Pcol Part 2

Continuing on…
vCardiovascular-Renal-Hematologic
Drugs
Centrally-Acting Sympathoplegics
ü Agents that reduce sympathetic outflow
1. Methyldopa
- Analog of L-DOPA
- Converted to alpha-methyldopamine and alpha-
methylnorepinephrine (false transmitter)
- MAJOR MOA: central alpha 2 receptor stimulation
- What is the nature of this receptor??? Correlate to effect!
↓ CATECHOLAMINE RELEASE
↓ SYMPATHETIC RESPONSE
↓ BLOOD PRESSURE
Methyldopa
- Used for HTN during pregnancy
- reduces PVR and CO
SE: sedation on onset

Long term: mental depression,
vertigo, lactation associated with
increased prolactin secretion, false
positive Coombs test (PACOP/BEQ)
• An abnormal (positive) direct Coombs test means you have antibodies that
act against your red blood cells. This may be due to:
• Autoimmune hemolytic anemia

• Chronic lymphocytic leukemia or similar disorder
• Blood disease in newborns called erythroblastosis fetalis (also called
hemolytic disease of the newborn)
• Infectious mononucleosis
• Mycoplasma infection
• Syphilis
• Systemic lupus erythematosus
• Transfusion reaction, such as one due to improperly matched units of
blood
With prolonged methyldopa therapy, 10 to 20 percent of patients develop a positive direct Coombs test
which usually occurs between 6 and 12 months of methyldopa therapy.
• RECAP: Drugs that may cause hemolytic anemia
Cefotetan & Ceftriaxone (cephalosporins)
Piperacillin (penicillins)
Methyldopa (alpha 2 agonist)
Quinidine (Class Ia antiarrhythmic)
Dapsone (for Leprosy/Hansen’s Disease)
Nitrofurantoin (for UTI)
Fludarabine (antimetabolite for leukemia)
• The direct Coombs test is used to detect antibodies that are stuck
to the surface of red blood cells. These antibodies sometimes
destroy red blood cells and cause anemia. Your health care
provider may recommend this test if you have signs or symptoms
of anemia or jaundice (yellowing of the skin or eyes).
2. Clonidine
- Reduces CO and PVR
- causes brief rise in BP followed by prolonged hypotension
(partial alpha agonist)
- reduces sympathetic tone = low BP and bradycardia
- decrease in catecholamines
Clonidine
Toxicity: dry mouth and sedation

Sudden withdrawal: hypertensive crisis
(nervousness, tachycardia, HA, sweating)
How to avoid, Future Pharmacist???
CI : Patients with mental depression
3. Guanfacine and Guanabenz

- Central alpha adrenoceptor stimulation
- Same with clonidine; No advantage; rarely used
NE release inhibitors (New agents) à bethanidine &
debrisoquin
VMAT inhibitor: Reserpine

SE: depression, sedation, parkinsonism symptoms, GI upset
AOTA Result à depletion of catecholamines

Adrenoceptor Blocking Agents
ü alpha and beta blockers
ü ALPHA 1 BLOCKERS
- Prazosin, Doxazosin, Terazosin,
Alfuzosin, Tamsulosin
- Vasodilation
- Less reflex tachycardia than
phentolamine/phenoxybenzamine
- more effective when combined
with BB and diuretic
- Indications: HTN & BPH
ü alpha and beta blockers
ü BETA-BLOCKERS
- MOA: inhibition of stimulation of renin production by
catecholamines and decrease in HR via beta 1 blockade
- Nonselective Beta blockers
SE: bradycardia, bronchoconstriction
- Discontinuation after prolonged use à withdrawal
syndrome (nervousness, tachycardia, angina, MI)
BETA-BLOCKERS Partial agonists/Intrinsic
sympathomimetics
Beta 1-selective:
Betaxolol, Bisoprolol Pindolol, Penbutolol
Esmolol
Bopindolol, Celiprolol
Atenolol, Acebutolol
Metoprolol Carteolol, Acebutolol,
Oxprenolol (sing J )
Nebivolol
Celiprolol
Local anesthetic effect Alpha 1 and Beta Blocker
Betaxolol Carvedilol
Acebutolol Labetalol
Labetalol ADV: with vasodilating properties that help
relax blood vessels and lower blood pressure
Metoprolol
Pindolol
Propranolol
BETA-BLOCKERS
Clinical indications:
HTN, angina, arrhythmias,
hyperthyroidism, glaucoma
BB for glaucoma as topical drops:

Timolol, betaxolol, carteolol,
levobunolol, metipranolol
Ideal BB for pts. Who have experienced
MI:
Propranolol, Metoprolol, Timolol (PMT)
Arrhythmias: Sotalol & Esmolol
HF: Metoprolol, Bisoprolol, Carvedilol

(MBC)
Thyroid storm;
Tremors;
Performance
anxiety:
Propranolol
Migraine HA: metoprolol,
atenolol, timolol, nadolol
“TiMe AwtNa”
blood pressure have it under control. Hypertension is a major cause of premature death worldwide. Blood pressure is written
as two numbers. The first number refers to the systolic blood pressure in blood vessels when the heart beats or contracts
while the second number refers to the diastolic blood pressure which represents the pressure in blood vessels when the
Vasodilators
heart rests or relaxes between beats. Hypertension is diagnosed when it is measured on two different days wherein the
systolic blood pressure reading on both days is greater than or equal to 140 mm Hg AND/OR the diastolic blood pressure
reading on both days is greater than or equal to 90 mm Hg. Note: mm Hg ).
Classification of hypertension on the basis of blood pressure:

ü Oral: Hydralazine, Minoxidil
- For HTN
Category Systolic/Diastolic Pressure (mm Hg)
Normal < 120 / < 80 mm Hg
ü Parenteral:
Prehypertension Nitroprusside,
120-139 / 80-89 Diazoxide, Fenoldopam
- For HTNsive emergencies
Hypertension > 140/90 140/90 mm Hg)
ü CCBs
Stage 1 140-159 / 90-99 mm Hg
Stage 2 > 160/100
- HTN and/or HTNsive emergencies; angina
Hypertensive Crisis:
Hypertensive urgency (Asymptomatic Severely Elevated Blood Pressure) acute and severe rise in BP
without impending end-organ damage (> 160-180 mm Hg/100-120 mm Hg; usually 180/110 mm Hg)
Hypertensive emergency acute and severe rise in BP with impending end-organ damage (> 180 mm Hg/120
mm Hg; usually greater than 200/120 mm Hg)
Uncontrolled elevated blood pressure leads to risks of end-organ damage (especially to the kidneys, heart, and brain).
üNitrates
Risk factors include: a family history of cardiovascular disease, smoking, metabolic syndrome, including obesity,
- Primarily for
dyslipidemia, and angina
diabetes
Vasodilators
General MOA: vasodilation à decrease in PVR à low BP
Vasodilators
v Calcium channel blockers: DHP (-dipines) and Non-DHP (verapamil &
diltiazem)
v D1 agonist: Fenoldopam
RELEASE OF NITRIC OXIDE:

v Hydralazine
v Sodium nitroprusside
v Nitrates
v K+ channels: Diazoxide & Minoxidil (stabilizes membranes = less

contraction)
Toxicity
v Hydralazine
- HA, Nausea, Anorexia, Palpitations, Sweating, Flushing,
Reflex tachycardia
- Slow acetylators: drug-induced SLE (arthralgia, myalgia,
rashes, fever à HIPS = hydralazine, isoniazid,
procainamide, sulfa drugs)
v Minoxidil
- tachycardia, palpitations, angina, edema, HA, sweating,
HYPERTRICHOSIS (“Werewolf syndrome”)
v CCB – hypotension; reflex tachycardia (DHP)

Toxicity
v Sodium nitroprusside
- Accumulation of cyanide, metabolic acidosis, arrhythmias, hypotension
- Antidote for CN toxicity: hydroxocobalamin
v Diazoxide
- hypotension, angina, salt and water retention, inhibits insulin release
v Fenoldopam
- Reflex tachycardia, HA, flushing (CI: glaucoma since it increases IOP)
Drugs acting on RAAS
v ACE = peptidyl peptidase or kininase II
vAll ACE inhibitors are prodrugs except: C & L J
v ACE inhibitors – useful for tx of pts. With CKD since they diminish
proteinuria and stabilize renal function; ideal also for diabetics or
reduce incidence of diabetes for those with high CVD risk; useful
for HF
v Adverse effects: hypotension, hyperkalemia, dry cough (may
include wheezing), angioedema, allergic reactions
v CI: pregnancy à RENAL DYSGENESIS!!
Drugs acting on RAAS
v Angiotensin II Type 1 (AT1) Receptor Blockers
- Losartan, Valsartan, Candesartan, Irbesartan, Telmisartan
- Useful for pts. With HF or CKD
- Adverse effects: hypotension, hyperkalemia, allergic reactions
v CI: pregnancy
Renal tubular dysgenesis is a severe
kidney disorder characterized by
abnormal development of the
kidneys before birth.
In particular, kidney structures called

proximal tubules are absent or
underdeveloped.
Heart Failure
v Diuretics – reduce peripheral & pulmonary edema

a. Furosemide – acute & chronic HF with edematous
conditions
b. HCTZ – mild chronic HF
v Aldosterone Antagonist – salt & water excretion &

reduces cardiac remodeling (reduces mortality)
a. Spironolactone & Eplerenone – chronic heart failure
Pharmacological treatment of cardiac remodeling. ACE: Angiotensin-converting-enzyme; ARBs: Angiotensin receptor
blockers. In the consolidated strategy group, angiotensin-converting enzyme inhibitors, beta blockers, and aldosterone
antagonists have been consistently shown to decrease remodeling in animal models (Azevedo et al., 2016).
Heart Failure
v ACE inhibitors
- vasodilation; reduce aldosterone secretion; reduce cardiac
remodeling (reduces mortality)
- Captopril, Enalapril, etc. for chronic HF/HTN/Diabetic or renal
disease
v ARBs
- vasodilation; reduce aldosterone secretion; reduce cardiac
remodeling (reduces mortality)
- Losartan, Candesartan, etc. for patients intolerant to ACE inhibitors
Heart Failure
vBeta blockers
- For chronic HF
- Carvedilol, Metoprolol, Bisoprolol, Nebivolol
- Slows HR, reduces BP, reduces mortality in moderate and severe HF
v Cardiac glycoside
- Digoxin
- Inhibits sodium-potassium pump and increases cardiac contractility
- For chronic symptomatic HF and atrial fibrillation
Cardiovascular Drugs
v Cardiac glycosides
- Increase the force of myocardial contractions
- Treatment of heart failure
- Toxicity: N&V, diarrhea, arrhythmias, visual
changes
- Usually given when diuretics and ACE
inhibitors failed to control symptoms
- Narrow therapeutic index (TDM)
- Antidote for toxicity: Digitalis antibodies
(digoxin immune fab)
1. Disturbance
in impulse
formation
2. Disturbance
in impulse
conduction
By Stella Gustilo, RPh
Anti-arrhythmics
• Supraventricular tachycardia (SVT)
is an abnormally fast heart rhythm
arising from improper electrical
activity in the upper part of the
heart.
• Main types: atrial fibrillation,
paroxysmal supraventricular
tachycardia (PSVT), atrial flutter
By Stella Gustilo, RPh
Anti-arrhythmics
CLASS 1A (PA Na+ ni QPD)
- Sodium channel blockers
- Prolong action potential
vQuinidine – for most atrial and ventricular arrhythmia but more

toxic in causing Torsade de Pointes (TDP) and cinchonism (HA,
dizziness, tinnitus)
vProcainamide – for most atrial and ventricular arrhythmia; ideal for
sustained ventricular arrhythmias associated with acute MI
vDisopyramide – same with procainamide but with additional
antimuscarinic effects; rarely used
Anti-arrhythmics
CLASS 1B
- Shorten action potential
Lidocaine (local anesthetic)

- For ventricular tachycardia and prevention of ventricular fibrillation
Mexiletine, Phenytoin (anticonvulsant), Tocainide
- For ventricular arrhythmia
Anti-arrhythmics
CLASS 1C
- No effect on action potential
Flecainide/Encainide – for supraventricular arrhythmias (not to be

used post-MI)
Moricizine – for ventricular arrhythmias
Propafenone – for supraventricular arrhythmias
Anti-arrhythmics
CLASS II
Beta blockers: slow SA node
automaticity and AV node conduction
velocity
- Propranolol for atrial arrhythmias

and prevention of sudden death
- Esmolol (short-acting) for acute
arrhythmias such as during an
operation
Anti-arrhythmics
CLASS III
- Potassium channel blockers:
Vernakalant – for atrial fibrillation

Ibutilide – for atrial flutter/fibrillation
Dofetilide – for atrial fibrillation
Dronaderone – amiodarine derivative; reduces mortality in A-fib
Amiodarone – for supraventricular arrhythmias
Sotalol – also a BB; for ventricular arrhythmias & atrial fibrillation
Anti-arrhythmics
CLASS IV
- CCBs:
Verapamil (<3) & diltiazem
- Decrease cardiac
contractility & lowers BP
- Slows SA node automaticity
and AV node conduction
velocity
- For supraventricular
tachycardia, HTN, and
angina
Anti-arrhythmics
MISCELLANEOUS AGENTS
1. ADENOSINE – for paroxysmal supraventricular tachycardia
2. MAGNESIUM – for TDP and digitalis-induced arrhythmias
3. POTASSIUM – for arrhythmia associated with hypokalemia or
digitalis-induced
Drugs for Coagulation Disorders
Promoters of coagulation:
1. Thromboxane – platelet activator

2. Adenosine diphosphate – platelet aggregation
inducer
3. Serotonin – stimulates aggregation and
vasoconstriction
Terms:
Thrombosis - Thrombus formation à blood
clot/coagulation
Fibrinolysis à fibrin digestion by
protease enzyme (Plasmin)
Blood coagulates
when (ultimately)
thrombin (Factor IIa)
activated fibrinogen
(Factor I) into fibrin
After lunch :3
INDIRECT THROMBIN INHIBITORS
- Interact with an endogenous anticoagulant (ANTITHROMBIN)
ØHeparin –heterogenous mixture of sulfated mucopolysaccharides

A. Unfractionated/High Molecular Weight Heparin (UFH)/(HMWH)
B. Low Molecular Weight Heparin (LMWH)
C. Synthetic pentasaccharide (Fondaparinux)
- They bind to antithrombin and enhance its inactivation of factor Xa

Heparin (IV or SC only)
- Antithrombin inhibits thrombin (IIa), IXa, and Xa
LMW Heparins: Enoxaparin, Dalteparin, Tinzaparin

LMW Heparinoid: Danaparoid
Monitoring: activated partial thromboplastin time (for UFH)
Toxicity of Heparin: Bleeding, alopecia, osteoporosis, thrombocytopenia

Antidote: Protamine sulfate (Type of antagonism?)
v Warfarin
- Coumarin anticoagulant
(“Tonka Tree” à “Coumarou”)
- Blocks the carboxylation of glutamate residues in
prothrombin (II), factors VII, IX, and X (9-10-7-2)
- Inhibits Vitamin K epoxide reductase
- Anticoagulant effect is not immediate since it causes
DEPLETION of procoagulant clotting factors
(heparin is used to achieve immediate anticoagulation)
v Warfarin
- Toxicity: bleeding, teratogenic,
cutaneous necrosis
- Monitoring: Prothrombin Time
- Drug interactions: subject to enzyme
induction or inhibition
- Competitive antagonism: Vit. K
- Drug displacement interactions:
phenylbutazone, sulfa antibiotics
- Cholestyramine: binds warfarin and
decreases absorption
ORAL DIRECT FACTOR Xa INHIBITORS
- Oral anticoagulants that need NO MONITORING

- rivaroXAban, apiXAban, edoXAban
- MOA: inhibit factor Xa
- For prevention of embolic stroke in patients with A-Fib
- For prevention of venous thromboembolism
- For treatment of DVT
DIRECT THROMBIN INHIBITORS
Parenteral:
Hirudin – irreversible thrombin inhibitor from leech saliva
Bivalirudin – recombinant; for coronary angioplasty
Lepirudin – recombinant; for Heparin-induced
thrombocytopenia (HIT)
Argatroban – for HIT and coronary angioplasty
Oral:
Dabigatran
– reduce risk of stroke or systemic embolism in pts. With A-
Fib
FIBRINOLYTICS
MOA: Rapidly lyse thrombi through

conversion of precursor zymogen
PLASMINOGEN to PLASMIN (serine
protease)
- Major application: For Acute Myocardial

Infarction
- StreptoKINASE, UroKINASE
FIBRINOLYTICS
Plasminogen can be activated

endogenously by TISSUE PLASMINOGEN
ACTIVATORS (t-PAs)
- Alteplase; Reteplase; Tenecteplase –

recombinant human t-Pas
- IV bolus
- For pulmonary embolism, severe DVT,

acute MI
ANTIPLATELET AGENTS/PLATELET INHIBITORS
1. Aspirin – inhibits production of TXA2 by irreversible

acetylation of COX and interferes in platelet aggregation
- prophylaxis against MI
2. Thienopyridines: Clopidogrel, Ticlopidine, Prasugrel
- MOA: inhibit ADP (adenosine diphosphate)
- Prevention of thrombosis/stroke/MI
ANTIPLATELET AGENTS/PLATELET INHIBITORS
3. Glycoprotein IIb/IIIa antagonists

- Tirofiban, Abciximab, Eptifibatide
- Prevents platelet aggregation
4. Phosphodiesterase inhibitors
- Dipyridamole
- For prevention of cerebrovascular ischemia in
combination with ASA or prevention of
thromboemboli in patients with prosthetic heart
valves in combination with warfarin
- Cilostazol (for intermittent claudication)
Drugs for Bleeding
Aminocaproic acid
- Inhibitor of fibrinolysis
Tranexamic acid
- Analog of aminocaproic acid
Use: adjunct in treatment of hemophilia, used in cases of

bleeding from fibrinolytic therapy, prophylaxis for rebleeding
from intracranial aneurysms (abnormal swelling or bulge in
the wall of a blood vessel)
Drugs for Bleeding
APROTININ
- Serine protease inhibitor
- Inhibits fibrinolysis by free plasmin
- Reduces bleeding for surgeries like organ transplants
PHYTONADIONE (VIT. K1) –found in food (aka phylloquinone)

MENAQUINONE (VIT. K2) – found in human tissues and synthesized
by intestinal microflora
- These two or treatment of warfarin toxicity
**MENADIONE (VIT. K3) – should NOT be used since ineffective in
treatment of warfarin overdosage
Agents for Dyslipidemia
HMG-CoA Reductase
• 3-hydroxy-3-methylglutaryl-coenzyme A reductase
• Mediates the first step in cholesterol biosynthesis
• Enzyme targeted by STATINS or HMG-CoA reductase inhibitors
ü Statins are most effective in lowering LDL

ü Lactone prodrugs: Lovastatin, Simvastatin
ü Lactone, active: Pravastatin
ü Fluorine containing congeners: Atorvastatin, Fluvastatin, Rosuvastatin
ü Long acting: Atorvastatin (t1/2 = 14 hrs) & Rosuvastatin (19 hrs)
HMG-CoA Reductase Inhibitors
• May be used alone or in combination with bile acid sequestrants, niacin,
ezetimibe in reducing LDL for prevention of atherosclerotic vascular
disease
• Toxicity: myopathy, hepatic dysfunction
Fibric acid derivatives/Fibrates
• Gemfibrozil, Fenofibrate, Bezafibrate, Clofibrate
• PPAR-alpha agonist (peroxisome proliferator-activated receptor alpha)
• Decrease VLDL and LDL; increase HDL
• For hypertriglyceridemia
• Toxicity: myopathy and hepatic dysfunction, GI upset, rashes
Nicotinic acid/Niacin
• Vitamin B3
• Inhibits VLDL secretion = Decreases triglycerides and LDL
• Increases HDL
• For hypercholesterolemia
• Toxicity: flushing, gastric irritation
pyridinecarboxylic acid
Bile acid-binding resins
• Colestipol, Cholestyramine, Colesevelam
• Decrease LDL
• Biles acids are metabolites of cholesterol and the agents will bind the
bile acids and prevent their reabsorption
• For hypertriglyceridemia, elevated LDL
• Toxicity: constipation, bloating, malabsorption of fat-soluble vitamins
• May bind other drugs such as digoxin, warfarin, tetracycline, folic acid,
aspirin, iron salts, statins, etc. (solution: give 1 hr before or 2 hrs after
the resin to ensure adequate absorption)
Cholesterol Absorption Inhibitor
• Ezetimibe
- Reduction of LDL
- Inhibits cholesterol absorption by targeting Niemann-Pick C1-Like 1
(NPC1L1) sterol transporter in the intestines
- For hypercholesterolemia, elevated LDL
- Toxicity: low incidence of myositis and hepatic dysfunction
Agents used in Anemias and Hematopoietic
Growth Factors
Terminologies:
Hematopoiesis the formation of blood cellular components or the production from undifferentiated stem cells of
circulating erythrocytes, platelets, and leukocytes; occurs within the hematopoietic system (primarily in the bone
marrow, but also involves other organs like the spleen, lymph nodes, and liver); essential nutrients for this process
are IRON, VITAMIN B 12, and FOLIC ACID in the presence of hematopoietic growth factors.
Anemia a deficiency in oxygen-carrying erythrocytes or red-blood cells
Sickle cell anemia a condition resulting from a genetic alteration in the hemoglobin molecule; an important
genetic cause of hemolytic anemia due to increased erythrocyte destruction
Thrombocytopenia
This document abnormally
and the information thereonlow levels
is the of platelets,
property of also known as thrombocytes, in the blood
PHINMA Neutropenia abnormallyoflow
Education (Department 1 of 7
number of neutrophils (a type of white blood cell) in the blood. (if severe, significantly
Pharmacy)
increases the risk of life-threatening infection; often a side effect of the treatment of cancer with chemotherapy or
radiation therapy)
Pancytopenia low levels of all of the types of blood cells including red blood cells (anemia), white blood cells
(leukopenia), and platelets (thrombocytopenia)
Iron deficiency anemia the most common cause of chronic anemia; leads to pallor, fatigue, dizziness, exertional
dyspnea, and other generalized symptoms of tissue hypoxia; patient may experience tachycardia and condition
may worsen if he/she has underlying cardiac disease due to increased cardiac output; Iron forms the nucleus of the
iron-porphyrin heme ring, which together with globin chains forms hemoglobin that binds oxygen and delivers it to
the lungs and other tissues (inadequate iron gives rise to microcytic hypochromic anemia wherein red blood cells
are small and pale since they have insufficient hemoglobin formed); Iron deficiency anemia is treated with oral or
parenteral iron preparations
Oral iron therapy: Ferrous iron for is most efficiently absorbed that is why ferrous salts should be used.
Ferrous sulfate, ferrous gluconate, and ferrous fumarate are all effective and inexpensive and are
recommended for the treatment of most patients. Common adverse effects of oral iron therapy include
nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea. These effects are usually
dose-related and often can be overcome by lowering the daily dose of iron or by taking the tablets
Neutropenia abnormally low number of neutrophils (a type of white blood cell) in the blood. (if severe, significantly
increases the risk of life-threatening infection; often a side effect of the treatment of cancer with chemotherapy or
radiation therapy)
Pancytopenia low levels of all of the types of blood cells including red blood cells (anemia), white blood cells
(leukopenia), and platelets (thrombocytopenia)
Iron deficiency anemia the most common cause of chronic anemia; leads to pallor, fatigue, dizziness, exertional
dyspnea, and other generalized symptoms of tissue hypoxia; patient may experience tachycardia and condition
may worsen if he/she has underlying cardiac disease due to increased cardiac output; Iron forms the nucleus of the
iron-porphyrin heme ring, which together with globin chains forms hemoglobin that binds oxygen and delivers it to
the lungs and other tissues (inadequate iron gives rise to microcytic hypochromic anemia wherein red blood cells
are small and pale since they have insufficient hemoglobin formed); Iron deficiency anemia is treated with oral or
parenteral iron preparations
Oral iron therapy: Ferrous iron for is most efficiently absorbed that is why ferrous salts should be used.
Ferrous sulfate, ferrous gluconate, and ferrous fumarate are all effective and inexpensive and are
recommended for the treatment of most patients. Common adverse effects of oral iron therapy include
nausea, epigastric discomfort, abdominal cramps, constipation, and diarrhea. These effects are usually
dose-related and often can be overcome by lowering the daily dose of iron or by taking the tablets
immediately after or with meals
Parenteral iron therapy: iron dextran, sodium ferric gluconate complex, and iron sucrose
Antidote for iron toxicity/overload/hemochromatosis: Iron chelation therapy using parenteral deferoxamine or the
oral iron chelators deferasirox or deferiprone
2021 B.E.Q.
Do not replicate or distribute without prior consent and permis
QUESTION
1. Treatment for iron deficiency anemia
A. Elemental iron
B. Ferrous sulfate
C. Ferric sulfate
D. Ferric & ferrous sulfate
2. Element used for the surgical repair of bones; Metal una

body fluids, used in surgical repair of bones, nerves and
A. Titanium
• “At physiological pH, iron exists in the oxidized, ferric (Fe3+) state. To be absorbed,
iron must be in the ferrous (Fe2+) state or bound by a protein such as heme.”
• “The low pH of gastric acid in the proximal duodenum allows a ferric reductase
enzyme, duodenal cytochrome B, on the brush border of the enterocytes to convert the
insoluble ferric (Fe3+) to absorbable ferrous (Fe2+) ions.”
• “Gastric acid production plays a key role in plasma iron homeostasis. When proton-
pump inhibiting drugs such as omeprazole are used, iron absorption is greatly
reduced.”
Ems T, St Lucia K, Huecker MR. Biochemistry, Iron Absorption. [Updated 2021 Apr 26]. In: StatPearls [Internet]. Treasure Island
(FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448204/
• Drug-Food Interactions
à Polyphenols are found in black and herbal tea,

coffee, wine, legumes, cereals, fruit, and vegetables
and have been demonstrated to inhibit iron
absorption
à Animal proteins such as casein, whey, egg
whites, and proteins from plants (soy protein) have
been shown to inhibit iron absorption in humans.
à Oxalic acid is found in spinach, chard, beans, and
nuts and acts to bind and inhibit iron absorption.
• Enhanced Iron Absorption
”Ascorbic acid (vitamin C) can overcome

the effects of all dietary inhibitors when it is
included in a diet with high non-heme iron
availability (usually a meal heavy in
vegetables). Ascorbic acid forms a chelate
with ferric (Fe3+) iron in the low pH of the
stomach, which persists and remains soluble
in the alkaline environment of the
duodenum.”
v Iron is an essential element of various metabolic processes in humans:
- DNA synthesis
à Iron is an essential redox element that functions as a cofactor in critical enzymes
in DNA metabolism, including multiple DNA repair enzymes (helicases, nucleases,
glycosylases, demethylases) and ribonucleotide reductase
- Electron transport chain

à Cofactor of mitochondrial cytochrome c oxidase (complex IV) of the respiratory
chain (during electron process, heme iron metal center interconverts between
ferrous and ferric oxidation states—allowing electrons to be accepted or donated
- Oxygen transport
à hemoglobin/myoglobin
https://chem.libretexts.org/Courses/Saint_Marys_College_Notre_Dame_IN/CHEM_342%3A_Bio-
inorganic_Chemistry/Readings/Metals_in_Biological_Systems_(Saint_Mary%27s_College)/Cytochrome_C
Ems T, St Lucia K, Huecker MR. Biochemistry, Iron Absorption. [Updated 2021 Apr 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448204/
Puig S, Ramos-Alonso L, Romero AM, Martínez-Pastor MT. The elemental role of iron in DNA synthesis and repair. Metallomics.
2017 Nov 15;9(11):1483-1500. doi: 10.1039/c7mt00116a. PMID: 28879348.
B.E.Q.
Ø Anemia occurs if your body makes too
few red blood cells (RBCs), destroys too
many RBCs, or loses too many RBCs.
Ø RBCs contain hemoglobin, a protein that

carries oxygen throughout your body.
Ø When you don’t have enough RBCs or the

amount of hemoglobin in your blood is
low, your body doesn’t get all the oxygen
it needs. As a result, you may feel tired or
have other symptoms.
Ø Many diseases, conditions, and other factors can cause anemia.
Ø For example, anemia may occur during pregnancy if the body can’t meet its
increased need for RBCs.
Ø Certain autoimmune disorders and other conditions may cause your body to make
proteins that destroy your RBCs, which can lead to anemia.
Ø Heavy internal or external bleeding—from injuries, for example—may cause
anemia because your body loses too many RBCs.
Ø The causes of anemia can be acquired or inherited.
Ø “Acquired” means you aren’t born with the condition, but you develop it.
“Inherited” means your parents passed the gene for the condition on to you.
Sometimes the cause of anemia is unknown.
B.E.Q.
B.E.Q.
Aplastic anemia is also sometimes associated with exposure to toxins such
as benzene, or with the use of certain drugs, including chloramphenicol,
carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone.
•Cephalosporins
•Dapsone
•Levodopa
•Levofloxacin
•Methyldopa
•Nitrofurantoin
•Nonsteroidal anti-
inflammatory drugs (NSAIDs)
•Penicillin and its derivatives
•Antimalarials
•Infections/blood cancers/lupus
Sickle cell anemia is an inherited red blood cell disorder in which there
aren't enough healthy red blood cells to carry oxygen throughout your body.
Normally, the flexible, round red blood cells move easily through blood
vessels. In sickle cell anemia, the red blood are shaped like sickles or
crescent moons
SCD is a form of hemolytic anemia, with red cell survival of around 10-20 days.
https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/diagnosis-treatment/drc-20355882
Vitamin B12 for parenteral injection is available as cyanocobalamin or hydroxocobalamin.
Hydroxocobalamin is preferred because it is more highly protein-bound and therefore remains longer in
the circulation.
HEMATOPOIETIC GROWTH FACTORS

- glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells in
the bone marrow
Erythropoietin (epoetin alfa and epoetin beta)
- Endogenous erythropoietin is produced primarily in the kidney; Erythropoietin stimulates erythroid
proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors; induces
release of reticulocytes from the bone marrow; for patients with renal disease (chronic kidney disease);
common adverse effects are increased blood pressure and thrombotic complications
Myeloid Growth Factors:
Granulocyte colony-stimulating factor (G-CSF)
- example: filgrastim (note suffix difference: -GRASTIM
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
- example: sargramostim (note suffix difference: -GRAMOSTIM
- levels;
this means that neutropenia refers to low levels of neutrophils a type of white blood cell/granulocyte
that is crucial in fighting off infections)
G-CSF and GM-CSF have also proved to be effective in treating neutropenia associated with
congenital neutropenia, cyclic neutropenia, myelodysplasia, and aplastic anemia
Megakaryocyte Growth Factors:

Reference:
1. Enumerate the principal and secondary hormonal
regulators for bone homeostasis Katzung, B.G. (2018). Bas
2. Discuss the indications, mechanism of action, clinical Pharmacology (14th ed.).
effects, adverse effects and contraindications of agents Medical Books/McGraw H
affecting bone homeostasis
Agents that affect Bone Homeostasis
LESSON REVIEW/PREVIEW & HOOK ACTIVITY (5 minutes)
Introductory Questions: Answers:

1. What mineral is essential for bone health and is Calcium
often taken as a dietary supplement?
2. What lipid-soluble vitamin is important to support Vitamin D
bone health?
MAIN LESSON (50 minutes)

Calcium and phosphate, the major mineral
constituents of bone, are also two of the most
Three hormones serve as the principal regulators
of LESSON
MAIN calcium (50and
minutes)phosphate homeostasis:
parathyroid hormone (PTH), fibroblast growth
Calcium
factor 23 and phosphate,
(FGF23), and vitaminthe Dmajorvia itsmineral
active
constituents1,25-dihydroxyvitamin
metabolite of bone, are also two D of the most
important
The minerals
role of for general
calcitonin (CT) is cellular function
less critical during
Three life
adult hormones
but may serve
playas the principalrole
a greater regulators
during
of calciumand and
pregnancy phosphate
lactation. The termhomeostasis:
vitamin D,
parathyroid
when hormonea (PTH),
used without subscript,fibroblast
refers togrowth
both
factor 23D2
vitamin (FGF23), and vitaminand
(ergocalciferol) D via its active
vitamin D3
metabolite 1,25-dihydroxyvitamin D
(cholecalciferol)
The roleDofis calcitonin
Vitamin considered(CT) is less critical
a prohormone duringit
because
adult life
must but maymetabolized
be further play a greater to gain role biologic
during
pregnancy and lactation. The term vitamin D,
activity
when used
Vitamin D3 iswithout
produceda subscript,
in the skin refers
under to ultra-
both
vitamin
violet D2 (ergocalciferol)
B (UVB) radiation (e.g., inand vitamin
sunlight) from D3
its
(cholecalciferol)
precursor, 7-dehydrocholesterol. The initial
Vitamin D ispre-vitamin
product, considered a prohormone
D3, because ait
undergoes
must be further metabolized
temperature-sensitive isomerizationto togain biologic
vitamin D3.
activity
The precursor of vitamin D2 is ergosterol, found in
Vitaminand
plants D3 fungi
is produced in the skin
(mushrooms). under ultra-
It undergoes a
violet B transformation
similar (UVB) radiationto(e.g., in sunlight)
vitamin D2 with from
UVBits
precursor, Vitamin
radiation. 7-dehydrocholesterol.
D2 thus comes only Thefrominitial
the
product,
diet, whereas pre-vitamin
vitamin D3 comesD3, from undergoes
the skin or a
temperature-sensitive
the diet, or both. isomerization to vitamin D3.
The precursor of vitamin D2 is ergosterol, found in
This document and the information thereon is the property of
PHINMA Education (Department of Pharmacy) 2 of 5
Antibacterial Agents:
Cell Wall & Cell Membrane
Inhibitors
Introductory Question: Who first discovered penicillin? How did he discover such antibiotic?
Answer:
Sir Alexander Fleming, a Scottish researcher, is credited with the serendipitous discovery of penicillin in 1928. At the time,
Fleming was experimenting with the influenza virus in the Laboratory
in London. Often described as a careless lab technician, Fleming returned from a two-week vacation to find that a mold had
developed on an accidentally contaminated staphylococcus culture plate. Upon examination of the mold, he noticed that
the culture prevented the growth of staphylococci.
one is not looking for. When I woke up just after dawn on Sept. 28, 1928, I certainly
Though Fleming stopped
studying penicillin in 1931, his research was continued and finished by Howard Flory and Ernst Chain, researchers at
University of Oxford who are credited with the development of penicillin for use as a medicine in mice.
The penicillins share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics with
- -lactam compounds, so named because
of their four-membered lactam ring.
Penicillins can be assigned to one of three groups (below). Within each of these groups are compounds that are relatively
stable to gastric acid and suitable for oral administration, eg, penicillin V, dicloxacillin, and amoxicillin.
1. Penicillins (eg, penicillin G) These have greatest activity against Gram-positive organisms, Gram-negative
cocci, and non- -lactamase-producing anaerobes. However, they have little activity against Gram-negative rods,
-lactamases.
The penicillins share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics with
- -lactam compounds, so named because
of their four-membered lactam ring.
Penicillins can be assigned to one of three groups (below). Within each of these groups are compounds that are relatively
stable to gastric acid and suitable for oral administration, eg, penicillin V, dicloxacillin, and amoxicillin.
1. Penicillins (eg, penicillin G) These have greatest activity against Gram-positive organisms, Gram-negative
cocci, and non- -lactamase-producing anaerobes. However, they have little activity against Gram-negative rods,
-lactamases.
2. Antistaphylococcal penicillins (eg, nafcillin) -lactamases.
They are active against staphylococci and streptococci but not against enterococci, anaerobic bacteria, and Gram-
negative cocci and rods.
3. Extended-spectrum penicillins (aminopenicillins and antipseudomonal penicillins) These drugs retain the anti-
bacterial spectrum of penicillin and have improved activity against Gram-negative rods. Like penicillin, however,
they are relatively
This document susceptiblethereon
and the information to hydrolys -lactamases.
is the property of
Cephalosporins are similar to penicillins but are more stable to
-lactamases and, therefore, have a broader
spectrum of activity. However, strains of E coli and Klebsiella sp
expressing extended- -lactamases that can hydrolyze
most cephalosporins are a growing clinical concern.
Cephalosporins are not active against L monocytogenes, and of
the available cephalosporins, only ceftaroline has some activity
against enterococci.
First-generation cephalosporins include cefazolin, cefadroxil,

cephalexin, cephalothin, cephapirin, and cephradine; cefazolin and
cephalexin are the only two available in the USA. These drugs are
very active against Gram-positive cocci, such as streptococci and
staphylococci. Traditional cephalosporins are not active against
methicillin-resistant strains of staphylococci; however, new
-lactam antibiotics. Doripenem, ertapenem, imipenem, and meropenem
are licensed for use in the USA. Imipenem, the first drug of this class, has a wide spectrum with good activity against most
Gram-negative rods, including P aeruginosa, Gram- -lactamases
but not carbapenemases or metallo- -lactamases. Enterococcus faecium, methicillin-resistant strains of staphylococci,
Clostridium difficile, Burkholderia cepacia, and Stenotrophomonas maltophilia are resistant.
Imipenem is inactivated by dehydropeptidases in renal tubules, resulting in low urinary concentrations. Consequently, it is
adminstered together with an inhibitor of renal dehydropeptidase, cilastatin, for clinical use. Doripenem and meropenem are
similar to imipenem but have slightly greater activity against Gram-negative aerobes and slightly less activity against Gram-
positives. They are not significantly degraded by renal dehydropeptidase and do not require an inhibitor. Unlike the other
carbapenems, ertapenem does not have appreciable activity against P aeruginosa and Acinetobacter species. It is not
degraded by renal dehydropeptidase.
A carbapenem is indicated for infections caused by susceptible organisms that are resistant to other available drugs, eg, P
aeruginosa, and for treatment of mixed aerobic and anaerobic infections. Carbapenems are active against many penicillin-
non- susceptible strains of pneumococci. Carbapenems are highly active in the treatment of Enterobacter infections because
-lactamase produced by these organisms.
The most common adverse effects of carbapenems which tend to be more common with imipenem are nausea, vomiting,
diarrhea, skin rashes, and reactions at the infusion sites. Excessive levels of imipenem in patients with renal failure may
lead to seizures. Meropenem, doripenem, and ertapenem are much less likely to cause seizures than imipenem. Patients
Cilastatin is a chemical compound which inhibits the human
allergic to penicillins may be allergic to carbapenems, but the incidence of cross-reactivity is thought to be less than 1%.
enzyme dehydropeptidase. Renal Dehydropeptidase degrades
the antibiotic imipenem. Cilastatin is therefore combined
intravenously with imipenem in order to protect it from
dehydropeptidase and prolong its antibacterial effect.
MONOBACTAM ANTIBIOTIC
-lactam ring.
Their spectrum of activity is limited to aerobic Gram- -

lactam antibiotics, they have no activity against Gram-positive bacteria or anaerobes.
Aztreonam is the only monobactam available. It is often referred to as the silver bullet against gram-negative
infections.
Aztreonam is given intravenously every 8 hours in a dose of 1 2 g, providing peak serum levels of 100 mcg/mL.
The half-life is 1 2 hours and is greatly prolonged in renal failure.
Penicillin-allergic patients tolerate aztreonam without reaction.
BETA-LACTAMASE INHIBITORS
- -lactam molecules but

they have very weak antibacterial action. Their beneficial pharmacodynamic interaction with penicillins (e.g.,
amoxicillin + clavulanic acid in co-amoxiclav) is POTENTIATION since beta-lactamase inhibitors do not kill or

Penicillin-allergic patients tolerate aztreonam without reaction.
BETA-LACTAMASE INHIBITORS
- -lactam molecules but

they have very weak antibacterial action. Their beneficial pharmacodynamic interaction with penicillins (e.g.,
amoxicillin + clavulanic acid in co-amoxiclav) is POTENTIATION since beta-lactamase inhibitors do not kill or
inhibit the bacteria, rather it protects the active antibacterial agent (e.g., amoxicillin) from being degraded by the
bacterial enzyme beta-lactamase.
PHINMA Education (Department of Pharmacy) 1 of 5from
-lactamases and can protect hydrolyzable penicillins
inactivation by these enzymes. Beta-lactamase inhibitors are available only in fixed combinations with specific
penicillins and cephalosporins.
Ampicillin- -lactamase-producing S aureus and H influenzae but not against Serratia,

-lactamase that is not inhibited by sulbactam. Similarly, if a strain of P aeruginosa is resistant
to piperacillin, it is also resistant to piperacillin-tazobactam because tazobactam does not inhibit the chromosomal
-lactamase produced by P aeruginosa.
Beta-lactam -lactamase inhibitor combinations are frequently used as empirical therapy for infections caused by
a wide range of potential pathogens in both immunocompromised and immunocompetent patients. Adjustments
for renal insufficie -lactam component.
GLYCOPEPTIDE ANTIBIOTICS
Vancomycin is active primarily against Gram-positive bacteria due to its large molecular weight and lack of
penetration through Gram-negative cell membranes. The intravenous product is water soluble and stable for 14
GLYCOPEPTIDE ANTIBIOTICS
Vancomycin is active primarily against Gram-positive bacteria due to its large molecular weight and lack of
penetration through Gram-negative cell membranes. The intravenous product is water soluble and stable for 14
days in the refrigerator following reconstitution.
Vancomycin inhibits cell wall synthesis by binding firmly to the d-Ala-d-Ala terminus of nascent peptidoglycan
pentapeptide. This inhibits the transglycosylase, preventing further elongation of peptidoglycan and cross-linking.
The peptidoglycan is thus weakened, and the cell becomes susceptible to lysis. The cell membrane is also
damaged, which contributes to the antibacterial effect.
Teicoplanin is a glycopeptide antibiotic that is very similar to vancomycin in mechanism of action and antibacterial
spectrum. Unlike vancomycin, it can be given intramuscularly as well as intravenously. Teicoplanin has a long half-
life (45 70 hours), permitting once-daily dosing.
Telavancin is a semisynthetic lipoglycopeptide derived from vancomycin. Telavancin is active versus Gram-positive
bacteria and has in vitro activity against many strains with reduced susceptibility to vancomycin. Telavancin has
two mechanisms of action. Like vancomycin, telavancin inhibits cell wall synthesis by binding to the d-Ala-d-Ala
terminus of peptidoglycan in the growing cell wall. In addition, it disrupts the bacterial cell membrane potential and
increases membrane permeability. The half-life of telavancin is approximately 8 hours, which supports once-daily
intravenous dosing. The drug is approved for treatment of complicated skin and soft tissue infections and hospital-
acquired pneumonia at a dose of 10 mg/kg IV daily.
Dalbavancin and oritavancin are semisynthetic lipoglycopeptides derived from teicoplanin. Dalbavancin and
oritavancin inhibit cell wall synthesis via the same mechanism of action as vancomycin and teicoplanin; oritavancin
works by additional mechanisms, including disruption of cell membrane permeability and inhibition of RNA
Red man
syndrome (RMS) is
an anaphylactoid
reaction caused by the
rapid infusion of the
glycopeptide
antibiotic vancomycin
.
works by additional mechanisms, including disruption of cell membrane permeability and inhibition of RNA
synthesis.
LIPOPEPTIDE ANTIBIOTIC
Daptomycin is a novel cyclic lipopeptide fermentation product of Streptomyces roseosporus. Its spectrum of activity
is similar to that of vancomycin except that it may be active against vancomycin-resistant strains of enterococci and
S aureus. The approved doses are 4 mg/kg/dose for treatment of skin and soft tissue infections and 6 mg/kg/dose
for treatment of bacteremia and endocarditis once daily in patients with normal renal function
MISCELLANEOUS
Fosfomycin trometamol, a stable salt of fosfomycin (phosphonomycin), inhibits a very early stage of bacterial cell
wall synthesis. An analog of phosphoenolpyruvate, it is structurally unrelated to any other antimicrobial agent. It
inhibits the cytoplasmic enzyme enolpyruvate transferase by covalently binding to the cysteine residue of the active
site and blocking the addition of phosphoenolpyruvate to UDP-N-acetylglucosamine. This reaction is the first step
in the formation of UDP-N-acetylmuramic acid, the precursor of N-acetylmuramic acid, which is found only in
bacterial cell walls. The drug is transported into the bacterial cell by glycerophosphate or glucose 6-phosphate

Gram-positive and Gram-negative o L. Fosfomycin is approved for use as
a single 3-g dose for treatment of uncomplicated lower urinary tract infections (UTI) in women.
Bacitracin is a cyclic peptide mixture first obtained from the Tracy strain of Bacillus subtilis in 1943. It is active
against Gram-positive microorganisms. Bacitracin inhibits cell wall formation by interfering with dephosphorylation
in cycling of the lipid carrier that transfers peptidoglycan subunits to the growing cell wall. There is no cross-
resistance between bacitracin and other antimicrobial drugs. Bacitracin is highly nephrotoxic when administered
systemically and is only used topically. Bacitracin is commonly associated with hypersensitivity and should not be
applied to wounds for the purpose of preventing infection.
Cycloserine is an antibiotic produced by Streptomyces orchidaceous. It is water soluble and very unstable at acid
pH. Cycloserine inhibits many Gram-positive and Gram-negative organisms, but it is used almost exclusively to
treat tuberculosis caused by strains of Mycobacterium tuberculosis resistant to first-line agents. Cycloserine is a
structural analog of d-alanine and inhibits the incorporation of d-alanine into peptidoglycan pentapeptide by
inhibiting alanine racemase, which converts l-alanine to d-alanine, and d-alanyl-d-alanine ligase. Cycloserine
causes serious, dose-related central nervous system toxicity with headaches, tremors, acute psychosis, and
convulsions. If oral dosages are maintained below 0.75 g/d, such effects can usually be avoided.
SUMMARY (MECHANISM EFFECT INDICATION/CLINICAL USE ADVERSE EFFECTS)

Cycloserine is an antibiotic produced by Streptomyces orchidaceous. It is water soluble and very unstable at acid
pH. Cycloserine inhibits many Gram-positive and Gram-negative organisms, but it is used almost exclusively to
treat tuberculosis caused by strains of Mycobacterium tuberculosis resistant to first-line agents. Cycloserine is a
structural analog of d-alanine and inhibits the incorporation of d-alanine into peptidoglycan pentapeptide by
inhibiting alanine racemase, which converts l-alanine to d-alanine, and d-alanyl-d-alanine ligase. Cycloserine
causes serious, dose-related central nervous system toxicity with headaches, tremors, acute psychosis, and
convulsions. If oral dosages are maintained below 0.75 g/d, such effects can usually be avoided.

Antifolates/Antimetabolites
be much more
Sulfonamides soluble at
are infrequently alkaline
used than
as single at acid pH. Most
agents.
Manycanstrains of formerly susceptible
be prepared as sodiumspecies,
salts, including
which are used for
meningococci, pneumococci, streptococci,
intravenous administration.
staphylococci, and gonococci, are now resistant. The
fixed-drug combination of trimethoprim-
As structuralis analogs
sulfamethoxazole the drug ofofchoice
PABA, sulfonamides inhibit
for infections
suchdihydropteroate
as Pneumocystis synthase and P folate
jiroveci (formerly carinii) production.
pneumonia, toxoplasmosis,
Sulfonamides inhibit and nocardiosis.
both Gram-positive bacteria, such
as Staphylococcus sp and Gram-negative enteric
The most common adverse effects are fever, skin
bacteria
rashes, such dermatitis,
exfoliative as Escherichia coli, Klebsiella
photosensitivity,
pneumoniae,
urticaria, Salmonella,
nausea, vomiting, Shigella,
diarrhea, and Enterobacter sp,
and difficulties
as wellto astheNocardia
referable sp, Chlamydia
urinary tract. trachomatis, and
Stevens-Johnson
syndrome, although relatively uncommon (<1% of
some protozoa
treatment courses), is a particularly serious and
potentially fatal type of skin and mucous membrane
Combination
eruption associatedof witha sulfonamide
sulfonamide use.withOtheran inhibitor of
dihydrofolate
unwanted effects reductase (trimethoprim
include stomatitis, or pyrimethamine)
conjunctivitis,
provides
arthritis, synergistic
hematopoietic activity hepatitis,
disturbances, becauseand,of sequential
rarely, polyarteritis
inhibition nodosa
of folate and psychosis.
synthesis (Figure 46 2).
Trimethoprim, a trimethoxybenzylpyrimidine,
selectively inhibits bacterial dihydrofolic acid
reductase, which converts dihydrofolic acid to
tetrahydrofolic acid, a step leading to the synthesis of
are susceptible to
Pyrimethamine thesulfadiazine
and high concentrations
are usedthat aretreatment
in the found in the urine (200 600 mcg/mL).
of toxoplasmosis.
Trimethoprim-sulfamethoxazole is commonly
Trimethoprim produces the predictable usedeffects
adverse for theoftreatment of uncomplicated
an antifolate drug, especiallyskinmegaloblastic
and soft tissue infections.
anemia, leukopenia,
Pyrimethamine and sulfadiazine
and granulocytopenia. are usedtrimethoprim-sulfamethoxazole
The combination in the treatment of toxoplasmosis. may cause all of the untoward reactions associated
with sulfonamides. Nausea and vomiting, drug fever, vasculitis, renal damage, and central nervous system disturbances
Trimethoprim
occasionally produces the predictable
occur. Patients adverse
with AIDS effects of an antifolate
and pneumocystis pneumonia drug, especially
have megaloblastic
a particularly anemia, leukopenia,
high frequency of untoward
and granulocytopenia.
reactions The combination trimethoprim-sulfamethoxazole
to trimethoprim-sulfamethoxazole, especially fever, rashes, may cause all of thediarrhea,
leukopenia, untoward elevations
reactions associated
of hepatic
with sulfonamides. Nausea
aminotransferases, and vomiting,
hyperkalemia, drug fever, vasculitis,
and hyponatremia. Trimethoprim renalinhibits
damage, and central
secretion nervousatsystem
of creatinine disturbances
the distal renal tubule,
occasionally occur.elevation
resulting in mild Patientsofwith AIDScreatinine
serum and pneumocystis pneumoniaof have
without impairment a particularly
glomerular filtrationhigh
rate.frequency of untoward
This nontoxic effect is
reactions to trimethoprim-sulfamethoxazole, especially fever, rashes,
important to distinguish from true nephrotoxicity that may be caused by sulfonamides. leukopenia, diarrhea, elevations of hepatic
aminotransferases, hyperkalemia, and hyponatremia. Trimethoprim inhibits secretion of creatinine at the distal renal tubule,
resulting in mild elevation of serum creatinine without impairment of glomerular filtration rate. This nontoxic effect is
important to distinguish from true nephrotoxicity that may be caused by sulfonamides.
among their classmates for 15-20 minutes.
________ 1. Pyrimethamine and sulfadiazine are used in the treatment of _________.

a. SHIGELLOSIS
b. TOXOPLASMOSIS
c. SALMONELLOSOS
d. ANTHRAX
ANSWER: B (1ST LINE FOR TOXOPLASMA GONDII INFECTION)
________2. All are toxicities of folate antagonists except

a. BONE MARROW SUPPRESSION
b. HYPOKALEMIA
c. NEPHROTOXICITY
d. RASH
ANSWER: B (HYPERKALEMIA IS A SIDE EFFECT OF ANTIFOLATES, NOT HYPOKALEMIA)
________3. SECOND-LINE TREATMENT FOR MALARIA

a. SULFADIAZINE
b. PYRIMETHAMINE-SULFADIAZINE
c. PYRIMETHAMINE-SULFADOXINE
d. TRIMETHOPRIM-SULFAMETHOXAZOLE
ANSWER: C (SEE SUMMARY TABLE)
________4. TRUE ABOUT CO-TRIMOXAZOLE EXCEPT

a. TRIMETHOPRIME + SULFAMETHOXAZOLE
b. BACTERIOSTATIC
c. INDICATED FOR URINARY TRACT INFECTIONS
d. SYNERGISTIC COMBINATION BLOCKING PURINE PRODUCTION AND NUCLEIC ACID SYNTHESIS
ANSWER: B (BACTERICIDAL)
________5. As structural analogs of PABA, sulfonamides inhibit dihydropteroate synthase.

Trimethoprim selectively inhibits bacterial dihydrofolic acid reductase.
a. ONLY THE FIRST STATEMENT IS TRUE.
b. ONLY THE SECOND STATEMENT IS TRUE.
c. BOTH STATEMENTS ARE TRUE.
d. BOTH STATEMENTS ARE FALSE.
ANSWER: C
DNA gyrase inhibitors
FLUOROQUINOLONES
The clinically relevant quinolones are synthetic fluorinated analogs

of nalidixic acid (Figure 46 3). They are active against a variety of
Gram-positive and Gram-negative bacteria.
MECHANISM:
Quinolones block bacterial DNA synthesis by inhibiting bacterial

topoisomerase II (DNA gyrase) and topoisomerase IV. Inhibition of
DNA gyrase prevents the relaxation of positively supercoiled DNA
that is required for normal transcription and replication. Inhibition
of topoisomerase IV interferes with separation of replicated
chromosomal DNA into the respective daughter cells during cell
division.
Fluoroquinolones were originally developed because of their

excellent activity against Gram-negative aerobic bacteria; the
earliest agents had limited activity against Gram-positive
organisms. Subsequent members of the group have improved
activity against Gram-positive cocci. The relative activity against
Gram-negative versus Gram-positive species is useful for
differentiating these agents
against P aeruginosa.
CLINICAL USES:
Fluoroquinolones (other than moxifloxacin, which achieves relatively low urinary levels) are effective in urinary tract
infections caused by many organisms, including P aeruginosa. These agents are also effective for bacterial diarrhea caused
by Shigella, Salmonella, toxigenic E coli, and Campylobacter.
Fluoroquinolones (except norfloxacin, which does not achieve adequate systemic concentrations) are used in infections of
soft tissues, bones, and joints and in intra-abdominal and respiratory tract infections, including those caused by multidrug-
resistant organisms such as Pseudomonas and Enterobacter. Ciprofloxacin is a drug of choice for prophylaxis and treatment
of anthrax/
Ciprofloxacin and levofloxacin are no longer recommended for the treatment of gonococcal infection in the USA, as
resistance is now common; however, gemifloxacin may be used in combination with azithromycin as an alternate to
ceftriaxone. Levofloxacin and ofloxacin are recommended by the Centers for Disease Control and Prevention as alternative
treatment options for chlamydial urethritis or cervicitis. Ciprofloxacin, levofloxacin, or moxifloxacin is occasionally used as
part of a treatment regimen for tuberculosis and non-tuberculous mycobacterial infections. These agents are suitable for
eradication of meningococci from carriers and for prophylaxis of bacterial infection in neutropenic cancer patients.
With their enhanced Gram-positive activity and activity against atypical pneumonia agents (chlamydiae, Mycoplasma, and
Legionella), levofloxacin, gemifloxacin, and moxifloxacin so-called respiratory fluoroquinolones are effective for
treatment of lower respiratory tract infections.
ADVERSE EFFECTS:

Fluoroquinolones are generally well tolerated. The most common effects are nausea, vomiting, and diarrhea. Occasionally,
headache, dizziness, insomnia, skin rash, or abnormal liver function tests develop. Photosensitivity has been reported with
lomefloxacin and pefloxacin. Prolongation of the QTc interval may occur with gatifloxacin, levofloxacin, gemifloxacin, and
moxifloxacin; these drugs should be avoided or used with caution in patients with known QTc interval prolongation or
uncorrected hypokalemia; in those receiving class 1A (eg, quinidine or procainamide) or class 3 antiarrhythmic agents
(sotalol, ibutilide, amiodarone); and in patients receiving other agents known to increase the QTc interval (eg, erythromycin,
tricyclic antidepressants). Gatifloxacin has been associated with hyperglycemia in diabetic patients and with hypoglycemia
in patients also receiving oral hypoglycemic agents. Tendonitis, a complication in adults, can be serious because of the risk
of tendon rupture. Risk factors for tendonitis include advanced age, renal insufficiency, and concurrent steroid use.
Fluoroquinolones should be avoided during pregnancy in the absence of specific data documenting their safety. Oral or
intravenously administered fluoroquinolones have also been associated with peripheral neuropathy. Neuropathy can occur
at any time during treatment with fluoroquinolones and may persist for months to years after the drug is stopped. In some
cases it may be permanent. Although many potential adverse effects are uncommon, the FDA called for updated warnings
for all fluoroquinolones in 2016, stating that these agents should be reserved for patients who do not have alternative
options, particularly in less severe infections such as upper respiratory infections or uncomplicated cystitis.
Matching Type (Part 1: Match the specific agent with the antibiotic subclass)
_______ 1. AMIKACIN
CHOICES FOR 1-15:
_______ 2. CLARITHROMYCIN
A. AMINOGLYCOSIDES
_______ 3. TIGECYCLINE B. TETRACYCLINES
C. MACROLIDES
_______ 4. TELITHROMYCIN D. LINCOSAMIDE
_______ 5. QUINUPRISTIN E. STREPTOGRAMINS
Antibacterial
F. OXAZOLIDINONES
_______ 6. STREPTOMYCIN
Agents: _______ 7. TEDIZOLID
_______ 8. CLINDAMYCIN
Protein synthesis _______ 9. KANAMYCIN
inhibitors _______ 10. MINOCYCLINE
_______ 11. GENTAMICIN
_______ 12. ERYTHROMYCIN
_______ 13. DALFOPRISTIN
_______ 14. LINEZOLID
_______ 15. DOXYCYCLINE
Matching Type (Part 2: Match the antibiotic with the mechanism of action)
_______ 11. GENTAMICIN
_______ 12. ERYTHROMYCIN
_______ 13. DALFOPRISTIN
_______ 14. LINEZOLID
_______ 15. DOXYCYCLINE
Matching Type (Part 2: Match the antibiotic with the mechanism of action)
_______ 16. CHLORAMPHENICOL CHOICES FOR 16-20:
_______ 17. AZITHROMYCIN A. INHIBITS 30S RIBOSOMAL SUBUNIT
_______ 18. NEOMYCIN

B. INHIBITS 50S RIBOSOMAL SUBUNIT
_______ 19. CLINDAMYCIN
_______ 20. TOBRAMYCIN

PHINMA Education (Department of Pharmacy)

Antimycobacterial agents
SECOND-LINE DRUGS FOR TUBERCULOSIS (Mycobacterium tuberculosis with resistance to 1st-line drugs)
The alternative/second-line agents are usually considered only (1) in case of resistance to first-line agents; (2) in case of
failure of clinical response to conventional therapy; and (3) in case of serious treatment-limiting adverse drug reactions.
Expert guidance is desirable in dealing with the toxic effects of these second-line drugs.
Streptomycin aminoglycoside; Streptomycin sulfate is used when an injectable drug is needed or desirable and
in the treatment of infections resistant to other drugs. Streptomycin is ototoxic and nephrotoxic. Vertigo and hearing
loss are the most common adverse effects and may be permanent. Toxicity is dose-related, and the risk is increased
in the elderly. (Kanamycin had been used for treatment of tuberculosis caused by streptomycin-resistant strains;
Amikacin is playing a greater role in the treatment of tuberculosis due to the prevalence of multidrug-resistant
strains; Amikacin is indicated for treatment of tuberculosis suspected or known to be caused by streptomycin-
resistant or multidrug- resistant strains. This drug must be used in combination with at least one and preferably two
or three other drugs to which the isolate is susceptible for treatment of drug-resistant cases.)
Ethionamide chemically related to isoniazid and similarly blocks the synthesis of mycolic acids. It is poorly water
soluble and available only for oral use.
Capreomycin is a peptide protein synthesis inhibitor antibiotic obtained from Streptomyces capreolus.
Capreomycin (15 mg/kg/d) is an important injectable agent for treatment of drug-resistant tuberculosis.
Capreomycin is nephrotoxic and ototoxic. Tinnitus, deafness, and vestibular disturbances occur. The injection
causes significant local pain, and sterile abscesses may develop.
Cycloserine a structural analog of d-alanine inhibits cell wall synthesis; the most serious toxic effects are
peripheral neuropathy and central nervous system dysfunction, including depression and psychoses. Pyridoxine,
100 mg or more per day, should be given with cycloserine because this ameliorates neurologic toxicity.
Aminosalicylic acid (PAS) is a folate synthesis antagonist that is active almost exclusively against M tuberculosis.
It is structurally similar to p-amino-benzoic acid (PABA) and is thought to have a similar mechanism of action to the
sulfonamide. Gastrointestinal symptoms are common but occur less frequently with the delayed-release granules;
they may be diminished by giving the drug with meals and with antacids. Peptic ulceration and hemorrhage may
occur. Hypersensitivity
This document reactions
and the information manifested
thereon by fever,
is the property of joint pains, skin rashes, hepatosplenomegaly, hepatitis,
PHINMA adenopathy, and granulocytopenia
Education (Department often occur after 3 8 weeks of PAS therapy, making it necessary2to
of Pharmacy ofstop
6
administration temporarily or permanently.
Fluoroquinolones In addition to their activity against many Gram-positive and Gram-negative bacteria
ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin inhibit strains of M tuberculosis at concentrations less than
2 mcg/mL. They are also active against atypical mycobacteria. Moxifloxacin is the most active against M
administration
such temporarily
as moxifloxacin or permanently.
or levofloxacin.
Fluoroquinolones
Linezolid inhibits strains In addition to their in
of M tuberculosis activity
vitro atagainst many of
concentrations Gram-positive
4 8 mcg/mL. and Gram-negative
It achieves good intra-bacteria
cellular
ciprofloxacin, levofloxacin,
concentrations, and it is activegatifloxacin,
in murineand moxifloxacin
models inhibit strains
of tuberculosis. of Mhas
Linezolid tuberculosis
been used atinconcentrations
combination with lessother
than
2 mcg/mL.
second- and They are drugs
third-line also to active
treat against
patients atypical mycobacteria.
with tuberculosis causedMoxifloxacin is the most
by multidrug-resistant active
strains. against M
Conversion of
tuberculosis
sputum culturesin vitro. Levofloxacin
to negative tends to bewith
was associated slightly more use
linezolid activein than
theseciprofloxacin againstadverse
cases. Significant M tuberculosis, whereas
effects, including
ciprofloxacin
bone marrow is slightly more
suppression and active againstperipheral
irreversible atypical mycobacteria.
and optic neuropathy, have been reported with the prolonged
Fluoroquinolones
courses of therapyare thatanareimportant
necessary addition to the drugs
for treatment available for tuberculosis, especially for strains that are
of tuberculosis.
resistant to
Rifabutin first- linefrom
is derived agents. The World
rifamycin and isHealth
relatedOrganization
to rifampin. It recommends using
has significant a later
activity generation
against fluoroquinolone
M tuberculosis, MAC,
suchMycobacterium
and as moxifloxacinfortuitum.
or levofloxacin.
Its activity is similar to that of rifampin. Rifabutin is associated with similar rates of
Linezolid inhibits
hepatotoxicity strains
or rash of M tuberculosis
compared to rifampin;init vitro
can at concentrations
also cause leukopenia,of 4 8thrombocytopenia,
mcg/mL. It achieves good
and opticintra- cellular
neuritis.
concentrations,
Rifapentine and it isanalog
is another active of in rifampin.
murine models of tuberculosis.
It is active against both Linezolid has been
M tuberculosis used
and MAC.in combination with other
As with all rifamycins,
itsecond- and third-line
is a bacterial drugs to treat
RNA polymerase patients
inhibitor, andwith tuberculosis caused
cross-resistance betweenby multidrug-resistant
rifampin and rifapentine strains. Conversion
is complete. of
Like
sputum cultures
rifampin, rifapentine to negative
is a potent wasinducer
associated with linezolid
of cytochrome P450 useenzymes,
in these cases. Significant
and it has the same adverse effects, including
drug interaction profile;
bone marrow
however, when suppression
rifapentineand is irreversible
administered peripheral and optic
intermittently, neuropathy,
induction have beenofreported
of metabolism with the prolonged
other medications is less
courses of therapy
pronounced compared that to
are necessary
rifampin. for treatment
Toxicity is similaroftotuberculosis.
that of rifampin.
Rifabutin is derived
Bedaquiline, from rifamycin
a diarylquinoline, andfirst
is the is related
drug withto rifampin.
a novelItmech-
has significant
anism ofactivity
action against
against M Mtuberculosis,
tuberculosis MAC, to be
and Mycobacterium fortuitum. Its activity is similar to that of rifampin.(ATP)
-triphosphate Rifabutin is associated
synthase with similar
in mycobacteria, hasrates of
in vitro
hepatotoxicity
activity againstorboth rashreplicating
comparedand to rifampin; it can also
nonreplicating cause
bacilli, and leukopenia, thrombocytopenia,
has bactericidal and optic
and sterilizing activity in neuritis.
the murine
Rifapentine
model is another analog
of tuberculosis. of rifampin. It has
Cross-resistance is active
beenagainst
reported bothbetween
M tuberculosis and MAC.
bedaquiline and As with all rifamycins,
clofazimine. Current
it is a bacterial RNA
recommendations polymerase
state inhibitor,in
that bedaquiline, and cross-resistance
combination with at between rifampin
least three and rifapentine
other active medications,is complete.
may be used Like
rifampin,
for rifapentine
24 weeks is a potent
of treatment inducer
in adults withoflaboratory-confirmed
cytochrome P450 enzymes, pulmonaryandtuberculosis
it has the same drug
if the interaction
isolate profile;
is resistant to
however,
both when
isoniazid andrifapentine
rifampin. is administered intermittently, induction of metabolism of other medications is less
pronounced compared to rifampin. Toxicity is similar to that of rifampin.
Bedaquiline, a diarylquinoline, is the first drug with a novel mechanism of action against M tuberculosis to be
Many mycobacterial infections seen in clinical practice are caused -triphosphate (ATP) synthase
by nontuberculous in mycobacteria,
mycobacteria (NTM), formerly has in vitro
known
activity against both replicating and nonreplicating bacilli, and has bactericidal and sterilizing activity in the murine
and are model of not
generally tuberculosis.
communicable Cross-resistance
from person tohas been As
person. reported between
a rule, these bedaquilinespecies
mycobacterial and clofazimine. Current
are less susceptible
recommendations
than M tuberculosis to anti-TB statedrugs.
that bedaquiline, in combination with at least three other active medications, may be used
AGENTS FOR LEPROSY (Mycobacterium leprae)
Mycobacterium leprae has never been grown in vitro, but animal models, such as growth in injected mouse footpads,
have permitted laboratory evaluation of drugs.
Several drugs closely related to the sulfonamides have been used effectively in the long-term treatment of leprosy. The
most widely used is dapsone (diaminodiphenylsulfone). Like the sulfonamides, it inhibits folate synthesis. Resistance can
emerge in large populations of M leprae, eg, in lepromatous leprosy, particularly if low doses are given. Therefore, the
combination of dapsone, rifampin, and clofazimine is recommended for initial therapy of lepromatous leprosy. A combination
of dapsone plus rifampin is commonly used for leprosy with a lower organism burden. Dapsone may also be used to prevent
and treat Pneumocystis jiroveci pneumonia in AIDS patients.
Dapsone is usually well tolerated. Many patients develop some hemolysis, particularly if they have glucose-6-phosphate
dehydrogenase deficiency. Methemoglobinemia is common but usually is not clinically significant. Gastrointestinal
intolerance, fever, pruritus, and rash occur. During dapsone therapy of lepromatous leprosy, erythema nodosum leprosum
often develops. It is sometimes difficult to distinguish reactions to dapsone from manifestations of the underlying illness.
Erythema nodosum leprosum may be suppressed by thalidomide
Rifampin in a dosage of 600 mg daily is highly effective in leprosy and is given with at least one other drug to prevent
emergence of resistance. Even a dose of 600 mg per month may be beneficial in combination therapy.
Clofazimine is a phenazine dye used in the treatment of multibacillary leprosy, which is defined as having a positive smear
from any site of infection. Its mechanism of action has not been clearly established. The most prominent adverse effect is
discoloration of the skin and conjunctivae. Gastrointestinal side effects are common.
RATIONALIZATION ACTIVITY (DURING THE FACE TO FACE INTERACTION WITH THE STUDENTS)
The instructor will now rationalize the answers to the students and will encourage them to ask questions and to discuss
among their classmates for 15-20 minutes.
1. INHIBITS MYCOLIC ACID SYNTHESIS
A. RIFAMYCIN
B. ISONIAZID
C. ETHAMBUTOL
D. PYRAZINAMIDE
ANSWER: B
2. PYRAZINAMIDE ADVERSE EFFECTS

I. PERIPHERAL NEUROPATHY
II. THROMBOCYTOPENIA
III. HEPATOTOXICITY
IV. HYPERURICEMIA
A. I, II B. II, III C. III, IV D. I, II, III
ANSWER: C (PERIPHERAL NEUROPATHY IS THE TOXICITY OF ISONIAZID; THROMBOCYTOPENIA IS A SIDE

EFFECT OF RIFAMYCINS)

PHINMA Education (Department of Pharmacy 4 of 6
3. INHIBITS RNA SYNTHESIS
A. RIFAMPIN
B. ISONIAZID
C. ETHAMBUTOL
D. PYRAZINAMIDE
ANSWER: A
4. ETHAMBUTOL TARGETS WHICH ENZYME?

A. RNA POLYMERASE
B. BETA-LACTAMASE
C. ARABINOSYL TRANSFERASE
D. DNA GYRASE
ANSWER: C
5. DRUGS USED IN LEPROSY

A. DAPSONE
B. RIFAMPIN
C. CLOFAZIMINE
D. ALL OF THE ABOVE
ANSWER: D
Antifungal Agents
Patients on antifungal agents are immuno-compromised at onset
Antifungals (Antimycotic drugs) are used to treat mycosis, or infections caused by fungi. Fungi are different from bacteria
in the sense that their cell walls are made up of chitin and various polysaccharides rendering these organisms resistant to
antibiotics.
Common fungal infections
1. is a fungal infection that affects the skin on your feet, often between your toes.
itching, or a burning, stinging sensation between your toes or
on the soles of your feet; skin that appears red, scaly, dry, or flaky; cracked or blistered skin
2. Jock itch (tinea cruris) is a fungal skin infection that happens in the area of your groin and thighs
most common in men and adolescent boys.
The main symptom is an itchy red rash that typically starts in the groin area or around the upper inner
thighs. The rash may get worse after exercise or other physical activity and can spread to the buttocks
and abdomen.
The affected skin may also appear scaly, flaky, or cracked. The outer border of the rash can be slightly
This document andand
raised the information
darker. thereon is the property of
PHINMA Educationof(Department
3. Ringworm of Pharmacy)
the scalp (tinea 1 of 7
capitis) This fungal infection affects the skin of the scalp and the associated
as well as antifungal shampoo. The symptoms can include:

localized bald patches that may appear scaly or red
associated scaling and itching
associated tenderness or pain in the patches
4. Tinea versicolor sometimes called pityriasis versicolor, is a fungal/yeast skin infection that causes small
called Malassezia, which is naturally present on the skin of about 90 percent of adults.
These discolored skin patches most often occur on the back, chest, and upper arms. They may
look lighter or darker than the rest of your skin, and can be red, pink, tan, or brown. These patches
can be itchy, flaky, or scaly.
Tinea versicolor is more likely during the summer or in areas with a warm, wet climate. The condition
as well as antifungal shampoo. The symptoms can include:
localized bald patches that may appear scaly or red
associated scaling and itching
associated tenderness or pain in the patches
4. Tinea versicolor sometimes called pityriasis versicolor, is a fungal/yeast skin infection that causes small
called Malassezia, which is naturally present on the skin of about 90 percent of adults.
These discolored skin patches most often occur on the back, chest, and upper arms. They may
look lighter or darker than the rest of your skin, and can be red, pink, tan, or brown. These patches
can be itchy, flaky, or scaly.
Tinea versicolor is more likely during the summer or in areas with a warm, wet climate. The condition
can sometimes return following treatment.
5. Cutaneous candidiasis is a skin infection Candida fungi. This type of fungi is naturally
present on and inside our bodies. When it overgrows, an infection can happen.
Candida skin infections occur in areas that are warm, moist, and poorly ventilated. Some examples
of typical areas that can be affected include under the breasts and in the folds of the buttocks, such
as in diaper rash.
The symptoms of a Candida infection of the skin can include: a red rash, itching, small red pustules
6. Onychomycosis (tinea unguium) is a fungal infection of your nails. It can affect the fingernails or the
toenails, although infections of the toenails are more common.
You may have onychomycosis if you have nails that are: discolored, typically yellow, brown, or white,
brittle or break easily & thickened
Antifungals can be systemic and/or topical

Systemic antifungals are used to treat systemic mycoses and can be toxic to the host and not to be used
indiscriminately. It is important to get a culture of the fungus causing the infection to ensure that the right drug
brittle or break easily & thickened
Antifungals can be systemic and/or topical

Systemic antifungals are used to treat systemic mycoses and can be toxic to the host and not to be used
indiscriminately. It is important to get a culture of the fungus causing the infection to ensure that the right drug
is being used so that the patient is not put at additional risk from the toxic adverse effects associated with these
drugs.
Topical antifungals are used to treat a variety of mycoses of skin and mucous membranes. Some systemic
antifungals have topical forms.
MICONAZOLE
UNDECYLENIC ACID
Claasification of Antifungal Drugs and Mechanism of Action
1. Polyenes: Act by binding to ergo sterol in the fungal cell membrane. This binding results in depolarization
of the membrane. This binding results in depolarization of the membrane and formation of pores that
increase permeability to proteins and monovalent and divalent cations, eventually leading to cell death.
2. Echinocandins: noncompetitively inhibit beta-1,3-D-glucan synthase enzyme complex in susceptible fungi
to disturb fungal cell glucan synthesis. Beta-glucan destruction prevents resistance against osmotic
forces, which leads to cell lysis. They have fungistatic activity against Aspergillus species
3. Antimetabolites: Inhibits fungal protein synthesis by replacing uracil with 5 fluro uracil in fungal RNA, also
inhibit thymidilate synthetase via 5-flourodeoxy-uridine monophosphate and thus interferes with fungal
DNA synthesis.
4. Allylamines: Inhibits ergo sterol synthesis by inhibiting the enzyme squalene epoxidase.
5. Azoles: Inhibition of cytochrome P450 14a-demethylase. This enzyme is in the sterol biosynthesis
pathway that leads from lanosterol to ergo sterol.
UNDECYLENIC
ACID
INDICATIONS:
Amphotericin B
Aspergillosis
Leishmaniasis
Cryptococcosis
Blastomycosis
Moniliasis
Coccidioidomycosis
Histoplasmosis
Mucormycosis
Candida infections (topically)
Amphotericin B
Indications: progressive, potentially fatal fungal infections
Pharmacokinetics: IV form, excreted in the urine
Contraindication: kidney disease
This document
Adverseand the information
reaction: thereon is the property of
kidney failure
PHINMA Education (Department of Pharmacy) 3o
Systemic Antifungal Agents
Caspofungin (Cancidas) (IV) : Approved for the treatment of invasive aspergillosis in patients who are refra
other treatments
Flucytosine (Ancobon) (oral) : Less toxic drug used for the treatment of systemic infections caused by Ca
Cryptococcus
Nystatin (Mycostatin, Nilstat) (oral): Used for the treatment of intestinal candidiasis; also available in a nu
Pharmacokinetics: IV form, excreted in the urine
Contraindication: kidney disease
Adverse reaction: kidney failure
Systemic Antifungal Agents

Caspofungin (Cancidas) (IV) : Approved for the treatment of invasive aspergillosis in patients who are refractory to
other treatments
Flucytosine (Ancobon) (oral) : Less toxic drug used for the treatment of systemic infections caused by Candida or
Cryptococcus
Nystatin (Mycostatin, Nilstat) (oral): Used for the treatment of intestinal candidiasis; also available in a number of
topical preparations
Voriconazole & Terbinafine
Voriconazole (Vfend) : Available in oral and IV forms. Treats invasive aspergillosis and serious infections caused
by Scedosporium apiospermum and Fusarium species
Terbinafine (Lamisil) : Blocks the formation of ergosterol, Inhibits a CYP2D6 enzyme system. Oral drug for the
treatment of onychomycosis of the toenail or fingernail
Azoles
o Newer class of drugs used to treat systemic fungal infections. Less toxic than amphotericin B, Less effective than
amphotericin B
Ketoconazole (Nizoral)
Used orally to treat many of the same mycoses as amphotericin B
Works by blocking the activity of a steroid in the fungal wall
Has side effect of blocking the activity of human steroids, including testosterone and cortisol
Pharmacokinetics: absorbed from the GI tract, metabolized in the liver, excreted in the feces
Terbinafine (Lamisil) : Blocks the formation of ergosterol, Inhibits a CYP2D6 enzyme system. Oral drug for the
treatment of onychomycosis of the toenail or fingernail
Azoles
o Newer class of drugs used to treat systemic fungal infections. Less toxic than amphotericin B, Less effective than
amphotericin B
Ketoconazole (Nizoral)
Used orally to treat many of the same mycoses as amphotericin B
Works by blocking the activity of a steroid in the fungal wall
Has side effect of blocking the activity of human steroids, including testosterone and cortisol
Pharmacokinetics: absorbed from the GI tract, metabolized in the liver, excreted in the feces
Contraindications: not drug of choice for patients with endocrine or fertility problems
Adverse reaction: hepatic toxicity
Drug-to-drug interactions: many
Fluconazole (Diflucan)
Not associated with the endocrine problems seen with ketoconazole
Used to treat candidiasis, cryptococcal meningitis, and other systemic fungal infections
Prophylactic agent for reducing the incidence of candidiasis in bone marrow transplant recipients
Pharmacokinetics: available in oral and IV preparations, excreted unchanged in the urine
Contraindications: renal dysfunction
Adverse reactions:
Drug-to-drug interactions: inhibits CYP450 and may be associated with drug-to-drug interactions
Itraconazole (Sporanox)
An oral agent used for the treatment of assorted systemic mycoses
Associated with hepatic failure
Slowly absorbed from the GI tract, it is metabolized in the liver by the CYP450 system
Excreted in the urine and feces
There is an increased incidence of fungal infections in immunocompromised patients (e.g., patients with AIDS, those
Itraconazole (Sporanox)
An oral agent used for the treatment of assorted systemic mycoses
Associated with hepatic failure
Slowly absorbed from the GI tract, it is metabolized in the liver by the CYP450 system
Excreted in the urine and feces
There is an increased incidence of fungal infections in immunocompromised patients (e.g., patients with AIDS, those
taking immunosuppressants like organ transplant recipients, etc.).
Overall Contraindications to Systemic Antifungal Agents

Anyone with a known allergy
Pregnant or lactating women (with the exception of terbinafine for life-threatening infections)
Patients with renal or liver disease : Drug metabolism or excretion may be altered, or condition may worsen as a
result of the actions of the drug
Overall Adverse Reactions to Systemic Antifungal Agents

CNS effects : Headache, dizziness, fever, shaking, and chills
GI effects: Nausea, vomiting, dyspepsia, and anorexia
Hepatic dysfunction
Dermatologic effects :Rash and pruritus associated with local irritation
Renal dysfunction

Antiviral Agents
Characteristics of Antiviral Drugs

Able to enter the cells infected with virus
Interfere with viral nucleic acid synthesis and/or regulation
Some agents interfere with the ability of the virus to bind to cells
Common Respiratory Viruses

Influenza A
Influenza B
Respiratory syncytial virus
ANTIVIRAL DRUGS
Antivirals are agents used to treat the diseases caused by viruses such as warts and common colds.
Viruses are composed of a single DNA or RNA inside a protein coat. Viruses must enter a cell in order for them to carry
on with their metabolic processes.
Upon successful entry, viruses inject their DNA or RNA to the cell and the cell is altered in such a manner that it is now
Because viruses are contained in the cells, researchers find it difficult to develop vaccines. However, viruses respond
to some antiviral therapy including influenza A viruses, herpes viruses, CMV, HIV, hepatitis B and C viruses, and some
viruses that cause warts and eye infections.
Viruses That Respond to Antiviral Therapy

Influenza A and some respiratory viruses
Herpes viruses
Cytomegalovirus (CMV)
Human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS)
Some viruses that cause warts and certain eye infections
Constitutional symptoms: fever lasting more than a month, involuntary weight loss, chronic fatigue
Neurologic disease: dementia
Secondary infections: pneumocystis carinii and disseminated herpes simplex
Drugs for Influenza A & Respiratory Viruses

Action: prevent shedding of the viral protein coat
Pharmacokinetics: administered orally and excreted unchanged in the urine
Contraindications: allergy, pregnancy, and lactation
Adverse reactions: dizziness, insomnia, nausea, orthostatic hypotension
Drug-to-drug interactions: anticholinergic agents
Drugs for Herpes & Cytomegalovirus

Action: inhibit viral DNA replication by competing with viral substrates to form shorter, noneffective DNA
chains
Pharmacokinetics: administered orally, IV, or topically; excreted unchanged in the urine
Contraindications: pregnancy and lactation
Adverse reactions: nausea, vomiting, headache, rash, and hair loss
Drug-to drug-interactions: nephrotoxic drugs and zidovudine
Drugs Used to Treat HIV/AIDS
Reverse Transcriptase Inhibitors

Action: bind directly to HIV reverse transcriptase, blocking both RNA- and DNA-dependent DNA
polymerase activities
Pharmacokinetics: given orally, metabolized in the liver, and excreted in the urine
Adverse reactions: nausea, vomiting, headache, rash, and hair loss
Drug-to drug-interactions: nephrotoxic drugs and zidovudine
Drugs Used to Treat HIV/AIDS
Reverse Transcriptase Inhibitors

Action: bind directly to HIV reverse transcriptase, blocking both RNA- and DNA-dependent DNA
polymerase activities
Pharmacokinetics: given orally, metabolized in the liver, and excreted in the urine
Adverse reactions: HA, insomnia, dizziness, nausea, diarrhea, fever, and rash
Adverse reactions: headache, nausea, vomiting, rash, chills, fever, and diarrhea
PHINMA Inhibitors
Protease Education (Department of Pharmacy)
(end in -navir) 3 of 7
Action: block protease activity within the HIV virus
Pharmacokinetics: agents are teratogenic except for saquinavir
Fusion Inhibitors
Action: prevent the fusion of the virus with the human cellular membrane
Pharmacokinetics: given sub-q, metabolized in the liver, recycled in the tissues, and not excreted
Contraindication: no true contraindication
Adverse reactions: HA, dizziness, myalgia, nausea, vomiting, and diarrhea
Drug-to-drug interactions: pimozide, rifampin, triazolam, midazolam, and oral contraceptives
SUMMARY TABLE FOR DRUG CLASS FAMILIARIZATION
AGENTS FOR AGENTS FOR ANTIRETROVIRAL ANTIHEPATITIS ANTI-INFLUENZA
HERPES SIMPLEX CYTOMEGALO- AGENTS AGENTS AGENTS
VIRUS (HSV) & VIRUS (FOR HIV/AIDS)
VARICELLA- (CMV)
ZOSTER VIRUS INFECTIONS
(VZV)
Acyclovir Valganciclovir NUCLEOSIDE For treatment of NEURAMINIDASE

Famciclovir Ganciclovir REVERSE Hepatitis B Virus INHIBITORS:
Valacyclovir Foscarnet TRANSCRIPTASE infection: Oseltamivir
Docosanol Cidofovir INHIBITORS (NRTIs) Zanamivir
Penciclovir Interferon alfa Peramivir
Ganciclovir - Abacavir Adefovir
Trifluridine - Tenofovir Entecavir VIRAL
Foscarnet - Didanosine Telbivudine UNCOATING
- Emtricitabine INHIBITORS:
- Lamivudine Antiretrovirals which Amantadine
- Stavudine act against Hepatitis Rimantadine
- Zidovudine B virus (HBV):
Tenofovir
NONNUCLEOSIDE Lamivudine
REVERSE
TRANSCRIPTASE
INHIBITORS (NNRTIs) For treatment of
- Delavirdine Hepatitis C infection:
- Efavirenz
- Etravirine Daclatasvir
- Rilpivirine Elbasvir
- Nevirapine Ledipasvir
Ombitasvir
PROTEASE Velpatasvir
INHIBITORS
- Tipranavir Dasabuvir
- Nelfinavir Sofosbuvir
- Nelfinavir
- Ritonavir Grazoprevir
- Indinavir Paritaprevir
- Lopinavir Simeprevir
- Atazanavir
- Darunavir Ribavirin
- Saquinavir
FUSION INHIBITORS
- Enfuvirtide
ENTRY INHIBITORS
- Maraviroc (CCR5
receptor inhibitor)
INTEGRASE STRAND
TRANSFER INHIBITORS
(INSTIs)
- Dolutegravir
- Elvitegravir
- Raltegravir
Antiprotozoal
ANTIPROTOZOAL AGENTS
Antiprotozoals are agents used to treat protozoan infections. Protozoan infections are common in tropical areas.
Protozoans are single-celled organisms that pass through several stages in their life cycles, including at least one phase
as a human parasite. While protozoans thrive in tropical climate, they may also survive and reproduce in any area where
people live in very crowded and unsanitary conditions.
Causes of Protozoal Infections

1. Insect bites : Malaria, Trypanosomiasis, Leishmaniasis
2. Ingestion or contact with the causal organism : Amebiasis, Giardiasis, Trichomoniasis
Protozoal Parasites Identified as Causes of Malaria
1. Plasmodium falciparum : Considered the most dangerous type of protozoan

2. Plasmodium vivax : Milder form of the disease; seldom results in death
3. Plasmodium malariae : Endemic in tropical countries; mild symptoms
4. Plasmodium ovale : Rarely seen; in the process of being eradicated
PLASMODIUM LIFE CYCLE
Protozoal Diseases:
Malaria
It is a disease characterized by a cycle of fever and chills transmitted through a bite of a female Anopheles mosquito.
Identified causes include Plasmodium falciparum, P. vivax, P. malariae, and P. ovale. Malaria is endemic in many parts
of the world.
Sporozoites travel through bloodstream and become lodged in the liver and other tissues.
Amebiasis
It is an intestinal infection caused by Entamoeba histolytica. It is often known as amoebic dysentery. The disease is
transmitted through fecal-oral route.
Amebiasis is characterized by mild to fulminant diarrhea. In worst cases, it is able to invade extraintestinal tissue.
Leishmaniasis
Is a disease caused by a protozoan that is passed from sand flies to humans. It is characterized by serious lesions in
the skin, viscera, and mucous membranes of host.
Trypanosomiasis
Is caused by Trypanosoma
African sleeping sickness is caused by T.brucei gambiense and is transmitted by tsetse fly. It is characterized by
lethargy, prolonged sleep, and even death.
is caused by T.cruzi and is passed to humans by common housefly. It is characterized by severe
cardiomyopathy.
Trichomoniasis
Is caused by T.vaginalis, a common cause of vaginitis (reddened, inflamed vaginal mucosa, itching, burning, and
yellowish-green discharge).
It is usually transmitted through sexual intercourse.
Asymptomatic in men
Giardiasis
Is caused by G.lamblia, the most commonly diagnosed intestinal parasite in the United States.
Transmission is through contaminated water or food, and trophozoites.
Characterized by diarrhea, rotten egg-smelling stool, and pale and mucus-filled stool. Some patients experience
epigastric pain, weight loss, and malnutrition.
Commonly used oral antiprotozoal drugs can be generally classified into two main groups: antimalarial drugs and
miscellaneous antiprotozoals. In addition to their use as antiprotozoals, some of them such as metronidazole and
doxycycline are also used for treating bacterial infections
Antimalarials: Antimalarials are agents used to attack Plasmodium at various stages of its life cycle. Through this, it
becomes possible to prevent acute malarial reaction in individuals who have been infected by the parasite.
These agents can be:
o schizonticidal (acting against the red-blood-cell phase of the life cycle),
o gametocytocidal (acting against the gametocytes),
o sporontocidal (acting against the parasites that are developing in the mosquito)
Quinine (Qualaquine) was the first drug found to be effective in the treatment of malaria. Treatment of
chloroquine-resistant plasmodial infections
Chloroquine (Aralen): Prevention and treatment of plasmodial malaria; treatment of extraintestinal amebiasis
Halofantrine (Halfan): Treatment of plasmodial malaria in combination with other drugs
Hydroxychloroquine (Plaquenil): Treatment of plasmodial malaria in combination with other drugs (particularly
primaquine)
Mefloquine (Lariam): Prevention and treatment of plasmodial malaria in combination with other drugs
Primaquine (generic): Prevention of relapses of Plasmodium vivax and Plasmodium malariae infections;
Radical cure of P. vivax malaria
Pyrimethamine (Daraprim) : Prevention of plasmodial malaria in combination with other agents to suppress
Therapeutic Action of antimalarials:

Radical cure of P. vivax malaria
Pyrimethamine (Daraprim) : Prevention of plasmodial malaria in combination with other agents to suppress
Therapeutic Action of antimalarials:

Entering human red blood cells and changing the metabolic pathways necessary for the reproduction. Chloroquine, the
mainstay of treatment, in addition to this main mechanism, is directly toxic to parasites and decreases the ability of the
parasite to synthesize DNA.
Interrupt plasmodial reproduction of protein synthesis
Agents that do not appear to affect the sporozoites are used for prophylaxis
Contraindications: Known allergy, Liver disease, Alcoholism, Lactation

Cautions: Retinal disease or damage, Psoriasis
Adverse Effects: Headache, Dizziness, Fever, Chills, Malaise, Nausea, Vomiting, Hepatic dysfunction
Drug-to-Drug Interactions
Quinine derivatives and quinine create risk for cardiac toxicity
Antifolate drugs with pyrimethamine can increase risk of bone marrow suppression
Other Antiprotozoal Drugs

Actions:
leading to cell death
Contraindications: Known allergy, pregnancy, CNS disease, and hepatic disease
Adverse reactions: Headache, dizziness, ataxia, nausea, vomiting, and diarrhea
STUDY THIS SUMMARY TABLE FOR ANTIPROTOZOALS
ANTIMALARIALS Chloroquine, Amodiaquine, Piperaquine, Primaquine, Sufladoxine,

Pyrimethamine, Proguanil, Quinine, Mefloquine, Halofantrine, Lumefantrine,
Causative agent: Atovaquone, Artemisinin, Pyronaridine
Plasmodium spp.
AGENTS FOR AMEBIASIS Diloxanide furoate, Iodoquinol, Paromomycin, Metronidazole, Tinidazole
Causative agent: (Antibiotics that may be used as alternative treatment: Tetracycline,

Entamoeba hystolitca erythromycin)
AGENTS FOR AFRICAN Pentamidine, Suramin, Eflornithine, Melarsoprol, Nifurtimox

SLEEPING SICKNESS
(TRYPANOSOMIASIS)
Causative agent:
Trypanosoma brucei gambiense
(From Tse-Tse Fly)
AGENTS FOR TRICHOMONIASIS Metronidazole, Tinidazole
Causative agents:
Trichomonas vaginalis
AGENTS FOR TOXOPLASMOSIS Pyrimethamine + Clindamycin + Folinic acid

Trichomonas vaginalis
AGENTS FOR TOXOPLASMOSIS Pyrimethamine + Clindamycin + Folinic acid

Spiramycin
Causative agents: Pyrimethamine + Sulfadiazine + Folinic acid
Toxoplasma gondii
(usually from cats)
AGENTS FOR LEISHMANIASIS Sodium stibogluconate

Meglumine antimonate
Causative agents: Miltefosine
Leishmania donovano
Leishmania braziliensis
Leishmania tropica
Leishmania major
Leishmania Mexicana
Leishmania chagasi
AGENTS FOR GIARDIASIS Metronidazole, Tinidazole, Furazolidone
Causative agents:
Giardia lamblia
AGENTS FOR BALANTIDIASIS Drug of choice is the broad-spectrum antibiotic Tetracycline but alternative can
be metronidazole
Causative agents:
Balantidium coli
(usually from swine)

2. Describe the pharmacokinetic, mechanism of drug Katzung, B.G. (2018)
action & drug resistance, clinical uses and adverse drug Pharmacology (14th e
reactions of antihelminthic drugs Medical Books/McGra
Anthelmintic Agents
Introductory Activity:
RECALL THE CLASSIFICATIONS OF HELMINTHS. MATCH ACCORDINGLY:
A ROUNDWORMS B TAPEWORMS C - FLUKES
1. NEMATODES ANSWER: A
2. CESTODES ANSWER: B
3. TREMATODES ANSWER: C
ANTHELMINTIC AGENTS
ANTHELMINTIC AGENTS
Two General Classe of Helminths Commonly Infecting Humans

1. Nematodes or roundworms: Pinworms, whipworms, threadworms, Ascaris, and hookworms
2. Platyhelminthes or flatworms : Cestodes (tapeworms) and Trematodes/flukes (schistosomes)
Measures to Control Infection

Keep nails short
Keep hands clean
Frequent handwashing
Shower in the morning
Change and launder undergarments, bed linens, and pajamas daily
Disinfect toilet seat daily
Handwashing after using the bathroom
Tissue-Invading Worms
Trichinosis : Caused by ingestion of the encysted larvae of the roundworm, Trichinella spiralis, in undercooked pork
Filariasis: Infection of the blood and tissues of healthy individuals by worm embryos, injected by insects
Schistosomiasis : Infection by a fluke that is carried usually by a snail
Mebendazole (Vermox)
Most commonly used of all of the anthelmintics
Effective against pinworms, roundworms, whipworms, and hookworms
Available in the form of a chewable tablet
Few adverse effects
Not metabolized in the body; most is excreted unchanged in the feces
Should not be used during pregnancy
Pyrantel (Antiminth, Pin-Rid, Pin-

Oral drug effective against pinworms and roundworms
Given as a single dose
Poorly absorbed; excreted unchanged in the feces
Not recommended for use during pregnancy and lactation
Safety not established for children age <2 years
Adverse effects may include GI side effects and diarrhea
Thiabendazole (Mintezol)
Treats roundworm, hookworm, and whipworm infections
Not the anthelmintic drug of choice (not as effective, more adverse effects)
Best drug for treatment of threadworm infections
Readily absorbed from the GI tract; reaches peak levels in 1 to 2 hours
Metabolized in the liver and excreted in the urine
Albendazole (Albenza)
Metabolized in the liver and excreted in the urine
Albendazole (Albenza)
Treats active lesions caused by pork tapeworm and cystic disease of the liver, lungs, and peritoneum
caused by dog tapeworm
Serious adverse effects
Should be used only after causative worm is identified
Poorly absorbed from the GI tract; reaches peak levels in about 5 hours
Metabolized in the liver and primarily excreted in the urine
Should not be used during pregnancy and lactation
Ivermectin (Stromectol)
Effective against the nematode that causes onchocerciasis or river blindness
Used to treat threadworm disease or strongyloidiasis
Readily absorbed from the GI tract; reaches peak plasma levels in 4 hours
Completely metabolized in the liver with a half-life of 16 hours; excreted through the feces
Should never be taken during pregnancy; used with caution during lactation
Praziquantel (Biltricide)
Very effective in the treatment of a wide number of schistosomes, or flukes
Taken in a series of three doses at 4- to 6-hour intervals
Has relatively few adverse effects
Rapidly absorbed from the GI tract; reaches peak plasma levels within 1 to 3 hours
Metabolized in the liver with a half-life of 0.8 to 1.5 hours
Excreted primarily through the urine
Lifestyle factors
Environmental factors
Classifications of Tumors
Antineoplastic Agents: Solid tumors
May originate in any body organ
A. Cancer, its causes, and overview of
Carcinomas (originate in epithelial cells)
Sarcomas (originate in the mesenchyma)
cancer treatment modalities
Hematologic malignancies
Leukemias and lymphomas that occur in the blood-forming organs
B. Oncologic Pharmacology
Medical management of cancer includes the use of chemotherapy. First used in t
(Chemotherapeutic Drugs)
80 effective drugs available. Chemotherapy is method of choice when there is su
malignant cells.
Goal of Cancer Treatment

To destroy cancer cells using the following methods:
o Surgical removal
o Stimulation of the immune system to destroy them
o Radiation therapy to destroy them
o Drug therapy to kill them during various phases of the cell cycle
CANCER
Cancer: is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the
body.
Types of Cancer
Carcinoma is a cancer that starts in the skin or the tissues that line other organs. These are most commonly
diagnosed cancers
Sarcoma is a cancer of connective tissues such as bones, muscles, cartilage, and blood vessels.
Leukemia is a cancer of bone marrow, which creates blood cells.
Lymphoma and myeloma are cancers of the immune system.
Melanoma are cancers that arise in the cells that make the pigment in the skin
Neoplasm Cancer Mechanisms of Growth
a. Anaplasia : Cancerous cells lose cellular differentiation and organization and are unable to function normally
b. Autonomy : Cancerous cells grow without the usual homeostatic restrictions that regulate cell growth and control. This
allows the cells to form a tumor
c. Metastasis: Cancer cells travel from the place of origin to develop new tumors in other areas of the body
d. Angiogenesis : Abnormal cells release enzymes to generate blood vessels and supply oxygen and nutrients to the
cells, generating growth. Cancerous cells rob the host cells of energy and nutrients and block normal lymph
Can damage or destroy some neoplastic cells

T cells recognize the abnormal cells and destroy them
Antibodies form in response to parts of the abnormal cell protein
cells
Possible Causes of Cancer

Genetic predisposition
Viral infection
Constant irritation and cell turnover
Stress
Lifestyle factors
Environmental factors
Classifications of Tumors
ANTINEOPLASTIC AGENTS
comprise one aspect of chemotherapy. These drugs act on and kill altered human cells. While their
action is intended to target abnormal cells, normal cells are also affected. These drugs can work by
affecting cell survival or by boosting the immune system in its efforts to combat the abnormal cells.
Drug Classification
Drugs classified by group into those that act on a certain phase of cell reproduction (cell cycle specific) or those that do
not reproduce (cell cycle nonspecific).
A. Cell cycle specific agents: antimetabolites and mitotic inhibitors.

Act on the cell during a particular phase of reproduction.
Most effective in tumors where a large number of cells are dividing.
Divided doses produce greater cytotoxic effects (not all cells will be in the same phase at the same time).
Antimetabolites.
a. Specific for the S phase
b. Examples of antimetabolites: Trexall (methotrexate), Purinethol (6-mercaptopurine), Adrucil (5-fluorouracil),
This document Vidaza
and the(azacitidine),
information Cytosar-U
thereon is(cytarabine),
the propertyHydrea
of (hydroxyurea).
Plant alkaloids. 2 of 7
a. Specific for the M phase prevent cell division by destroying the mitotic spindle.
b. Examples of mitotic inhibitors: plant alkaloids Oncovin (vincristine), Eldisine (vindesine), Velban (vinblastine),
Vumon (teniposide).
B. Cell cycle nonspecific drugs: alkylating agents, antitumor antibiotics, and nitrosoureas.
Act on cells during any phase of reproduction some drugs will attack cells in the resting phase (not actively
dividing).
Agents are dose dependent the more drug given, the more cells destroyed.
a. Specific for the M phase prevent cell division by destroying the mitotic spindle.
b. Examples of mitotic inhibitors: plant alkaloids Oncovin (vincristine), Eldisine (vindesine), Velban (vinblastine),
Vumon (teniposide).
B. Cell cycle nonspecific drugs: alkylating agents, antitumor antibiotics, and nitrosoureas.
Act on cells during any phase of reproduction some drugs will attack cells in the resting phase (not actively
dividing).
Agents are dose dependent the more drug given, the more cells destroyed.
These drugs are more toxic to normal tissue because they are less selective.
Alkylating agents
a. These drugs
phases of the cell cycle.
b. Included in almost all chemotherapy regimens.
c. Examples of alkylating agents: Cytoxan (cyclophosphamide), Myleran (busulfan), Alkeran (melphalan
[L-PAM]), Thioplex (thiotepa), Platinol (cisplatin).
Antitumor antibiotics.
a. These drugs attack DNA (they act like alkylating drugs) by slipping between the DNA strands and
preventing replication.
b. Examples of antitumor antibiotics: Adriamycin (doxorubicin), Cosmegen (dactinomycin).
Nitrosoureas.
a. Alkylating agents that are stronger and have a greater ability to attack cells in the resting phase of cell
growth.
b. These drugs can cross the blood brain barrier.
c. Examples of nitrosoureas: Zanosar (streptozocin), semustine (methyl-CCNU), Gliadel (carmustine or
BCNU), azacitidine (chlorozotocin or DCNU).
C. Hormonal agents (estrogens, androgen, progestins) work in all cycles and are used in therapy to affect the
hormonal environment (Decadron [dexamethasone], DES, Halotestin [fluoxymesterone], Nolvadex
Blenoxane (bleomycin), Velban, and dacarbazine
Studies at Stanford University now suggest ABVD and a fifth or sixth chemotherapy drug be combined with
C. Hormonal agents (estrogens, androgen, progestins) work in all cycles and are used in therapy to affect the
hormonal environment
Cancer cells divide(Decadron [dexamethasone],
erratically on DES,
different schedules; thusHalotestin [fluoxymesterone],
drugs that are Nolvadex
effective alone and have different
[tamoxifen], Deltasone
mechanisms [prednisone]).
of action can combine to destroy even more cells.
Affect used
Drugs the growth of hormone-dependent
in combination for synergistic tumors.
activity.
Steroids interfere
Guidelines for drugwith the synthesis
administration areofcarefully
protein and alterand
planned cell referred
metabolism
to as(lymphomas
protocols orand leukemias).
regimens.
a. Package inserts
Antihormones are based
(Nolvadex andon single-agent
Evista therapy,
[Raloxifene]) blocksotumor
it is important
growth bytodepriving
adhere tothe
thetumor
ordered protocol.
of the necessary
b. Dosages of drugs are based on height and weight calculated as body surface area.
hormones.
D. Combination chemotherapy.
E. Other chemotherapeutic agents
Most often administered in that do not fall
combination, intoenhances
which specific categories.
the response rate: for example, Adriamycin,
Elspar (asparaginase)
Blenoxane (bleomycin),anVelban,
enzyme used
and to treat lymphocytic leukemia; Eulexin (flutamide) antiandrogen used
dacarbazine
toStudies
treat prostate cancer;
at Stanford and Taxol
University now(paclitaxel)
suggest ABVD usedand
to treat
a fifthovarian,
or sixthbreast, and cell drug
chemotherapy lung cancers.
be combined with
Chemotherapeutic drugs cause myelosuppression; nursing interventions include blood counts and instituting
precautions
Cancer cellsif blood
dividecount falls below
erratically normal,
on different and assess
schedules; fordrugs
thus infection.
that are effective alone and have different
mechanisms of action can combine to destroy even more cells.
Drugs used in combination for synergistic activity.
This document and theforinformation
Guidelines thereon isare
drug administration thecarefully
property planned
of and referred to as protocols or regimens.
a. Package inserts are based on single-agent therapy, so it is important to adhere to the ordered protocol. 3 of 7
b. Dosages of drugs are based on height and weight calculated as body surface area.
E. Other chemotherapeutic agents that do not fall into specific categories.

Elspar (asparaginase) an enzyme used to treat lymphocytic leukemia; Eulexin (flutamide) antiandrogen used
to treat prostate cancer; and Taxol (paclitaxel) used to treat ovarian, breast, and cell lung cancers.
Chemotherapeutic drugs cause myelosuppression; nursing interventions include blood counts and instituting
FAMILIARIZE WHICH
AGENTS BELONG PER
MAJOR ANTI-CANCER
DRUG CLASS
1. PLATINUM ANALOGS CELL-CYCLE NON-SPECIFIC
2. TAXANES CELL-CYCLE SPECIFIC
3. ANTHRACYCLINES CELL-CYCLE NON-SPECIFIC
4. VINCA ALKALOIDS CELL-CYCLE SPECIFIC
5. TOPOISOMERASE INHIBITORS CELL-CYCLE SPECIFIC
Primary chemotherapy refers to chemotherapy administered as the primary treatment in patients who present with
advanced cancer for which no alternative treatment exists
Neoadjuvant chemotherapy refers to the use of chemotherapy in patients who present with localized cancer for
which alternative local therapies, such as surgery, exist but which have been shown to be less than completely
effective.
Adjuvant chemotherapy is administered after surgery has been performed, and the goal of chemotherapy is to
reduce the incidence of both local and systemic recurrence and to improve the overall survival of patients.

Nutritional Supplements:
Historical, Regulatory Factors, and Clinical Aspects
of Botanicals and Supplements
superimpositions. Match the supplement/botanical with the related pharmacologic effect.
________ 1. Milk Thistle ANSWER: H CHOICES:
A. FOR ANXIETY
________ 2. Garlic ANSWER: C
B. BRONCHODILATOR
________ 3. Kava-kava ANSWER: A
C. CHOLESTEROL-LOWERING
________ 4. Aconite ANSWER: G D. FOR DEMENTIA
________ 5. Melatonin ANSWER: I or A E. FOR MYOPATHY
________ 6. Coenzyme Q10 ANSWER: E F. OSTEOARTHRITIS
G. ANALGESIC
________ 7. Ginkgo ANSWER: D
H. HEPATOPROTECTIVE
________ 8. ANSWER: J
I. FOR INSOMNIA
________ 9. Glucosamine ANSWER: F
J. ANTIDEPRESSANT
________ 10. Ephedra ANSWER: B
LESSON WRAP-UP (5 minutes)

Definition of Terms (according to the WHO)

https://www.who.int/traditional-complementary-integrative-medicine/about/en/
Traditional medicine
Traditional medicine has a long history. It is the sum total of the knowledge, skill, and practices based on the
theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the
maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental
illness.
Complementary medicine
not part and the information thereon is the property of

This document -
care system. They are used interchangeably with traditional medicine in some countries. 1 of 4
Herbal medicines
Herbal medicines include herbs, herbal materials, herbal preparations and finished herbal products, that contain as
active ingredients parts of plants, or other plant materials, or combinations.
According to the National Center for Complementary and Integrative Health

(https://www.nccih.nih.gov/health/dietary-and-herbal-supplements)
Herbal supplements sometimes called botanicals are a type of dietary supplement containing one or more herbs.
The amount of scientific evidence on dietary supplements varies widely there is a lot of information on some and
Supplements you buy from stores or online may differ in important ways from products tested in research studies.
Rules for manufacturing and distributing dietary supplements are less strict than those for prescription or over-the-
counter drugs. Although the Food and Drug Administration (FDA) requires that companies submit safety data about
any new ingredient in a dietary supplement, the FDA is not authorized to review dietary supplements for safety and
effectiveness before they are marketed.
COMMON BOTANICAL SUBSTANCES & THEIR PHARMACOLOGIC EFFECTS:
1. Echinacea immune modulation, anti-inflammatory, antibacterial, antifungal, antiviral, and antioxidant

2. Garlic antioxidant and anti-lipidemic (cholesterol-lowering); lowers blood pressure; antimicrobial; antineoplastic
3. Ginkgo promotes vasodilation; improves cognitive function in people with dementia; antioxidant
4. Ginseng immune modulation; antioxidant; anti-inflammatory; cardioprotective; anticancer
5. Milk thistle hepatoprotective; anticancer; lactation-inducing
6. antidepressant; antiviral; anticarcinogenic
7. Saw palmetto for benign prostatic hyperplasia; anti-inflammatory
PURIFIED NUTRITIONAL SUPPLEMENTS
1. COENZYME Q10 aka CoQ, CoQ10, or ubiquinone; antioxidant; for hypertension; for heart disease; prevent statin-
induced myopathy
2. GLUCOSAMINE used for pain associated with knee osteoarthritis
3. MELATONIN for jetlag/insomnia, anxiety, reproductive health supplement
Bible Verses on Fear to Gain Victory in Your Life
God has not given us a spirit of fear
For God has not given us a spirit of fear, but of power,

love and a sound mind. 2 Timothy 1:7
What power do I have? The power that raised Jesus from

the dead is in me, giving me victory over anything that
comes against me.
Whose love do I have? His perfect love that casts out

every fear.
Why is my mind sound? I’ve been given the mind of

Christ, which is in perfect peace.
God is our strength
So do not fear, for I am with you; do not be

dismayed, for I am your God. I will strengthen
you and help you; I will uphold you with my
righteous right hand. Isaiah 41:10
When fear convinces us that we aren’t strong

enough to handle whatever comes our way, we
can be confident in the Lord.

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Continuing on…

SE: sedation on onset

• Autoimmune hemolytic anemia

Toxicity: dry mouth and sedation

3. Guanfacine and Guanabenz

VMAT inhibitor: Reserpine

AOTA Result à depletion of catecholamines

BB for glaucoma as topical drops:

Arrhythmias: Sotalol & Esmolol

HF: Metoprolol, Bisoprolol, Carvedilol

Classification of hypertension on the basis of blood pressure:

RELEASE OF NITRIC OXIDE:

v K+ channels: Diazoxide & Minoxidil (stabilizes membranes = less

v CCB – hypotension; reflex tachycardia (DHP)

In particular, kidney structures called

v Diuretics – reduce peripheral & pulmonary edema

v Aldosterone Antagonist – salt & water excretion &

vQuinidine – for most atrial and ventricular arrhythmia but more

Lidocaine (local anesthetic)

Flecainide/Encainide – for supraventricular arrhythmias (not to be

- Propranolol for atrial arrhythmias

Vernakalant – for atrial fibrillation

1. Thromboxane – platelet activator

ØHeparin –heterogenous mixture of sulfated mucopolysaccharides

- They bind to antithrombin and enhance its inactivation of factor Xa

LMW Heparins: Enoxaparin, Dalteparin, Tinzaparin

Monitoring: activated partial thromboplastin time (for UFH)

Toxicity of Heparin: Bleeding, alopecia, osteoporosis, thrombocytopenia

- Oral anticoagulants that need NO MONITORING

MOA: Rapidly lyse thrombi through

- Major application: For Acute Myocardial

Plasminogen can be activated

- Alteplase; Reteplase; Tenecteplase –

- For pulmonary embolism, severe DVT,

1. Aspirin – inhibits production of TXA2 by irreversible

3. Glycoprotein IIb/IIIa antagonists

Use: adjunct in treatment of hemophilia, used in cases of

PHYTONADIONE (VIT. K1) –found in food (aka phylloquinone)

ü Statins are most effective in lowering LDL

2. Element used for the surgical repair of bones; Metal una

à Polyphenols are found in black and herbal tea,

”Ascorbic acid (vitamin C) can overcome

- Electron transport chain

Ø RBCs contain hemoglobin, a protein that

Ø When you don’t have enough RBCs or the

HEMATOPOIETIC GROWTH FACTORS

Megakaryocyte Growth Factors:

Introductory Questions: Answers:

MAIN LESSON (50 minutes)

MAIN LESSON (50 minutes)

First-generation cephalosporins include cefazolin, cefadroxil,

Their spectrum of activity is limited to aerobic Gram- -

Penicillin-allergic patients tolerate aztreonam without reaction.

- -lactam molecules but

This document and the information thereon is the property of

- -lactam molecules but

Ampicillin- -lactamase-producing S aureus and H influenzae but not against Serratia,

This document and the information thereon is the property of

SUMMARY (MECHANISM EFFECT INDICATION/CLINICAL USE ADVERSE EFFECTS)

1. Pyrimethamine and sulfadiazine are used in the treatment of _.