVS. Edema, hypertension, stroke, MI, increased risk of thromboembolic
diseases (deep vein thrombosis). Prolonged used of unopposed estrogens
(estrogen given without progesterone) in postmenstrual women increases
the risk of endometrial cancer. RISK OF BREAST CANCER.
Chloasma (skin pigmentation).
Contraindications Deep vein thrombosis or (thromboembolic diseases), coronary artery

diseases, vaginal bleeding, migraine with aura, active liver disease.
breast cancer and pregnancy.
Estrogen: Increase blood coagulation by decreasing antithrombin effect, thereby increase risk
of edema, hypertension, stroke, MI, and increased risk of thromboembolic diseases. Estrogen
↑ risk of endometrial cancer and ↑ risk of breast cancer.
Question Alerts!
1) Estrogen can cause endometrial and breast cancer
2) Estrogen CIs in CADs, thrombosis.
3) Estrogen increases blood coagulation by decreasing antithrombin effect.
4) What is the most common SEs of estrogen & progesterone is? N & V
25-2
PharmacyPrep.
Antiestrogens
Tamoxifen, and Clomiphene
Mechanism Inhibit or modify the action of estrogen. These drugs are non-steroidal
antiestrogenic compounds equally effective in oral or injection.
Tamoxifen
Mechanism • Tamoxifen competes for binding to the estrogen receptors thereby inhibits
the action of estrogen.
Indication • Tamoxifen is indicated in advanced breast cancer in postmenopausal
women.
Side effects • Hot flashes. Low emetogenic or least nauseating anticancer drugs. Vaginal
bleeding, menstrual irregularities and risk of endometrial cancer.
Clomiphene
Mechanism • Clomiphene interferes with negative feedback of estrogen on
hypothalamus (↓ESTROGEN) and pituitary thereby increases the
secretion of gonadotropin releasing hormone (GnRH) and causes
stimulation of ovulation (partial agonist and antagonist).
Therapeutic use • Clomiphene is used to treat infertility associated with anovulatory
cycles.
Contraindication • Not effective in women whose ovulatory dysfunction is due to pituitary
or ovarian failure.
Side effects • Dose related, ovarian enlargement, vasomotor flushing, and visual
disturbances, could give multiple birth.
Dosing The recommended dose for the first course of clomiphene is 50 mg (1 tablet) daily
for 5 days. The regimen of 50 mg daily for 5 days should be started on or about the
fifth day of the cycle.
SelectiveEstrogen Receptor Modulator (SERM) Question Alerts!

Raloxifene SEs? Hot flashes
Raloxifene
Reduces bone resorption thereby decrease bone turnover. Only used in postmenopausal
women to treat osteoporosis.
• Exhibit estrogen like (agonist) effect on bones and lipid metabolism. Exhibit estrogen
antagonist action on uterine and breast tissues.
• Therapeutic use in prevention and treatment of osteoporosis.
Side effects: vasomotor symptoms.

25-3
PharmacyPrep.
Progesterone
Progestins are female sex hormones that may be used with estrogens in oral contraceptive pills,
hormone replacement therapy, and treat menstrual irregularities, and as cancer treatment.
Classification of Two types of progesterone

progesterone. • 17-alpha hydroxyprogesterone
• Medroxyprogesterone acetate
• Megestrol acetate
Important! Androgenic
progesterone like • 17-alpha ethinyl androgens (androgenic progesterone's)
norethindrone are • Norethindrone
potent. • Norethynodrel
Commonly used in combined oral contraceptives because
Potent oral activity
More lipid soluble
Less first pass metabolism
Mechanism • Progestins in females promote the development of a secretor
endometrium that can accommodate implantation of newly formed
embryo.
• The high level of progestins produced in second half of menstrual cycle
inhibits the production of gonadotropins and thereby further ovulation.
Therapeutic use • Major clinical use in contraception, generally used with estrogen.
• Not widely used as alone because of its rapid metabolism results in low
bioavailability.
• Progestins are indicated in uterine bleeding, dysmenorrhea, suppression
of postpartum lactone, and endometrium cancer.
• Endometriosis
Side Effects • Weight gain, edema, and depression. Menstrual irregularities
(breakthrough bleeding, amenorrhea).
• Androgen like progestins can increase LDL and HDL ratio cholesterol
(↑LDL AND ↓HDL), weight gain and edema. Hirsutism and acne can
cause thrombophlebitis (inflammation of wall of vein).
17-alpha ethinyl androgens 17-alpha hydroxyprogesterone

(androgenic progesterone's)
Potent and orally stable Injections

Norethindrones or norgesterols. Medroxy progesterone
25-4
PharmacyPrep.
Antiprogestins-Mifepristone
Mifepristone (RU – 486)

Mechanism Progestin antagonist with partial agonist activity.
Mifepristone also has anti glucocorticoid property. Causes abortion if
administered in early pregnancy (85%) due to interference with progestins
and decrease in production of hCG (human Chorionic Gonadotropin).
Therapeutic Abortificient. Administration of mifepristone used as contraceptive given once
use a month when progestin levels are high (Prostaglandin E1 and misoprostol
orally after single dose of mifepristone effectively terminates the gestation.
Side Effects Uterine bleeding and possibility of incomplete abortion.
Androgens
Testosterone is the androgen that leads to the Question Alerts!
development of male secondary sexual characteristics 1) Nandrolone and oxandrolone
and maintains the male reproductive system. have anabolic action!
Androgens are used to treat delayed puberty in males who do not develop normal testicular
function. They are also used illegally by athletes to build muscle mass. They are very
dangerous when used for this as they may lead to aggressive behavior, and may cause liver and
or brain tumors and death.
Androgens Danazol
Nandrolone and oxandrolone
Stanozolol
Fluoxymesterone
Mechanism Testosterone is commonly prescribed in the treatment of female breast

cancer, androgen deficiency, and for stimulation of growth, weight gain, and
red blood cell production. Commonly known as "anabolic steroids" because
they promote muscle growth. They are also commonly used to help patients
recover from a surgery and cancer treatment that resulted in damage to
muscle tissue.
Therapeutic • Used in males with inadequate androgen secretion.
use • Anabolic steroids can be used in sever burns, for speedy recovery from
surgery. Indicated in conjunction with other hormones in pituitary
dwarfism.
• Non-approved uses androgenic steroids in increase of lean body mass,
muscle strength, aggressiveness in body builders and athletes.
25-5
PharmacyPrep.
• Danazol indicated in endometriosis (ectopic growth of the endometrium).

• Androgens orally ineffective.
Side effects • In males: priapism (continuous erection), impotency, and gynecomastia.
• In females; masculinization, acne, hirsutism, deepening of voice, menstrual
irregularities.
• Contra indicated in pregnancy.
• Increase LDL, decrease HDL levels, increase coronary artery disease, and
fluid retention (edema).
Antiandrogens: Finasteride
Finasteride, Dutasteride, and Flutamide, Cyproterone acetate
Mechanism Inhibit the synthesis of androgen. Finasteride inhibits the 5-alpha reductase.
Competitive and specific inhibitor of type II 5-alpha reductase.
5-alpha reductase
Testosterone ---- -------------------------> Dihydrotestosterone
Therapeutic use • Indicated in BPH and to treat alopecia men who have lost scalp hair.
Side effects • Decrease libido, sexual dysfunction. Breast tenderness and hirsutism.
• Hypersensitive reactions like rashes, pruritic, swelling face and lips
and testicular pain.
Dose • PROSCAR 5 mg for BPH treatment. PROPESIA 1 mg daily for 3 months for
hair growth in men.
Contraindication Not indicated in woman and children. Woman should not handle or break
tablet when they are pregnant. Finasteride may cause external genitalia
abnormalities in male fetus.
Question Alerts!
1) 5-alpha reductase catalyses testosterone formation of dihydrotestosterone.
2) Finasteride inhibit 5-alpha reductase
2) Hirsutism is? hair growth on scalp
3) hypertrichosis? Excessive hair growth
Tips
• Finasteride is type II and dutasteride is type I and II isoenzyme
• The effect of vasopressin on kidney Antidiuretic

HRT Hormone Replacement Therapy LDL Low-density Lipoprotein
ADH Antidiuretic Hormone BPH Benign Prostate Hyperplasia
GnRH Gonadotropin-Releasing Hormone ACTH Adrenocorticotropic Hormone
25-6
PharmacyPrep.
www.PharmacyPrep.Com Adrenal Corticosteroids
26
Adrenal Corticosteroids
Glucocorticoids and mineral corticoids
Generic brand Generic Brand
Cortisone Cortone Triamcilone
Hydrocortisone A-hydroCort, Ala-Cort, Methylprednisolone Depo-Medrol, Medralone
Betamethasone Diprosone, Diprolene Ketoconazole Nizoral Shampoo, Nizoral,
Beclomethasone Beconase, Qvar , Spironolactone Aldactone, Spirono
Prednisolone AK-Pred, Econopred, Mifepristone Mifeprex
Prednisone Deltasone, Predone, Sterapred, Metyrapone Metopirone
Aminoglutethimide Aminoglutethimide
The adrenal hormones, or corticosteroids, are drugs with powerful anti-inflammatory effects.
These are used for replacement therapy in conditions such as, Addison’s disease, a condition of
adrenal insufficiency. In replacement therapy, the adverse effects are minimal since hormones
are being replaced and are not added to those already in the body. Corticosteroids are used for
their anti-inflammatory, antiallergic and anti-stress effects. Prednisone is used as replacement
therapy and also for its anti-inflammatory effects in many conditions, such as arthritis, allergies
and asthma.
Glucocorticoids Mineral corticoids

“cortisones” Aldosterone’s
Middle layer of cortex Outer layer cortex
Anti-inflammatory, metabolizing hormone Salt/water retention, anti-inflammatory
Hydrocortisone, prednisone, Fludrocortisone
betamethasone, dexamethasone,
budesonide, and triamcinolone.
Glucocorticoids potency ranking.

Topical glucocorticoids potency ranking Inhaled and intranasal corticosteroids
• Very high potency: Betamethasone • Beclomethasone
(0.05%) dipropionate, Clobetasol • Budesonide (highly potent nonhalogenated
26-1
PharmacyPrep.
(0.05%). steroid).
• High potency: Amcinonide, • Flunisolide
Triamcinolone 0.5% • Triamcinolone
• Medium potency. Betamethasone • Fluticasone
benzoate (0.025%), Triamcinolone • Mometasone (quick onset, more local
0.025 to 0.1 absorption and lowest systemic absorption,
• Low potency: dexamethasone, consequently fewest systemic SEs).
hydrocortisone
Glucocorticoids
Short acting (8-12 • Hydrocortisone

hour) • Cortisone
Intermediate acting • Prednisone

(18-36 hours) • Prednisolone
• Methylprednisolone
• Triamcilone
Long acting (1-3 days) • Betamethasone
• Dexamethasone
• Paramethasone
Mechanism • For anti-inflammatory corticoids: Glucocorticoids effects on the
distribution, concentration, and function of leukocytes. These
include decrease in concentration of lymphocytes T and B cells)
and increase in concentration of neutrophils.
• Decrease basophils, eosinophils and monocytes, and inhibition of
the ability of leukocyte and macrophages to responds mitogen and
antigen.
• The above Inhibitory response also results in reduce the amount of
histamine release from basophils to inhibit kinins.
Side Effects • High doses stimulate gastric acid and pepsin production and may
cause peptic ulcers.
• Chronic use causes sever bone loss (Due to decrease in calcium)
and myopathy leads to weakness
• Concentration of topical Glucocorticoids depends on site of use on
the body.
Drug and Food • Take with food. Should not be stopped suddenly, taper off or
interactions gradually decrease dose.
• Diabetic drugs: glyburide, chlorpropamide, glipizide, tolbutamide.
Can rise blood sugar noticeably. Monitor blood sugar levels
Therapeutic use • To treat severe allergic reaction
• To treat chronic ulcerative colitis
26-2
PharmacyPrep.
• To treat nephrotic syndrome and renal diseases

• Topical agent to treat diaper rash and dermatitis
• Topical agents for ophthalmic disorders
• To treat rheumatic carditis
• To treat severe arthritis
• To treat acute and chronic adrenal deficiencies
• To treat nausea and vomiting associated with cancer
chemotherapy.
Side effects • GI: Peptic ulcer, hemorrhage, acute pancreatitis, ulcerative
esophagitis.
• CNS: headache, increased IOP (glaucoma), muscle weakness,
euphoria and dysphoria.
• Hormonal: Weight gain, osteoporosis, hyperglycemia (diabetes),
flushing of face and neck.
• Cushingoid (moon face and buffalo hump) and increase risk of
infections.
• CV: edema and hypertension
• Skin thinning
• Growth suppression (interfere pituitary hypothalamic axis).
The degree of systemic side effects is dose dependent related to the half-life of the drug,
frequency of administration, time of the day when administered, and route administration.
Corticosteroid side effects Rationales

Hypertension ↑ Na and Water retention
Hyperglycemia ↑ gluconeogenesis, ↑ glycogenolysis, ↑ glucose
Osteoporosis Dissolve bone calcium
Weight gain (edema) edema
Increase risk of infections ↓lymphocytes
Poor wound healing
Cushingoid (red cheeks)
Question Alerts!
What is NOT a side effect of oral steroids? Weight loss, gastritis, arthritis, dermatitis
and allergies, hypoglycemia, urticaria, Addison disease.
Tips
• What is steroid sparing drug → Leukotriene antagonist
• Steroid avoiders → Mast cell stabilizers
26-3
PharmacyPrep.
• Addison disease → Hypo corticosteroids

• Cushingoid disease → Hyper corticosteroids
• Inhale corticosteroids can cause oral thrush (Candida). How to minimize → rinse mouth
after inhalation.
26-4
PharmacyPrep.
www.PharmacyPrep.Com Oral Contraceptives
27
Oral Contraceptives
Oral contraceptives (birth control pills) are combinations of estrogen and progestins or
progestins only.
Mechanism
· The biological activity of OCs can result from the estrogen and/or progestin component.
· Prevention of ovulation, alteration of cervical mucus and alteration of endometrial
lining.
· Provide (-)ve feedback to the pituitary gland resulting in suppression of FSH and LH
release from pituitary thus prevents the development and maturation of the follicle egg,
resulting in the prevention of ovulation.
· Stop the pituitary gland from producing follicle stimulating hormone (FSH) and
luteinizing hormone (LH) in order to prevent ovulation.
· Support the uterine lining (endometrium) to prevent breakthrough bleeding mid-cycle.
· Stop the pituitary gland from producing LH in order to prevent egg release.
· Make the uterine lining inhospitable to a fertilized egg.
· Partially limit the sperm's ability to fertilize the egg.
· Thicken the cervical mucus to hinder sperm movement (although this effect may not be
key to preventing pregnancy).
The combination preparations may be monophasic, biphasic or triphasic. They contain various
estrogens and progestins. Some common ones are listed:
Oral contraceptives
Combination Oral Contraceptives Pills

Progestin only
(ESTROGEN AND PROGESTIN)
Monophasic Biphasic Triphasic
PharmacyPrep.
27-1
Three types of combination products

Monophasic: Fixed ratio of estrogen to progestin through the menstrual cycle.
Biphasic: The amount of estrogen is fixed through out the cycle but the amount of progestin
varies (low in the first half and high in the last half).
Triphasic: Low doses of both hormones with minimal effects. The amount of both estrogen
and progestin varies through the cycle in different ratios.
Progestin only
Mechanism of Action: Alteration of cervical mucus, alteration of the endometrium to inhibit
implantation decreased side effects does not suppress the hypothalamus and the pituitary to
the same extent as the combination preparation thus low pregnancy prevention rate increase
in breakthrough bleeding.
Side effects of estrogen: Nausea, bloating, headache, and mastalgia

Side effects of progesterone: Weight gain, hirsutism, acne, tiredness, depression, ↓HDL and
↑LDL.
Benefit of oral contraceptives

↓ Dysmenorrhea
↓ Acne (Pimples)
↓ Endometriosis
↓ Osteoporosis
↓ Pelvic inflammatory disease (PVD)
↓ Risk of endometrial and cervical cancers
Component of an oral contraceptive is responsible for the following side effects

Hypertension Estrogen
Hyperglycemia Estrogen
Hyperlipidemia Estrogen (so more gallbladder infection)
Post pill amenorrhea Progestin
Chloasma Estrogen
Depression Progestin
Ophthalmic disorders Estrogen
Absolute or complete contraindications

Question Alerts!
· Breast cancer and endometrial cancer
1) Absolute CIs of oral contraceptive pills?
· Cerebrovascular disease (DVT and PE) 2) Suspecting pregnancy?
· Coronary artery disease myocardial
infarction.
PharmacyPrep.
27-2
· Hepatic tumors and impaired liver functions.

· History of jaundice during pregnancy
· Genital bleeding
· Pregnancy and planning to pregnant
Women over 35 year with smoker (more than 15 cigarettes/day).
· Uncontrolled hypertension SBP>160 and DBP>100.
· Migraine with aura
Side effects due to EXCESSIVE ESTROGEN - Side effects due to ESTROGEN DEFICIENCY¯
Nausea and vomiting, dizziness Nervousness
Fluid retention; edema Dyspareunia (painful intercourse)
Bloatedness Vaginitis
Enlargement and tenderness of the breast Vaginal bleeding (early cycle bleeding)
Chloasma (skin pigmentation) Oligomenorrhea
Leg cramps
Alteration in cornea
Visual changes, headaches
Hypertension
Venous thrombosis
Pulmonary embolism
Depression
Side effects due to EXCESSIVE PROGESTINS - Side effects due to PROGESTIN DIFICIENCY
Increase appetite Dysmenorrhea
Weight gain Decrease breast size
Oily skin and scalp Heavy menstrual flow with clots (late cycle
Acne bleeding)
Depression
Vaginitis
Increase hair growth
When is appropriate to start oral contraceptives pills?

Miss pills Missed one pill. Take as soon as you remember and take usual pill
next day. This means that you might take two pills in a day.
· Miss two pills in a row.
· First two weeks. Take two pills the day you remember and two
pills next day. Then take one pill until you finish pack.
· Use back up method of birth control, if you have sex in next
seven days of missing pill.
· Third week. Safely dispose remained pills and start new pack
same day. (If you’re on Sunday start schedule continue one pill
until Sunday). You may not have periods this month. If you
miss two periods in a row call doctor.
Emergency Levonorgestrel 0.75 mg per dose (Plan B) or Minipill or morning
Contraceptives after pill.
PharmacyPrep.
27-3
Progestin only. Very effective within 24 hrs and can be used up to

3 days (72 hr) unprotected sex.
· Contains 2 pills (use 2nd pill after 12 hours of 1st pill).
· To treat nausea and vomiting associated with this pill can be
treated by dimenhydrinate.
Side effects Nausea (23.1%), vomiting (5%), dizziness, and fatigue and also
progestins side effects.
Tips
· Oral contraceptives that are used for the treatment of ACNE include Dian 35, and
Alesse. Diane 35 approved for acne only. (True/False)
· If missed one contraceptive pill? →Double dose next day
· Plan B is used for emergency contraception→ this should be used immediately after
unprotected intercourse.
· The most common side effect of plan B is nausea & vomiting (True/False)
· Absolute contraindications of OCP are pregnancy, CAD, DVT, breast cancer, genital
bleeding, uncontrolled BP, liver cirrhosis. (True/False)
· The danger signals of oral contraceptive pills ACHES. Danger signals, abdominal pain /
Chest pain / Headaches / Eye problems / severe leg pain.
PharmacyPrep.
27-4
www.PharmacyPrep.Com Osteoarthritis
28
Osteoarthritis
Acetaminophen Betamethasone Synovial Fluid Replacement
Non-steroidal Anti- Cortisone acetate Hyaluronic acid sodium
inflammatory Drug Dexamethasone Sodium hyaluronate
Dexamethasone sodium
Methyl prednisolone acetate
Topical Pain relievers Prednisolone
Capsaicin Triamcinolone
Methyl salicylate Triamcinolone diacetate
Diclofenac
PharmacyPrep.
28-1
Osteoarthritis Rheumatoid Arthritis

Stiffness Mainly effects on weight In the morning (last 1 hour) stiffness,
bearing joints. fatigue, myalgias, joint swelling (synovitis),
Localized Morning or after inactivity joint pain, weakness, low grade fever, loss
Pain (last 30 min). of appetite.
Limited affected joints. Not localized. Worsens with prolong
Worsens with activity or inactivity. (Usually improves with activity).
after prolong use, (weight Weight bearing and non- weight bearing
bearing activity). joints (involvement of small joints in hands
and wrists).
Pain full swollen joints
Affects on soft tissue
Inflammation Uncommon Common
Risk factor >65 years Autoimmune inflammatory condition
Symptoms Degenerative joint disease Bone degenerative disease.
caused by breakdown of the Chronic systemic. Symmetrical synovitis
cartilage between bones, affecting similar joints bilateral.
degradation of articular Inflammation.
cartilage in synovial joints.
Treatment Drug of choice is Drug of choice is DMARDs (Disease
acetaminophen 650 mg q4-6 Modifying Anti-Rheumatoid Arthritis) drugs.
h daily. Max 4 g/day.
Physical Exercise (stretching, low Exercise (aerobic)
activity impact, aerobic, swimming,
stationary cycling, walking)
Acetaminophen
Drug of choice for osteoarthritis.
· Dose of acetaminophen for arthritis 650 mg Q4 to 6h maximum 4 g.
· No cross allergy with NSAID, ASA and Cox-II inhibitors.
· Side effects: Rash and at high dose acetaminophen Question Alerts!
induce hepatotoxicity. Acetaminophen dose in
· Antidote is N-acetyl cysteine, should be administered osteoarthritis?
with 8 hours of overdose (binds to benzoquinoneimine
reactive metabolite).
· Overdose. 7 to 10 g daily refers to poison control centre. Overdose 10 to 13 g daily dose is
lethal.
PharmacyPrep.
28-2
· 3 drinks/day alcohol - increase risk of hepatotoxicity. Warfarin anticoagulant effect is ->2 g

is used. High dose combined with CBZ, phenytoin, barbiturates may - acetaminophen
metabolism and can cause hepatotoxicity.
· Monitoring. AST and ALT elevated.
NSAIDs: Diclofenac (IR, SR), etodolac, sulindac, pyroxicam, meloxicam, tenoxicam, ibuprofen,
naproxen, ASA, diflunisal
· Avoid NSAIDS and COX II in ASA allergies. However, acetaminophen can be used.
· Avoid concomitant use of 2 NSAIDs.
· Past history of GI ulcers, and avoid Question Alert!
in CrCl <50 ml/min. 1) ASA or NSAIDS allergy patient can use only
· ASA anticoagulant effect currently acetaminophen
using warfarin avoid in age over 65 2) Avoid use of two NSAIDS together
years due to increase risk of GI NSAIDS: GI, RENAL, CVD, AND RESPIRATORY TOXICITY
bleeding and renal disease.
· All NSAIDs contraindicated in severe
renal disease (CrCl <30 ml/min) since NSAIDs can cause renal failure.
All NSAIDS can increase blood pressure and worsen pre-existing BP.
At initiating NSAIDs patient should be assessed for gastrointestinal, cardiovascular (MI, stroke,
fluid retention, hypertension) and renal risk factors and should be monitored for toxicities.
Elderly patients, history of GI ulcers, cardiovascular disease patient taking long term NSAID
should be combined with PPI or misoprostol. (Diclofenac + misoprostol,
naproxen+esomeprazole).
Avoid NSAIDs including cox2 inh If history of peptic ulcer disease, cardiovascular risk factors,
renal failure (CrCl <30), heart failure or asthma.
COX-2 INHIBITORS: Celecoxib

Cox-2 released at site of inflammation. Has NO effect on gastric protection, so less common GI
complications.
· Usual dose does not appear to have antiplatelets action.
· Contraindicated in sulfa allergy.
· Avoid in patient with serious heart diseases like congestive heart failure. Cox2 can
exacerbate hypertension, and promote edema.
The risk of increased cardiovascular events can occur with Celecoxib. Avoid in patient history of
MI, stroke, serious heart diseases, chest pain, CHF.
Lumiracoxib (Prexig): Withdrawn due to CHF risk and fetal hepatotoxicity can get by special
access program of health Canada.
PharmacyPrep.
28-3
Topical NSAIDs. Diclofenac topical and Methyl salicylates

· For external use only, approved for treatment regiment not more than 3 months duration
(continuous or intermittent).
· SEs: skin dryness or irritation, hypersensitivity, serious GI toxicity has NOT been reported.
· Note: Patient with GI ulcers history should avoid NSAIDs, Cox-II, anticoagulants, and
corticosteroids.
· Methyl salicylate: May increase warfarin anticoagulant effect. Avoid contact with eye and
mucous membrane.
Methyl salicylate
· Avoid contact with eyes and mucus membrane warfarin anticoagulant effect is -.
· Avoid in ASA allergic patients.
Capsaicin
Counter irritant: Capsaicin extracted from capsicum. Question Alerts!
· Takes 2 to 3 weeks for pain relief with daily use. Maximum Capsaicin is obtained from
effect can take up to 4 wks. capsicum
· Avoid contact with eyes and open wound.
· Do not apply large area of skin. Transient burning/tingling on application usually decrease
within 72 hrs with repeated use ( pre-treatment with Lidocaine can decrease burning).
· Do not cover with tight or occlusive dressing. Do not place heating devices (hot water
bottle, or heating pad).
Steroids
Intra articular injections: Methyl Question Watch!

prednisone. 1) Intraarticular injection of methyl prednisone
· Maximum 3 injections/joint/year. 2) Given maximum 3 inj. per year.
Minimize activity for 3 days after
injection benefit last 4-6 weeks
inexpensive, safe and effective therapy for individual joints for esp. hip, and knee.
Systemic corticosteroids
· Systemic corticosteroids are generally not use for OA. Local (intra articular) may be used in
case of signs of inflammation (minimum in OA) but take to max 3 injections per year per
joint (knee joint).
Viscous supplements: Hyaluron derivatives

· The hyaluronic derivatives (also known as viscous supplements) have a longer duration of
action than the local corticosteroid injections. Usually given as a weekly injection for 5 to 6
weeks, the effect is seen after the last injection (caution in case of allergy to avian
PharmacyPrep.
28-4
proteins/feathers/egg products). Weight bearing/strenuous activity should be avoided

within 48-72 hours following treatment. (also for corticosteroids 48 to 72 hrs).
· Note: The hyaluronic derivatives (hyaluronidase) may also be used in the management of
extravasations caused by antineoplastic drugs/chemotherapeutic agents.
· Hyaluronans. 1 injection/wk given once or repeated depends on product can give pseudo
gout.
Opioids: Severe pain

Morphine
· Lidocaine potential enhancement of opioids effect
· Oxycodone IR5-10 mg QID for short for acting formulations
Glucosamine sulfate: Short time efficacy in pain control.

Chondroitin sulfate 1200 mg/d symptomatic benefit.
Tips
· Risk factors for renal toxicity associated with NSAIDs and COX II inhibitors include à
volume depletion, diabetes, age, and cirrhosis.
· Counseling of Capsaicin à Do not apply on open wounds, cuts, and eyes. Wash your
hand after applies. Do not apply on large areas.
· Osteoarthritis recommended? Weight bearing exercise (walk, run, jog, jump, light
lifting).
· Glucosamine/chondroitin? Increase synovial fluid
· Viscous supplement hyaluronic acid is? Long acting than steroids.
· Risk factor in osteoarthritis? Obesity
PharmacyPrep.
28-5
PharmacyPrep.
28-6
www.PharmacyPrep.Com Disease Modifying Antirheumatic Drugs
29
Disease Modifying Antirheumatic Drugs
DMARD’s Drug Name Trade Drug Name Trade Name
Name
Cytotoxics Methotrexate Azathioprine
Gold Aurothioglucose
preparations Sodium
aurothioglucose
Other DMARDs Cyclosporine Neoral Sulfasalazine Salazoprin
Hydroxychloroquine Penicillamine Cuprimine
Leflunomide Arava Tacrolimus
Minocycline
Biological Adalimumab Humira Etanercept Embrel
response Anakinra Kineret Infliximab Remicade
modifiers
A chronic inflammatory disease with frequent acute attacks. The immune system is involved in
attacking the joints and surrounding structures such as muscle tendons and most other
connective tissue. There is inflammation of the synovial membrane.
PharmacyPrep.
29-1
Biological Response Modifiers

TNFalpha inhibitors (Infliximab, Adalimumab, Etanercept) and Non-TNF alpha inhibitors
(Rituximab, Anakinra, Tocilizumab)
TNFalpha inhibitors
Mechanism. Tumor necrosis factor alpha (TNFalpha),
appears to responsible for tissue injury in the Question Alerts!
disease. Mechanism of biological response
modifiers like infliximab?
Infliximab. Antibody specific for tumor necrosis factor
(TNFα). It does not bind to TNF-
β (lymphotoxin α). Inhibit interleukin-1 (IL-1), a key mediator of inflammatory necrosis factor
synovitis as well as bone and cartilage destruction.
• Improve the sign and symptom of active rheumatoid arthritis. Must be given with
methotrexate to prevent formation of antibodies.
• Infliximab is available as powder for injection in 20 ml single use vials containing 100 mg of
the drug. The vials do not contain antibacterial preservative so solution should be used
immediately after reconstitution.
• Storage. Refrigerator (2 to 8°C), do not freeze. Administered by infusion 3-5 mg/kg at 0, 2,
and 6 wk and then every 4-8 week there after by iv.
Most serious side effects is respiratory tract infections (Pneumonitis), and tuberculosis.
Neurological problems include dizziness, visual disturbance and infusion site reaction. Heart
failure if >5 mg/kg/infusion.
ETANERCEPT: Binds to the tumor necrosis factor (TNF alpha and beta).
• Given SC weekly 4 times, it is self injection.
• Side effects. Most common respiratory tract infections.
ADALIMUMAB:
As with other TNF-blockers, patients should be monitored closely for infections (including
tuberculosis) before, during and after treatment.
NON-TNF INHIBITORS Question Alert!

• Rituximab (Rituxan): B lymphocytes depletor. Rituximab mechanism?
• Abatacept (Orencia): T cell co-stimulation inhibitors B Lymphocyte depletes
• Anakinra (Kinaret): Interleukin-1 (IL-1) receptor inhibitors.
• Toclizumab (Acterma).: Interleukin-6 (IL-6) inhibitors.
PharmacyPrep.
29-2
Methotrexate
Question Alert!
Mechanism Folate analog that inhibits
1) Methotrexate dose to treat RA is maximum
dihydrofolate reductase. This
25 mg/wk and given once a week.
enzyme is responsible for
2) MTX SEs: GI, Hepatotoxicity, Bone marrow
production of tetrahydrofolate
suppression, pneumonitis, and Teratogenic
cofactor necessary for purine
and thymidylate biosynthesis.
Therapeutic • The drug of choice to treat rheumatoid arthritis (1st line therapy).
use Also used as an anticancer drug and treat uncontrolled psoriasis.
Side effects • GI SE nausea, vomiting and diarrhea are common.
• Flu-like aches (headache, backache, chills, fever) Oral ulcers
(mouth ulcer) treated by folic acid or folinic supplements 5-7
mg/weekly or 1 mg daily also reduce liver toxicity, and GI side
effects.
• Bone marrow and immunosuppressant leucopenia.
• Hepatotoxicity (liver toxicity) abnormal LFT.
• Renal failure
• Pulmonary toxicities (pneumonitis) in children
• Susceptible to infections (P. carinii)
Dose • Starting 7.5 to 15 mg po Qwk. Increase by 2.5 to 5 mg Q 2-4 wk.
Maximum 25 mg/wk. Maintenance dose 7.5 to 20 mg po, sc or IM
Q wk (single dose if tolerated or divided in 2 or 3 doses Q12h).
• Effectiveness seen after 2 or 6 weeks and administered PO, IM, SC
• If GI upset occurs start 2.5 mg (12 h after) 2.5 mg (12 h after) 2.5
mg
• Methotrexate weekly doses 20 to 25 mg (orally or parenteral) for
at least three months.
• Concurrent use of folic acid reduces oral ulcers side effect. Alcohol
restriction may minimize hepatotoxicity.
Monitoring Regular monitoring is mandatory. Baseline hepatitis B and C

serology, Chest X-ray, CBC, LFT’s and Creatinine Q 1 to 2 months.
PharmacyPrep.
29-3
Pteridine + PABA
Dihydropteroate synthase Sulfonamide

METHOTREXATE
HEMATOLOGICAL
HEPATOTOXICITY Dihydropteroic acid
GI (ORAL ULCERS) Question Alert!
RENAL TOXICITY 1) Methotrexate inhibit dihydrofolate
PULMONARY reductase and prevent formation of
EMBRYOTOXICITY Dihydrofolic acid tetrahydrofolic acid.
ENCEPHALOPATHY
Dihydrofolate reductase Trimethoprim, pyrimethamine
Tetrahydrofolic acid (THF)
THF cofactors
Thymine Purines Methionine

Glycine
f-met-tRNA
DNA DNA
RNA Proteins
Methotrexate
Toxicity monitored
Pulmonary fibrosis Chest x-ray x 3
Hepatotoxicity LFT
Cardio toxicity? NO cardiotoxicity
Myelosuppression. CBC
Renal RFT
Mucositis (oral ulcers) Ulcers, treated by leucovorin (synthetic folate)
Infections
Reproductive
Neurological toxicity
Azathioprine
Therapeutic use • Refractory rheumatoid arthritis 1 mg/kg (50-100 mg) daily.

Therapeutic response occurs after 6-8 wks. Adequate trial for 12 wks.
• Mechanism cytotoxic agent that suppress T-cell activity
• Azathioprine is cleaved in vivo to mercaptopurine.
Metabolism
Drug interaction with allopurinol (↑ azathioprine toxicity), decrease
1/4 dose of azathioprine.
PharmacyPrep.
29-4
Side effects • Hematologic. Leukopenia and/or thrombocytopenia and rarely as

agranulocytosis.
• GI effects: Nausea and vomiting
• Hepatic: Hepatotoxicity
Contraindications • Pregnancy and children.
• Patients with rheumatoid arthritis previously treated with alkylating
agents (cyclophosphamide, chlorambucil, melphalan or others) may
have a prohibitive risk of neoplasia if treated with azathioprine.
Hydroxychloroquine
Mechanism Anti-inflammatory and antimalarial

Therapeutic Used for mild to moderate rheumatoid arthritis, and malaria
use
Side Effects Retinopathy: Irreversible retinal damage (but is rare. In its early form, it
appears reversible upon discontinuation of the drug). Eye exam before
initiation and annually during therapy. Discontinue if changes in vision
immediately.
Skin rashes and GI disturbances
Pregnancy: It is considered safe.
Overdose For management of a suspected drug overdose. CPhA recommends that you
management contact your regional Poison Control Centre.
Sulfasalazine
Sulfasalazine: Azulfidine, Salazoprin

Mechanism • A chemical combination of SULFAPYRIDINE is sulfonamide and 5-
amino salicylate (5-ASA).
• Sulfasalazine is a relatively weak inhibitor of the cyclo-oxygenase
enzyme, but a potent inhibitor of 15-prostaglandin dehydrogenase
(PGDH), which is the main metabolic pathway for the
prostaglandins
Therapeutic use • May be used in RA with pregnancy. Second line therapy in
ulcerative colitis (UC)
Side effects • Blood dyscrasias: aplastic anemia, agranulocytosis, purpura,
thrombocytopenia and hypoprothrombinemia, pancytopenia,
macrocytosis.
• Hypersensitivity: erythema multiforme (Stevens-Johnson
syndrome)
PharmacyPrep.
29-5
• Skin: facial edema,

• Gastrointestinal: hepatitis, pancreatitis
• Nervous System: smell and taste disorders
Dose • PO or rectally
Pharmacokinetics • About 20% of sulfasalazine is absorbed in the small intestine after
oral administration
Contraindications • In patients with hypersensitivity to component of the product,
sulfonamides, or salicylates. In patients in whom acute asthmatic
attacks, urticaria, rhinitis or other allergic manifestations are
precipitated by ASA or other nonsteroidal anti-inflammatory
agents. Fatal anaphylactic reactions have occurred in such
individuals.
• In patients with intestinal and urinary obstructions.
• In patients with porphyria, as these drugs have been reported to
precipitate an acute attack.
• Infants under 2-year age.
Allergies • If allergic to the following drug avoid sulphasalazine
• ASA, Furosemide, Thiazide diuretics, carbonic anhydrase inhibitors,
sulfonamides, sulfa pyridine and sulfonylureas
Counseling • Discolors urine and may color skin orange yellow.
• May permanently stain soft lenses
• Take drug after meals to reduce GI distress and to facilitate
passage into intestine.
Leflunomide
Mechanism • Isoxazole immunomodulator, inhibits dihydrooratate dehydrogenase. A

rate limiting enzyme in de novo synthesis of pyrimidine. Reduce
lymphocyte proliferation. It metabolizes to active form teriflunomide.
Therapeutic • It reduces pain and inflammation and slow progression of structural
use damage.
Side Effects • Diarrhea (17%) and nausea
• Weight loss
Question Alerts!
• Flu like syndrome Leflunomide is washed out by cholestyramine resin.
• Skin rash
• Alopecia (10%)
• Hypokalemia, Hypertension (10%)
• Hepatotoxicity (alcohol use is potential for additive hepatotoxicity).
Monitoring • Male patient has possible male mediated fetal toxicity. Reliable
contraception during treatment should be guaranteed.
PharmacyPrep.
29-6
• Pregnancy must be avoided if either partner receiving leflunomide.

• Leflunomide T1/2 4 to 28 days. Action in one month. Avoid in pregnancy
for 2 yrs.
• For men having received leflunomide and wishing to have children.
Plasma levels of active metabolite should be less than 0.02 mg/L.
Washout • Using cholestyramine resin.
Cyclosporine
Cyclosporin PO • Mechanism: inhibits calcineurin, which is responsible for

activating the transcription of interleukin-2.
• 3-10 mg/Kg/day for RA
Therapeutic use • Kidney transplantation, organ transplantation rejection
• Psoriasis/Rheumatoid Arthritis/Nephrotic Syndrome
Side effects • Renal toxicity; very common: renal dysfunction
• CVS; very common: hypertension (particularly in heart
transplant patients)
• CNS; Very common: tremor, headache
• Metabolic; Very common: hyperlipidemia, gingival
hyperplasia, and hypertrichosis.
Precautions • NSAID therapy should be discontinued or close monitoring of
renal function require. For RA contraindicated if patient with
renal disease, uncontrolled hypertension, skin cancers.
Drug interactions Drugs that increase cyclosporine serum concentration (CYP3A4

inhibitors) such as Ketoconazole, fluconazole, and itraconazole
Macrolide antibiotics (mainly erythromycin and clarithromycin)
Corticosteroids, and oral contraceptives. Norethisterone or
danazol Calcium channel blockers: Diltiazem, Verapamil,
Nicardipine. Metoclopramide and grapefruit juice should be
avoided.
Drugs that decrease cyclosporine serum concentration (CYP3A4
inducers). As cyclosporin is metabolized by CYP3A4.
Phenytoin or phenobarbital, Rifampin i.v. Sulfadimine i.v. and
trimethoprim i.v. Nafcillin, Carbamazepine, Octreotide,
Barbiturates, Metamizole, Probucol, Orlistat, Hypericum
perforatum (St. John's wort), Troglitazone
PharmacyPrep.
29-7
Minocycline
Therapeutic use Rheumatoid arthritis, Acne

Chlamydia (lymphogranuloma, Psittacosis)
Rickettsia (Rocky mountain spotted fever)
Mycoplasma pneumonia
Lyme disease
Side Effects Less photo toxicity than tetracycline
CNS; Vestibular problems: dizziness, nausea, vomiting
GI; anorexia, nausea, vomiting, diarrhea, stomatitis, glossitis,
enterocolitis, pancreatitis, pruritus and constipation
Skin; maculopapular and erythematous rashes, SJS
Contraindication Pregnancy, children under 13 yrs, breast-feeding.
Newborns, infants and children. The use of tetracycline’s, including
minocycline, during tooth development in last half of pregnancy.
Teeth and Bone. Dental staining (yellow-gray-brown) in infants of
patient who have last half term of pregnancy.
Drug and food Antacids containing aluminum, calcium or magnesium and oral iron
interactions preparations impair absorption and should not be given to patients
taking oral minocycline.
D-penicillamine
Mechanism Chelating agent
Therapeutic Wilson’s disease (excess copper), chronic lead poisoning
use Active rheumatoid arthritis, for refractory RA, if other drugs fail.
Side Effects Urticaria, Pruritus, Rashes, Bone marrow depression,
Thrombocytopenia, Leucopenia, Tinnitus, Proteinuria and
diarrhea (17%).
Non-Wilson 5 to 10 mg of copper can have administered as 5-10 drops of Copper
disease sulphate solutions in fruit juice twice daily (do not use in Wilson
patients disease patients). Penicillamine should be given empty stomach.
(increase absorption)
Gold sodiumthiomalate
Therapeutic • Treat Rheumatoid arthritis

use
Side Effects • Most common
PharmacyPrep.
29-8
• Skin rashes
• Proteinuria (after IM admin.)
• Nitritoid reaction (low blood pressure and syncope after
injections)
• Pruritis (pruriginous), dermatitis
• Angioedema
• Thrombocytopenia
• Aplastic anemia
• Diarrhea
• Stomatitis
• Proteinuria
Post dose • Arthralgia, flushing, hypotension
reactions
Tips
• Which DMARD cannot be given for life →azathioprine
• Shorter onset of action in DMARDs →penicillamine
• Osteoporosis associated with the use of which of OA drug -->corticosteroids
• Which DMARDs require ophthalmic examination monitoring--> hydroxyquinoline
• Examples of TNF-alpha inhibitors -->Infliximab, adalimumab, Certolizumab, etanercept,
golimumab
• Pannus means Inflammation of the cornea or conjunctiva particularly in trachoma
• Symptoms of rheumatoid arthritis is --> morning stiffness, and effects on weight bearing
and non- weight bearing joints.
• Drugs that require eye exam? Hydrochloroquine.
• Stomatitis associated with methotrexate is treated by? Folic acid
• Infliximab cardiovascular side effects? Congestive heart failure. The role of TNFa in
reduce inotropic effects; reduce b-receptor mediated response and increases
myocardial cell apoptosis.
• TNF-alpha inhibitors SEs. Common bacterial infections, opportunistic infection (TB),
Malignancy, worsening of CHF.
• What drugs require eye exams? Hydrochloroquine, Quinine, Amiodarone
TRUE OR FALSE
• The drug of choice in RA is DMARDs (Methotrexate) (True/False)
• Infliximab mechanism TNF alpha inhibitor (True/False)
• Infliximab storage conditions; refrigerator (True/False)
• ASA antipyretic mechanism due to PGE2 inhibitor action inhibits pyrogen (True/False)
• ASA toxicity ;metabolic acidosis, tinnitus (True/False)
• Nutropin is human growth hormone (True/False)
PharmacyPrep.
29-9
• Methotrexate used for RA, psoriasis, and anticancer (True/False)

• Mucositis (stomatitis) is side effects of methotrexate (True/False)
• Patient taking methotrexate, to prevent buccal ulcer, should recommend folic acid
supplements (True/False)
• Mucositis is side effect of methotrexate (True/False)
• Pannus means inflammation of cornea and conjunctiva (True/False)
PharmacyPrep.
29-10
www.PharmacyPrep.Com Acute Gout and Hyperuricemia
30
Acute Gout and Hyperuricemia
Drugs to treat gout and hyperuricemia
Acute gout therapy Anti-Hyperuricemia therapy
NSAIDs Antimitotic Corticosteroids

Indomethacin Colchicines Dexamethasone Uricosurics
Phenylbutazone Hydrocortisone Probenecid
Sulindac Methyl prednisolone Sulfinpyrazone
Naproxen Prednisone
Triamcinolone
Xanthine Oxidase
Inhibitors
Allopurinol
Fibuxistat

Colchicine Allopurinol Zyloprim
Indomethacin Indocin Sulfinpyrazone Anturane
Probenecid Benemid, Probalan
Gout is a disease in which monosodium urate monohydrate (MSU) crystal deposit in joints, soft tissues
such as cartilage, tendon and bursa or renal tissues such as glomeruli, interstitium tubules.
Gout arthritis involves 4 stages: Asymptomatic hyperuricemia, acute gouty attacks, intercritical gout
and tophaceous gout.
Acute gout attacks:

Acute gout attacks are treated by FIRST LINE THERAPIES anti-inflammatory drugs like NSAIDS
(Indomethacin), colchicine and oral corticosteroids. Treatment for acute gout should be initiated as
quickly as possible after onset.
30-1
However, chronic hyperuricemia is treated by antihyperuricemic agents like allopurinol, sulfinpyrazone

and probenecid.
NSAIDs:Indomethacin
Mechanism · Anti-inflammatory action

Therapeutic · Use to treat gout arthritis
use
Side effects · Headache (10%). Indomethacin may cause renal damage or bone marrow
depression. Less common GI, fluid retention and hypertension.
· Hepatotoxicity
Contraindications Renal diseases, Cardiovascular and GI bleeding.
Colchicine
Mechanism · Antimitotics. Colchicine is as selective inhibitor of microtubule assembly, reduced

leukocyte migration and phagocytosis. The drug may also reduce production of
leukotriene B 4 .
· Because it reacts with tubulin and interferes with microtubule assembly, this is
general mitotic poison. Tubulin is necessary for normal cell division, motility and
much other process; therefore, colchicine has systemic side effects if used in
excess.
Therapeutic · Used only for gout attack. NOT recommended if patient presented more than 36
use hr after onset of symptoms. Can be used as IV and low dose for hyperuricemia
· Anti-inflammatory action thus gives pain relief in acute gout attack. It should be
used only during acute gout (intercritical period), after the gout attack and until
the patient serum levels are controlled with urate lowering therapy.
Side effects · GI TOXICITIES: Diarrhea, nausea, vomiting and abdominal pain (GI distress).
Colchicine should be discontinued immediately if sever GI side effects appear, as
they are early sign of toxicity includes diarrhea, cramping, nausea, vomiting and
abdominal pain. In particularly troublesome in the presence of peptic ulcer or
spastic colon.
· Chronic use can produce hemorrhagic gastroenteritis, hematuria, alopecia,
agranulocytosis and peripheral neuropathy
Drug-Drug · CYP3A4 inhibitors (clarithromycin, erythromycin, Itraconazole, ketoconazole,
interactions antiretroviral drugs, verapamil) increase colchicine toxicity (GI symptoms, fever,
leucopenia).
30-2
Probenecid
Mechanism · Uric acid is both actively secreted and actively reabsorbed in the
kidney. Probenecid partially inhibits both the active secretion and
the active reabsorption.
· Uricosuric agents are weak acids that compete with uric acid, in
the S2 segment of the proximal renal tubule, for reabsorption by
weak acid mechanism
Therapeutic use · hyperuricemia
Side effects · Before using probenecid check to see that the patient is not a
high excreter of uric acid, otherwise the use of drug may
precipitate uric acid crystals in the kidney
Counselling · Take plenty of water
Sulfinpyrazone
Mechanism · Uricosuric agent

· Sulfinpyrazone partially inhibits both the active secretion and the
active reabsorption
· Inhibits platelet aggregation
Therapeutic use · Gout arthritis
Side effects Urate crystal formation
Counseling Take plenty of water
Allopurinol(Zyloprim)
Question Alert!
Xanthine oxidase is substrate for
mercaptopurine (Azathioprine, 5FU).
Azathioprine, a prodrug of 6-
mercaptopurine in blood and
subsequently metabolizes to inactive
metabolite in liver and GI tract to 6-
thiouric acid by xanthine oxidase.
30-3
Mechanism Allopurinol is a suicide inhibitor of xanthine oxidase (XO)

Inhibits conversion of purine to uric acid.
Metabolism Allopurinol metabolizes to oxypurinol.
Therapeutic Hyperuricemia starting dose >100 mg daily. (Max 800 mg daily).
use
Side effects Hypersensitivity rashes (SJS), (Allopurinol should be discontinued at first
appearance of skin rash or any sign of serious side effects), peripheral
neuritis and necrotizing vasculitis.
GI intolerance, diarrhea. LIVER ENZYMES, RENAL FUNCTION TEST AND CBC
SHOULD BE PERFORMED BEFORE INITIATING THERAPY.
In condition with large purine turnover xanthine stone formation may occur.
Alkalinize the urine to increase solubility
Drug-Drug With 6-mercaptopurine like azathioprine combination allopurinol.
interactions Must decrease by 1/4 if used with allopurinol because Xanthine oxidase is
main bio transforming enzyme for 6-mercaptopurine.
Counseling Take plenty of water (can cause urolithiasis).
Febuxostat: Xanthine oxidase inh.

Chemically distinct from allopurinol. (can be used in patient allergy to allopurinol). Can be used in
patients with renal disease.
Avoid. Drug interaction with azathioprine, mercaptopurine, theophylline due to inhibition of XO.
Uricases (Pegloticase and Rasburicase)

It is a uricolytic agent
Fenofibrate and losartan can be used as anithyperuricemic agents.
Question Alerts!
1) Drugs taken with full glass of water?
Sulfinpyrazone, probenecid, allopurinol, bisphosphonates, clindamycin, metronidazole, tetracycline,
losartan.
Antihistamine (to avoid N&V, epigastric distress).
Calcium carbonates (to minimize constipation)
Antibiotics (cotrimoxazole, nitrofurantoin, quinolones).
Tips
· What analgesic is not used in acute gout attack→ acetaminophen

· A uricosuric drug is one that à promotes uric acid excretion in urine.
Find answers from the table
1 Azathioprine 4 Allopurinol
30-4
2 Sulfinpyrazone 5 Probenecid
3 Uric acid 6 Colchicine
· Purine like structure present in …( 4 )
· Take plenty of fluids (water) with à 2, 4, 5.
· Anti-inflammatory and antimitotic, and analgesic effect. ( 6)
· The end product purine metabolism in human. ( 3 )
· Uricosuric agent ( 2, 5 )
· Mainly used for acute gout attacks. ( 6 )
· What drug has drug interaction with Allopurinol? (1)
TRUE OR FALSE
· Colchicine relieve pain in 24 hours Purine structure present in allopurinol, nucleic acid bases
(adenine, and guanine) (True/False)
· Take plenty of fluids (water) with allopurinol, sulfinpyrazone and probenecid (True/False)
· Colchicine act as anti-inflammatory (True/False)
· The end product of purine metabolism is uric acid (True/False)
· Sulfinpyrazone is used as uricosuric agent (True/False)
· A uricosuric drug is one that increase excretion of uric acid (True/False)
· Colchicine is mainly used for gout arthritis (True/False)
· Decrease (1/3) dose of allopurinol if using with azathioprine (False)
· Examples of drugs may be useful as moderate uricosuric effect (losartan and fenofibrate)
(True/False)
· Purine structure present in allopurinol, nucleic acid bases (adenine, and guanine) (True/False)
· Take plenty of fluids (water) with allopurinol, sulfinpyrazone and probenecid (True/False)
· Colchicine act as anti-inflammatory (True/False)
· The end product of purine metabolism is uric acid (True/False)
· Sulfinpyrazone is used as uricosuria agent (True/False)
· A uricosuric drug is one that increase excretion of uric acid (True/False)
· Colchicine is mainly used for gout arthritis (True/False)
· Decrease (1/4) dose of allopurinol if using with azathioprine (False)
· Examples of drugs may be useful as moderate uricosuric effect (losartan and fenofibrate)
(True/False)
30-5
30-6
www.PharmacyPrep.Com Osteoporosis
31
Osteoporosis
Osteoporosis Treatment
Bisphosphonates Calcium Parathyroid SERMs Zoledronic acid

Supplements hormones
Alendronate Raloxifene
Calcium carbonate Teriparatide hydrochloride
Etidronate
Risedronate Calcium gluconate
Pamidronate

Alendronate Fosamax Etidronate Didronel
Alendronate+Vit D Fosavance Risedronate Actonel
Raloxifene Evista
Overall reduction of bone mass (bone mineral density) is osteopenia, this resulting in
thin, fragile bones that is prone to fracture can be characterized as osteoporosis.
Paget’s disease is bone remodeling disorder, resulting in excessive bone resorption
followed by disorganized.
Screening
· All post menopausal women and men over 50 yr age.
· Bone mineral density testing for >65 yr age and high risk based on major risk factor.
· Height loss >4 cm total or >2 cm in 1 yr
· Steroid use >3 mo
Diagnosis
· Bone mineral density (BMD) scan using Dual Energy X-ray Absorptiometry (DEXA)
machine.
31-1
· Portable ultrasound
· X-ray
· T-Score compares BMD values to healthy reference
· Normal > -1
· Osteopenia > -1 to -2.5
· Osteoporosis > -2.5
Non- modifiable Risk factors Modifiable Risk factors

· Age >65 y · Low calcium intake (<1000 mg elemental
· Vertebral compression fractures calcium per day). LOW BMD.
· Postmenopausal woman (not on · Inadequate sun exposure or vitamin D.
estrogen therapy). · Cigarette smoking
· Premature menopause (<45 years) · Excessive alcohol intake
· Gender (female) · Caffeine containing beverages.
· Family history · Sedentary life style
· Thin and small boned · Excessive heparin therapy.
· Low body weight (<60 kg) or major · Oral corticosteroid therapy (at least 3
weight loss (>10% of weight at age mo).
25).
· Hypogonadism QAlerts!
· Race. Asians, Caucasians. What is Not a risk factor? overweight,
· Hyperparathyroidism
· Hypocalcemia
· Rheumatoid arthritis
Calcium Supplements: A study shows 61% of adults with osteoporosis did not take
calcium supplements. Inadequate intake of calcium and vitamin D increase risk of
osteoporosis.
· Calcium carbonate (40% elemental calcium)
· Calcium phosphate or Tricalcium phosphate or tribasic (39%)
· Calcium chloride (27%)
· Calcium citrate (21%)
· Calcium lactate (13%)
· Calcium gluconate (9.3%)
Calcium carbonate provides most calcium because it has highest elemental calcium,
some products of calcium carbonate are obtained from oyster example O-Calcium.
calcium gluconate has least elemental calcium.
The highest elemental calcium is present in? CaCO 3 >CaPO4>CaCl2>Cacitrate>

Calactate> Ca gluconate
31-2
Dose and administration

· Calcium carbonate is more soluble in acidic medium and therefore should be
administered before meals (empty stomach) when stomach acidity is highest.
Perimenopausal woman not less than 1000 mg/day. Men and women over 50 year
1200 mg/day and vitamin D 400 Units. Pregnant and lactating woman >18 year 1000
mg/day.
Calcium Drug Interactions: Acid suppressing agents such as H 2 RAs and proton pump
inhibitors may reduce phosphate binding capacity of calcium carbonate by increasing
gastric pH. Calcium acetate is better absorbed in alkaline pH. Calcium interaction
interact with drug such as thyroxin, tetracycline, quinolones, and bisphosphonates.
Vitamin D: Active vitamin D is Calcitriol, is recommended only in those who may have
renal or hepatic impairment and are not able to activate vitamin D.
Vitamin D 3 (cholecalciferol).
Vitamin D2 Ergocalciferol
Osteoporosis Canada recommends vitamin D 10–25 µg (400–1000 IU) daily for
adults under 50 years of age who are at low risk of osteoporosis and 20–50 µg
(800–2000 IU) daily for high-risk and older adults.
Bisphosphonates
Bisphosphonates: Alendronate, Risedronate, Etidronate, Pamidronate, and Zoledronic
acid (Zoledronate).
1st generation: Etidronate (Least potency)

2nd generation: Alendronate and pamidronate (Amino terminal group)
3rd generation: Risedronate and zoledronic acid (3rd gen. Highest potency)
Bisphosphonates are synthetic analog of pyrophosphate that bind to the

hydroxyapatite that found in bone.
Mechanism · Decrease bone resorption via several mechanisms. Inhibition of the
osteoclastic proton pumps necessary for dissolution of hydroxyapatite.
· Osteoclast increases apoptosis (cell death). Bisphosphonates act as a
potent, specific inhibitor of osteoclast mediated bone death.
Therapeutic · Osteoporosis prevention and treatment. Treatment of post menopause

use bone loss. Treatment of glucocorticoid induced osteoporosis. Paget’s
disease. Excessive activity of osteoclasts. Metastatic bone cancer.
· Bisphosphonates have decreased rate of bone fracture in osteoporosis
and Paget’s disease patients.
31-3
Side Effects · Diarrhea, nausea, altered taste, abdominal pain, nighttime leg cramps.
Muscle or bone pain, jaw pain. Esophageal ulcers especially if not taken
properly. Bisphosphonates have NO known impact on cardiovascular
diseases, or breast or endometrial cancer. Stop taking drug if pain or
difficulty in swallowing, new or worsening of heart burn.
· Osteomalacia (etidronate only).
Dose
and · Take first thing in the morning empty stomach and take with plenty of
administration water.
· Do not lie down for 30 to 45 min after medications (stay upright).
· Calcium supplements should be at least separated by 2 hours before or
after.
Alendronate
· Alendronate increase bone mass of all skeleton, and reduces non- vertebral
fracture or decrease vertebral fractures or all fracture (including hip).
· Available dosage forms 5 mg daily 10 mg daily, 35 mg wk, 40 mg wk, and 70 mg
once weekly. Fosavance 70 mg + 2800IU vitamin D QWK, and 70 mg + 5600IU
vitamin D QWK.
· Prevention of osteoporosis in postmenopausal women once 5 mg daily or 35 mg
weekly.
· Treatment of osteoporosis in women 10 mg once daily or 70 mg tablet once weekly.
· Take empty stomach, 1st in the morning. Do not lie down 30-40 min.
Etidronate
· Increase bone density and secondary prevention of vertebral fractures.
· Etidronate and calcium is used in cyclical therapy to increase bone density and
prevents vertebral fracture. Etidronate 400 mg/day for 14 days than 76 days
calcium 500 mg supplements. Calcium supplements are avoided during the 2 weeks
of cycle etidronate. Antacids and Iron supplements should be given at least 2 hr
before or after etidronate.
· Calcium is taken between the cycles of etidronate.
· Etidronate has lowest anti resorptive activity.
Risedronate
· Risedronate has highest anti resorptive activity and than alendronate.
· Risedronate available dosage forms 5 mg/day or 35 mg once weekly, 75 mg two
consecutive DAYS for 1 mo. or 150 mg Q month.
31-4
· Take at least 30 min before the first food, beverage, or medication. NOT lie down
for 30 min after taking.
· Actonel DR 35 mg; should be taken in the morning, with breakfast (this may
include high fat foods, coffee, tea, milk, orange juice etc.)
· Side effects: Esophageal ulceration, night leg cramps, GI symptoms taste changes.
Zoledronic acid intravenous 5 mg once yearly.
Pamidronate 30 to 60 mg iv over 2 to 3 hrs every 3 months.
Raloxifene
Mechanism · Selective estrogen receptor modulator (SERM). Estrogen like action on
bone and lipid metabolism and estrogen antagonist action in breast and
endometrium (has estrogenic and antiestrogenic activity).
Therapeutic · Prevents postmenopausal bone loss, increases bone density
use approximately 3%, decrease vertebral fractures.
Side Effects · Increase risk of deep vein thrombosis (leg swelling, leg pain, leg
discoloration), avoid in who are pregnant and planning to become
pregnant. Aggravate hot flushes. Increase risk of stroke.
· Co administration of cholestyramine reduces absorption up to 60%. Do
not take together.
· Lower cholesterol and LDL but no effect on HDL and TG.
ESTROGEN AGONIST ESTROGEN ANTAGONIST

HELPS IN BONE GROWTH CAUSE VASOMOTOR SYMPTOMS
Calcitonin salmon
Calcitonin is a hormone secreted from thyroid gland. Hypercalcemia stimulates the
production of calcitonin from thyroid gland. Calcitonin hormone helps bone formation
by transporting calcium from blood to bones.
Mechanism. Directly effect on osteoclast and decrease bone resorption through direct
effect.
Two products are available: Miacalcin 200 IU/day intranasally once daily. Common SEs is
nasal irritation. Calcimar, caltine 50 to 100 IU sc/day or Q 2nd day or 5 days/wk. Not
approved for osteoporosis but can be used short term fracture pain management.
Teriparatide (androgen analog):
31-5
A parathyroid hormone (PTH) analogue is an anabolic agent that cause a steady gain in
bone density and 50% reduction in osteoporotic fractures. It may also reduce the pain
associated with vertebral fractures.
RANK ligand inhibitor: Denosumab (Prolia): 60 mg once every 6 mo SC.

Human monoclonal antibody that binds receptor activator of nuclear factor-kappa B
(RANK) ligand.
Drugs used to treat osteoporosis

Generic/Name Side effects Pre Treat Tips
ven ment
tion
Bisphosphonates increase bone mass reduce risk of fracture (at least 50%) and ↓vertebral & non- vertebral
fractures (all fractures).
Alendronate Esophageal ulcers, X X Take on an empty stomach
Fosamax muscle pain, do NOT lie down for 30 min after taking.
TAB: 5, 10, 35 and osteonecrosis of the jaw CrCl <35 ml/min is NOT used. (all
70 mg, (ONJ) bisphosphonates renally eliminated).
Fosavance X X Caution on vitamin D supplements

70 mg + Vit.D
2,800 U
70 mg + Vit D,
5,600 U
Risedronate Risedronate/Ca (Actonel Plus Ca) 35 mg
(Actonel) TAB: 5, risedronate 1st day of week and next 6 days
35 mg, 75 mg calcium.
ACTONEL DR 35 mg weekly. Take with meals. 75
Risedronate/Ca mg on two consecutive week
(Actonel Plus) once monthly. 150 mg monthly.
ACTONEL DR 35
mg.
Etidronate Day 1 to 14 Etidronate X X Didrocal packaged with calcium in 3 month kit.

(Didronel) (day 15 to 3 mo) Cyclic Taken for 14 days every 3 months followed by 76
days calcium 500 mg.
While taking etidronate do NOT take calcium
supplement.
Zoledronic acid X also used for moderate to severe hypercalcemia.
(Reclast)
5 mg intravenous
infusion yearly
Pomidronate Parenteral injection used for moderate to severe
hypercalcemia.
SERM: Prevents postmenopausal bone loss, increases bone density approximately 3%, decrease vertebral
fractures.
Raloxifene ↑ risk of DVT (leg X X Avoid in who are pregnant and planning to
(Evista) 60 mg swelling, leg pain, leg become pregnant. NO ↑cardiovascular risk
31-6
daily discoloration), Aggravate absence of hip fracture prevention data consider

hot flushes. ↑ risk of after bisphosphonates therapy
stroke.
Teriparatide Leg cramps, X Parathyroid hormone (PTH) analogue. Consider
(Forteo); Inj. hypercalcemia. for severe cases characterized by more than one
fragility fracture and a very low BMD.
SC 20 mcg daily for up to 2 years
orthostatic hypotension (in a supine or sitting
position for administration).
Calcitonin salmon Warning. Breast Cancer X Second line therapy, reduces pain associated
(Miacalcin) with acute vertebral fractures
Nasal spray prevent vertebral fractures.
200 units intranasal daily, alternating nares every
other day.
Denosumab 60 mg once Q 6 month SC inj.
(Prolia) RANK Keep refrigerated.
Ligand inhibitor (human MAB, binds receptor activator nuclear
factor Kappa-B ligand.
Tips
· Calcium carbonate (40% elemental calcium) provides most calcium. Usually

require an acidic environment for absorption.
· What is NOT risk factor of osteoporosis → obesity or overweight
· Recommended daily allowance of vitamin D is for adults <50 year old?à 400 to
1000 IU
· Elderly may absorb calcium poorly due to à Decrease gastric acid secretion and
active vitamin D 3 (1, 25 dihydroxy vit-D 3 concentration).
· Paget’s disease of the bone à is a condition of abnormal bone formation leading
to skeletal malformation & abnormality.
· Risk factors of osteoporosisà Post menopause, gender, family history, race,
inadequate Ca and vitamin D, and estrogen deficiency.
· Deficiency of estrogen, may cause? Osteoporosis.

SERM Selective Estrogen Receptor Modulator PTH Parathyroid hormone
SEs Side effects BMD Bone mineral density
DIs Drug Interactions H2RA H2 receptor antagonist
PPI Proton pump inhibitors
31-7
31-8
www.PharmacyPrep.Com Asthma and COPD
32
Asthma and COPD
BRANCHODILATORS Anti-inflammatory drugs

Leukotriene antagonists
Muscarinic Methyl
β2 agonist xanthene Corticosteroids Mast cell stabilizers
antagonist
Steroid avoiders Leukotriene
receptors antagonist
Theophylline (Steroid sparing)
Aminophylline Cromolyn sodium
Nedocromil
Ipratropium (short acting) Zafirlukast
Tiotropium (long acting) Montelukast
Inhaled corticosteroids aerosol (ICS)
Fluticasone, beclomethasone, budesonide
oral. prednisone or prednisolone
iv. hydrocortisone, methyl prednisolone
Short acting (Rescue)
SABA
Albuterol (Salbutamol) Long acting (Maintenance) LABA
Formoterol (full agonist), quick onset
Terbutaline
Salmeterol (partial agonist)
Formoterol fumarate dihydrate (Oxeze)
ULTRA LONG ACTING BETA AGONIST
Indacaterol and Oladaterol

Salbutamol Ventolin
Salmeterol Advir, Serevent Fluticasone Flonase, Flovent
Metaproterenol Alupent Budesonide Entocort, Pulmicort, Rhinocort,
Terbutaline Brenthin, Bricanyl Beclomethasone Ati-Beclomethasone, Qvar,
Prednisone/ Inflamase, Formoterol + Symbicort
prednisolone Budesonide
Salmeterol + Fluticasone Adviar
32-1
PharmacyPrep.
Asthma is inflammatory disease that triggers by following factors (factors that increase
Triggers: Early asthmatic response. Symptoms only (i.e. bronchoconstriction).
Cold air, exercise, emotional stress, pets (cats, dogs), environments and non adherence.
Late asthmatic response;

Worsening asthma
• Allergens (pollens, cockroach, molds, animal dander)
• Respiratory viruses
• Occupational chemicals
• Drugs; ASA, NSAIDs, beta blockers
• Food additives such as sulfites, tartrazine
• Air pollution (including cigarette smoke)
• GERD
• Sinusitis
Bronchodilators
Helps to open airways, decrease bronchospasm, and decrease mucus secretion.
Beta2 Agonist Short acting beta2 agonist (SABA) (onset 1- 3 min).
Salbutamol
Terbutaline
Long acting beta2 agonist (LABA)

Salmeterol
Formoterol (onset 1- 3 min and long duration 12 hours)
Ultralong acting: Indacaterol and Oladaterol
Mechanism B2 receptors agonist relaxes airway smooth muscles through activation of

adenylyl cyclase (AC). This enzyme catalyses the formation of cAMP.
cAMP causes bronchodilatation, vasodilatation and inhibition of
mediator release.
• Slightly decrease peripheral resistance.
• Increase muscle and liver glycogenolysis.
• Relax uterine muscles.
• Increase release of glucagon
Therapeutic use • Treat asthma
Short acting • Rapid onset of action and provide relief for 4 to 6 hours.
beta 2 agonist: • Indicated in symptomatic treatments, rescue agents, combat acute
Albuterol, bronchoconstriction.
32-2
PharmacyPrep.
terbutaline, • Albuterol, terbutaline, has little alpha1 and beta1 effects.

• Does not effect by COMT enzymes because these are activated by non
COMT.
• Inhalation route has less toxic side effects than systemic routes.
• Have less tachycardia, hyperglycemia, and hypokalemia effects with
inhalations routes.
• Short acting are the best reserved for treatment of acute
exacerbations and prophylaxis of exercise induce asthma.
Long acting • Salmeterol has long duration of action, providing bronchodilation for
beta 2 agonist: at least 12 hours, and slow onset of action.
Salmeterol • Indicated in maintenance treatment in combination with
corticosteroids especially for nocturnal asthma, EIA, and COPD.
• Not indicated in acute asthmatic attacks.
Side effects • Tremors (shaking) due to effect on beta2 receptors of muscles.
• Short acting 1- 3 min. Cardiovascular SE (tachycardia, palpitation) due
to effect on beta1 receptors.
Short acting Bronchodilators (SABA)

Salbutamol Ventolin
Mechanism Sympathomimetics bronchodilator that relaxes the muscle
surrounding the bronchioles. Aerosol deposition depends on the
particle size 2 to 5 µm, pattern of breathing, and size of the airways.
Therapeutic use Relieve symptoms of asthma, chronic bronchitis and emphysema.
Side effects
Fine tremor of the hands, anxiety, and tension restlessness.
Recommendation Inhalation is considered more effective because drug is delivered
directly to the bronchioles.
Contraindication Caution in diabetes, hyperparathyroidism, and cardiovascular
disorders
Onset of Onset is 3-5 min
bronchodilator
Duration of 4-5 hours
bronchodilation
Question Alerts!
1) Inhalations results in the greatest local effects on airway smooth
muscle with least systemic SEs.
2) Lungs have high surface area.
32-3
PharmacyPrep.
Long acting Bronchodilators(LABA)

Salmeterol and Formoterol
Mechanism • It has longest duration of bronchodilation
Therapeutic use • Indicated in COPD and Emphysema
• Prevention of Nocturnal Asthma
• Prevention of Exercise Induced Asthma
Side effects • Dry and irritated nose, throat (Inhalations), Tremors,
Nervousness, cough, wheezing.
Drug-drug • There is an increase risk of low blood potassium levels when high
interaction doses of salmeterol are taken with corticosteroids, theophylline
and diuretics.
Corticosteroids
Corticosteroids • Prednisone PO, Prednisolone PO, Beclomethasone, Budesonide,
• Fluticasone, Triamcilone
Mechanism • Steroids have no effect on the airway smooth muscles rather
decrease the number and activity of cells involved in airway
inflammation. (Macrophage, eosinophils, and T-lymphocytes).
• Prolonged use for several months reduces the hyper
responsiveness of smooth muscles.
• Anti-inflammatory response reduced by reversal of mucosal
edema.
Therapeutic use • Asthma, Allergic rhinitis
• Inhaled glucocorticosteroid are the drug of choice in moderate to
severe asthma that requires beta2 agonist more than once daily.
• Inhaled corticosteroids are deposited in the airway and mouth
• Severe asthma systemic glucocorticoids (short time use only)
• Glucocorticoids most effective when taken continuous.
Side effects • Oral thrush (candidiasis) and hoarseness (dysphonia). Can be
reduced by rinsing mouth or using spacer or aerochamber.
• Spacers or aero chamber reduces systemic side effects and
reduces thrush.
• Nasal sprays. Systemic absorption is minimal and side effects are
localized nasal irritation, nosebleed, sore throat, hoarseness,
rarely candidiasis.
Recommendation • To reduce corticoids side effects rinse and gargle mouth after
32-4
PharmacyPrep.
inhalations.
Combination Advair. Salmeterol (LABA) + Fluticasone
products Symbicort. Formoterol (LABA) + Budesonide
Prednisone/Prednisolone
Mechanism • Prednisolone is the active form of prednisone, is a powerful

corticosteroid.
Therapeutic use • Skin diseases, rheumatic disorders, and certain blood disorders.
Side effects • Long-term treatment with high doses can cause fluid retention,
indigestion, diabetes, hypertension and acne.
Drug-Drug • It may increase the adverse effects of diuretics.
interaction
Recommendation • Prolonged systemic use can lead to such adverse effects as
diabetes, glaucoma, cataracts, and fragile bones, and may retard
growth in children.
• Dosages are usually tailored to minimize these effects.
Fluticasone
Fluticasone • Flonase, Flovent
Mechanism • It does not produce relief immediately, so it is important to take
it regularly.
Therapeutic use • Prevent asthma attack (by inhaler)
• Prevent allergic rhinitis
Side effects • Fungal infection causing irritation of the mouth and throat
(inhaled form)
• To minimize side effects thorough rinsing the mouth and gargling
with water after inhalation is recommended
Monitoring • Periodic checks of adrenal functions may be required if large
doses are being taken.
Budesonide
Budesonide • Entocort, Pulmicort, Rhinocort, Rhinocort Aqua

Mechanism •
Therapeutic use • Prevent attacks of asthma but not stop an existing attack.
• Enema to treat ulcerative colitis
• Relieve symptoms of Crohn’s disease
32-5
PharmacyPrep.
Side effects • Fewer and less serious side effects

Drug-Drug • Ketoconazole and other azole antifungal can increase the blood
interaction level of oral budesonide.
Monitoring • When taking in a large dose, periodic checks may be needed to
insure the adrenal glands are working properly
• Children inhalers may have their growth (height) monitored
regularly.
Beclomethasone
Beclomethasone • Ati-Beclomethasone, Qvar, Rivanase AQ

Mechanism •
Therapeutic use • Relieve the symptoms of allergic rhinitis and to control asthma
• Helps to reduce symptoms such as wheezing and coughing
• Given to people whose asthma is not responding to
bronchodilators alone.
Side effects • Fungal infections causing irritation of the mouth and throat
(inhalers)
Recommendation • Rinse mouth and gargle with water after each inhalation.
Monitoring • When large doses are being used, periodic checks is required to
ensure that the adrenal glands are functioning healthy.
Question Alerts!
Ipratropium: short acting Anticholinergic used for rescue
Tiotropium: long acting once daily for maintenance of COPD
Anticholinergics
Ipratropium, tiotropium, glycopyrronium, aclidinium (BID) and umeclidinium
Mechanism An anticholinergic bronchodilator that relaxes the muscles. surrounding

the bronchioles. Have longer affect but slower onset.
Therapeutic use Anticholinergics are effective bronchodilators and have low lipid soluble
and poor transport across membrane (does not cross blood brain barrier).
Side effects Anticholinergic (dry mouth, metallic taste, mydriasis, glaucoma if released
in eye, urinary retention), and constipation.
Onset of effect 5 to 15 minutes

Duration of 8 hours
action
32-6
PharmacyPrep.
Tiotropium • Long acting muscarinic blocker. Available as capsule administered by

(Spiriva) special devise handihaler.
Combivent • Ipratropium bromide + salbutamol (MDI) and nebulizers
Question Alerts!
Leukotriene inhibitors are steroid
sparing agent and the drug of choice to
treat ASA induced asthma
All MDI Should shake before use.
Leukotriene inhibitors
Zafirlukast
Mechanism • Inhibitors of LTC4 and LTD4 receptors. Steroid sparing properties (Instead
increasing steroid dose LTRA are added.
Therapeutic • Anti-inflammatory and bronchodilator activity. Reduce bronchospasm

use and associated symptoms that are mediated through leukotriene.
• Used for exercise induced asthma and the drug for ASA induced asthma.
Side effects • Sudden withdrawal of corticosteroid patient taking Zafirlukast
precipitated Churg-Strauss syndrome (severe asthma with increase
eosinophil count in blood).
• Vasculitis angitis: A patchy inflammation of the walls of small blood
vessels.
Drug-Food • Zafirlukast; Food reduces bioavailability take 1 hour before or 2 after
interaction meals. Oral tablets taken an empty stomach.
• Used in 12 years or over 12-year-old only.
Chewable tablets and granules.
Montelukast
Mechanism Inhibitors of LTC4 and LTD4 receptors.
Therapeutic Steroid sparing agents. Have anti-inflammatory and bronchodilator activity.
use Reduce bronchospasm and associated symptoms that are mediated through
leukotriene. Used in exercise induced asthma and the drug of choice for ASA
induced asthma.
Side effects Headache, nausea and diarrhea, and abdominal pain.
Drug-Food Montelukast may be taken with or without food.
interaction
Over 2-year-old can be used
32-7
PharmacyPrep.
Theophylline and Aminophylline
Mechanism • (Aminophylline will break down to theophylline in the body)

• phosphodiesterase (PDE) inhibitors
• Alter intracellular calcium
• Adenosine antagonisms
• Increase circulating catecholamine's.
Therapeutic use • Anti inflammatory action
• Chronic asthma mainly decreases symptoms
• Bronchitis and emphysema
• Use as a preventive measure, and is added to standard therapy
Side Effects • GI effects. Nausea, vomiting, abdominal cramps, diarrhea, headache,
• CVS: Palpitation or tachycardia.
• CNS effects: Insomnia, seizures, dizziness, nervousness, restlessness
Recommendation • Overdose causes seizures, and arrhythmias.
• Dosage should be adjusted based on serum levels
• Sustain release theophylline allow for a longer dosing interval and
improve compliance. Compliance to oral theophylline also may better
than that inhaled bronchodilators and corticosteroids.
• Oral therapy. Sustained released theophylline allows for longer dosing
interval and improve compliance.
Monitoring Periodic checks on blood levels are require especially the serum level.
Question Alerts!
1) Theophylline clearance in children? Require high doses
2) Theophylline clearance is increased by smoking and protein diet.
Theophylline are contraindicated in patients with hypersensitivity to

xanthenes compounds. Caution inpatient with peptic ulcers and seizure
diseases.
Factors that alter Increase theophylline clearance (decrease levels) in age 1 to 9 years, high
theophylline protein diet, smoking (tobacco, marijuana), fever, drugs such as
clearance carbamazepine, phenobarbital, phenytoin and rifampin.
Decrease theophylline clearance (increase levels) in age (elderly, infants,

under 6 months age, premature neonates), CHF, fatty food, high
carbohydrate diet, liver dysfunction and drugs such as oral contraceptives,
non-selective beta blockers, CCBs, macrolide antibiotics (erythromycin and
clarithromycin), clindamycin, fluroquinolones (ciprofloxacin), zafirlukast, and
allopurinol.
32-8
PharmacyPrep.
Cromolynand Nedocromil
Mechanism • Mast cell stabilizer and has anti-inflammatory action.
Therapeutic use • Effective in prophylactic, has anti-inflammatory effect in allergic
rhinitis.
• Not used in acute asthmatic attacks due to its slow onset of
action.
• Cromolyn administered by inhalation of microfine powder or as
an aerosol solution.
• Cromolyn poor absorption causes more side effects that can be
reduced by powder or aerosol formulations.
• Internasal cromolyn reduces allergic rhinitis symptoms
Side Effects • Bitter taste. Irritation of nasal mucosa, pharynx, larynx
Chronic Obstructive Pulmonary Diseases

Chronic obstructive pulmonary diseases (COPD) is due to chronic obstruction in airway passage.
COPD and/or emphysema (high altitude sickness) and chronic bronchitis.
EMPHYSEMA is a disease in which the small air exchange sacs (alveoli) in the lungs become
permanently enlarged and damaged (alveoli walls destroyed) decreasing oxygen absorption and
resulting in shortness of breath.
CHRONIC BRONCHITIS is an inflammation of the airways in the lungs that causes lungs to
produce excessive amounts of mucus (phlegm). This reduces the flow of air to the lungs. Onset
age 45 years. The major risk factors are smoking (80-90%), family history, occupational
exposures to certain ducts and fumes, air pollution, second hand smoke and asthma.
Chronic Obstructive Pulmonary Disease (COPD).
SABD
SAAC Ipratropium
SABA Salbutamol
Terbutaline
LABD (long acting
bronchodilators)
LAAC Glycopyrronium
Long acting Tiotropium
anticholinergics Aclidinium
LABA Formoterol
Salmeterol
Indacaterol
Combinations Salbutamol + ipratropium
32-9
PharmacyPrep.
ICS/LABA budesonide / formoterol; fluticasone/salmeterol

fluticasone / vilanterol
LABA/LAAC indacaterol/glycopyrronium
(LAMA/LABA) umeclidinium/vilanterol
PDE4 Inh roflumilast
Drug used for the treatment of COPD. Beta adrenergic agonists, corticosteroids, ipratropium,
and theophylline. Patients with COPD, antibiotic or oral corticosteroid therapy in last 3 months
use, a class of antibiotic which was not previously prescribed. Antibiotic therapy to treat chronic
bronchitis. Azithromycin, doxycycline, amoxicillin and quinolones. Do not use erythromycin.
Tips
• Theophylline inhibit activity of Phosphodiesterase (PDE) induction (True/False)

• Leukotrienes are chemical derivatives of arachidonic acid(True/False)
• Leukotrienes are produced from arachidonic acid by catalyzed by lipoxygenase (True/False)
• Long term use of oral corticosteroids may cause osteoporosis, diabetes, Cushing syndrome,
susceptible to infections (True/False)
• Leukotriene antagonist act on LTC4 and LTD4 (True/False)
• Drug of choice for aspirin induced asthma LTRAs(True/False)
• Patient has COPD and pneumonia, what is drug of choice penicillin's doxycycline,
azithromycin(True/False).
• Oral contraceptive effect on theophylline decrease clearance of theophylline(True/False)
• Dry cough is caused by accumulation of bradykinin(True/False)
• What is differentiating symptoms of asthma from COPD wheezing in asthma
• Smoking is very high-risk factor for COPD(True/False)
• What asthma devices do not require shaking powder dose inhalers(True/False)
• Asthma exacerbations are NOT triggered by warm air(True/False)
• Obstruction of airways in lungs is referred as COPD (True/False)
• Permanent enlargement of alveoli is referred as emphysema (True/False)
• Highest clearance of theophylline in which age group 1 to 9 yrs(True/False)
• When can we use leukotriene receptor inhibitors to avoid or minimize use of steroids
(True/False)
• What is important to counsel in patient using steroid inhalers --> rinse mouth after each use
• Histamines are released from mast cells and basophile(True/False)
• What kinds of changes can you expect to see in aminophylline solutions exposed to air? -->
crystal formation of theophylline
32-10
PharmacyPrep.
www.PharmacyPrep.Com Anticancer Drugs and Chemotherapy
33
Anticancer Drugs and Chemotherapy
Question Alerts!
Examples of antimetabolites
Action of DNA
Damage DNA or interfere with Inhibit synthesis of DNA, RNA or

replication of DNA functions, protein synthesis
Alkylating agents
Mechlorethamine Antimetabolites
Others
Cyclophosphamide 5-fluorouracil
Actinomycin D
Ifosfamide Cytarabine
Etoposide
Chlorambucil Gemcitabine
Teniposide
Melphalan Mercaptopurine Anticancer antibiotics
Amsacrine
Busulfan (azathioprine) (Topoisomerase
Lomustine Inhibitors)
Free radicals Thioguanine
Carmustine Doxorubicin
Streptozolin Bleomycin Fludarabine
Methotrexate Daunorubicin
PLATINUMS Topotecan
Cisplatin Irinotecan
Carboplatin Interfere with mitotic
Dacarbazine spindle formation
Procarbazine Vincristine
Altretamine/Hexamet Vinblastine
hylmelamine TAXANES
Mitomycin Peclitaxel
THALIDOMIDES and analogs: Thalodomide.

MONOCLONAL ANTIBODIES: Trastuzumab, bevacizumab, rituximab, alemtuzumab.
33-1
PharmacyPrep.

Fluoroucil Adrucil, Carac, Efudex, Cyclophosphamide Cytoxan, Procytox
Fluoroplex
Methotrexate Rheumatrex, Trexall Irinotecan Camptosar
Cytarabine Cytosar Carmustine BiCNU
Fludarabine Fludara Topotecan Hycamtin
Bleomycin Blenoxane Vincristine Oncovin
Mitomycin C Mitozytrex, Mutamycin Mercaptopurine, 6-MP Purinethol
Vincristine Oncovin, Vincasar Doxorubicin Adriamycin, Rubex
Vinblastine Velban Dactinomycin Cosmegen
Docetaxel TaxotereT Mechlorethamine Mustargen
Etoposide Etopophos, Toposar Paclitaxel Taxol
Cell Cycle Phases

· All cells must traverse the cell cycle phases before and during cell division.
· Anticancer drugs may act on specific phase. Tumor cells are more responsive to specific
drugs.
· G0 phase – Resting phase
· G1 phase – Synthesis of enzymes needed for DNA synthesis
· S phase – DNA replication (DNA synthesis)
· G2 phase – Synthesis of components needed for mitosis.
· M phase: Mitotic tubule formation. Example vincristine, vinblastine, and paclitaxel.
Cell cycle phase specific drugs. More active against

cells that are specific phase of cycle. Question Alerts!
· G 1 phase: L-asparagines and prednisone Vincristine and vinblastine,
· S phase: Methotrexate, 6-thioguanine, paclitaxel acts on M phase
cytarabine inhibit mitotic spindle.
· G 2 specific. Bleomycin and etoposide
· M phase: Vincristine vinblastine, and paclitaxel.
Cell cycle specific drug (phase-non-specific): Alkylating agents, antitumor antibiotic and
cisplatin.
Cell cycle non-specific agents: Effective

whether cancer cells are in cycle or
resting phase, radiation, nitrosoureas,
and mechlorethamine.
Alkylating agents: Act by alkylating

DNA. The most common site of
alkylation is N-7 position of guanine.
The alkylating agent appear to be the
33-2
PharmacyPrep.
most effective on G 1 or S phase. Highly reactive agent can alkylate or bind covalently with
cellular components of DNA.
Cyclophosphamide
Cyclophosphamide · Cytoxan, Procytox

Mechanism · An alkylating agent use to treat cancer.
Therapeutic use · Lymphomas (lymph gland cancers)
· Leukemia
· Solid tumors (breast and lung)
· Also use for autoimmune diseases
Side Effects · Nausea, vomiting, and hair loss
· Irregular menstruation
· Can affect heart, lungs, liver and acute hemorrhagic cystitis, and
this prevented by using uroprotective agent MESNA.
· Bladder damage in susceptible people
Drug-Drug · Phenytoin can increase the breakdown of cyclophosphamide
interaction · Allopurinol and phenothiazines can inhibit breakdown of
cyclophosphamide.
Contraindication · Not advisable for pregnant and lactating mothers.
Monitoring · Periodic checks on blood composition and on all effects of the
drug are usually required.
Antimetabolites:
Antimetabolites prevents the biosynthesis of normal cellular metabolites. Inhibits essential
components of cell synthesis by competing with the natural substrate for enzyme involved in
synthesis of cell components.
Mercaptopurine (6-MP)
Mechanism AZATHIOPRINE, FLUDARABINE, 6-MP, 6-THIOGUANINE,

CLADRIBINE.
Inhibits purine synthesis. Analog of hypoxanthine. Causes RNA
and DNA dysfunction
Structurally similar to allopurinol (purines). Azathioprine an
immunosuppressant exert effect after converting 6-MP.
Side effects GI; Nausea, vomiting, diarrhea

Bone marrow depression
Hepatotoxicity
33-3
PharmacyPrep.
Doxorubicin, DAUNORUBICIN, IDARUBICIN, EPIRUBICIN
Mechanism Effect maximal at S and G2 phase

Anticancer antibiotics
Therapeutic use Widely used anticancer drug (breast, lung etc)

Side effects Irreversible cardio toxicity, HEART FAILURE. (DEXARAZOXANE is
cardioprotective agent used for prevention of cardiotoxocity).
Myelosuppression
Stomatitis
Alopecia
Nausea and vomiting
Compounding Should be carried in Vertical laminar air flow hood
Dactinomycin, bleomycin, mitomycin C
Mechanism Anticancer antibiotics

Form stable DNA complex and interfere with DNA dependent
RNA polymerase
Side effects Major dose limiting toxicity—bone marrow depression.
Mechlorethamine
Mechanism Alkylating agent
Therapeutic use Primarily used in Hodgkin’s disease (malignant disease of

lymphatic tissue) as part of MOPP regimen (Mechlorethamine,
Oncovin, Prednisone, Procarbazine).
Side effects Severe nausea and vomiting. EXTRAVASATION. (Sodium

thiosulfate is used as antidote).
Sever bone marrow depression
Myelosuppression
Anorexia
Gonadal dysfunction
Vincristine and vinblastine
Mechanism Mitotic spindle is part of cytoskeleton and essential for internal

movement occurring in the cytoplasm of all eukaryocytic cells.
Mitotic spindle is essential for partitioning two DNA daughter
cells.
33-4
PharmacyPrep.
Side effects Myelosuppression

Paralytic ileus AND CONSTIPATION
Alopecia
Stomatitis
CENTRAL AND AUTONOMIC NEUROTOXICITY (CNS TOXICITY).
Paclitaxel or Taxanes
Mechanism · Reversible microtubule inhibitor.

Side effects · Serious hypersensitivity reaction,
· Patient should be premedicated with dexamethasone and
diphenhydramine as well as H 2 blockers.
· Myelosuppression
· Peripheral neuropathy
· Alopecia
· Mucositis
· Anaphylaxis (HYPERSENSITIVE REACTION mediated by IgE
histamine and mast cells).
· Dyspnea
· EXTRAVASATION.
Chemotherapy
The treatment of cancer with drugs is called chemotherapy. Antineoplastic drugs, also referred
to as chemotherapeutic agents, are drugs that are used to treat cancer.
Side effects of chemotherapy

Skin and tissue
Acute: Extravasations, Thrombophlebitis, hypersensitive reaction, Rapid tumor lysis syndrome
and nausea & vomiting.
· Extravasations effects the adjacent tissue. Leakage from iv line into surrounding tissue
resulting in inflammation and necrosis.
· Hand foot syndrome is cool hands and feet during treatment.
· Vesicant drugs damage to tissue/necrosis (burning at site of injection). Example
bleomycin, cisplatin, dactinomycin, daunorubicin, vincristine, and vinblastin etc.
· Thrombophlebitis (inflammation associated with thrombus): Patient with cancer can
develop thrombosis after chemotherapy. Due to activation of fibrinogen. To manage
thrombophlebitis, administer offending agent slowly.
Hypersensitive reactions: Examples etoposide, paclitaxel, rituximab (28%), trastuzumab.

Manage by stop infusion.
Monoclonal antibody infusion reactions are cytokine mediated or result of interactions with
molecular target.
33-5
PharmacyPrep.
Rapid tumor lysis syndrome: Due to large number of tumor cells lysed by chemotherapy.
(HYPERURICEMIA, KALEMIA, PHOSPHATEMIA & HYPOCALCEMIA), RENAL FAILURE AND
CARDIAC ARRHYTHMIAS, SEIZURE.
Chemo side effects Onset

Nausea and vomiting during infusion to days
Alopecia within weeks to months
myocardial ischemia within hrs to days
MYELOSUPPRESSION WITHIN 2WKS
heart failure within mo to yrs
Anemia weeks to months
Chronic, organ specific. Question Alerts!

Which cells are depleted the most in bone
· Skin. marrow suppression associated with
· Alopecia, dry skin, nail changes, chemotherapy?
pigmentation (melanoma), and A) Anemia
xerostomia. B) Neutrophil
· Alopecia is the loss of hair. Drug that C) Thrombocytes
causes alopecia is doxorubicin, D) Platelets
daunorubicin, cyclophosphamide, E) Erythrocytes
vincristine, and paclitaxel.
· Vesicant agents include dactinomycin,
doxorubicin, mechlorethamine, mitomycin, vincristine, and vinblastine.
· Hair re-growth occurs after 1 to 2 months after stopping chemotherapy.
· Xerostomia: Dry mouth is one of the most common complications associated with radiation
therapy. Reversible after 6 to 12 months of therapy. Can be managed by sugar free hard
candy, chewing sugar free gum stimulates salivation. Ice chips, sugarless candies, and
commercially available saliva substitute or cholinergic agonist (Pilocarpine 5 mg tab).
Bone marrow depression (Myelosuppression):

· Complications: Bone marrow depression or suppression is the most dose limiting side effect
of cancer.
· Myelosuppression in general the onset is 7 to 10 days and peak are 10 to 14 days. Recovery
count occurs usually occurs in 2 to 3 weeks.
· Bone marrow depression can cause neutropenia, and thrombocytopenia. Absolute
neutrophil count and platelet count (usually 10 d after chemotherapy) and CBC before next
dose of chemotherapy.
· Neutropenia treated by colony stimulating factors (G-CSF and GM-CSF) filgrastim or
pegfilgrastim.
· Thrombocytopenia for prevention use Oprelvekin (Inerleukin-11).
33-6
PharmacyPrep.
· Megaloblastic anemia by methotrexate is treated folinic acid (leucovorin, 5-

formyltetrahydrofolic acid).
· Least bone marrow depression anticancer drugs is bleomycin.
· Cancer patient with anemia are treated by erythropoietin’s.
Side effects Onset time Therapies

Neutropenia (most common) Within days to weeks Filgrastim or pegfilgrastim.
Thrombocytopenia (rare) Within weeks Oprelvekin
Anemia Within weeks to Epoetin alpha, darbepoetin alpha,
months iron dextran or iron sucrose
Darbepoetin alpha sc/iv weekly
Epoeitin alpha sc/iv 3 times/wk
Cardiotoxicity
· Risk of congestive heart failure (CHF), commonly seen with (anthracyclines) doxorubicin,
daunorubicin, epirubicin, mitoxantrone and trastuzumab.
· 5-FU, capecitabine can cause coronary spasms, or myocardial ischemia mimicking a
myocardial infarction (avoid in known coronary artery disease patients).
· Cardio toxicity can have prevented or lessens by using cardio protective agent
dexrazoxane. Use of dexrazoxane (500 mg/m2) 30 min prior to administration of
doxorubicin protects against cardiomyopathy.
Question Alert!
1) Cardio protective agent dexrazoxane.
2) Use vertical laminar airflow hood in daunorubicin and doxorubicin preps.
Coronary spasm and MI <hr to days Fluoropyrimidines: Fluorouracil, capecitabine

CHF <mo to yrs Transtuzumab, daunorubicin, doxorubicin,
DVT <wks to Thalidomide’s, bevacizumab
Months
Neurotoxicity
· Common with vinca alkaloids such as vincristine, vinblastine, cytarabines, methotrexate

(very little), 5FU, and interferon alpha.
· Peripheral neuropathies associated with vincristine, paclitaxel can cause paresthesia
(numbness and tingling, pin feeling) can occur with vincristine, which often appears within
few weeks of therapy.
33-7
PharmacyPrep.
· High dose of cytarabine may produce cerebellar toxicity that manifest initially as loss of eye
hand coordination and progress to coma.
· Fludarabine cause severe neurotoxicity.
· Caramustine and other alkylating agents cause little or no neurotoxicity.
GI toxicity
Mucositis is generalized burning, and pain on the ventral surface of tongue. Floor of tongue,
mouth looks erythromatus.
Stomatitis is generalized inflammation of oral mucosa or mucus membrane of mouth.
Mucositis common with doxorubicin, methotrexate, 5-fluorouracil, actinomycin, bleomycin and
capecitabine.
· Recommend mouth hygiene, xylocaine, viscous sucralfate, nystatin, sodium bicarbonate, for
severe cases peliformin (growth factor) can be used. Avoid alcohol, antihistamine, steroids,
and spicy food.
· Mucositis treatment and prevention. Topical anesthetics for small ulcers apply
benzocaine in orabase. For generalized mucositis topical rinses like viscous lidocaine, or
dyclonine 0.5 or 1%.
· Corticosteroid provides anti-inflammatory action.
· Capsaicin. Produces burning and pain and ultimately desensitizes pain.
· Sucralfate suspension may provide benefit by coating.
· For localized effect use benzocaine in orabase.
· Mucositis prevention: Chlorhexidine gluconate 0.12%, may reduce severity and
frequency of mucositis infections.
Nausea and vomiting
· Very high emetics anticancer drugs (High >60%)

· Cisplatin
· Streptozocin
· Cyclophosphamide
· Carmustine
· High emetics anticancer drugs or moderate (30-60%)
· Doxorubicin, daunorubicin
· Methotrexate (250 mg to 1000 mg), 5-flurouracil, etoposide,
· Cytarabine, cisplatin <50 mg/m2
· Lowest emetic anticancer drugs low (<30%)
· Bleomycin
· Methotrexate (under 50 mg)
· Vincristine
· Vinblastine
· Tamoxifen
33-8
PharmacyPrep.
· Trastuzumab (Herceptin)
· Rituximab
· Androgen
Management of nausea and vomiting associated with cancer chemotherapy

· The low emetogenic drugs nausea and vomiting is treated by dexamethasone,
metoclopramide, ondansetron’s, or chlorpromazine.
· High (moderate and very high emitogenic drugs) associated acute nausea and vomiting is
treated by serotonin 5HT 3 antagonist + dexamethasone +/- aprepitant
· Drug of choice to treat delayed nausea and vomiting dexamethasone.
· Anticipatory nausea and vomiting benzodiazepine.
Aprepitant is neurokinin (NK-1) receptor antagonist. Fosaprepitant is prodrug and used iv.
Acute: Starting within 24 hours of chemotherapy.

Delayed: Starting >24 hours after chemotherapy.
Anticipatory: Starting before chemotherapy as a conditioned response.
1st gen 5-HT3 receptor antagonist: Ondansetron and granisetron: for prevention of acute N&V
2nd gen: Palonosetron iv. For prevention of acute and delayed N&V.
Hepatotoxicity
Hepatoxic drugs such as asparaginase, cytarabine, mercaptopurine, and methotrexate.
Hepatotoxicity monitor LFT, jaundice, or hepatitis.
Nephropathy
Methotrexate may precipitate in kidney. Monitor elevate BUN and electrolyte abnormalities:
Cisplatin and streptozocin. Amifostine may be used to protect the kidney from the
nephrotoxicity associated with cisplatin.
Sexual dysfunction
Cyclophosphamide, melphalan, and procarbazine associated with significant infertility in men
and women.
Hemorrhagic cystitis
It is a bladder toxicity (bloodstained urine) that is seen most commonly after administration of
cyclophosphamide and ifosfamide.
· These drugs produce a metabolite called acrolein. This Question Alerts!
cause chemical irritation in bladder mucosa, resulting Example of uroprotective agents
in bleeding. MESNA
33-9
PharmacyPrep.
· Hemorrhagic cystitis caused by acrolein can be prevented by excessive hydration and

subsequent frequent urination. The other method is by administering uroprotecting agent
called MESNA, which bind acrolein and prevent from contacting the bladder mucosa.
Pulmonary toxicity
· Pneumonitis, pulmonary fibrosis commonly seen with bleomycin, carmustine,

cyclophosphamide, mitomycin, methotrexate, and vinca alkaloids.
· Symptoms of pulmonary toxicity includes SOB, non-productive cough, and rarely low-grade
fever.
· The most common with bleomycin, mitomycin, and carmustine.
· Rationale for combination therapy is overcoming or preventing resistance, cytotoxicity to
resting and dividing cells. Biochemical enhancement of effect. Beneficial drug interactions
rescue host cells.
· Some agents can be administered intrathecally. Methotrexate, cytarabine, and thiotepa.
· Warning: Vincristine should be labeled as Intravenous only. Intrathecally vincristine causes
death.

MOPP Mechlorethamine, Oncovin, Prednisone,
Procarbazine
PSA Prostate specific antigen
· Neoplasm. New and diseased form of tissue growth
· Benign neoplasms; Non-cancer form of tissue growth, which can be removed by surgery. No
metastases.
· Malignant neoplasms; Cancer form of tissue growth. Invasive growth of cancer.
· Malignant neoplasms can be categorized as.
· Bone marrow; Leukemia (cancer of cells in blood)
· Connective tissue; Sarcoma
· Epithelium; Carcinoma
· Lymphoid tissue; Lymphoma (also named as Hodgkin’s disease)
· Myeloid stem cells; Myeloid leukemia
· Endothelium; Kaposi’s sarcoma
· Skin (melanocytes); Malignant melanoma
Tips
· Melanoma is skin cancer

· dexamethasone is more effective to treat nausea related to chemotherapy
· Methotrexate is used to treat cancer, RA and psoriasis
· Which anticancer drugs cause pulmonary fibrosis→ bleomycin
33-10
PharmacyPrep.
· Hypertrophy is increase in cell size

· Hyperplasia is increase in number of cells (leads to tumor)
· Least emetic anticancer drug is bleomycin, tamoxifen, methotrexate
· Cancer patient on cancer chemotherapy, reports shortness of breath, non-productive
cough, she may be using drug bleomycin
· What is the drug of choice for delayed nausea and vomiting → dexamethasone
· Mesna is uroprotective agent
· Doxorubicin preparation should be performed in →vertical laminar airflow hood
· Melatonin induce sleep
· Paclitaxel and docetaxel act on M phase
· Cancer estimated deaths in men: Lung cancer 31% and prostate cancer 11%
· Cancer estimated deaths in women: Lung cancer 25% and breast cancer 15%
· Competitive inhibitor of estrogen is --> tamoxifen
· Myelosuppression is dose limiting for --> paclitaxel, methotrexate and etoposide.
· What is the screening test is used for prostate cancer --> Prostate specific antigen (PSA)
Find answers from the table

1 Metoclopramide 8 Filgastrim 15 Mesna
2 Tamoxifene 9 Methotrexate 16 5FU
3 cyclophosphamid 10 Bleomycin 17 Dexrazoxane
e
4 Carmustine 11 Mitomycin 18 Doxorubicin
5 Dexamethasone 12 Serotonin antagonist 19 Paclitaxel
6 Melatonin 13 Docetaxel 20 Etoposide
7 Erythropoeitins 14 lymphocytes
· Drugs that are considered to be more effective in nausea related to cancer
chemotherapy. (5, 12)
· What is used for RA, cancer and psoriasis. (9)
· Which anticancer drugs cause pulmonary fibrosis? (10)
· Least emetic anticancer drug is .. (10, 2,9 )
· Cancer patient on cancer chemotherapy, reports shortness of breath, non-productive
cough, she may be using which drug. (10 )
· Drug of choice for delayed nausea and vomiting. (5)
· Drug of choice for acute chemotherapy induced N & V. ( 5+12)
· Uroprotective agent. (15)
· Example of drug preparation should be performed in vertical laminar airflow hood.
(doxorubicin, daunorubicin)
· A neurohormone, it is a sleep-inducing hormone secreted by pineal gland in response to
darkness or low light levels. (melatonin)
· M phase (mitotic tubule inhibitor (19, 13)
· Examples of drugs that are antimetabolites? (5FU, 9, 16)
33-11
PharmacyPrep.
· Cardio protective agent in chemotherapy. (dexrazoxane)

· The most effected cells with antineoplastic drugs. (14)
· Filgrastim indicated for --> neutropenia
· Erythropoietin's are indicated for -->anemia
· Melanoma is àskin cancer or pigmentation
· Hypertrophy is à Increase in cell size
· Hyperplasia is à Increase in number cells
33-12
PharmacyPrep.
www.PharmacyPrep.Com Gastrointestinal Drugs
34
Gastrointestinal Drugs
GI Drugs
Antacids Foaming agents H2 receptor Proton pump

Aluminum hydroxide Alginic acid antagonists inhibitors
Calcium carbonate Sodium alginate Cimetidine Lansoprazole
Magnesium hydroxide Famotidine Omeprazole
Gastroprotective Nizatidine Pantoprazole
Sodium carbonate
agent Ranitidine Rabeprazole
Sucralfate Esomeprazole

Omeprazole Losec Cimetidine Tagamet
Lansoprazole Prevacid Famotidine Pepcid
Pantoprazole Pantolac Nizatidine Axid
Rabeprazole Ranitidine Zantac
Esomeprazole Nexium
Antacids
Antacids are used to treat stomach upset,
heartburn and sometimes ulcers. They are Question Alert!
simple chemical compounds that are mildly 1) Al and Ca gives constipation
alkaline, and some also act as chemical Mg antacids give diarrhea. (Mg = must go)
buffers. They act by neutralizing stomach and 2) Antacids DIs. Tetracycline, thyroxin,
coating the mucosal lining of the stomach. bisphosphonates, and quinolone, H2RA, PPI
Simethicone is an agent added to antacids and Ketoconazole, digoxin. separate 2 hr
that helps relieve gas.
Mild GERD or heartburn: Antacids, OTC H2RA,
Types of antacids
· Aluminum hydroxide. Side effects. Constipation. avoid in renal dysfunction.
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and it is 34-1
PharmacyPrep.
· Calcium carbonate. Side effects. Constipation

· Mg hydroxide, Mg trisilicate, Mg sulphate (Epson salts), Mg citrate. Side effects Diarrhea
(Mg: Must go), cathartic. Avoid renal dysfunction.
· Na carbonate. SEs. hypertension
Magnesium salts are osmotic/saline laxative. onset of action is 30 min-6 hours.
Alginates
· Antacids combined with alginates or foaming Question Alert!
agents. 1) Alginate are foaming agent
· Alginates are intended to float on the content of 2) Simethicone is antiflatulant
the stomach to produce a neutralizing layer to 3) Sucralfate is mucosal protective agent
subdue acid that can otherwise rise into (Al silicate salt).
esophagus, causing heartburn.
Simethicone is antiflatulant agents are intended to relieve flatulence.
Drug interactions with antacids: Tetracycline chelation with bi and trivalent ions, thereby this
can reduce absorption of tetracycline. Antacids decrease absorption of fluroquinolones,
bisphosphonates, and thyroid hormones, by complexation. Rosuvastatin, gabapentin,
levodopa. Antacids increase absorption of levodopa.
Ketoconazole and PPIs. The antifungal ketoconazole requires acidic medium for absorption.
Concomitant use of antacids can reduce absorption of ketoconazole.
Antacids Drugs interactions Mechanism/ space timing Timing

Fluroquinolones, tetracycline, Separate antacids dosing by 2 h
digoxin, thyroid hormones,
bisphosphonates.
Rosuvastatin, gabapentin, Levodopa 1 hr, gabapentin and
levodopa rosuvastatin 2h
Ketoconazole and PPIs, H 2 RA, PPI empty stomach, (30 min If antacids with sucralfate,
sucralfate before meals) PPI they should be taken at
PPI decrease ketoconazole least 30 min before or after.
absorption
Al, Mg, Ca, Alginates PRN after meals and at
bedtime as needed
Combination
Alginate/Aluminum hydroxide (Gaviscon liquid)--> take after meals
Alginate/Magnesium carbonate (Gaviscon tab) --> take after meals.
PharmacyPrep.
Question Alert!
1) What is proton pump? H+/K+ ATPase
2) Esomeprazole is an isomer of omeprazole. This isomer has more first pass metabolism therefore
have more local effect in GI tract.
3) Pantoprazole Sodium and magnesium salt available. Pantoprazole magnesium cause diarrhea.
4) All PPI are taken an empty stomach.
5) Naproxen + esomeprazole (Vimovo) is taken? 30 min before meals.
6) PPI inhibit CYP 2C19, and this is substrate for Clopidogrel? Except pantoprazole
Moderate to severe GERD: The drug of choice is PPI.

PPI are the drug of choice for most GERD patients with or without mucosal injury and
extraesophageal manifestation.
Proton Pump Inhibitors

Omeprazole, esomeprazole, pantoprazole Na and Pantoprazole Mg, lansoprazole and
rabeprazole dexlansoprazole, are proton pump inhibitors, powerful anti-ulcerogenic drugs that
work by stopping the production of stomach acid completely.
Mechanism Irreversible inhibition of gastric parietal cell proton pump H+/K+ ATPase.
(Hydrogen Pump)
Therapeutic The PPIs are the drug of choice in in most or moderate to severe GERD
use patients. Prevention of reoccurrence of duodenal ulcers and esophagitis.
Pathology hypersecretory states. Multiple endocrine neoplasia’s healing of
NSAID induces peptic ulcers. Drug of choice for Ellison Zollinger Syndrome.
Duration Short term treatment (4 to 8 weeks) as empiric therapy.
Side effects Abdominal pain (nausea), diarrhea and headache are common.
Drug Inhibits CYP2C19. Increase levels of CBZ, BZD, digoxin, warfarin. Thus, avoid
interactions combination of PPI and clopidogrel. Pantoprazole has weak interaction, and
can be combined.
Taken 30 min before food because PPIs are prodrugs requiring proton
pump activation. Initial therapy should be once day before breakfast. May ↓
bioavailability of iron salts, digoxin, ketoconazole, ↓ theophylline levels.
H2receptor antagonists
PharmacyPrep.
H 2 -receptor antagonists inhibit the action of a special type of histamine receptor present in the
stomach. This reduces the amount of gastric acid production, which helps heal ulcers.
H 2 receptor Cimetidine, ranitidine, famotidine, and nizatidine

antagonists
Therapeutic Due to its rapid onset of action of H2RA, used "on-demand" use for
use mild GERD (<3 times per week). Preventing reoccurrence of ulcers.
Management of Zollinger-Ellison syndrome.
Side effects Gynecomastia. elevation of prolactin (cimetidine).
Headaches. famotidine and ranitidine, hematologic abnormalities
Decreased hepatic microsomal metabolism of some drugs like
cimetidine, which decreases the metabolism of warfarin, theophylline,
diazepam and phenytoin.
Diarrhea, constipation, fatigue, confusion, cardiac effects. Side effects
are more common in elderly and decrease renal function patients.
Tips Nizatidine is preferable used in elderly and renal disorder patients
Cimetidine and famotidine are now available without prescription for
the treatment of dyspepsia (2 weeks supply).
Drug Cimetidine. Increases the effects of anticoagulants. Inhibit CYP 3A4
interactions metabolism, thereby inhibit metabolism of warfarin, phenytoin,
theophylline.
ALARMS or > 55 yo are NOT symptoms of GERD.

A = anemia
L = loss of weight
A = anorexia
R = recent onset of progressive symptoms
M = malena/hematemisis
S = swallowing difficulty
Cytoprotective Agents (Mucosal Protective Sulfate)
Sucralfate binds to the ulcer site by forming a viscid sticky gel Question Alerts!
that coats the ulcer site and acts as a protecting. Sucralfate is taken?
Sucralfate · Aluminum sucrose sulfate is a sulfated disaccharide.

Mechanism · Selectively binds to necrotic ulcer tissues (acts as a barrier to acid,
pepsin and bile). Directly absorb bile thus has chelating property.
Stimulates endogenous prostaglandin synthesis mucus secretion.
Therapeutic · Effective in the healing of stress induced duodenal ulcers.
use · Reduces the number of H. pylori
Side effects · Causes constipation.
PharmacyPrep.
Dose · Dose 1 g qid, take empty stomach

Drug · Requires acid pH to be activated should not be administered with
interactions antacids, H 2 antagonists or proton blockers.
BismuthCompounds
Mechanism · Selectively binds to necrotic ulcer tissues

· Stimulation of mucous production
· Inhibition of pepsin activity
Therapeutic use · Possess antimicrobial activity against H. pylori
· When combined with antibiotics like metronidazole and
tetracycline has 98% healing rate for ulcer
Contraindications · Should not be given in renal disease and pregnancy
GERD
· Mild GERD, relief of symptoms is with antacids, alginates or non-prescription strength H 2 RA.
· Severe GERD. PPI are the drug of choice. Use PPI for 2 to 4 weeks.
· The goal is to raise the intragastric pH 4 during periods when reflux is likely to occur.
Peptic ulcers: The common cause of ulcers are due to H. pylori infection or drug induced.
· Gastric ulcers. Due to reflux since has weak pyloric sphincter
· Duodenal ulcers. Excessive secretion HCl from parietal cells
· Acute stress ulcers (Curling’s ulcer) can cause tumors.
· Pathologic acid-hypersecretory states is Zollinger-Ellison syndrome.
Risk factors for peptic ulcers are smoking, regular use of NSAIDs, or ASA.
Tips
· An example of ecosanide is misoprostol
· Misoprostol is PGE 1 analog used for mucosal protection in drug induced ulcers
· Type of pain in GERD is epigastric pain
· Increase in bilirubin cause cholestatis
· Aluminum salts and calcium can cause SEs constipation
· Magnesium antacids cause SE diarrhea, and cathartic
· H. pylori infections cause ulcers
· What type of hepatitis is chronic → hepatitis B and C
· What is treatment of hepatitis →interferon's
· NSAIDs induced ulcers can be treated by PPI
· Independent risk factors for peptic ulcers are H. pylori and NSAIDs (T/F)
· Chronic hepatitis? hepatitis B and C
· Epsom salt is? Magnesium sulfate
PharmacyPrep.
· Ulcerative colitis occurs at? colon

· Antiflatulance agent? Simethicone
· What vaccine can be used for traveler’s diarrhea? Dukoral
SELECT TRUE/FALSE STATEMENTS

· Na bicarbonate is contraindicated in-patient with hypertension, CHF, severe renal
disease, and edema? (T/F)
· CaCO 3 antacids have rebound acidity due to stimulation of acid secretion.
· CaCO 3 antacids avoid in hypercalcemia patients. (T/F)
· Hypophosphetemia and osteomalacia can occur with long-term use of aluminum
containing antacids. (T/F)
· Antacids bind with tetracycline, and fluroquinolones and reduce absorption. (T/F)
· Antacids may destroy coating of enteric-coated drugs. (T/F)
· Mg antacids can cause cathartic side effects. (T/F)
· Zollinger-Ellison syndrome is gastric hypersecretory states in systemic mastocytosis
which is a rare disorder with increase number of mast cells systematically and in skin.
(T/F)
· H. pylori is gram negative bacteria that cause gastric ulcer (T/F)
· Sucralfate is taken --> empty stomach because it makes layer ulcer.
PharmacyPrep.
Pharmacyprep.com Drugs in renal diseases
35
Drugs in Renal Diseases
STAGES CrCl (GFR ml/min/1.73m2)
OF CKD
1 >90; slight kidney damage with - filtration
2 60-80 mild ¯ kidney function
3 30-59 moderate ¯ kidney function
4 15-29 severe ¯ kidney function
5 <15 or dialysis: Kidney Failure
Approximate renal dysfunction

Creatinine clearance range 80 to 120 mL/min and renal disease <50% renal elimination.
Rate of excretion = rate of filtration + rate of secretion - rate of reabsorption.
Cockcroft and Gault

Empiric dose adjustment estimate using the weight corrected creatinine clearance
(easier to calculate).
Male: CrCl (mL/s/70kg) = [(140-age) x 1.5]/serum creatinine (mmol/L)

Female: CrCl (mL/s/70kg) = 0.85 x above equation
The normal CrCl for 70 kg male (1.8 to 2 mL/s)
Nephrotoxic Drugs: Potential to worsen renal function if patient renal function is CrCl
(<0.5 mL/s/70kg).
Avoid all of the following drugs:

NSAIDs (<30 ml/min)
Aminoglycosides, cyclosporine, bisphosphonates, foscarnet, glyburide, lithium, cox 2,
vancomycin
· Alendronate, clodronate, etidronate (nephrotoxic)
· Amphotericin
Copyright © 2000-2018 TIPS Inc. Unauthorized reproduction of this manual is strictly prohibited and 35-1
conducted by PharmacyPrep
· Benzafibrate
· ASA, Celecoxib
· Indomethacin
· Ibuprofen
· Meloxicam
· Mefenamic acid
· Metformin
· Lithium
· Methotrexate
NEPHROTOXIC Drugs AVOID IF

NSAIDs <30 ml/min
Colchicine
Metformin <30 ml/min
Methotrexate
Lithium
Theophylline
Aminoglycoside
Radiocontrast media
LMWH <30 ml/min
*THIAZIDES <30 ml/min
Amphotericin B
Cisplatin
Cyclosporine
Most thiazide diuretics are ineffective once creatinine clearance falls below 30
mL/min. Switching to a loop diuretic once creatinine clearance falls below 50
mL/min is recommended. Metolazone is the only thiazide-like diuretic that may
produce diuresis in patients with creatinine clearances less than 20 mL/min.
Indapamide may also be effective in patients with renal impairment but efficacy
declines in proportion to renal function.
Drugs with active and toxic metabolites:

Drugs Toxicity
Meperidine Nor-meperidine cause seizure
Question Alerts!
Drugs in renal diseases 1) Aminoglycosides cause acute
Dose of renally eliminated drugs need to be adjusted are; tubular necrosis (nephrotoxic).
· All penicillin’s, except nafcillin or dicloxacillin 2) Aminoglycosides cause dose
· Most cephalosporin's (not ceftriaxone) dependent toxicity.
· H 2 blockers (except. nizatidine).
All Aminoglycosides
The nephrotoxicity is acute tubular necrosis.
· Dose will remain same
· Intervals are increased
· The normal half life 2 to 5 hours and renal disease patient ~30 hr?
· Eliminate after 10 to 20 days thereby this give post dose antibiotic effect.
· Serum creatinine concentration is monitored frequently every 2 to 4 days.
If aim is to achieve steady state maximum/peak and minimum/trough concentrations

the interval between aminoglycosides doses should be extended.
Cisplatin and carboplatin nephrotoxicity

Platinum containing anticancer drugs like cisplatin cause renal tubular damage.
Toxicity is prevented by dose reduction and decrease frequency of administration and
avoiding concurrent use other nephrotoxic drugs.
Radiographic contrast media nephrotoxicity

The nephrotoxicity is caused by direct tubular toxicity or renal ischemia. Pre-existing
disease particular diabetes is the major risk factor.
Digoxin (not digitoxin)

· Half life 36 hours
· V d can be reduced in renal failure
· Prolong distribution phase (6 to 12 hours)
· Gastrointestinal metabolism
· Digitalis toxicity. Hypokalemia drugs (thiazide, CA inhibitors, loop diuretics),
quinidine, verapamil, erythromycin, tetracycline, amiodarone, and nifedipine.
· Digitalis toxicity. Cardiac toxicity (arrhythmias).
Hepatically eliminated will need to have dose adjustments

· May produce active metabolically active metabolites that are renally eliminated
· Meperidine; normeperidine
· Verapamil; nor verapamil
· Codeine metabolized to morphine and then gives morphine-6-glucuronide
Drugs needed monitor their therapeutic range. Serum dose concentration monitoring
(SDCM). may help guide dose adjustment.
· Lithium à0.5 to 1.5 mEq/L
· Valproic acidà50 to 100 mg/L
· Procainamideà4 to 10 mg/L Question Alerts!
· Carbamazepineà 4 to 12 mg/L Lithium serum level over 2 mEq/L can
· Quinidine à2 to 6 mg/L cause lithium toxicity
· Vancomycin
· Theophylline
· Aminoglycosides
· Phenytoin
· Cyclosporine
Phenytoin (NON-nephrotoxic)
· Hepatically metabolized. Non-linear (saturated) clearance.
· Decrease plasma protein binding in-patient with renal failure meaning therapeutic
affect occur at lower serum concentrations.
· Half-life 20 to 40 hours.
Question Alerts!
Theophylline (Non-nephrotoxic) Theophylline clearance in children age 1 to 9 yr?
· Hepatic metabolism Increased
· Clearance is greater in smokers and
children
· Clearance is reduced in patient with heart failure
· Saturation of metabolism may occur at high dose.
· Do not give immediate release products twice a day.
· Dose dumping will select once a day product taken in conjunction with fatty meal.
· Significant drug interactions with erythromycin, clarithromycin and ciprofloxacin.
· Oral theophylline 100% bioavailability.
Nephrotoxic drugs that are avoided (CrCl <0.5 ml/s):

Antacids like mg, and Al (avoid long term use in renal disease)
Colchicine
Dolasetron
Ethacrynic acid, Hydrochlorothiazide, spironolactone
Foscarnet
Leflunomide
Indapamide
Meperidine
Nalidixic acid, nitrofurantoin, Probenecid
Tips
· Oliguria: Urine output <400 mL/day
· BUN/Creatinine ratio, normally 10/1.
· Renal azotemia is uremia
· Pyelonephritis is? Pelvic inflammation or infections
In renal disease patient what happens to half life of drug and steady state
concentration?
ko
Css = ko = rate of infusion
CL
CL = total body clearance
DL = loading dose
DL = Css x Vd
DM = maintenance dose
Vd = volume of distribution
DM = Css x CL x t
t = dosing intervals
ko
Css =
VdK
K el = 0.693/ t 1/2
CL T = V d x (0.693/t 1/2 )
www.PharmacyPrep.Com Immunomodulator
36
Immunomodulators
Immunomodulators
Immunosuppressants Immunostimulants
Drugs Antibodies
Monoclonal antibodies: Antilymphocyte globulin

Antibiotics (Biological response
Cyclosporin Lymphocyte immune globulin
modifiers) Immune globuline
Pimecrolimus Infliximab, Muromonab,
Tacrolimus trastuzumab, adalimumab
Glucocorticosteroids
Prednisone Lymphokine Colony stimulating
Interferons factors (CSF)
Prednisolone Aldesleukin
Inteferon-a-2a Filgrastim,
Interferon-b-1b Sargramostim
Anti-TNF a agents Interferon-y-1b
Etanercept
Thalidomide
Cytotoxic agents
Azthioprine
Cyclophosphamide
Methotrexate
Enzyme inhibitors
Mycophenolate mofetil
Leflunomide
illegal to reproduce without permission. This manual is being used during review sessions conducted by 36-1
PharmacyPrep.
www.PharmacyPrep.Com Immunomodulator
Monoclomal chimeric antibodies (biological response modifiers): Infliximab, daclizumab

Indicated in treatment of rhuemathoid arthritis, ulcerative colitis and chrons disease.
· Mechanism. Tumor nechrosis factor (TNFa) inhibitor.
Immunosupressant antibiotics
· Cyclosporin. Mechanism: Calcineurin inhibitor
· Indicated for organ transplant rejection, rheumatoid arthritis and as anticancer drug.
CYCLOSPORIN & TACROLIMUS

ANTIGEN CELL àBINDS TO TCELL RECEPTORS à CALCINEURIN ----x--àACTIVATED TCELLS
CALCINEURIN IS: a Ca2 dependant phosphatase.
Tacrolimus and Pimecrolimus

Topical Calcineurin inhibitors: These drugs selectively decrease T helper 2 and mast cell activity.
Target skin inflammation without causing immunosuppression.
· Indicated for treatment of eczema, atopic dermatitis and immunosuppressant in organ
transplantation.
· Tacrolimus ointment 0.03% (pediatric >2 yr), and 0.1% (adult). Moderate to severe to atopic
dermatitis.
· Pimecrolimus cream 1% indicated for mild to moderate atopic dermatitis. Apply thin layer.
Cytotoxic drugs
Methotrexate: Indicated for the treatment of cancer, rheumatoid arthritis and psoriasis.
Immunostimulants
· Indicated for the treatment of
· Anemia
· Thrombocytopenia
· Neutropenia
· Bone marrow depression (myelosupression)
· Immunodeficiencies such as HIV.
Filgrastim and Sargramostim: Indicated for the treatment of neutropenia associated with
cancer chemotherapy.
Interferons: Indicated for viral infection like hepatitis B and C and multiple sclerosis. The most
common SE interferon is flu like symptoms.
illegal to reproduce without permission. This manual is being used during review sessions conducted by 36-2
PharmacyPrep.
www.PharmacyPrep.Com Ophthalmic drugs
37
Ophthalmic Drugs
Autonamic activity on eye
Cholinergic Drugs Adrenergic Drugs
Agonist Agonist Antagonist

Antagonist
Pilocarpine * Cause mydriosis by cause miosis
Atropine
Gives miosis radial muscle
By spincter muscle
Tropicamides
* contraction
contraction Cause mydriosis
Nonselective Selective
Phenylephrine Timolol Betaxolol
Brimonidine
Pseudoephedrine
Xylometazoline
Epinephrine
Propine
Glaucoma
· Is due to increase intraocular pressure (IOP)
Question Alerts!
· Due to closing of schlem canal
Mechanism in glaucoma for
· Due to increase in aquous humor
1) Timolol
2) Dorzolamide
Treatment
3) latanoprost
· Use medications that gives miosis or mydriosis 4) epinephrine
· Medication that gives mydriosis open schlem
canal
Cholinergic drugs
· Cholinergic agonist (muscarinic receptor activators or parasympathomimetics)
· Directly stimulate muscarinic receptors to contract ciliary muscle and increase trabecular
outflow. Open up schlem canal and ↑ outflow schlem canal.
PharmacyPrep.
· Piolocarpine (1%, 2%, 4%, 6% DROPS) is naturally occurring compound, not hydrolysed by
acetylcholinesterase, indicated in the treatment of open angle glaucoma and xerostomia
(dry mouth).
Cholinergic antagonist
· Atropine is plant Belladona atropa product. It is tertiary amine, it enters, where it acts as an
M receptor antagonist.
· Pharmacological effects at higher doses Mydriasis and cyclopegia (paralysed
accommodation ciliary muscles), hyperthermia, tachycardia, sedation, urinary retention,
constipation, behavioral excitation, and hallucinations.
· Tropicamide: Indicated ophthalmology ocular exams (topical).
Beta blockers
· Timolol and betaxalol: They decrease IOP by inhibiting formation of aqueous humor.
· Decrease aquous humor formation by acting on NE at celiary epithelium.
· Timolol is non-selective beta blockers and betaxalol is selective beta 1 blocker.
Adrenergic agonists sympathomimetics: Concept!

Phenylephrine (a1 ). Occular decongestant, mydriasis HYPEREMIA: Reboud conjunctival
without cyclopegia. hyperemia upon prolong use of
Tetrahydrozoline, oxymetazoline, nephazoline Topical IMIDAZOLE DERIVATIVE:
decongestant. All constrict superficial conjunctival tetrahydrozoline (0.05%),
vessel within minutes. Prolong and excessive use use oxymetazoline (0.025%) and
causes rebound hyperemia. naphazoline (0.012%, 0.05%, 0.1%)
Are used for RED EYE.
Epinephrine epinephrine cause ↑ outflow.
· Decrease aquous humor formation by acting on NE at celiary epithelium.
· Nor epinephrine shows action by vasoconstriction to celiary body blood vessells.
PGF 2a analog ("Prost"): Latanoprost, bimatoprost, travoprost

· Lower IOP by increase outflow of aqueous humor through uvescleral pathway.
· Side Effects: Eye brown pigmentation of iris, lengthening of eye lashes
· ↑ outflow of aqueous humor through schlem canal thus decrease IOP.
Topical CA inhibitors (Dorzalomide, Brinzolamide): Decrease IOP by inhibiting CA enzyme that

involved in formation of aqueous humor.
Acetazolamide is oral only.
Brinzolamide eye drop suspension.
PharmacyPrep.
Question Alerts!
Mechanism in glaucoma for
1) Timolol: inhibit formation of aqueous humor
2) Dorzolamide and acetazolamide: inhibit enzyme involved in formation of aqueous humor
thereby decrease IOP.
3) epinephrine (Sympathomimetics). increase outflow
4) pilocarpine: Increase outflow
5) prosts: increase outflow of aqueous humor
Drugs to treat ophthalmic disorders
Ophthalmic Lubrication
Carbopol 940 Ophthalmic lubrication
for Artificial eye
Carboxymethylcellulose
Tyloxapol
(CMC)
Dextran 70/hydroxypropyl Enzymatic preparations;
Opthalmic antiobiotics
methylcellulose Fusidic acid and polysporin
Chymotrypsin
Glycerin Ophthalmic surgical implant;
Hydroxypropyl cellulose Gelatin, absorbable film
Opthalmic antivirals.
Hydroxypropyl Viscoelastic preparations; Sodium
Trifluridine hyaluronate
methylcellulose (HPMC)
Hypromellose Prostaglandin PGF2a analog
Polyethylene glycol "prost"
Polysorbate 80
Polyvinyl alcohol
Sodium hyaluronate Question Alerts!
1) HPMC in ophthalmic preps, is used as? viscosity enhancer
Ophthalmic local anesthesia (increase drug contact time with cornea).
Proparacaine 2) Polyvinyl alcohol in ophthalmic preps, is used as?
Tetracaine ophthalmic lubricant.
3) benzalkonium chloride 0.004% is the most commonly
used in ophthalmic drops as? bacterial preservative (toxic to
corneal epithelium).
Congunctivitis (red eye or pink eye)

· Allergic is treated by antihistamine
· Bacterial is treated by antibacterial like polymixin, and fusidic acid.
· Viral eye infection is also known keratoconjuntivitis and is treated by acyclovir, trifluridine
and idoxuridine.
Benzalkonium chloride: a preservative known to cause toxic to corneal epthelium. So avoid in

moderate to severe dry eye disease (DED). Alternate oxidative preservatives, such as
PharmacyPrep.
polyquaternium-1, sodium chlorite or sodium perborate (also know as vanishing preservatives)

can be used.
Viscosity enhancer: Increase tear retention time and help to protect ocular surface. examples.
CMC, HPMC, polyvinyl alcohol, propylene glycol, and hydroxypropyl-guar.
Tips
· Glaucoma is two types: Open angle glaucoma (95%), close angle glaucoma (5%)
· Open angle glaucoma: Fluid drains too slowly from anterior chamber. Pressure gradually
rises (increase IOP), almost always in both eyes, causes optic nerve damage. If not treated,
can lead to blindness. What is the drug of choice? à Timolol
· Emergencies of open angle glaucoma à Pilocarpine
· Close angle glaucoma sudden attacks of increased pressure, usually in one eye (T/F)
· Diabetic retinopathy leading cause of blindness, affects the retina. The best way to prevent
is control diabetic condition (T/F)
· Drugs that cause dilation of pupil are à Mydriatic
· Blind spot is also known as à Optic disk
· When light rays come to a focus behind the retina, the eye is characterized as à
Hypermetropic
· The part of the eye that related to focus of eye is à Lens
· Tropicamide indicated in ophthalmology à ocular exams (topical).
PharmacyPrep.
www.PharmacyPrep.Com Antimicrobials
38
Antimicrobials
Antibiotics classifications
Cell Wall synthesis Penicillins
inhibitors Cephalosporin's Question Alert!
Vancomycin Cephalosporin's, quinolones
and sulfa drugs mechanisms
Protein Synthesis Amino glycosides
inhibitors Macrolides
Tetracycline’s
Lincosamide
DNA Synthesis Quinolones/Fluoroquinolones

inhibitors Metronidazole
Folate Inhibitors Sulfonamides

Trimethoprim
Staph. (coagulase +ve)

Strep. (coagulase –ve)
Strep categorized as
Non hemolytic: S. viridans
Hemolytic
Group A (Strep. pyogenes) (GAS)
Group B (Strep. pneumonia)
Group C
Question Alert!
Acid labile (acid sensitive) 1) Acid sensitive oral preps are not
• Penicillin G……………….β-lactamase sensitive available!
• Methicillin…………………β-lactamase resistant 2) "PAPA" is sensitive to beta lactamase.
• Nafcillin……………………β-lactamase resistant
38-1
PharmacyPrep.
Acid stable (acid resistant)

• Penicillin V…………………β-lactamase sensitive
• Oxacillin……………………β-lactamase resistant Beta-Lactamase Inhibitors
• Amoxicillin…………………β-lactamase sensitive
• Ampicillin…………………..β-lactamase sensitive • Clavulanate
• Sulbactam
Tips. PAPA is sensitive to beta lactamases • Tazobactam
Clavulanic acid
• Beta-lactamase inhibitors such as clavulanic acid can be combined with sensitive Beta-
lactams to yield an active combination with resistant organisms.
Penicillin's: Types of sensitivity reactions.

1) Immediate reaction occurs within 20 minutes (IgE mediated anaphylactic reaction.
2) Accelerated reactions, occurs within 30-40 hours. Manifested by rash and sometimes
fever.
3) Delayed reaction: occurs after 3 days usually it consist of skin reactions or other
systemic reactions such as nephritis or serum sickness.
Penicillin resistance: Beta lactamase breaks a bond in the beta lactam ring of penicillin that
disables the molecules. Bacterial that produce beta lactamase can resist the effect of penicillin
and other beta lactams.
Penicillins • Penicillin G
• Penicillin V
• Methicillin
• Nafcillin
• Oxacillin
• Carbenicillin
• Ticarcillin
• Piperacillin
Aminopenicillins • Amoxicillin
• Ampicillin
Mechanism • Cell wall synthesis inhibitors

Therapeutic uses • Gram + ve and Gram –ve
Side effects • Hypersensitive reactions, rash, nausea & vomiting,
• Pseudomembranous colitis cause diarrhea
• Intestinal nephritis
• Hemolytic anemia (Coombs test)
38-2
PharmacyPrep.
• Penicillin's or all beta lactams are NOT effective for mycoplasma

bacteria.
PenicillinsG
Penicillin G Available as IM and IV

Therapeutic uses • Gram + ve (all of them), Gram –ve for Neisseria
Side effects Hypersensitive reactions, rash,
• Nausea & Vomiting
• Pseudomembranous colitis
• Intestinal nephritis
Side effects
management
Drug interactions • Interferes and alters test results for urine and serum protein levels. It
does not interfere with test using bromophenol blue.
• Aminoglycoside causes synergistic effect. Most effective endocarditis
infections.
• Penicillin G is the drug of choice for syphilis.
• Primary, secondary and early latent (<1 y duration) syphilis:
Benzathine Penicillin G 2.4 million units IM × single dose (consider
a second dose 1 wk later if patient is pregnant).
• Ceftriaxone is an alternate for syphilis infections.
PenicillinV
Penicillin V Oral tablets and liquid

Uses • Gram + ve (all of them)

• Gram –ve for Neisseria
Side Effects Hypersensitive reactions, rash. GI effects. Nausea & Vomiting,
Pseudomembranous colitis
SE management • Give 1 hour before or 2 hour after meals for max absorption.
Drug interactions • Interferes and alters test results for urine and serum protein levels.
It does not interfere with test using bromophenol blue.
PiperacillinandCarbenicillin
Therapeutic use Gram –ve (E.coli, Enterobacter, Klebsiella, Pseudomonas.

38-3
PharmacyPrep.
Side Effects
Drug interaction Used combination with β-lactamase inhibitors.
Often mixed with aminoglycoside (not in same IV bag)
AmoxicillinandAmpicillin
Therapeuti Amoxicillin HELPS enterococci. ("HELPS" = H. influenza, E. coli, Listeria

•
c use monocytogenes, Pseudomonas, Salmonella. S. pneumonia).
• The drug of choice for otitis media, dental prophylaxis, sore throat, H. pylori,
CAP.
• Synergistic effect with clavulanate, tazobactam and sulbactams.
Side Effects • Hypersensitivity, anaphylaxis
• GI affects nausea & vomiting, and P. colitis (diarrhea).
• Blood related. Thrombocytopenia, leucopenia, agranulocytosis
Drug • Allopurinol. Increases rashes. Penicillin's decreases contraceptive effect.
interaction Methotrexate-effects renal tubular absorption.
1st gen: Gram +Ve
2nd gen. less +ve more -ve
Cephalosporin's 3rd gen: -ve only
4th gen: -ve only
1st generation Cefazolin (iv) Long duration of action in 1st gen. Good penetration into bone.
None of them Cephalothin
enter in CNS. Cephalexin (po) Oral (DOC pharyngitis, cellulites, impetigo, skin and soft
Gram +ve tissue), 4 times daily. Alternate to penicillin (MILD allergy only)
cocci, staph, for Staph and Strep infection.
skin and soft Cephapirin Renal and hepatic elimination. Shortest half life (0.6 to 0.8 h)
tissue Cephradine (PO & IM)
Cefadroxil (po) Oral
2nd generation Cefaclor Oral (associated with serum sickness)
Gram +ve and Cefamandole
Gram -ve Cefoxitin (iv)
Cefuroxime Can cross BBB, can be used in community acquired bronchitis
sodium (iv) or pneumonia in elderly for H. influenza
Cefuroxime axetil Oral, stable for 24 hours when it dissolved in apple juice. It is a
(po) prodrug. Active against beta lactamases producing strain.
Commonly used for Gonorrhea and H. influenza infections.
Cefotetan (iv)
Cefproxil Oral
Cefonicid
Loracarbef
38-4
PharmacyPrep.
3rd generation Cefixime (po) Oral once daily, commonly used for UTI and also for
Contain Gonorrhea. The preferred treatment for Gonorrhea.
methylthiotetr Cefoperazone Hepatic elimination only, does not get in CNS
azole side Cefotaxime (iv) Renal and hepatic elimination. Can penetrate in CSF.
chain. Can Cefpodoxime
cause Ceftazidime (iv) Active against Pseudomonas aeruginosa
hypoprothrom Ceftriaxone (iv) Longest half life (8 hours). Single dose, it has bile excretion.
bonemia and Can be used renal diseases. Good penetration in bone.
bleeding The drug of choice to treat Gonorrhea. (Adults and
problems children ≥9 y: 250 mg IM × single dose + azithromycin 1 g
Gram -ve PO × single dose)
Cefdinir Oral once daily
Ceftibuten Oral
4th generation Cefepime (iv) Activity is same as 3rd generation, but more resistance to β-
lactamases.
Cephalosporin's gives positive coombs test

All cephalosporins have NO activity against “LAME”: Listeria, Atypical (Mycoplasma/chlamydia),
MRSA and Enterococci.
Cephalosporins1stGeneration
1st Cefazolin, Cephalothin

Generation
Therapeuti Surgical prophylaxis (best for gram +ve)
c use
Side effects Allergic reaction (5-15%), anaphylaxis, skin rash, fever, diarrhea
hemolytic anemia, granulocytopenia. Candida infections (vaginitis).
Local irritation at site of injection.
Seizure in high doses in IV form
Dose IV and PO
Cephalosporins.2ndGeneration
2nd Generation Cefaclor

Cefamandole
Cefoxitin
Cefuroxime
Clinical use Gram -ve coverage.

Parenteral administration except: cefaclor
38-5
PharmacyPrep.
Side effects Allergic reaction (5-15%), Skin rash, Anaphylaxis

Fever,
Local irritation at site of injection
Blood related  Hemolytic anemia, Granulocytopenia
Dose IV and PO
Cephalosporins-3rdGeneration
3rd Generation Cefixime

Methylthiotetrazole Cefoperazone
ring and Isoxazole ring Cefotaxime
Cefpodoxime
Ceftazidime
Ceftriaxone
Clinical use Gram negative only. Reserved for serious infections (bacterial
meningitis).
These drugs can penetrate Cerebrospinal fluids (CSF) thereby
it indicated for bacterial meningitis infections.
Nosocomial infections (hospital acquired infections).
Unknown origin infections Sepsis in immunocompromised
patients.

Fever, Local irritation at site of injection
Blood related, Hemolytic anemia, Granulocytopenia
methylthiotetrazole side chain can cause
hypoprothrombonemia and bleeding problems
Dose IV and PO
Cephalosporins-4thGeneration
4th Generation Cefepime

Clinical use Best for Gram -ve
Higher potency
Fever, Local irritation at site of injection
Blood related. Hemolytic anemia, granulocytopenia
Dose IV and IM
38-6
PharmacyPrep.
Vancomycin
Mechanism Cell wall synthesis inhibitor. It is unaffected by beta lactamase, thus used in
treatment of penicillin resistant strains. Bactericidal antibiotic against gram
+ve.
Therapeuti A very important drug for treating methicillin-resistant Staphylococcus aureus
c use infections (MRSA).
Vancomycin oral is an alternate drug for treating super infection (superbug)
by Clostridium difficile in patients with P. colitis.
Narrow spectrum of activity against Staphylococcus, Streptococcus and
Clostridium sp. (gram + ve bacteria).
Side effects Chills, fever, ototoxicity, and nephrotoxicity (>75% renal elimination).
Monitor, renal function and Serum drug concentration.
Precautions Rapid administration (infused <1h) causes red man syndrome
(flushing/rash/hypotension). In renal failure patient drug will accumulate.
Dose adjustment is guided by monitoring serum drug concentration.
Dosage iv for MRSA and oral (oral is used in only treatment of P. colitis) and half
life 6 to 8 h.
MRSA C. difficle
The drug of choice is the The drug of choice is mild-moderate C. difficle
vancomycin iv. metronidazole po.
Alternate linezolid Severe: vancomycin po + metronidazole iv
C. difficle treatment of antibiotic-associated pseudomembranous colitis produced by C. difficile.

Oral vancomycin is generally reserved for patients who are severely ill, have failed
metronidazole treatment, or are unable to take metronidazole.
Use metronidazole 500 mg orally 3 times daily for 10 days for mild-moderate initial episodes
of C. difficile-associated diarrhea.7,9,34 Use oral vancomycin125 mg 4 times daily for 10 days if
the patient is unable to take metronidazole, or for severe initial episodes.7,9,34 Use oral
vancomycin plus IV metronidazole for severe and complicated disease with no significant
abdominal distention.7,9 Use a combination of high-dose oral and rectal vancomycin plus IV
metronidazole for severe and complicated CDI with ileus or toxic colitis and/or significant
abdominal distention.7
Question Alerts!
1) What antibiotics are used treat MRSA? vancomycin iv
2) Drug of choice to treat Pseudomembranous colitis caused diarrhea? Metronidazole
or vancomycin PO.
3) Causative organism of P. colitis is? C. difficle
38-7
PharmacyPrep.
Inhibitors of Protein Synthesis
50 S Antibacterial Agents 30 S Antibacterial Agents
Amino glycosides Tetracycline's

Macrolides Lincosamides Gentamycin Demeclocycline
Erythromycin Clindamycin Streptomycin Doxycycline
Azithromycin Lincomycin Kanamycin Minocycline
Clarithromycin
"TEST CC" T= tetracycline, E = erythromycin S = Sulfadrugs, T = trimethoprim, C = clindamycin C

= Chloramphenicol, are bacteriostatic.
Amino glycosides
Gentamicin, Streptomycin, Tobramycin, Kanamycin, and Amikacin
Therapeutic use: severe abdominal, urinary tract, ophthalmic use and endocarditis infections.
Dosage forms: topical, IM, IV.
Pharmacokinetics: All amino glycosides renally eliminated. Can renal toxicity.

Half-life 2 to 5 hours. Post dose antibiotic effect (PDAE)
• Only kanamycin and neomycin have oral and topical
• Commonly amino glycosides used as IM or IV
• Streptomycin has only IM.
• Pharmacokinetics is not completely understood.
• Contain amino sugars structures and have low bioavailability
• Primarily used in infections associated with gram –ve.
• Amino glycoside has little activity against anaerobic.
Nephrotoxicity (reversible) is due to increased number of amino groups.

Neomycin has 6 amino group- more toxic
Streptomycin has 3 amino group-less toxic
Aminoglycosides display bactericidal concentration dependant killing action and are active
against a wide range of aerobic negative bacilli and gram positive.
Aminoglycoside are effective even when the bacterial inoculum is large and resistant rarely
develop. "inoculum is a small amount of material containing bacteria, virus or other
microorganism"
Gentamicin
Therapeutic Uses Gram –ve

Drug uptake depends of oxygen: active against aerobes
38-8
PharmacyPrep.
Second line treatment for tuberculosis (mainly streptomycin)

Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
Combined with cephalosporin's (2nd and 3rd) to reduce resistance
Side Effects Respiratory paralysis (decrease Ach at NMJ).
Nephrotoxicity (proximal tubular cell)
Ototoxicity (also occurs in unborn fetus)
Streptomycin
Streptomycin
Uses Gram –ve.
Second line treatment for tuberculosis (mainly streptomycin).
Treatment for plague (streptomycin). Pseudomonas (streptomycin).
Side effects Otic nerve toxicity-8th cranial nerve (mainly streptomycin)
Highest ototoxicity and least nephrotoxic.
Ototoxicity. Streptomycin = Kanamycin>amikacin = gentamycin = tobramcycin> netilmycin.
Tobramycin
Uses Gram -ve

Treatment for plague (streptomycin). Pseudomonas
(streptomycin). Combined with cephalosporin's (2nd and 3rd) to
reduce resistance.
Side Effects Respiratory paralysis (decrease Ach at NMJ)

Ototoxicity (also occurs in unborn fetus).
Amikacin
Uses Gram -ve

Treatment for plague (streptomycin).
Pseudomonas (streptomycin)
38-9
PharmacyPrep.
Side Effects Respiratory paralysis (decrease Ach at NMJ)

Ototoxicity (also occurs in unborn fetus)
Amino glycoside side effects "AMINO"

• Half-life is 2 to 5 h, however parenteral • A = Allergy
injections are given every 6 to 12 h.
• M = neuroMuscular Blockade
• Highest ototoxicity is with streptomycin
• I = Inactivated when physically
• Highest nephrotoxic is neomycin.
mixed with beta lactam
• Ototoxicity symptoms associated with
• N = Nephrotoxicity
gentamycin and streptomycin are
• O = Ototoxicity, Optic nerve toxicity
vestibular damage this can cause
tinnitus, vertigo, and ataxia.
• Ototoxicity symptoms associated with amikacin and kanamycin are auditory damage this
can cause hearing loss.
• Tobramycin can cause both vestibular and auditory damage.
• To prevent serious side effects associated with amino glycosides monitor blood drug levels,
BUN, and serum creatinine levels.
• Blood levels are monitored by peak and trough levels, trough levels of gentamycin greater
than 2 mcg/ml can cause nephrotoxic.
Question Alert!
1) Erythromycin have sever GI disturbances.
2) Ery, Clari are potent CYP 3A4 inhibitor
3) Clarithromycin and Azithromycin suspension are stored at room temperature.
4) Erythromycin estolate SEs is hepatitis/cholestatic jaundice more common in adults (not in
children) (elimates from liver) and susp. stored in fridge.
5) Erythromycin base, estolate, stearate. The estolate has greater blood concentration than
stearate.
Macrolides
Erythromycin (po, parenteral), Clarithromycin (po), Azithromycin (po), and Telethromycin (po)
(ketolides).
Side effects: Erythromycin and clarithromycin have severe GI disturbances.
• Pharmacokinetics: All of macrolides hepatically eliminated, except clarithromycin, which is
renally eliminated.
• All macrolides have oral dosage and erythromycin gluceptate and lactobionate is IV.
• Azithromycin has long half-life 68 hours and used single daily doses.
• Erythromycin has short half-life 1.2 to 2.6 hours.
• Erythromycin are preferred drug for treatment of Mycoplasma infection.
38-10
PharmacyPrep.
• Important alternate in patient allergic to penicillin's.

• Erythromycin estolate may cause cholestatic jaundice in-patient used more than 10 to 14
days (resolved after discontinued treatment).
• Erythromycin and clarithromycin is inhibitor of CYP3A4, thereby potentiates toxicities of
drugs that are metabolized by CYP3A4, e.g. digoxin, corticosteroids, lovastatin or (ALS),
sildenafil, tadalafil, vardenafil and carbamazepine.
• Clarithromycin increase warfarin INR (monitor PT), increases digoxin and theophylline
levels.
• Azithromycin is more active against gram –ve H. influenza than erythromycin.
• Clarithromycin is effective for H. pylori (used along with PPIs in triple therapy).
• Erythromycin, clarithromycin & azithromycin cause QT prolongation. Use cautiously with
other drugs that cause QT prolongation.
Erythromycin
Use Gram + ve (all of them), gram –ve for Neisseria

Side effects Epigastric distress (due to stimulation of motolin receptors)
cholestatic jaundice (in estolate form).
Estolate is salt of lauryl ester.
Ototoxicity (more with erythromycin)
Drug Interactions Contraindicated in patient with hepatic dysfunction (it accumulates in
liver), theophylline, warfarin, Terfenadine, and statins.
Clarithromycin
Use Same as erythromycin. H. influenza, Chlamydia, and Legionella

Side Effects Epigastric distress (nausea, vomiting, burning stomach, diarrhea),
renal (azotemia), Liver. Hepatitis (cholestatic hepatitis).
Contraindication Patient with hepatic dysfunction.
Do not refrigerate the reconstituted suspension. Clarithromycin
may increase levels of benzodiazepine, statins (ALS), CBZ,
theophylline, cyclosporine and tacrolimus.
Azithromycin
Use The drug of choice for uncomplicated pneumonia, chlamydia, . Alternate

to middle ear infection, travelers’ diarrhea. Less active for Staph. and
Strep than erythromycin. Far more active H. influenza, Moraxella
38-11
PharmacyPrep.
catarrhalis. Mycobacterium avium, except HIV.

Side Effects Epigastric distress (better tolerated than erythromycin &clarithromycin).
Oral preps have less nausea and vomiting.
Contraindicated in patient with hepatic dysfunction.
Counseling Suspension do not refrigerate.
may increase warfarin effect (clarithromycin >azithromycin).
Question Alert!
Azithromycin is more active against H. influenza.
Suspension do not refrigerate
Question Alert!
1) Tetracyclines DIs with Ca, Al, Mg, Fe and dairy (chelation).
2) Tetracycline taken an empty stomach.
3) Doxycycline taken with or after meals.
4) Minocycline taken with or without meals.
5) Tetracycline chelates with bivalent and trivalent ions.
6) Tetracyclines are CI in pregnancy children, due to cartilage damage.
7) Side effect Teeth discoloration in small children
Tetracycline’s. Tetracycline, doxycycline, and minocycline
Tetracycline
Tetracycline Broad spectrum antibiotics.
Therapeutic Uses Acne treatment (P. acnes), chlamydia (Lymphogranuloma, Psittacosis).
Rickettsia (Rocky mountain spotted fever), Mycoplasma pneumonia and
Lyme disease.
Side Effects Tetracycline should not be treated to renally impaired patient.
(accumulated increase azotemia).
Contraindication Pregnancy, breast feeding, children under 8 old.
Counseling Must take empty stomach with glass of water (one hour before or two
hours after meals). Chelates with bi and tri valent ions such as calcium,
magnesium and aluminum ions.
Tetracycline may stain teeth and for topical can stain cloth.
Photosensitive erythematic. Avoid prolong sun exposure.
Doxycycline
Uses Broad spectrum
Prophylaxis in traveler’s diarrhea
38-12
PharmacyPrep.
Lyme disease, Chlamydia (lymphogranuloma, psittacosis),

Rickettsia (Rocky mountain spotted fever)
Mycoplasma pneumonia
Side Effects Gastric discomfort (nausea and vomiting). Effect on calcified
tissues deposition in the bone and primary dentination occurs
during growing children.
Discoloration and hypoplasia of the teeth and temporary stunting
of growth, and fetal hepatotoxicity
Photo toxicity-Severe sunburn.
Super infection (over growth of candida in vagina or resistance to
Staphylococcus in intestine).
Contraindication Pregnancy, children under 8 old, and breast feeding.
iron or antacids ↓ doxycycline absorption. However, is taken with
meals or after meal. (food decrease GI SEs, take with glass of
water to avoid esophageal ulceration. Avoid concomitant use of
milk, antacids or drug containing Al, Mg, Ca, and Fe.
Counseling Take entire medication even if you feel better. Oral take with or
after meal with glass of water. (Food decreases GI side effects
avoid milk, antacids, iron).
Tell patient to check tongue for fungal infection. Stress good oral
hygiene. Avoid prolong sun exposure.
Minocycline
Therapeutic use Acne, and rheumatoid arthritis.

Side Effects photo toxicity
Vestibular problems. dizziness, nausea, vomiting
Contraindication Pregnancy, breast-feeding, children under 8 old
Take with or without food
Question Alert!
1) Mechanism of quinolones? DNA gyrase inhibitors.
2) Quinolones resistance mechanism is by modification of DNA gyrase enzyme.
3) Cipro is the drug of choice for traveler’s diarrhea.
4) Moxifloxacin does NOT require dose adjustment in renal disease.
5) All quinolones bioavailbility is decreased by Ca, Mg, Fe, and Al. Except. Moxifloxacin.
Question Alert!
1) Clindamycin diarrhea should be treated by metronidazole or vancomycin.
2) Can we treat clindamycin diarrhea with OTC antidiarrheal?
38-13
PharmacyPrep.
Clindamycin
Clindamycin Lincosamides class of drug.

Uses • Gram + ve and anaerobic bacteria Bacteroid fragilis (abdominal
infection). Topical clindamycin is used to treat Propionibacterium
acnes. Alternate to penicillin allergies for endocarditis prophylaxis.
Side Effects • Diarrhea (C. difficile is resistant to clindamycin). Managed by
discontinue medication. C. difficile diarrhea is treated by vancomycin or
metronidazole (oral).
Contraindication • History of colitis, regional entities, or antibiotic associated colitis.
Counseling • Take with or without food (discourage with food).
• Capsule. Take with full glass (240 ml) of water to prevent dysphagia.
• Do not refrigerate the reconstituted solution since under condition of
low temp, the solution may thicken and difficult to pour.
• Stable at room temp for 14 days.
Precaution • I.M. injection may be painful
Quinolones & Fluoroquinolones

Quinolones & Fluoroquinolones
Quinolones Nalidixic acid (disinfectant)
Fluoroquinolones 1st
Nalidixic acid
Norfloxacin
2nd
Ciprofloxacin (t, po, parenteral)
Ofloxacin (t, po, parenteral)
3rd (Respiratory tract antibiotics)

Moxifloxacin (po, parenteral)
Levofloxacin (t, po, parenteral)
Gatifloxacin (ophthalmic)
4th Trovafloxacin, Besifloxacin (t)
Therapeutic use
Nalidixic, norfloxacin Less potent than cipro. Used for pseudomonas, UTI.
Ciprofloxacin, Ofloxacin GI, UTI, Respiratory Tract. Ofloxacin mainly for gonorrhea.
Moxifloxacin, levofloxacin Respiratory Infections CAP
Trovafloxacin, Besifloxacin Respiratory Infections
38-14
PharmacyPrep.
Ciprofloxacin
Mechanism Inhibits topoisomerase II that prevents DNAg (gyrase) which stops

replication of bacteria.
Inhibition of DNA gyrase (topoisomerase II) and topoisomerase IV makes cell

inaccessible and leads to cell death. Different quinolones inhibit
different extent of topoisomerase II and IV. DNA gyrase seems more
important in gram –ve. Topoisomerase IV in gram +ve.
Therapeutic UTI. E. coli, STD. Gonorrhea, GI infections. E. coli traveler’s diarrhea.

Uses
Side Effects Most common nausea and vomiting, light-headedness, and nephrotoxicity.
Cartilage toxicity, avoid in children and pregnancy.
Tendonitis/tendon rupture common in elderly and renal failure patient.
Counseling Ciprofloxacin otic suspension. Store cipro otic suspension at room temp (15
to 25oC). Do not use otic suspension under 2 year of age.
Auxiliary labels With or without food. The preferred time is 2 hours after meal or empty
stomach (for faster absorption), with full glass of water, (avoid dairy
products). Do not take dairy product alone or within 2 hrs of Calcium intake
>800 mg, avoid excessive caffeine intake.
Avoid taking with antacid, iron, or calcium together, take calcium after two
hours.
Photo toxicity Photosensitive: Recommend sunscreen (UVA&B). If sunscreens not
effective, drug should be discontinued at the first of sign of toxicity-sun burn
like rashes.
Ofloxacin
Ofloxacin
Mechanism Inhibits DNA replication of bacterial DNA gyrase
Uses Mainly for E. coli in UTI and STD with exception syphilis.
alternate in gonorrhea
Side effects Hypoglycemia, leukopenia, Neutropenia
Counseling Tell patient to drink fluids liberally.
Separate doses of vitamins, antacids by 2 hours.
Gatifloxacin
Mechanism A quinolone, use to treat several types of bacterial infections.
38-15
PharmacyPrep.
Therapeutic use Chest infections (pneumonia), Sinus infection, urinary tract infection
Side Effects Q-T prolongation
Drug-drug Oral iron preparation and antacids containing magnesium and
interaction aluminum can interfere the absorption of gatifloxacin
Contraindication Not recommended in children
Monitoring
Question Alert!
1) Metronidazole must avoid alcohol
2) "GET A Metro"
3) Can cause dark urine
4) What is the treatment of B. fragilis and C. dificcile
5) The drug of choice for Trichomonas vaginitis.
Metronidazole
Metronidazole Classified as antiprotozoal drug and has antibiotic actions (anaerobic).

Mechanism • Mode of action is thought to be breakage of cell DNA.
Therapeutic • Indicated in anaerobes such as Bacteroides, C. difficile, C. vaginalis.
use Protozoans (Giardia, Entamoeba, Trichomonas) and H. pylori. "GET A
METRO"
• This drug is also active against trophozoites in the intestinal lumen
and walls.
• Metronidazole has direct anti-inflammatory effect (antioxidant action
that contributes to its anti-inflammatory activity).
• Giardiasis and trichomoniasis metronidazole used orally.
Side effects • Metallic taste, furry tongue, and glossitis.
• Must avoid taking alcohol while on this drug can cause disulfiram like
reactions (Flushing, nausea and vomiting). Disulfiram causes acute
psychosis ever if taken within two weeks.
• Rarely be neurotoxic.
Drug-Drug • Cimetidine prolongs metronidazole half-life and decrease its plasma
interaction concentration. Warfarin potentiates effects resulting in prolongation
of prothrombin time. Phenobarbitone. Increases metronidazole
metabolism.
Precautions • It can cause dark urine
• Do not mix iv metronidazole with any other drug.
Pregnancy and • Caution require in pregnancy and lactation.
lactations
Dosage • Oral capsule and oral tablets.
38-16
PharmacyPrep.
• Injection. to treat anaerobic infections and protozoa infection

• Vaginal cream and inserts, vaginal gel: for treatment of bacterial
vaginitis
• Topical cream or gel drug of choice for rosacea applied effected twice
daily morning and evening for 9 weeks, then as needed.
FolateantagonistSulfaDrugs
Sulfa drugs Sulfamethoxazole, Sulfadiazine, Sulfasalazine and

Trimethoprim.
Combination drugs Cotrimoxazole (Sulfamethoxazole+trimethoprim).
Mechanism Structural analog of PABA that inhibit bacterial dihydropteroate

synthase to block folic acid synthesis and cell growth.
Therapeutic Use The drug of choice in uncomplicated UTI (cystitis) for 3 days.
Chlamydia trachoma, the most common cause of preventable
blindness.
Topical. burns and wounds.
Side effects Crystalluria: Adequate hydration and alkalization prevent this
problem
Hypersensitivity: rashes, Stevens-Johnson syndrome, and sulfa
allergies occurs with longer acting agent’s diuretics,
acetazolamide, thiazide, furosemide, bumetanide, and diazoxide.
Hemolytic anemia G6 PD deficiency.
Kernicterus. In newborns sulfa drugs displace bilirubin from
binding.
Counseling Sulfasalazine. Drugs colors urine and may color skin orange yellow.
May permanently stain soft lenses. Take drug after meals to
reduce GI distress and to facilitate passage into intestine.
38-17
PharmacyPrep.
Pteridine + PABA
Dihydropteroate synthase Sulfonamide
Dihydropteroic acid
Question Alerts!
Cotrimoxazole act on?
Dihydrofolic acid
Dihydrofolate reductase Trimethoprim, pyrimethamine
Tetrahydrofolic acid (THF)
THF cofactors
Thymine Purines Methionine

Glycine
f-met-tRNA
DNA DNA
RNA Proteins
Cotrimoxazole(SMX+TMP)
Cotrimoxazole
Therapeutic Use Chronic treatment of UTI
Gram –ve: H. influenza, Gonorrhea, E. coli, Klebsiella,
Salmonella, shigella sp. and V. cholera.
Gram +ve: S. pyogenes (GAS), S. viridans, S. aureus
UTI-Acute, recurrent, chronic.
Upper and lower rasp—chronic bronchitis.
Immunocompromised children P. carinii
Not indicated in infections associated with pseudomonas,
mycoplasma.
Side effects Skin reaction (severe in elderly)
GI. N and V
38-18
PharmacyPrep.
Blood related: Megaloblastic anemia, Thrombocytopenia,

Leukopenia: The above three effects can be reversed by
concurrent administration of folinic acid.
Hemolytic anemia-G6PD deficiency due to SMX
Counseling Drug is not for IM. Shake oral suspension thoroughly before use
Take oral dose with full glass of water.
With or without food. (food decreases GI side effect)
Store in amber glass of bottle.
Store at room temp until expiry and protect from moisture.
Contraindications Last trimester of pregnancy, lactation.
Children under 2 months. May cause kernicterus.
Steven-Johnson’s Syndrome (SJS): Rash, skin peeling, and sores on the mucus membrane. In
Steven Johnson’s syndrome, a person has blistering of mucus membrane, typically in mouth,
eyes and vagina. Patchy areas of rash. SJS can occur in all age groups.
Due to "SASPAN" Sulfonylurea, Anticonvulsant (phenytoin, carbamazepine, valproic acid,
lamotrigine,), Sulfonamide, Penicillin, Allopurinol and NSAIDs, chlorpromazine, Sulfa drugs
including topical sulfa drugs. Treatment of SJS is cortisone.
38-19
PharmacyPrep.
38-20
PharmacyPrep.
www.PharmacyPrep.Com Antifungal Agents
39
Antifungal Agents
Mechanisms of Action and Classification of Antifungal Agents
Antifungal Agents
After cell membrane permeability Block nucleic acid synthesis Disrupt microtubule function
Allylamine Pyrimidine
Azoles Polyene Penicillin
Analog
macrolide derivative
* Terbinafine
antibiotics * Flucytosine
* Naftifine * Griseofulvin
* Amphotericin B
Imidazoles Triazoles *Nystatin
* Ketoconazole * Fluconazole
* Miconazole * Itraconazole
* Clotrimazole
Antifungal act on ergosterol layer of fungal cell membrane. Whereas human cell
membrane contain cholesterol.
Allylamines Terbinafine po. The drug of choice for Onychomycosis

Antifungal Amphotericin B
Antibiotics Amphotericin B (lipid-based)
Griseofulvin
Systemic antifungals
Echinocandins Caspofungin acetate

Imidazole Ketoconazole
5 membered Clotrimazole.
ring with 2 Miconazole
nitrogen’s
Pyrimidines Flucytosine
Triazoles Fluconazole (oral) The alternate to treat Onychomycosis
5 membered Itraconazole (oral). The alternate to treat Onychomycosis
rings with 3
nitrogens
39-1
Allylamines Naftifine hydrochloride

Terbinafine hydrochloride.
Antifungal Nystatin. Candida, oral thrush, vaginitis
Antibiotics
Imidazole’s Clotrimazoles. Drug of choice Athletes foot and vaginal
candidiasis and complicated diaper rash.
Topical Antifungals
Econazole nitrate
Ketoconazole
Miconazole nitrate
Oxiconazole nitrate
Tioconazole
Other topical Chlorphenesin
antifungals Ciclopirox olamine; topical prep for onychomycosis
Clioquinol
Selenium sulfide
Tolnaftate powder, spray. Athletes foot
Undecylenic acid
Amphotericin B
• Fungistic, fungicidal.
Therapeutic use • Widest of any agent, systemic fungal infections; candidiasis;
cryptococcos; blastomycosis; histoplasmosis; coccodiodomycosis;
aspergillosis; sporotichosis; mycosis; leishmaniasis.
• Availability. 3% cream/lotion/oral suspension. Not absorbed in the GIT.
Mechanism • Bind to ergosterol from pores resulting in the leakage of cellular
contents.
Side effects • Very toxic: infusion related fever and chills, anorexia, muscle pain, and
headache.
• Non-infusion related nephrotoxic, hypokalemia, hypomagnesaemia,
tachycardia, anemia, thrombocytopenia, arrhythmias, VF, HTN,
tachypnea, leukoencephalopathy, dry skin, skin discoloration, SJS, toxic
epidermal necrolysis, agranulocytosis, jaundice, hemorrhage, sore
throat.
Contraindication • Allergies
Warning • Apply only to patients with progressive, potentially fatal infections and
should not be used to treat non-serious infection
• Monitor lab test sp. Renal function (frequently), liver function, serum
electrolytes particularly magnesium and potassium, blood count, Hgb
conc. Not use for dosage adjustment.
• Does not penetrate CSF therefore administered intrathecally
39-2
Drug interaction • Antineoplastics increase renal toxicity, bronchospasm, hypotension.

• Corticosteroids/ACTH, increase amphotericin B-induced hypokalemia,
renal toxicity.
• Nephrotoxic agents (Cisplatin, pentamidine, aminoglycoside,
cyclosporine) increase renal toxicity.
• Digitalis glycosides Amphotericin B-induced hypokalemia, increase
digitalis toxicity
• Skeletal muscle relaxantsenhance cureiform
• Others: AZT, chloramphenicol, antithyroid, colchicine, deferoxamine,
streptozocin, plicamycin, lithium, penicillamine.
• Overdose: cardiorespiratory arrest.
Precaution • Storage of dry powder; 2-8 deg, protect from light

• Give slow IV infusion
Counselling • When applying topical on the skin, protect nails and clothes as it may
stain
Question Alerts!
1) Nystatin is effective to treat? Candida, oral thrush
2) Nystatin is available as oral suspension? Swish & swirl and swallow. Stored at RT.
3) A child swallowed 5 g of nystatin cream? What to do? wait and watch
Nystatin
Category • Polyene antibiotic, structurally similar to Amphotericin B, fungicidal, and
fungistatic.
Therapeutic • Active against Candida sp. Primarily use as a topical agent in vaginal and
use oral candidiasis.
• Not very effective against dermatophytes (Tinea pedis).
Mechanism • Inhibit growth of yeast, binds to sterol in the fungal cell membrane,
increasing permeability and causing leakage of intracellular components.
Side effects • Irritation e.g. mild digestive upset, nausea & vomiting diarrhea,
cream/vaginal tablet itching, burning, and irritation.
Advantage • Can be use by pregnant women.
Precaution • Application of vaginal tablet

Counseling • Nystatin liquid (nystatin is too toxic to be used systemically, but since very
little drug is absorbed following oral administration so it may be
administered by mouth to treat fungal infection of mouth and GI tract).
• Skin ointment or cream.
39-3
• Powder. Dust the powder inside shoes and socks.

• Nystatin vaginal tab and cream.
Question Alerts!
1) Amphotericin is nephrotoxic
2) Administered by iv infusion in treatment of systemic infections of asperigillosis,
blastomycosis, candidiasis.
Fluconazole (Triazole), Ketoconazole (Imidazole),

• Triazole type antifungal • Imidazole type antifungal
• Inhibitors of ergo sterol synthesis by • Inhibitor ergo sterol synthesis
binding to cytochrome. • Not a single dose
• Single doses. • Doesn’t penetrate CNS
• Penetrate CNS (AIDS chemotherapy) • SEs. Hormonal effects such as
• CNS SEs dizziness, headache gynecomastia and menstrual
• No interaction with cimetidine, disturbances.
antacids. • Interaction with cimetidine, antacids
• For systemic infection UTI, peritonitis, • Require acidic conditions for absorption
pneumonia. (avoid antacids concomitantly).
• Potent inhibitor of CYP 2C9 (high) and • Ketoconazole. Potent inhibitor of CYP
CYP 3A4 3A4 (high) and CYP 2C9.
• Fluconazole taken with or without • Ketoconazole taken with food or after
food. food. Taken with cola beverage if
achlorhydric or on acid secrete
suppressor
Ketoconazole
_____________________________________________________________________________
Ketoconazole (Imidazole type)

Therapeutic use • Chronic mucocutaneous candidiasis, systemic and vaginal
candidiasis, Tinea corporis (ringworm), T. cruris (jock itch), T.
pedis (Athlete’s foot), Tinea versicolor (sun fungus),
histoplasmosis, blastomycosis, paracoccidioidomycosis, oral
thrush.
• Relative bioavailability 75 % with meals
• Available as tablet, cream and shampoo
Mechanism • Block the synthesis of ergosterol 14a demethylase in the fungal
CYP 450 complex; hepatic elimination
39-4
Side effects • Hormonal effects. Decreased male libido and potency,

gynecomastia, decreased plasma testosterone levels, affects
female menstrual problems, cardio effects hypertension, fluid
retention.
• GI upset, hepatotoxicity, dizziness, anorexia, Nausea & vomiting
Contraindication • Hypersensitivity, and teratogenicity.
WARNING • Rebound effect. Apply mild topical corticosteroids in the
morning and ketoconazole at night and gradually decrease
steroid over a period of 2 to 3 weeks. Cross sensitivity.
Precaution • Allergies with imidazole’s antifungals clotrimazole and
miconazole.
Counselling • Shampoo, 1% or 2%, Cream
Question Alerts!
Ketoconazole shampoo is used for the treatment of? Dandruff
Fluconazole
Mechanism • Block the synthesis of Ergosterol By Inhibit 14A-Demethylase In the
fungal CYP450 Complex
Therapeutic • Mucocutaneous Candidiasis (Esophageal). Alternative for
use Amphotericin B for treatment Of systemic candidiasis, Cryptococcal
Meningitis, Coccidioidomycosis, Cryptococcosis, HIV Associated
Infections
• Relative Bioavailability 85- 92% with meals
Side effects • Skin Rash
• GI Effects. Nausea, Vomiting Diarrhea or commonly Causing GI
Disturbances.
• Liver Effect. Increase liver enzymes, yellowing of the skin, and eyes,
Flu-Like Symptoms.
• CNS. Dizziness, headache, exfoliative Skin Reactions, Altered Taste
Buds, Extreme Tiredness, and seizures.
Drug • Decrease Levels With carbamazepine, H2 Blockers, INH, Phenytoin.
interaction • Increase levels of drugs that substrate of CYP2C9. phenytoin,
warfarin (greatly prolongs PT), and sulfonylureas.
• Less affect CYP3A4 substrates. Anticancer Drugs, Amiodarone,
Benzodiazepine, Cyclosporine, Disopyramide, OCP, Diuretics,
Moxifloxacin, Sotalol, Terfenadine, Quinidine, Valproic Acid,
Thioridazine And Tacrolimus.
Precaution • Decrease elimination of enzyme inducers like Rifampin, allergies to
Fluconazole and other antifungals, irregular heartbeat, Kidney or
Heart disease
39-5
Question Alerts!
1) Itraconazole oral tablet for treatment of onychomycosis.
2) Itraconazole Topical cream and spray for skin infections.
Itraconazole
Therapeutic use • More active treatment against Aspergillus spp., blastomycosis
other mycosis like mucor, fusarium pseudoallescherria boydii;
HIV associated infections; invasive and non-invasive pulmonary
aspergillosis; oral and esophageal candidiasis; chronic
histoplasmosis (acute immunocompromised, an alternative to
amphotericin); cutaneous and lymphatic sporotrichosis,
paracoccioidomycosis and chromomycosis.
• Dose Aspergillosis: 200 mg IV Q8H X 72 H then 200 mg IV Q12H
• Blastomycosis; 200 mg po BID
• Histoplasmosis: 200 to 400 mg QD po
• Take with meals for adequate absorption
Mechanism • Block the synthesis of ergosterol 14a demethylase in the fungal
CYP450 complex
Side effects • Nausea, epigastric pain rash, headache, edema, hypokalemia,
loss of appetite, shaking, dyspnea, bleeding gums, yellowing of
eyes and skin; hypertriglyceridemia, decrease libido
Contraindication • CHF, left ventricular dysfunction
Warning • Cause CHF; heart attack; irregular heart beat; lung/ kidney/liver
disease or other serious problems; SOB, coughing up white
phlegm; weakness; excessive tiredness, fast heart beat, swelling
of the feet, ankle or leg; sudden weight gain.
Drug interaction • Cisapride, pimozide, dofetilide, ergot meds, triazolam,

midazolam, quinidine, all may cause irregular heart beat.
• Take antacid one hour before or two hours after itraconazole
• Increased by Itraconazole. antiarrhythmics, anticonvulsants-
CBZ, antimycobacterial-rifabutin, antineoplastics,
antipsychotics, Benzodiazepine, Ca-channel blockers,
gastrointestinal motility agents, HMG-CoA reductase inhibitors
(ALS) Increase risk of developing rhabdomyolysis.
Immunosuppressants, oral hypoglycemic, protease inhibitors,
buspirone, and macrolides.
39-6
• Decrease by Itraconazole anticonvulsant, antimycobacterial,

gastric acid suppressants, and NNRTI.
Counselling • Oral solution. Swish 10 ml (2 tsp) in the mouth for a few
seconds and swallow. Repeat is necessary until entire dose is
taken. The solution is usually taken on an empty stomach once
daily or BID for 1-4 weeks.
• Tell doctor if taking itraconazole. Do not substitute the capsules
for the liquid because they have different use.
Question Alerts!
1)Drug of choice to treat Athletes foot? Clotrimazole twice daily
2) Athletes foot is caused by?
3) How do you apply tolnaftate powder for athletes foot?
A) Dry foot, spray powder on skin between toe and fingers
B) Dry foot, spray powder on cotton socks before wearing
C) Dry foot, spray powder in shoes before wearing
D) All of the above
Clotrimazole
Therapeutic use • The drug of choice for yeast infection (Vulvovaginal Candidiasis),
skin infections Athletes foot. The complicated diaper rash. High
concentration needed in bacterial infection.
• Availability. Topical cream 1%, and Vaginal cream (6d,1%, 3d,2%
and 1d, 10%) or vaginal tab 100 mg, 200 mg and 500 mg. lotion
or solution dermatophytes (skin infections), intravaginal
suppositories for vaginal candidiasis, lozenge for oral.
Mechanism • Block the synthesis of ergosterol 14α demethylase in the fungal
CYP 450 complex.
Side effects • Topical. blisters, edema, pruritus, burning, stinging, peeling skin
tissue, increase urinary frequency. Abdominal pain, and
irritation.
• Abnormal liver function test in patient taking lozenge
Contraindication • Not for first trimester of pregnancy.
Management • In case of vaginal infection, refrain from sexual intercourse cause
an ingredient in the cream may weaken certain latex condoms /
diaphragms. If first time of vaginal itching and discomfort, see a
doctor. Do not use products within 72 hours of this med. Wear
39-7
cotton underwear and loose-fitting pants; no lozenge for

children under 3y/o.
Precaution • Pregnancy
Miconazole
Category • Broad spectrum fungistatic
Mechanism • Block synthesis of ergosterol by inhibiting 14a-demethylase in
the fungal cytochrome P450 complex; selective inhibition of RNA
& DNA and mucopolysaccharide precursor.
Therapeutic use • Covers both dermatophytes and candidiasis (Advantage Over
Tolnaftate and Nystatin. Also, effective against Tinea infections
by T. pedis, T. cruris, T. corporis, T. versicolor
Side effects • Itching, skin rash, Nausea &vomiting, burning on the site of
application.
Contraindication • Sensitivity to any of the components of miconazole, not for
children < 2y/o unless directed by a doctor, do not use for the
infection of the nail.
Drug interaction • Anticoagulants, phenytoin, terbinafine, atypical anti-psychotics,
• Ciclosporins and some statins.
Availability • Topical 2%, aerosol powder, 2 % cream, a kit-2% powder 2y/o
and 2% tincture, 2% vaginal cream and 100 and 200 mg vaginal
suppositories.
Application • Aerosol powder
• Cream Apply sparingly, smoothen well and avoid maceration.
Massage area gently. Athlete’s foot. dry feet, and wear cotton
socks.
Tolnaftate
Category • Fungistic, fungicidal
Mechanism • Damage hyphae and stunt mycelial growth in susceptible fungi
Therapeutic use • Jock itch, athlete's foot, ringworm T. pedis, M. canis, Aspergillus
niger, C. albicans, M. gypseum, M. audounii, M. japonicum, T.
rubrum, T. mentagrophytes, T. schonleinii, A. fumigatus
Side effects • Slight irritation, sting (aerosol solution), burning and itching of
athlete's foot and jock itch should decrease with in 2-3 days
Administration • Do not apply dressings, or mix cosmetics or other skin
medications with tolnaftate treatment.
• Powder. Clean and dry affected area. Sprinkle it between toes
and in socks and shoes treated lightly.
39-8
• Spray should be shaken well before use. Apply it from a

distance of at least six inches away. Continue treatment until
symptoms disappear. A total of 4 to 6 weeks necessary. Do not
inhale powder, bring close to a hot object or flame
• Cream. Thoroughly clean the infected area. Allow it to dry and
then rub gently the medication until most of it disappears. Use
sufficient quantity to cover the affected area. Wash hands after
application.
• Solution: If it solidifies, dissolve by warming the closed
container in warm water then follow dosage as directed.
Tips
• Nystatin is indicated ? oral thrush, and vaginal candidiasis
• Ketoconazole require acidic conditions for higher bioavailability therefore? avoid
antacids and/or taken with carbonated beverages
• Meningitis fungal infections other CNS infections can be treated by? Amphotericin
• If a child swallowed 5 g of nystatin, and parents are panic, comes to your pharmacy,
what is appropriate action? watch and wait
• Nystatin is ineffective for ? skin infections
• The drug of choice to treat oral thrush? nystatin, miconazole
• The drug of choice to treat vaginal candidiasis? clotrimazole or miconazole,
nystatin’s
• Topical drug of choice to treat Athletes foot? clotrimazole
• Nystatin suspension counseling? swish, swirl and swallow
• Amphotericin B act by inhibiting the cell membrane function
39-9
39-10
www.PharmacyPrep.Com Anti-Mycobacterial Drugs
40
Anti-Mycobacterial Drugs
Rifampin Rifadin, generics Isoniazid Isoniazid, INH,
Streptomycin generics Rifabutin Mycobutin
Pyrazinamide generics Ethambutol Myambutol
There are two common infections associated

Question Alert!
with mycobacteria. These are Mycobacterium
1) Screening and treatment of inactive
tuberculosis and Mycobacterium leprae. tuberculosis?
2) Where does skin tuberculin test (Montex) is
Mycobacteriam tuberculosis can cause done? Forearm
Inactive tuberculosis (latent) skin test +ve 3) Acid fast bacteria? M. tuberculosis
(forearm) and chest x-ray +ve. 4) Tuberculin test is ? Type IV hypersensitive
The drug of choice for prophylaxis is reaction
isoniazid (INH).
Active tuberculosis: Skin test +ve & chest x-ray +ve, sputum test and symptoms weight loss,
cough, and fever.
The drug of choice for treatment INH + rifampin/rifabutin+ ethambutol or
fluoroquinolone/streptomycin.
Tuberculosis treatment
· Goal of treatment is must eradicate mycobacterium.
· Important issues in tuberculosis treatment are resistance to drugs.
· Drug of choice for the prophylaxis of tuberculosis --> isoniazid
· Drugs that have lowest resistance is --> Isoniazid, rifampin, streptomycin and combination
of these drugs with pyrazinamide, or ethambutol.
Antimycobacterial drugs: Isoniazid, Rifampin, Streptomycin, Pyrazinamide, and Ethambutol,

Capreomycin, and Rifabutin.
40-1
PharmacyPrep.
Rifampin or rifampicin
Mechanism Chemical structure of rifampin is a macrocyclin. This drug is bactericidal

and inhibits RNA synthesis
Therapeutic 1st line in active tuberculosis disease. Effective against M. tuberculosis,

use and M. leprae. Can be used in pregnancy.
Prophylactic for household members of exposed to meningitis caused by
meningococcal or H. influenza type b.
Side Effects Serious liver toxicity (hepatotoxicity) thereby LFT should be performed
regularly.
GI: Nausea, vomiting, and abdominal pain.
CNS. Headache, drowsiness, confusion, fatigue
Rifampin discolors urine, sweat, tears, saliva and feces to orange red.
Body fluids (contact lens staining).
Drug Rifampin is inducer of CYP 1A2, 2D6, 2C9, 2C19, 3A4. DO NOT COMBINE
interactions WITH PROTEASE INH. (Ritonavir, Sequinavir). It decreases >75% of
protease inh. affect and increase hepatotoxicity. Reduce efficacy oral
contraceptive.
Rifabutin: Strong inducer of CYP3A4 and CYP2C family. As result when combined with CYP3A4
and CYP2C substrate will show reduce activity.
Rifampin (rifampicin) and rifabutin are analogs.

Inducers CYP3A4 Substrates CYP3A4 Inhibitors CYP3A4
Rifampin/Rifabutin Ritonavir/Saquinavir Itraconazole
Phenobarbital Statins (ALS) Erythromycin,
clarithromycin
Carbamazepine
Phenytoin
ISONIAZID (INH)
Targets enzyme responsible for mycolic acid synthesis

Therapeutic use First line treatment for tuberculosis
Side Effects Most common: Peripheral neuritis or neuropathy (because of pyridoxine
deficiency) vitamin B 6 supplements. Skin rash, jaundice and fever are
common SEs. Supplementing breast fed mothers can provide pyridoxine 25
mg/day deficiency in children.
Most common. Hepatitis (hepatotoxicity symptoms fatigue, flu like,
anorexia and nausea & vomiting. may occurs within weeks to months) is
most severe-fatal, the risk of hepatitis increases with patient age and
40-2
PharmacyPrep.
alcohol abuse. Monitor LFT.

Hepatotoxicity is age related, more prevalent in elderly. Blood dyscariasis
(agranulocytosis, aplastic anemia, hemolytic anemia and
thrombocytopenia) thereby monitor CBC routinely.
CNS toxicity due to decrease in pyridoxine (vitamin B 6 ) levels. Administer
15 to 50 mg/day pyridoxine to minimize the peripheral neuropathy.
Symptoms of CNS or neurotoxicity are insomnia, restlessness,
hyperreflexia, psychosis and convulsions.
Pyrazinamide It is pyrazine analog of nicotinamide

(ZIN)
Mechanism Pyrazinamide enzyme converts into pyrazinoic acid (active form)
Therapeutic Use Combination with INH and rifampin. Pyrazinamide has activity only
against M . tuberculosis
Side effects Liver dysfunction, Urate retention. And may precipitate gouty attacks
Tips
· Drug of choice to treat tuberculosis --> INH, rifampin, pyrazinamide or/and ethambutol
· Peripheral neuritis caused by isoniazid can managed by administering? vitamin B6
· All antitubercular drug should be taken on empty stomach
· What infections gives granulomas? tuberculosis
· Montaoux test for tuberculin indicates? tuberculosis screening
· Tuberculin test is type of hypersensitive reaction? type 4
· Drugs that discolor urine, tears, saliva, feces, sweat --> rifampin and pyrantel pamoate
· Question Alerts!
· Rifampin is used as prophylaxis of meningitis.
· Drugs that causes red color urine? Rifampin, pyrantel pamoate, phenazopyridine, and
entacapone.
· Drugs that decrease vitamin B 6 and therefore require vitamin B 6 supplements? INH and
penicillamine.
· Vitamin B 6 deficiency decreases GABA levels (closes Cl- channel) and leads to convulsions.?
· all tuberculosis drugs taken empty stomach.
· Peripheral neuritis can be managed by administering 15 to 50 mg/day pyridoxine
· All antitubercular drugs should be taken empty stomach.
· What infections give granulomas? Mycobacterium tuberculosis
· Monteux test for tuberculin indicates? Mycobacterium tuberculosis infection
· Tuberculin test is type of hypersensitive reaction? Type IV
40-3
PharmacyPrep.
40-4
PharmacyPrep.
PharmacyPREP.COM Antiviral Drugs
41
Antiviral Drugs
Question Alerts!
1) Examples of herpes virus? HSV1, HSV2, VZV, and EBV
2) Cold sore and keratoconjunctivitis is caused by? HSV1
3) Antiviral drugs for HIV such as NRTIs, NNRTIs, NtRTIs, and protease inhibitors side
effects? Pancreatitis, neuralgia, and cardio toxicities.
4) Hepatitis A is acute and transmitted food & H2O
4) Hepatitis B&C are chronic and transmitted by sexual contact, blood transfusion etc.
5) Seasonal flu is caused by Influenza A & B
Common Viruses
DNA viruses: Herpes virus. HSV 1 , HSV 2 , VZV, EBV
· RNA virus: Hepatitis A, B, C, D, E viruses
· Influenza virus A, B (seasonal flu)
· RNA virus: HIV-AIDS
· Measles, Mumps viruses
· Others. Rabies, Rubella (German measles), Variola, Coxsackie virus.
Some Antiviral
· Acyclovir. Cover HSV 1 and 2, VZV. Well tolerated.
· Interferon; HBV, HCV. May cause fever like symptoms.
· Lamivudine; HBV, HIV
· Oseltamivir; Influenza A+B. May cause diarrhea
· NRTI, NNRTIs, NtRTI and Protease inhibitors are used to treat HIV
· Zidovudine (AZT); HIV. May cause rash
· Combivir; HIV. May cause N/V and diarrhea.
· Ritonavir; HIV. May cause N/V and diarrhea.
41-1
PharmacyPrep.
Question Alert!
1)Examples of herpes virus?
2) Vericella is a highly contagious disease caused by vericella zoster virus.
3) VZV manifest as chicken pox remains latent in dorsal ganglia. It reactivates as herpes
zoster or shingles. This gives post herpetic neuralgia.
4) Recurrent cold sore are treated by? Abreva (docasanol)
5) Herpes viral infection resistant to acyclovir could be treated with? Parenteral
foscarnet. However acyclo, vala, fami, and gain have cross resistance.
6) Orolabial herpes infection is treated by? oral acyclovir 400 mg 5 x daily x 5d
I) oral acyclovir
II) 2% cream acyclovir
III) acyclovir ointment
Ans; I and II. Ointment is NOT effective.
Examples of anti-viral mechanisms

VIRAL LIFE CYCLE ANTIVIRAL THERAPY EXAMPLES
1. Virus attaches to the cell Gamma-globulin (binds to virus) Hepatitis A and B
2. Virus penetrates the cell Gamma-globulin
3. Virus un-coats its nucleic acid Amantadine Influenza A
4a. Synthesis of key viral enzymes Acyclovir, Ribavirin (DNA Herpes simplex (HSV1,
such as polymerases polymerase inhibitor). HSV2, VZV, Epsteinbar).
(transcription) Valacyclovir The virus enters the
Viral nucleic acid replication Ganciclovir sensory nerve ending in
inhibitors Penciclovir the skin and remains
Famciclovir dormant until
reactivation.
Idoxuridine (ophthalmic drops)
Trifluridine (ophthalmic drops)
4b. Viral nucleic acid is synthesized Zidovudine (reverse HIV
transcriptase inhibitor).
5. Late viral structural proteins Indinavir (protease inhibitor) HIV
are synthesized (post
translational proteins)
6. Viral proteins and particles are
assembled
7. Viruses are released from host
cell
Specific inhibitor of herpes virus DNA polymerase: Acyclovir, valacyclovir, gancyclovir.
41-2
PharmacyPrep.
Acyclovir: Synthetic analog of deoxyguanosine, deoxyacyclovir is a pro-drug form of acyclovir.
Mechanism: Acyclovir is converted by viral thymidine kinase to acyclovir monophosphate,

which is then converted by host cell kinases to acyclovir triphosphate (ACV-TP). ACV-TP, in turn,
competitively inhibits and inactivates HSV-specified DNA preventing further viral DNA synthesis
without affecting the normal cellular processes.
Conversion of active acyclovir monophosphate by phosphorylation reaction. Acyclovir further
converted to di and triphosphate by normal cellular enzyme.
Early use of acyclovir shortens the duration of viral shedding and lesion pain.
Side effects: Potentially serious side effects include renal dysfunction and thrombocytopenia.
The common side effects nausea and diarrhea.
6-Deoxyacyclovir is pro-drug form of acyclovir which is rapidly metabolized to acyclovir by

xanthine oxidase. The 6-Deoxyacyclovir is used in the treatment of varicella zoster infections.
Valacyclovir is an amino acid (valine) ester pro-drug of acyclovir, which exhibit antiviral activity
only after metabolism first in the intestine walls or liver to acyclovir and then convert to
triphosphate. Valacyclovir benefit comes from an increased GI absorption. Oral valacyclovir is
used for acute, localized zoster infections in immunocompetent patient and recurrent genital
infection.
Valacyclovir --> transforms to active drug acyclovir

Famcyclovir --> transforms to active drug penciclovir
ACYCLOVIR VALACYCLOVIR FAMCYCLOVIR
5 TIMES DAILY BID TO TID BID TO TID
Anti-retroviral therapy
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Delavirdine mesylate Do not combine within the same NNRTIs class
Efavirenz CNS toxicity (~ 50%)
Nevirapine
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Abacavir
Didanosine Side effects: Pancreatitis, lactic acidosis, Neuropathy, leukopenia, and pneumonia.
(ddI) Increase amylase
Lamivudine Minimal toxicity/well tolerated. Lamivudine is an analog of didanosine.
(3TC)
Stavudine Caps/Stability of OS. Reconstituted solution is stable up to 30 days when refrigerated.
(d4T) SEs. Pancreatitis, reversible peripheral neuropathy, insomnia, depression, nasal
signs and dyslipidemia,
41-3
PharmacyPrep.
Zalcitabine SEs. Neuropathic pain (35%), oral ulcers/stomatitis, fatigue, hepatic, peripheral
(ddC) neuropathy, skin, blood abnormalities (anemia, leukopenia, eosinophilia,
thrombocytopenia). Zalcitabine cross blood brain barrier.
Zidovudine Capsule/Tablet/ oral solution protected from light
(AZT) SEs. Myocarditis, photophobia, and myopathy.
emtricitabine Well tolerated
Protease Inhibitors: Not recommended to combine with ergot alkaloids, lovastatin, fluticasone,
midazolam, rifampin, salmeterol, simvastatin, sildenafil when used for pulmonary hypertension.
Cannot be used with rifabutin.
Amprenavir
Indinavir SEs. nephrolithiasis, and hyperbilirubinemia.
sulphate Cap. Dispense and store in original container. Do not remove desiccant
Take on an empty stomach or with light meal.
Drink plenty of fluids
Nelfinavir
Ritonavir
Ritonavir/lopi Strong CYP3A4 inhibitors.
navir
Saquinavir Substrate of CYP3A4
Nucleotide Reverse transcriptase inhibitor (NtRTI)
Tenofovir Renal toxicity, monitor renal function and serum phosphate
Combination of antiviral drug therapy is a common approach for treatment of HiV infections.
due to the following benefits.
· Therapeutic antiviral effect
· Decreased toxicity
· Low incidence of drug resistance
· It prolongs the life of AIDS patient
Toxicities Antiviral drugs avoid combination

Pancreatitis Tenofavir, Didanosine, Stavudine (TDS)
Neuralgia Zalcitabine Didanosine Stavudine (ZDS)
Lactic acidosis
Myopathies
Preferred combinations: 2NRTI + 1NNRTI
Lamivudine + Zidovudine + Efavirenz or Nevirapine
Lamivudine + Tenofovir + Efavirenz or Nevirapine
Alternates NRTIs: didanosine, stavudine, abacavir due to severe toxicities.
Pre-exposure (PrEP): Among HIV-uninfected people at high risk of acquiring HIV

infection, continuous daily use of emtricitabine/tenofovir DF, starting before HIV
exposure and continuing after, has been shown to reduce the risk of acquiring HIV via
sexual transmission in combination with safer sex practices.
41-4
PharmacyPrep.
TIPS
· Abacavir (ABC), didanosine (ddl), emtricitabine (FTC), lamivudine (3TC), stavudine (d4T), and
zidovudine (AZT), are examples of what antiviral classification? (NRTI)
· Drugs that causes pancreatitis? Tenofavir, D, S
· Drugs that causes neuropathic pain? ZDS
· Drugs that causes lactic acidosis? Didanosine
· Drugs that cause myocarditis? Zidovudine
· Drug that cause stomatitis (oral ulcers)? Zalcitabine
· Tenofavir is an example of? NtRTIs
· Nephrolithiasis is caused by? Indinavir
· Myalgia, photophobia, myopathy is caused by? Zidovudine
· Drugs that cause neuropathy and pancreatitis? D and S
· Examples NtRTI (nucleotide Reverse Transcriptase Inhibitor. (Tenofovir (TDF))
· Efavirenz (EFV), Nevirapine (NVP), delavirdine (DLV) and etravirine (TMC-125) are examples
of what drug classification? (NNRTIs)
· Drugs of choice to treat keratoconjunctivitis (trifluridine)
· For influenza A only. (amantadine)
· Neuroaminidase inhibitors for influenza A and B. (oseltamivir and zanamivir)
· Indicated for influenza A and B. (oseltamivir)
· Herpes simplex virus causes infections of à Genital herpes, keratoconjunctivitis, cold sores
· Who should get flu vaccination à Patients with respiratory, cardio, DM, HIV, elderly over
65, health care workers, and professionals, patient living in long term care facilities, long
term care workers.
· Who is vector (carrier) of flu àHealth care workers.
· CD 4 count 100 patients require prophylaxis for à Penumocystis carinii Pneumonia
· Flu season in Canada à October to April
· Tenofovir a nucleotide reverse transcriptase inhibitor (NtRIs) gives --> renal toxicity,
monitor RFT
· Influenza A and B virus causes à flu
· TDS = Tinofovir, didanosine and stavudine; Do NOT combine because they cause
pancreatitis
· ZDS = Zalcitabine, didanosine and stavudine; Do NOT combine because they cause
neuropathic pain
41-5
PharmacyPrep.
41-6
PharmacyPrep.
www.PharmacyPrep.Com Anti-Malarial Drugs
42
Anti-Malarial Drugs
Primaquine Radical cure Chloroquine Aralem
Doxycycline Adoxa Pyrimethamine Daraprim
Mefloquine Lariam Atovaquone-proguanil Malarone
Malaria is infection of red blood cells with the single-celled parasite Plasmodium, which causes
fever, an enlarged spleen, and anemia.
Four species of malaria parasites, Plasmodium falciparum, Plasmodium vivax, Plasmodium

ovale, and Plasmodium malaria can infect people. Infected by malaria infected female
Anopheles mosquito.
Falciparum malaria, caused by Plasmodium falciparum, is the most dangerous form of malaria
and can be fatal.
Chloroquine is the drug of choice for treatment in a person who has malaria caused by
Plasmodium vivax, Plasmodium ovale, or Plasmodium malaria except in a very few areas where
resistance to chloroquine in people with Plasmodium vivax has been reported.
Primaquine is added to kill persistent parasites in the liver of a person infected with
Plasmodium vivax or Plasmodium ovale.
Before primaquine is given, a blood test is Question Alerts!
done to look for a relatively common enzyme 1) Malaria prevention in travelers?
deficiency (G6PD deficiency). People with A mosquito repellant DEET
G6PD deficiency who are given primaquine
may have a breakdown of their red blood cells.
Malaria Prevention: N, N-Diethyl-m-toluamide (DEET), 5%, 10%, 15% and 30% should be applied
on the skin before outdoor activities during the main hours of malarial transmission.
10% DEET for 8 yo. repels for 3 hr. 15-30% for adults. repels for 6 hr
· Citronella is usually effective for less than 1 hr.
· Avoid eye and mucus membrane.
PharmacyPrep.
42-1
Recommended:
Avoid in 1 yo (not used <6 mo), take mosquito nets.
Maximum TID
Apply sparingly exposed skin or/and cloth
Refer to travel clinic.
Treatment of malaria
Prophylaxis
P. falciparum Chloroquine
P. malaria Chloroquine
P. vivax Chloroquine + primaquine
P. ovale Chloroquine + primaquine
Chloroquine resistant Mefloquine, Primaquine, Quinine + doxycycline, atovaquone-
prophylaxis proguanil.
Treatment Quinine or mefloquine or pyrimethamine-sulfadoxine
Side effects of antimalarial drugs

Mefloquine Retinopathy, Nausea, dizziness, and trouble sleeping, may rarely produce
seizures, nightmares. psychiatric problems. Should also be avoided in people
with certain heart conditions. Contraindicated in seizures, active depression,
anxiety.
Prophylaxis: once a week, four weeks before travel and 2 weeks after travel and
the during trip.
Quinine Headache, nausea, vomiting, visual disturbances, and ringing in the ears a
condition known as cinchonism, and retinopathy.
Atovaquone- Nausea, vomiting, or abdominal pain and is not used in people with poor kidney
proguanil function, pregnant women, or infants.
Prevention: pyrimethamine-sulfadoxine or atovaquone-proguanil

G6PD Glucose-6-phosphate dehydrogenase
DEET N, N-Diethyl-m-toluamide
Tips Question Alerts!

Drugs that cause retinopathy?
Hydroxychloroquine
· The drugs used at Chloroquine malarial resistant area
Amiodarone
prophylaxis à mefloquine
Ethambutol
· Chloroquine resistant area treatmentà mefloquine
PharmacyPrep.
42-2
· Plasmodium vivax and ovale infections, treatment must include àprimaquine

· Cinchonism (ringing in ear, vertigo) is caused by? chloroquine
· Chloroquine side effect include retinopathy
Find answers from the table.
1 Quinine 2 Primaquine
3 Chloroquine 4 Quinidine
5 Mefloquine 6 Quinine
· Quinine + doxycycline or mefloquine is the prophylaxis in area resistant to what drug? (3)
· Treatment for Chloroquine resistant area. (5)
· Treatment Plasmodium vivax and ovale infections. (2)
· Quinine alkaloids that cause cinchonism. (3)
· Side effect of this drug includes retinopathy. (3)
· Mefloquine prophylaxis, weekly one dose, started 4 wks before travel and during trip and 2
wks after trip. (True/False)
PharmacyPrep.
42-3
PharmacyPrep.
42-4
www.PharmacyPrep.Com AnthelminthicDrugs
43
AnthelminthicDrugs
Helminthic Diseases and medication
Species Common infections Mode of transmission Treatment
Intestinal nematodes
Ascaris lumbricoides Round worm Ingestion Pyrantel pamoate,
mebendazole
Necator americanus Hook worm Percutaneous Pyrantel pamoate,
mebendazole
Trichuris trichuria Whipworm Ingestion Mebendazole
Enterobius Pinworm Ingestion/inhalation Pyrantel pamoate
vermiculars (oral suspension or
chewable tab, a single
dose is used)
Mebendazole
Strongyloides Threadworm Ingestion Thianendazole
Tissue nematodes
Wuchereria bancrofti Filariasis Percutaneous Diethylcarbamzine
Onchocerca volvulus River Percutaneous Livermectin
blindness/onchoceriasis
Trichinella spiralis Trichinosis Ingestion Thiabendazole
Cestodes (tapeworms)
Taenia solium Pork Ingestion Niclosamide
Taenia saginata beef ingestion Niclosamide
Diphyllobothrium Fish ingestion Niclosamide
latum
Hymenolepis nana Dwarf Praziquantel, niclosamide
Trematodes (flukes)
Schistosoma mansoni Blood Percutaneous Praziquantel
Schistosoma bilharziasis Praziquantel
haematobium
Clonorchis sinesis Liver ingestion Praziquantel
Fasciolopsis Intestinal Ingestion Praziquantel
Pragonimus Lung Ingestion Praziquantel
43-1
www.PharmacyPrep.Com AnthelminthicDrugs
Pinworm infestation can have prevented by non-medical recommendation in patients

with pinworm infection include. Bathing every morning, regular cleaning of
undergarments, bedding etc. Handwash, during the following week of treatment all
family members should wear cotton underpants. Frequent washing of toilet seats.
All close contact has to be treated.
Mebendazole
· Mechanism. Inhibits microtubule synthesis and glucose uptake in nematodes.
· Clinical Use. Pinworm and whipworm infections.
· Contraindicated in pregnancy.
Pyrantel pamoate
· Mechanism. Depolarizing neuromuscular blocker, which causes paralysis of
nematodes.
· Clinical use. Hookworm infections, pinworm infections, Roundworm.
· Caution. Red color urine, feces, stains on vomiting.
· Not used in pregnancy.
Praziquantel
· Mechanism. Increase membrane permeability to Ca2+ using muscular contraction
and paralysis of the nematode muscles.
· Clinical Use. Drug of choice for Schistosomiasis, clonorchiasis, and pranomiasis.
Niclosamide:
· Clinical Use: Infections from ingestion of beef, pork, and fish.
Tips
1 Mebanedazole 2 Pyrantel pamoate 3 Praziquantel

4 Niclosamide
· Which antihelmenthic drug can cause red color body fluids, such as urine, saliva etc?
Pyrantel pamoate (2)
· Inhibits microtubule synthesis and glucose uptake in nematodes ( 1 )
· use for infections from ingestion of beef, pork, and fish (4)
· depolarizing neuromuscular blocker, which causes paralysis of nematodes (2)
· it causes red color urine, feces, stains on vomiting ( 2 ).
· increase membrane permeability to Ca2+ using muscular contraction and paralysis of
nematode muscles (3).
· The drug of choice for schistosomiasis, clonorchiasis, and pranomiasis ( 3 ).
· The drug of choice for pinworm? 2
43-2

Clinical Pharmacology Book 2018

Uploaded by

Copyright:

Available Formats

Clinical Pharmacology Book 2018

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Clinical Pharmacology Book 2018

Uploaded by

Copyright:

Available Formats

What are the main divisions of the autonomic nervous system and their characteristics?

What are the main divisions of the autonomic nervous system and their characteristics?

What are some common helminthic diseases and their treatments discussed in the document?

What are some common helminthic diseases and their treatments discussed in the document?

Pharmacyprep.

com Clinical Pharmacology & Pharmacy Practice

Clinical Pharmacology &

Module 2. Cardiovascular Drugs

Module 3. Central Nervous System Drugs

Module 4. Anti-inflammatory Drugs and Autacoids

Module 5. Endocrine Pharmacology

Module 6. Drugs to Treat Musculoskeletal Disorders

Module 7: Drugs to Treat other Diseases

Module 8: Antimicrobial Pharmacology

Central Nervous System (CNS) Peripheral Nervous System (PNS)

Sensory Somatic Nervous System

Types of Neurons in ANS

ANS is responsible for regulation of

Parasympathetic Sympathetic (adrenergic)

Acetycholine Acetycholine Acetycholine (no ganglia)

Nicotinic Nicotinic Nicotinic

Neuroeffector Epinephrine (released

Effector Organ Sympathetic Parasympathetic

Abbreviation and Terminology

Adrenergic agonist Adrenergic antagonist

Alpha agonist Beta agonist Mixed agonist

Alpha antagonist Beta antagonist

a1 antagonist a2, antagonist a1,b2, mixed antagonist

Non-selective Cardioselective Partial alpha & Partial agonist &

Adrenergic receptors (Sympathetic receptors ᾳ 1, ᾳ 2, beta 1 and beta2 )

ADRENERGIC AGONIST. Increase heart rate, vascular constriction, branchodilatation

Mixed alpha and Dopamine, epinephrine, - HR, - CO

Hypertrophy (BPH or enlarged symptoms in recovering drug and alcohol

Contraindic Orthostatic hypotension Orthostatic hypotension and liver disease

Pharmacological · LOCALLY Constrict dilated arterioles in the nasal mucosa ¯ BLOOD

a2 agonist, centrally acting antihypertensive

a2 agonists · Methyldopa, Clonidine, Brimonidine

b agonists non Dobutamine (b 1>b 2 ) and isoproterenol (b 1 = b 2)

· vasodilation due to slightly decrease peripheral resistance

Short acting beta 2 agonist Long acting beta 2 agonist

Mixed a and b agonist

Mixed a and b · Dopamine, Epinephrine, Norepinephrine

Major affects · Vasoconstriction

· Vasoconstriction à causes peripheral resistance

Action a1, a2 at higher doses at lower doses b 1 and b 2

Hyperglycemia · Has significant hyperglycemic effect (↑glycogenolysis)

Mechanism: Act on D 1 , D 2 , D 3 , D 4 , D 5 , and mixed a1 and a2 , b 1 , b 2 agonist. Activate alpha and

alpha antagonist Beta antagonist

Non-selective Cardioselective Partial alpha & Partial agonist &

Yohimbine Yocon and odan

Phentolamine · Competitive, short acting agent

Therapeutic use · Used occasionally in patients to ↓BP (antihypertensive).

Nonselective CardioSelective Beta & Alpha Partial agonist

Nonselective (b 1 & Cardioselective b 1 , b 2 & a1 blockers Partial agonist &

Mixed beta1 & beta2

· Timolol. reduce intraocular pressure: decrease secretion of aqueous humor

Beta 1 blockers (Cardioselective)

· Produce vasodilation-decrease in blood pressure.

Beta-blockers therapeutic uses:

Beta blockers therapeutic Mechanism