Pharmacology 4R-F

Pharmacology Hacked
Multiple Choice
1. Ototoxicity and nephrotoxicity are characteristic adverse effects of
A. Aminoglycosides
B. β-lactam antibiotics
C. Chloramphenicol
D. Fluoroquinolones
2. Which of the following is the inhibitor of protein synthesis of bacteria

A. Penicillins
B. β-lactam antibiotics
C. Macrolides
D. Fluoroquinolones
3. Penicillin…
A. Bind to bacterial ribosomes to inhibit protein synthesis
B. Inhibit activity of bacterial DNA gyrase
C. Inhibit bacterial dihydropteroate synthase
D. Inhibit synthesis of the bacterial cell wall
4. Drugs may be released slowly from various drug reservoirs over long periods of
time. The body reservoir that holds the largest amount of the barbiturate
thiopental is:
A. Fat
B. Lung
C. Liver
D. Muscle
E. Serum albumin
5. The pharmacokinetic value that most reliably reflects the amount of drug
reaching the blood flow after oral administration is the area under the blood
concentration-time curve:
A. Peak blood concentration
B. Time to peak blood concentration
C. Elimination half-life
D. Volume of distribution
E. Area under the blood concentration-time curve
6. The onset and duration of action of a barbiturate are mainly a function of its:
A. Lipid solubility
B. Molecular weight
C. Plasma binding
D. Renal excretion
E. Method of administration
7. Which effect of chlorpromazine is comparable to its extrapyramidal action?

A. Antipsychotic effect
B. Sedative effect
C. Hypotension
D. Urinary retention
E. Nasal congestion
8. A major biochemical effect of cardiac glycosides is

A. Enhancement of cardiac ribosome function in protein synthesis
B. Enhancement of muscarine endplate receptor function in the heart
C. Inhibition of acetylcholinesterase
D. Enhancement of adenylate cyclase
E. Inhibition of Na+, K+ ATPase
9. Common effects of muscarinic stimulant drugs include all of the following

EXCEPT:
A. Tachycardia
B. Increased peristalsis
C. Miosis
D. Stimulation of sweat glands
E. Increased secretion by salivary glands
10. A predictably dangerous side effect of propranolol, which constitutes a

contraindication to its clinical use in susceptible patients, is the induction of:
A. Hypertension
B. Cardiac arrhythmia
C. Asthmatic attacks
D. Respiratory depression
E. Hypersensitivity
11. Which of the following is the treatment of choice for hypothyroidism?
A. Iodide
B. Levothyroxine (T4)
C. Liothyronine (T3)
D. Liotrix
E. Propylthiouracil
12. Which of the following drugs is considered to be one of the antithyroid drugs?
A. Thiamazole
B. Nitroglycerine
C. Spironolactone
D. Nifedipine
E. Insulin
13. Which of the following antipsychotic agents is most associated with the
possibility of a hematological dyscrasia such as agranulocytosis in a patient
being treated for schizophrenia?
A. Chlorpromazine
B. Buspirone
C. Asenapine
D. Clozapine
14. Which of the following statements about fentanyl is correct?

A. Fentanyl is 100 times more potent than morphine
B. Its withdrawal symptoms can be relieved by naloxone
C. The active metabolites of fentanyl can cause seizures
D. It is most effective by oral administration
15. A young woman is brought into the emergency room. She is unconscious, and
she has pupillary constriction and depressed respiration. Based on reports, an
opioid overdose is almost certain. Which of the listed phenanthrene opioids will
exhibit a full and immediate response to treatment with naloxone?
A. Meperidine
B. Morphine
C. Buprenorphine
D. Fentanyl
16. What is drug?

A. A herb
B. A chemical substance that can affect the physiological and biochemical
functions of the body
C. A kind of nutrient
D. A chemical substance used for the diagnosis
17. Please select all the true statements: (Multiple Choice)

A. Drug is poison
B. Vaccine is a kind of drug
C. Foods can also be drugs
D. Some neurotransmitters are drugs
18. ADME equals PK

A. True
B. False
19. Which one of the following statements is correct regarding benzodiazepines?

A. Benzodiazepines directly open chloride channels
B. Benzodiazepines show analgesic actions
C. Clinical improvement of anxiety requires 2 to 4 weeks of treatment with
benzodiazepines
D. All benzodiazepines have some sedative effects
20. Which receptor does Cimetidine bind?

A. M receptor
B. H1 receptor
C. H2 receptor
D. β2 receptor
21. Which protein does Omeprazole target?

A. Voltage dependent Na+ channel
B. H+-K+-ATPase
C. H2 receptor
D. M receptor
22. A 12-year-old girl with a childhood history of asthma complained of cough,

dyspnea, and wheezing after visiting a riding stable. Her symptoms became so
severe that her parents brought her to the emergency room. Which of the
following is the most appropriate drug to rapidly reverse her
bronchoconstriction?
A. Inhaled fluticasone
B. Inhaled beclomethasone
C. Short-acting β2 agonists (SABA)
D. Intravenous propranolol
E. Oral theophylline
23. A 9-year-old girl has severe asthma, which required three hospitalizations in
the last year. She is now receiving therapy that has greatly reduced the frequency
of these severe attacks. Which of the following therapies is most likely
responsible for this benefit?
A. Inhaled albuterol
B. Inhaled ipratropium
C. Inhaled fluticasone
D. Oral theophylline
E. Oral zafirlukast
24. A group of college students is planning a mountain climbing trip to the Andes.
Which would be appropriate for them to take to prevent mountain sickness?
A. A carbonic anhydrase inhibitor such as acetazolamide
B. A thiazide diuretic such as hydrochlorothiazide
C. An anticholinergic such as atropine
D. A loop diuretic such as furosemide
25. Which the following classes of diuretic drug targets mainly the proximal
tubule?
A. Inhibitors of carbonic anhydrase
B. Osmotic diuretics
C. Inhibitors of Na+/K+/2Cl- symport
D. Inhibitors of Na+/Cl- symport
E. Inhibitors of Na+ channels
26. Which of the following diuretic drugs has the highest efficiency?
A. Metolazone
B. Spironolactone
C. Furosemide
D. Hydrochlorothiazide
E. Triamterene
27. Which of the following components of the nephron is targeted by furosemide?
A. Thin descending limb
B. Proximal tubule
C. Distal tubule
D. Collecting duct
E. Thick ascending limb
28. Which of the following class of diuretic drugs has K+-sparing effect?
A. Inhibitors of the carbonic anhydrase
B. Inhibitors of the Na+/Cl- symporter
C. Inhibitors of the Na+/K+/2Cl- symporter
D. Inhibitors of the aldosterone receptor
E. Osmotic diuretics
29. Pilocarpine has the following effects: (Multiple choice)

A. Miosis
B. Increase intraocular pressure
C. Spasm of accommodation
D. Increase salivation
30. Thermoregulatory sweat glands in the body utilize what type of pathway?
A. Adrenergic nerves and alpha-1 receptors
B. Adrenergic nerves and beta-2 receptors
C. Cholinergic nerves and muscarinic receptors
D. Cholinergic nerves and NM receptors
31. Neostigmine differs from pilocarpine in having effects on:

A. Skeletal muscle
B. Bowel motility
C. Heart rate
D. Salivary glands
32. In the presence of naloxone, a higher concentration of morphine is required to

elicit full pain relief. Naloxone by itself has no effect. Which of the following is
correct regarding these medications?
A. Naloxone is a competitive antagonist
B. Morphine is a full agonist, and naloxone is a partial agonist
C. Morphine is less efficacious than is naloxone
D. Naloxone is a noncompetitive antagonist
33. A 60-year-old female patient started on a new antihypertensive medication

recently. Her blood pressure seems to be under control, but she complains of
fatigue, drowsiness, and fainting when she gets up from the bed (orthostatic
hypotension). Which of the following drugs is she most likely taking?
A. Metoprolol
B. Propranolol
C. Prazosin
D. Clonidine
34. A new antihypertensive drug was tested in an animal model of hypertension.

The drug when given alone reduces blood pressure in the animal. Norepinephrine
when given in the presence of this drug did not cause any significant change in
blood pressure or heart rate in the animal. The new drug is similar to which of the
following drugs in terms of its pharmacological mechanism of action?
A. Prazosin
B. Clonidine
C. Propranolol
D. Carvedilol
Norepinephrine activates both α1 and β1 receptors and causes an increase in heart rate and blood
pressure. A drug that prevents the increase in blood pressure caused by norepinephrine should be similar to
carvedilol that antagonizes both α1 and β1 receptors. Prazosin is an α1 antagonist, clonidine is an α2
agonist, and propranolol is β antagonists, and these drugs cannot completely prevent the cardiovascular
effects of norepinephrine.
35. Which of the following is correct regarding the autonomic nervous system
(ANS)?
A. Afferent neurons carry signals from the CNS to the effector organs
B. The neurotransmitter at the parasympathetic ganglion is norepinephrine (NE)
C. The neurotransmitter at the sympathetic ganglion is acetylcholine (ACh)
D. Sympathetic neurons release ACh in the effector organs
36. A 12-year-old boy who is allergic to peanuts was brought to the emergency
room after accidentally consuming peanuts contained in fast food. He is in
anaphylactic shock. Which of the following drugs would be most appropriate to
treat this patient?
A. Norepinephrine
B. Phenylephrine
C. Dobutamine
D. Epinephrine
37. An asthma patient was given a nonselective β agonist to relieve

bronchoconstriction. Which of the following adverse effects would you expect to
see in this patient?
A. Bradycardia
B. Tachycardia
C. Hypotension (reduction in blood pressure)
D. Worsening bronchoconstriction
38. A child is experiencing absence seizures that interrupt his ability to pay
attention during school and activities. Which of the following therapies would be
most appropriate for this patient?
A. Ethosuximide
B. Carbamazepine
C. Diazepam
D. Carbamazepine plus primidone
39. A 52-year-old man has had several focal complex partial seizures over the last
year. Which one of the following therapies would be the most appropriate initial
therapy for this patient?
A. Ethosuximide
B. Levetiracetam
C. Diazepam
D. Carbamazepine plus primidone
The patient has had many seizures, and the risks of not starting drug therapy would be substantially greater than the risks
of treating his seizures. Because the patient has impaired consciousness during the seizure, he is at risk for injury during
an attack. Monotherapy with primary agents is preferred for most patients. The advantages of monotherapy include
reduced frequency of adverse effects, absence of interactions between antiepileptic drugs, lower cost, and improved
compliance. Ethosuximide and diazepam are not indicated for complex partial seizures.
40. A 45-year-old man was just started on therapy for hypertension and developed
a persistent, dry cough. Which is most likely responsible for this side effect?
A. Enalapril
B. Losartan
C. Nifedipine
D. Prazosin
41. Which may cause reﬂex tachycardia and/or postural hypotension on initial
administration?
A. Atenolol
B. Hydrochlorothiazide
C. Verapamil
D. Prazosin
42. Which of the following drugs is considered to be effective in the treatment of

diabetes mellitus? (Multiple choice)
A. Metformin
B. Glyburide
C. Spironolactone
D. Nifedipine
E. Insulin
43. Which of the following conditions can be treated by insulin? (Multiple choice)
A. IDDM (insulin-dependent diabetes mellitus)
B. Diabetic ketoacidosis
C. Insulin resistance
D. Hyperosmolar coma
E. Hypoglycemia
44. Which must heparin bind to in order to exert its anticoagulant effect?
A. GP IIb/IIIa receptor
B. Thrombin
C. Antithrombin III
D. von Willebrand factor
45. Which is most appropriate for reversing the anticoagulant effects of heparin?
A. Aminocaproic acid
B. Protamine sulfate
C. Vitamin K1
D. Tranexamic acid
46. Which medication should be prescribed to all angina patients to treat an acute
attack?
A. Isosorbide dinitrate
B. Nitroglycerin patch
C. Nitroglycerin sublingual tablet or spray
D. Ranolazine
47. What can be treated by β-receptor blockers in the following diseases: (Multiple
answer)
A. Hypertension
B. Cardiac failure
C. Angina pectoris
D. Cardiac arrhythmia
E. Hyperlipidemia
48. Which of the following effects taken by Ca-antagonists: (Multiple answer)

A. to lower blood pressure
B. to anti-arrhythmia
C. to lower blood fat
D. to anti-angina
E. to anti-anaphylaxis
49. Which one of the following combinations of antiparkinsonian drugs is an

appropriate treatment plan?
A. Amantadine, carbidopa, and entacapone
B. Levodopa, carbidopa, and entacapone
C. Pramipexole, carbidopa, and entacapone
D. Ropinirole, selegiline, and entacapone
50. Peripheral adverse effects of levodopa, including nausea, hypotension, and

cardiac arrhythmias, can be diminished by including which of the following drugs
in the therapy?
A. Amantadine
B. Ropinirole
C. Carbidopa
D. Tolcapone
51. Corticosteroids are useful in the treatment of all of the following disorders
except:
A. Addison disease
B. Allergic rhinitis
C. Cushing syndrome
D. Inflammatory bowel disease
E. Rheumatoid arthritis
52. All of the following adverse effects commonly occur with glucocorticoid
therapy except:
A. Glaucoma
B. Increased risk of infection
C. Hypotension
D. Emotional disturbances
E. Peripheral edema
53. A 500-mg dose of a drug has therapeutic efficacy for 6h. If the half-life of the
drug is 8h, for how long would a 1-g dose be effective?
A. 8h
B. 12h
C. 14h
D. 24h
The fact that the drug has therapeutic efficacy for 6 h has no direct relationship to its half-life—it simply
means that the drug is above its minimal effective concentration for 6 h.Doubling the dose (to 1 g) means
that the drug level will be above the minimum for a longer period. Because the elimination half-life is 8 h, 500
mg of the drug will remain in the body 8 h after a dose of 1 g. Thus, the total duration of effectiveness must
be 8 + 6 = 14 h.
54. Drugs that are highly bound to albumin:

A. Effectively cross the BBB
B. Are easily filtered at the glomerulus
C. Have a large Vd
D. Can undergo competition with other drugs for albumin binding sites
55. Most drugs gain entry to cells by:

A. Passive diffusion with zero-order kinetics
B. Passive diffusion with first-order kinetics
C. Active transport with zero-order kinetics
D. Active transport with first-order kinetics
E. Passive diffusion through membrane pores
56. A woman is taking oral contraceptives (OCs). Which of the following drugs is
unlikely to reduce the effectiveness of the OCs?
A. Phenytoin
B. Cimetidine
C. Phenobarbital Rifampin
D. Rifampin
57. Urination in the human subject is decreased by:

A. Muscarinic agonists
B. Muscarinic antagonists
C. AChE inhibitors
D. Nicotinic agonists
58. What is the most serious side effects caused by penicillin G?

A. Anaphylactic shock
B. Nausea, vomiting
C. Hearing loss
D. Superinfections
59. What is the first line choice to treat treponema pallidum and leptospirosis?
A. Gentamycin
B. Erythromycin
C. Penicillin G
D. Tetracycline
60. Which microorganisms can penicillin G target?

A. Pneumococci
B. Pseudomonas aeruginosa
C. Bacillus proteus
D. Legionella
61. Comparing to penicillin G. Amoxicillin

A. Higher potency to G+ strains
B. Higher potency to G- strains
C. Stable to lactamases
D. Effective on P. aeruginosa
62. Which is not correct regarding common characters of aminoglycosides?
A. Effective on G- bacilli
B. Are bactericidal antimicrobials
C. Has to be given by I.V. for
D. Has ototoxicity and nephrotoxicity
E. No cross resistance among them
63. Which microorganism is aminoglycoside not effective against?

A. Anaerobes
B. Pseudomonas aeruginosa
C. Mycobacteria
D. G+ bacteria
E. G- bacteria
64. Where are aminoglycosides mainly distributed?

A. Plasma
B. Intracellular space
C. Extracellular space
D. CSF
E. Serous cavity
65. Which one is not the side effect caused by aminoglycosides?

A. Allergic reaction
B. Neuromuscular block
C. Bone marrow toxicity
D. Ototoxicity
E. Nephrotoxicity
66. Which one is not correct regarding the common characters of macrolides?
A. They have similar antibacterial spectrum
B. Their effects decrease in alkaline condition
C. Their effects decrease in acidic condition
D. They inhibit protein synthesis by binding the 50s subunit
E. They have cross resistance
67. Which of the following microorganism is macrolides not effective against?
A. Streptococcus
B. H. influenza
C. E. Coli
D. Legionella
E. Chlamydia and mycoplasma
68. The combination of erythromycin and clindamycin could:

A. Reduce toxicity
B. Increase antibacterial activity
C. Enlarge antibacterial spectrum
D. Compete for binding site
E. Reduce bacterial resistance
69. Which antimicrobial is the best for bone and joint infection?
A. Vancomycin
B. Clarithromycin
C. Clindamycin
D. Gentamycin
E. Clavulanic acid
70. Which of the following is not a reason to combine the antimicrobial agents?
A. Expand antimicrobial spectrum
B. Treat infections with unidentified origin
C. Extend effective time
D. Prevention of the emergence of resistant microorganisms
71. Which of the following is not sensitive to tetracycline?

A. G+ cocci
B. P. Aeruginosa
C. G-
D. Mycoplasma pneumonia
E. Rickettsia
72. Which is NOT correct regarding the side effects of tetracycline?

A. GI irritation
B. Tetracycline teeth
C. Superinfection
D. Does not cause hypersensitivity
E. Long term I.V. can cause liver damage
73. Which can be used to treat typhia and paratyphia?
A. A. Doxycycline
B. A. Tetracycline
C. A. Gentamycin
D. A. Chloramphenicol
E. A. Clindamycin
74. What is the most severe side effect caused by chloramphenicol?

A. Super-sensitivity
B. Superinfection
C. Bone marrow depression
D. GI irritation
E. Ototoxicity
75.Which of the following causes gray-baby syndrome?

A. Penicillin G
B. Erythromycin
C. Gentamycin
D. Chloramphenicol
E. Vancomycin
76. A patient returns to her health care provider for a routine monitoring 3 months
after her hypertension regimen was modified. Labs reveal elevated serum
potassium. Which is likely responsible for this hyperkalemia?
A. Clonidine
B. Furosemide
C. Losartan
D. Nifedipine
77. A 58-year-old female reports that she recently stopped taking her blood
pressure medications because of swelling in her feet that began shortly after she
started treatment. Which is most likely to cause peripheral edema?
A. Atenolol
B. Clonidine
C. Felodipine
D. Hydralazine
78. Which is important to monitor in patients taking digoxin?

A. Chloride
B. Potassium
C. Sodium
D. Zinc
79. Which best describes the action of ACE inhibitors on the failing heart?
A. ACE inhibitors increase vascular resistance
B. ACE inhibitors decrease cardiac output
C. ACE inhibitors reduce preload
D. ACE inhibitors increase aldosterone
80. Suppression of arrhythmias resulting from a reentry focus is most likely to

occur if the drug:
A. Has vagomimetic effects on the AV node
B. Is a B-blocker
C. Converts a unidirectional block to a bidirectional block
D. Slows conduction through the atria
81. What arrhythmia can be treated with lidocaine?

A. Paroxysmal supraventricular ventricular tachycardia
B. Atrial fibrillation
C. Atrial flutter
D. Ventricular tachycardia
82. A 78-year-old woman has been newly diagnosed with atrial fibrillation. She is
not currently having symptoms of palpitations of fatigue. Which is appropriate to
initiate for rate control as an outpatient?
A. Amiodarone
B. Dronedarone
C. Flecainide
D. Metoprolol
83. All of the following are adverse effects of amiodarone, except:

A. Cinchonism
B. Hypothyroidism
C. Pulmonary fibrosis
D. Blue skin discoloration
84. A 65-year old male experiences uncontrolled angina attacks that limit his
ability to do household chores. He is adherent to a maximized dose of B-blocker
with a low heart rate and low blood pressure. He was unable to tolerate an
increase in isosorbide mononitrate due to headache. Which is the most
appropriate addition to his antianginal therapy?
A. Amlodipine
B. Aspirin
C. Ranolazine
D. Verapamil
85. An elderly patient with a history of heart disease is brought to the emergency
room with difficulty breathing. Examination reveals that she has pulmonary
edema. Which treatment is indicated?
A. Acetazolamide
B. Hydrochlorothiazide
C. Furosemide
D. Spironolactone
86. The route of excretion for drugs or their metabolic derivatives that is
quantitively the least significant is which of the following?
A. Biliary tract
B. Kidneys
C. Lungs
D. Milk
87. Thermoregulatory sweat glands in the body utilize what type of pathway?
A. Neurohumorally-released epinephrine
B. Cholinergic nerves and muscarinic receptors
C. Adrenergic nerves and alpha-1 receptors
D. Adrenergic nerves and beta-2 receptors
88. Activation of postsynaptic M2 receptors on the heart is associated with:

A. Miosis
B. Decreased heart beat
C. Increased blood pressure
D. Increased conduction velocity from SA node to AV node
89. Fluoroquinolones…
A. Bind to bacterial ribosomes to inhibit protein synthesis
B. Inhibit activity of bacterial DNA gyrase
C. Inhibit bacterial dihydropteroate
D. Inhibit synthesis of the bacterial cell wall
90. Highly ionized drugs tend to accumulate in the:

A. Brain
B. Fat tissue
C. Heart
D. Urine
Definitions
Pharmacodynamics
The study of the biochemical and physiological effect of a drug, its mechanism of
action, as well as its clinical use and adverse effects.
Side Reaction
An unwanted or harmful reaction experienced following the administration of a
drug or combination of drugs under normal conditions of use, taken at the
therapeutic dose, and is suspected to be related to the drug.
Drug
A medicine or other substance which has a physiological effect when ingested or
otherwise introduced into the body.
Pharmacokinetics
The study of the time course of drug absorption, distribution, metabolism, and
excretion, as well as its change in concentration over different body fluids and
tissues. Clinical pharmacokinetics is the application of pharmacokinetic principles
to the safe and effective therapeutic management of drugs in an individual
patient.
Agonist
A substance which initiates a physiological response when combined with a
receptor.
Therapeutic index
The therapeutic index is a quantitative measurement of the relative safety of a
drug. It is a comparison of the amount of a therapeutic agent that causes the
therapeutic effect to the amount that causes toxicity.
Half life
The half-life is the time it takes for plasma concentration or the amount of drug in
the body to be reduced by 50%.
T1/2 = 0.693/ke
Tolerance
The gradual decrease in intensity of response to repeated administration of a
given dose of drug.
Antibiotics
Antibiotics are drugs that target bacteria. They can kill bacteria; in which cases
they are bactericidal. They can also inhibit their growth but not kill them directly,
in which case they are bacteriostatic.
Adverse drug reaction (ADR)

ADR refers to any response to the drug that is noxious and unintended and that
occurs at therapeutic doses. It is a broad term referring to unwanted,
uncomfortable, or dangerous effects that a drug may have. These could be:
⮚ Side effect
⮚ Toxic effect
⮚ After effect (residual effect)
⮚ Withdrawal reaction (rebound)
⮚ Idiosyncrasy (Allergic reaction)
Residual effect
Residual effects are adverse effects or significant effects which cannot be
avoided or mitigated through the addition of further treatment or therapy. These
effects may still exist after the withdrawal of the drug.
First pass effect

The first pass effect is a phenomenon of drug metabolism whereby the
concentration of a drug, specifically when administered orally, is greatly reduced
before it reaches the systemic circulation.
Resistance
Resistance is development of the ability to withstand the previously destructive
effect of a drug by microorganisms or tumor cells.
There are 2 types of resistance:

1. Inherent resistance (pre-existing)
2. Acquired resistance (requires genetic change in microorganism)
Toxic reaction
Drug toxicity can occur as a result of the over-ingestion of a medication—having
too much of a drug in a person's system at once. This can happen if the dose
taken exceeds the prescribed dose, either intentionally or accidentally. With
certain medications, drug toxicity can also occur as an adverse drug reaction
(ADR).
Antimicrobials
An antimicrobial is an agent that kills microorganisms, stops their growth, or their
pathogenic action. Antimicrobial medicines can be grouped according to the
microorganisms they act primarily against. For example, antibiotics are used
against bacteria.
Bacteriostatic drugs
Bacteriostatic drugs are biological or chemical agents that stops bacteria from
reproducing, while not necessarily killing them otherwise. Depending on their
application, bacteriostatic antibiotics, disinfectants, antiseptics and preservatives
can be distinguished.
Bactericidal drugs
Biological or chemical agents which kill bacteria. Bactericides are mainly
antibiotics.
MIC
The lowest antimicrobial concentration that prevents visible growth of an
organism after 24 hours of incubation.
MBC
The lowest concentration of antimicrobial agent that results in a 99.9% decline in
colony count after overnight broth dilution incubations
PAE
The post antibiotic effect (PAE) is defined as persistent suppression of bacterial
growth after a brief exposure (1 or 2 hours) of bacteria to an antibiotic even in the
absence of host defense mechanisms. Factors that affect the duration of the post
antibiotic effect include duration of antibiotic exposure, bacterial species, culture
medium and class of antibiotic.
Superinfection
A second infection superimposed on an earlier one, especially by a different
microbial agent of exogenous or endogenous origin, that is resistant to the
treatment being used against the first infection. Drug therapy, particularly with
broad-spectrum antimicrobials or combinations of agents can lead to alterations
of the normal microbial flora of the upper respiratory, oral, intestinal, and
genitourinary tracts, permitting the overgrowth of opportunistic organisms,
especially fungi or resistant bacteria.
Short questions
1. Why K+ sparing diuretics is often used in combination with thiazide
diuretics?
Diuretics are drugs that increase the volume of urine produced by promoting the
excretion of salt and water from the kidneys. There are several types of diuretics,
each working in a distinct way.
Thiazide diuretics inhibit sodium re-absorption at the beginning of the distal

convoluted tubules. Potassium sparing diuretics prevent excessive loss of
potassium at the distal convoluted tubules.
A combination of a potassium sparing diuretic with a thiazide diuretic is used to

reduce edema due to salt and water retention in disorders of the heart, kidneys,
liver or lungs. They are used commonly in treatment of hypertension.
2. Briefly describe the classification and clinical uses of antithrombotic

drugs.
An antithrombotic agent is a drug that reduces the formation of blood clots

(thrombi). Antithrombotic drugs can be used therapeutically for prevention or
treatment of a dangerous blood clot (acute thrombus).
Different antithrombotic drugs affect different blood clotting processes:
⮚ Antiplatelet drugs limit the migration or aggregation of platelets.

⮚ Anticoagulants limit the ability of the blood to clot.
⮚ Thrombolytic drugs act to dissolve clots after they have formed.
3. Try to compare heparin and warfarin from the following three aspects:
- Anticoagulant characteristics
Heparin:
Heparin is a medication and naturally occurring glycosaminoglycan. As a
medication it is used as an anticoagulant (blood thinner). Specifically, it is
also used in the treatment of heart attacks and unstable angina. It is given
by injection into a vein or under the skin. Other uses include inside test
tubes and kidney dialysis machines.
Warfarin: a medication that is used as an anticoagulant (blood thinner). It

is commonly used to treat blood clots such as deep vein thrombosis and
pulmonary embolism and to prevent stroke in people who have atrial
fibrillation, valvular heart disease or artificial heart valves. Less commonly
it is used following ST-segment elevation myocardial infarction (STEMI)
and orthopedic surgery. It is generally taken by mouth but may also be
used by injection into a vein. While warfarin is one of several drugs
popularly referred to as a "blood thinner", this is a misnomer since it does
not affect the viscosity of blood.
- Mechanism of action
Heparin:
Heparin binds to the enzyme inhibitor antithrombin III (AT), causing a
conformational change that results in its activation through an increase in
the flexibility of its reactive site loop.
Warfarin:
Warfarin decreases blood clotting by blocking an enzyme called vitamin K
epoxide reductase that reactivates vitamin K1. Without sufficient active
vitamin K1, clotting factors II, VII, IX, and X have decreased clotting
ability. The anticlotting protein C and protein S are also inhibited but to a
lesser degree. A few days are required for full effect to occur and these
effects can last for up to five days.
- Adverse reactions and antagonist drugs.
Heparin:
Common side effects include bleeding, pain at the injection site, and low
blood platelets. Serious side effects include heparin-induced
thrombocytopenia. Greater care is needed in those with poor kidney
function. A serious side-effect of heparin is heparin-induced
thrombocytopenia (HIT), caused by an immunological reaction that makes
platelets a target of immunological response, resulting in the degradation
of platelets, which causes thrombocytopenia. This condition is usually
reversed on discontinuation, and in general can be avoided with the use
of synthetic heparins. Two non-hemorrhagic side-effects of heparin
treatment are known. The first is elevation of serum aminotransferase
levels, which has been reported in as many as 80% of patients receiving
heparin. The other complication is hyperkalemia.
Warfarin:
The only common side effect of warfarin is bleeding. Other side effects
include necrosis, osteoporosis, purple toe syndrome and calcification.
highly protein bound drugs can displace warfarin from serum albumin and
cause an increase in the INR. When taken with nonsteroidal anti-
inflammatory drugs (NSAIDs), warfarin increases the risk for
gastrointestinal bleeding. Many commonly used antibiotics, such as
metronidazole or the macrolides, will greatly increase the effect of
warfarin by reducing the metabolism of warfarin in the body. Warfarin also
interacts with many herbs and spices and excessive alcohol intake.
4. Classification of antimicrobial agents by their sites of action.

5. What is the difference between the action and effect of a drug?
⮚ A drugs action is the primary action of a drug on the body as a
mechanism of molecular reaction
⮚ It has specificity
⮚ Pharmacological effect means the outcome produced by a drug action,
including the manifestations of organism reaction
⮚ It is the functional or morphological alteration of the body, induced by
drugs
⮚ It has selectivity
6. What is the most common process for drug transfer across cell
membranes and point out its characteristics?
The most common process for drug transfer across cell membranes is passive
diffusion.
Characteristics:
- Drugs are un-ionized moiety penetrate cell membrane by diffusion
- No carrier
- No energy
- No saturation
- No competition
- Need concentration gradient only
- Affected by pH and Pka
7. What are the final results of biotransformation?

⮚ In pharmacology, biotransformation is when a drug is changed chemically
within the body.
⮚ Drug chemical reactions in metabolism are classified as oxidation,
reduction, hydrolysis, and conjugation.
Results:
- Generate more polar, inactive metabolites
- Generate metabolite with potent biological activity
- Generate metabolite with toxic properties
- Inactive prodrugs are converted rapidly to biologically active metabolites
8. What are the pharmacological effects of Atropine?

In general, atropine counters the activity of glands regulated by the
parasympathetic nervous system. It is a competitive, reversible antagonist of the
muscarinic acetylcholine receptors with a high affinity for them. It is both a central
and peripheral muscarinic blocker.
It effects the following organ systems:
⮚ Cardiac - it works as a nonselective muscarinic acetyl cholinergic
antagonist, increasing firing of the sinoatrial node (SA) and conduction
through the atrioventricular node (AV) of the heart, opposes the actions of
the vagus nerve, blocks acetylcholine receptor sites, and decreases
bronchial secretions.
⮚ Eye - induces mydriasis by blocking contraction of the circular pupillary
sphincter muscle, which is normally stimulated by acetylcholine release,
thereby allowing the radial iris dilator muscle to contract and dilate the
pupil. Also induces cycloplegia by paralyzing the ciliary muscles, whose
action inhibits accommodation to allow accurate refraction in children,
helps to relieve pain associated with iridocyclitis, and treats ciliary block
(malignant) glaucoma.
⮚ CNS – Causes initial excitation then depression: tranquility, amnesia, anti
-Parkinson action
⮚ CVS – Low dose = Bradycardia High dose = Tachycardia
⮚ Respiratory system – Atropine and other antimuscarinics inhibits mouth,
bronchial and pharyngeal secretion, which reduce reflects laryngospasm
during general anesthesia abdominal surgeries
⮚ GIT – Tone and amplitude of contraction of stomach and intestine are
reduced – antispasmodic. Passage of chyme is low, constipation may
occur.
⮚ Urinary system – Reduced hyper motility states of the urinary bladder.
⮚ Secretions - Blocks the salivary glands on the oral mucous membrane;
xerostomia.
9. Briefly describe the classification of antihypertensive drugs.

⮚ Diuretics
▪ High ceiling/loop diuretic
▪ Thiazides
▪ Carbonic anhydrase inhibitors
▪ Potassium-sparing diuretics
▪ Calcium-sparing diuretics
▪ Osmotic diuretics
▪ Low ceiling diuretics
⮚ Calcium channel blockers

▪ Dihydropyridine
- Amlodipine
- Felodipine
- Isradipine
- Nicardipine
- Nimodipine
- Nifedipine
- And more
▪ Non-dihydropyridine
- Phenylalkylamine (Fendiline, Gallopamil, Verapamil)
- Benzothiazepine (Diltiazem)
⮚ RAAS (renin angiotensin aldosterone system) blockers
▪ Angiotensin converting enzyme inhibitors
- Captopril
- Enalapril
- Lisinopril
- Benazepril
- Fosinopril
- Quinapril
- Ramipril
- Spirapril
▪ Angiotensin receptor blocker
- Losartan
- Valsartan
- Irbesartan
- Candesartan
- Eprosartan
- Tasosartan
- Telmisartan
▪ Renin inhibitors
⮚ Sympatholytic drugs
▪ Alpha 1 adrenergic receptor blockers
- Prazosin
- Terazosin
▪ Beta blockers
- Beta 1,2 non-selective (sotalal)
- Beta-1-selective (esmolol)
- Beta-1,2/alpha 1 selective (Lavetalol, Carvedilol)
▪ Central alpha 2 agonists
- Clonidine
- Methyldopa
- Moxonidine
▪ Autonomic ganglionic inhibitors
- Mecamylamine
▪ Adrenergic neural terminal inhibitors
- Reserpine
- Guanethidine
⮚ Vasodilators
▪ Hydralazine
▪ Minoxidil
10. Compare mechanisms of ACEI and losartan

ACEI inhibitors antihypertensive mechanisms
⮚ Inhibition of circulating RAAS
⮚ Modulation of sympathetic activity
⮚ Decreased formation of endothelin from endothelium
⮚ Increased formation of bradykinin and vasodilatory prostaglandins
⮚ Decreased sodium retention (decreased aldosterone secretion, and/or
increased renal blood flow)
- Sartan are selective and competitive antagonist’s
angiotensin II type 1 (AT1) receptors and do not inhibit
AT2 inhibitors
Losartan mechanism
⮚ Inhibits aldosterone synthesis
⮚ Inhibits catecholamine release
⮚ Inhibits vasoconstrictions
⮚ Decreases renal sodium and water
11. List the pharmacological effects on heart and the mechanism of cardiac
glycosides.
Cardiac glycosides are a class of organic compounds that increase the output
force of the heart and increase its rate of contractions by acting on the cellular
sodium-potassium ATPase pump.
Inhibition of Na+/K+-ATPases → higher intracellular Na+ concentration →

reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+
concentration → increased vagal tone
→ In cardiomyocytes, this leads to increased contractility (positive inotropic

effect), reduced velocity of electric conduction (negative dromotropic effect), and
a reduction of the heart rate (negative chronotropic effect).
→ In neurons (of the vagal nerve), this leads to reduced velocity of electric
conduction and reduction of the heart rate (via a reflexive reduction of
sympathetic transmission).
Cardiac glycosides inhibit Na+/K+-ATPase, increasing cardiac contractility and

decreasing AV conduction and heart rate!
Mechanism explained
Cardiac glycosides affect the sodium-potassium ATPase pump in cardiac muscle
cells to alter their function. Normally, these sodium-potassium pumps move
potassium ions in and sodium ions out. Cardiac glycosides, however, inhibit this
pump by stabilizing it in the E2-P transition state, so that sodium cannot be
extruded: intracellular sodium concentration therefore increases. With regard to
potassium ion movement, because both cardiac glycosides and potassium
compete for binding to the ATPase pump, changes in extracellular potassium
concentration can potentially lead to altered drug efficacy. Nevertheless, by
carefully controlling the dosage, such adverse effects can be avoided. Continuing
on with the mechanism, raised intracellular sodium levels inhibit the function of a
second membrane ion exchanger, NCX, which is responsible for pumping
calcium ions out of the cell and sodium ions in at a ratio of 3Na+
/Ca2+. Thus, calcium ions are also not extruded and will begin to build up inside
the cell as well.
The disrupted calcium homeostasis and increased cytoplasmic calcium

concentrations cause increased calcium uptake into the sarcoplasmic reticulum
(SR) via the SERCA2 transporter. Raised calcium stores in the SR allow for
greater calcium release on stimulation, so the myocyte can achieve faster and
more powerful contraction by cross-bridge cycling. The refractory period of the
AV node is increased, so cardiac glycosides also function to decrease heart rate.
For example, the ingestion of digoxin leads to increased cardiac output and
decreased heart rate without significant changes in blood pressure; this quality
allows it to be widely used medicinally in the treatment of cardiac arrhythmias.
12. Describe the pharmacological basis of treating angina pectoris in

combination of nitroglycerin and propranolol
The pharmacological basis of treating angina pectoris in combination of
nitroglycerin and propranolol are:
Useful drug combinations = Nitrate + B blocker (propanolol)
Mechanisms of action:
⮚ Increasing therapeutic effects and decreasing side effects
⮚ In reducing O2 consumption, they have a synergistic effect
⮚ B blocker can prevent reflex tachycardia & positive inotropic effects
caused by nitrates
⮚ Nitrates can reduce the increase in end-diastolic volume & ejection time
caused by B blockers by increasing venous capacitance
13. How are the diuretic agents classified?
Class Drugs Site of action

High ceiling/loop diuretic Furosemide Ascending limb
Bumetanide (Na+/K+/2Cl-)
Torsemide
Ethacrynic acid
Thiazides Hydrochlorothiazide Distal (NaCl)

(Esidrix, Hydrodiuril)
Chlorthalidone
Trichlormethiazide
Thiazide-like diuretics Chlorthaliazide (Hygroton)
Metolazone (Mykrox,
Zaroxolyn)
Carbonic anhydrase Acetazolamide Proximal (decrease in

inhibitors CA)
Potassium-sparing Spironolactone (Aldactone) Distal & collecting (Na+ -
diuretics Triamterene (Dyrenium) K+ exchange)
Amiloride (Midamor)
Calcium-sparing diuretics
Osmotic diuretics Mannitol (Osmitrol)
Low ceiling diuretics
14. Compare the sites and mechanisms of action of loop diuretics and
thiazides
Loop diuretics mechanisms

Loop diuretics are 90% bonded to proteins and are secreted into the proximal
convoluted tubule through organic anion transporter 1 (OAT-1), OAT-2, and
ABCC4. Loop diuretics act on the Na+-K+-2Cl− symporter (NKCC2) in the thick
ascending limb of the loop of Henle to inhibit sodium, chloride and potassium
reabsorption. This is achieved by competing for the Cl− binding site. Loop
diuretics also inhibit NKCC2 at macula densa, reducing Na transported into
macula densa cells. This stimulates the release of renin, which through
renin–angiotensin system, increases fluid retention in the body, increases the
perfusion of glomerulus, thus increasing glomerular filtration rate (GFR). At the
same time, loop diuretics inhibits the tubuloglomerular feedback mechanism so
that increase in salts at the lumen near macula densa does not trigger a
response that reduces the GFR.
Loop diuretics also inhibits magnesium and calcium reabsorption in the thick
ascending limb. By disrupting the reabsorption of these ions, loop diuretics
prevent the generation of a hypertonic renal medulla. Without it, water has less of
an osmotic driving force to leave the collecting duct system, ultimately resulting in
increased urine production. Loop diuretics cause a decrease in the renal blood
flow by this mechanism. This diuresis leaves less water to be reabsorbed into the
blood, resulting in a decrease in blood volume.
A secondary effect of loop diuretics is to increase the production of

prostaglandins, which results in vasodilation and increased blood supply to the
kidney.
The collective effects of decreased blood volume and vasodilation decrease
blood pressure and ameliorate edema.
Thiazides mechanisms
Thiazide diuretics control hypertension in part by inhibiting reabsorption of
sodium (Na+) and chloride (Cl−) ions from the distal convoluted tubules in the
kidneys by blocking the thiazide-sensitive Na+-Cl− symporter.
Thiazide diuretics also increase calcium reabsorption at the distal tubule. By

lowering the sodium concentration in the tubule epithelial cells, thiazides
indirectly increase the activity of the basolateral Na+/Ca2+ antiporter to maintain
intracellular Na+ level, facilitating Ca2+ to leave the epithelial cells into the renal
interstitium. Thus, intracellular Ca2+ concentration is decreased, which allows
more Ca2+ from the lumen of the tubules to enter epithelial cells via apical Ca2+-
selective channels (TRPV5). In other words, less Ca2+ in the cell increases the
driving force for reabsorption from the lumen.
Thiazides are also thought to increase the reabsorption of Ca2+ by a mechanism

involving the reabsorption of sodium and calcium in the proximal tubule in
response to sodium depletion. Some of this response is due to augmentation of
the action of parathyroid hormone.
15. What are the pharmacological effects of glucocorticoids?

⮚ Anti-inflammatory effect
⮚ Immunosuppressive effect
⮚ Increase resistance to stress
⮚ Anti-shock effect
⮚ Alter blood picture
⮚ Decreasing the temperature
⮚ Other effects (Exciting CNS, bone system- Osteoporosis, digestion
system- inducing ulcers)
16. What are the common mechanisms by which antimicrobial agents work?
⮚ Agents that inhibit synthesis of bacterial cell wall
⮚ Agents that cause injury to the plasma membrane
⮚ Agents that affect the synthesis of bacterial protein
⮚ Agents that affect bacterial nucleic acid metabolism
⮚ Agents that block bacterial folate metabolism
17. List the CNS actions and mechanisms of morphine.
CNS actions
Morphine is a phenanthrene opioid receptor agonist – its main effect is binding to
and activating the μ-opioid receptor (MOR) in the central nervous system. Its
primary actions of therapeutic value are analgesia and sedation. Morphine is also
a κ-opioid receptor (KOR) and δ-opioid receptor (DOR) agonist. Activation of the
KOR is associated with spinal analgesia, miosis (pinpoint pupils), and
psychotomimetic effects. The DOR is thought to play a role in analgesia. The
rotation of morphine with chemically dissimilar opioids in the long-term treatment
of pain will slow down the growth of tolerance in the longer run.
In summary, morphine causes:
- Analgesia and sedation
- Sedation
- Euphoria
- Respiratory depression
- Cough suppression
- Nausea and vomiting
Mechanisms
M6G binds to μ-receptors and is half as potent an analgesic as morphine in
humans. Once treated with morphine, the p38 MAPK does not produce IL-10,
instead favoring production of IL-12. The exact mechanism through which the
production of one cytokine is increased in favor over another is not known. Most
likely, the morphine causes increased phosphorylation of the p38 MAPK.
Transcriptional level interactions between IL-10 and IL-12 may further increase
the production of IL-12 once IL-10 is not being produced. This increased
production of IL-12 causes increased T-cell immune response.
Morphine also influences the production of neutrophils and other cytokines. Since
cytokines are produced as part of the immediate immunological response
(inflammation), it has been suggested that they may also influence pain.
In summary, morphine mechanisms allow it to act as a:

- Opioid receptor
- Stimulating agent for endogenous opoid peptides
- Strengthening agent for the function of endogenous analgesic system
- Analgesic
18. How does chlorpromazine compare with aspirin in reducing hyperthermia?

Chlorpromazine (affects normal body temperature)
It is a dopamine receptor antagonist.
It also inhibits the temperature regulating center in hypothalamus that results in
the lowering of elevated body temperature (Hypothermia)
Aspirin (doesn’t affect normal body temperature)

It is an irreversible non-selective cox inhibitor (cox-1 and cox-2) that results
decrease in synthesis of PG.
By reducing PG synthesis, it decreases an elevated body temperature back to
normal temperature.
However moderate doses that produce this effect also increase oxygen
consumption and metabolic rate.
19. In what respects do benzodiazepines differ from the barbiturates?

⮚ Benzodiazepines increase the frequency of Cl ion channel opening while
barbiturates increase the duration of Cl channel opening.
⮚ Both cause sedative, hypnotic, and anesthesia effects, but
benzodiazepines toxicity doesn’t cause severe respiratory depression,
coma or death, while barbiturates toxicity can lead to all these things.
However, in the presence of other CNS depressant drugs,
benzodiazepines may also cause these effects.
⮚ Benzodiazepines toxicity can be reversed by flumazenil, but barbiturates
toxicity can’t be reversed by flumazenil.
⮚ Benzodiazepines don’t cause induction of hepatic cytochrome p450
enzyme, while barbiturates cause induction of hepatic cytochrome p450
enzyme.
⮚ Benzodiazepines can’t be used in pregnancy, but due to high plasma
bonds, barbiturates can.
20. What is the first line choice of drug to treat penicillin-induced allergic
shock? Why?
Epinephrine (0.5mg-1mg)
Adrenaline is the first line of DOC to treat penicillin induced allergic shock
because of its great efficiency at alpha 1 and beta 2 and beta 3 receptors…
stimulation of all three is helpful in reserving the physiological process.
21. What are the pharmacological effects of insulin?

⮚ Influences carbohydrate, fat and protein metabolism
⮚ It also stimulates RNA, DNA and protein synthesis and is essential for
growth
⮚ Lowers blood sugar:
- Decreases breakdown of glycogen and gluconeogenesis in the
liver
- Stimulates synthesis of glycogen and glycolysis
⮚ Decreases the breakdown of fat to fatty acids in adipose tissue
⮚ Decreases protein breakdown in muscles
22. What is the mechanism of fluoroquinolones?

Fluoroquinolones exert their antibacterial effect by preventing bacterial DNA from
unwinding and duplicating. Specifically, they inhibit the ligase activity of the type
II topoisomerases, gyrase, and topoisomerase IV, which cut DNA to introduce
supercoiling and with their ligase activity disrupted, release DNA with single- and
double-strand breaks that lead to cell death. They have a fluorine atom attached
to the central ring system, typically at the 6-position or C-7 position. Most of them
are named with the -oxacin suffix.
Fluoroquinolones are chemotherapeutic bactericidal drugs, eradicating bacteria

by interfering with DNA replication. They inhibit the bacterial DNA gyrase or the
topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription.
Topoisomerase II is also a target for a variety of quinolone-based drugs. High
activity against the eukaryotic type II enzyme is exhibited by drugs containing
aromatic substituents at their C-7 positions. First- and second-generation
fluoroquinolones selectively inhibit the topoisomerase II ligase domain, leaving
the two nuclease domains intact. This modification, coupled with the constant
action of the topoisomerase II in the bacterial cell, leads to DNA fragmentation
via the nuclease activity of the intact enzyme domains. Third- and fourth-
generation fluoroquinolones are more selective for the topoisomerase IV ligase
domain, thus have enhanced Gram-positive bacteria coverage.
23. List the clinical use of B-blockers.

B-blocker can help the conditions:
⮚ Angina pectoris
⮚ Myocardial infarction
⮚ Ventricular arrhythmia
⮚ Migraine prophylaxis
⮚ Heart failure
24. Compare the mechanism of Pilocarpine and neostigmine.

Pilocarpine
It is a muscarinic stimulant which reduces intraocular pressure by causing
contraction of ciliary body so as to facilitate overflow of aqueous humor and
perhaps also by diminishing the role of excretion.
Neostigmine
It is the acetylcholine esterase inhibitor so, its result into prolongation of
acetylcholine (half-life of acetylcholine) that has a muscarinic stimulant effect. It
also has direct action on the nicotinic receptors. It reverses the NMJ blockade
produced by curare and its derivatives.
25. Sites or mechanisms of antimicrobial therapy

Antimicrobials are drugs that destroy microbes, prevent their multiplication or
growth, or their pathogenic action.
Sites of antimicrobial therapy:

Mechanisms of resistance:
26. Inhibitors of cell wall synthesis
B lactam
β -lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-
lactam ring in their molecular structure. Most β-lactam antibiotics work by
inhibiting cell wall biosynthesis in the bacterial organism and are the most widely
used group of antibiotics. The first β-lactam antibiotic discovered was penicillin.
Chemical structure
A β-lactam ring is a four-membered lactam. A lactam is a cyclic amide, and beta-
lactams are named so because the nitrogen atom is attached to the β-carbon
atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. β-
lactams are significant structural units of medicines.
Mechanisms of action
⮚ Penicillin interferes with the last step of bacterial cell wall synthesis
(transpeptidation or cross-linkage), resulting in exposure of the
osmotically less stable membrane. Inhibition of cell wall synthesis occurs
in 3 steps:
- The β-lactam binds to Penicillin Binding Proteins (PBPs)
- Inhibition of transpeptidase
- Production of autolysins
⮚ Cell lysis can then occur, either through osmotic pressure or through the
activation of autolysins.
⮚ These drugs are bactericidal and work in a time-dependent fashion.
⮚ Penicillin is only effective against rapidly growing organisms that
synthesize a peptidoglycan cell wall.
Mechanisms of resistance
There are 3 mechanisms of resistance:
⮚ Inactivation of Antibiotic by β-Lactamase
- Hydrolyzes the cyclic amide bond of the β-lactam ring
- β-Lactamases either are constitutive, mostly produced by the bacterial
chromosome or, more commonly, are acquired by the transfer of
plasmids.
- Gram-positive organisms secrete β-lactamases extracellularly, whereas
gram-negative bacteria inactivate β-lactam drugs in the periplasmic
space.
⮚ Decreased permeability to the drug
- Decreased penetration of the antibiotic through the outer cell membrane
of the bacteria prevents the drug from reaching the target PBPs.
- The presence of an efflux pump can also reduce the amount of
intracellular drug
⮚ Altered PBPs
- Modified PBPs have a lower affinity for β-lactam antibiotics, requiring
clinically unattainable concentrations of the drug to effectively inhibit
bacterial growth.
Penicillin G
⮚ Properties
- High-yield, stable
- Narrow Antibacterial spectrum
- Not orally active - must be injected
- Susceptible to hydrolysis by
- β-lactamases
- Not toxic
⮚ Pharmacokinetics
- Absorption: Complete and rapid, body fluids and tissues
- Distribution: in most tissues. It is excreted into sputum and milk.
the CNS is poor.
- Excretion: kidneys
10% glomerular filtration
90% tubular secretion
- Half-life: 0.5～1.0 h
⮚ Antibacterial Effects
- Gram positive cocci (streptococci, pneumococci, staphylococci)
- Gram positive rods (Bacillus anthracis, diphtheria, Clostridium
tetani)
- Gram negative cocci (meningococci, diplococcus gonorrhoeae)
- Spirochete (treponema, pallidum, leptospirosis)
⮚ Antibacterial spectrum
⮚ Adverse reactions
Common
- Urticaria
- Fever
- Eosinophilia
- Angioneurotic edema
- Hemolytic anemia
Severe
- Anaphylactic shock
⮚ Treatment
Epinephrine (0.5～1mg)
If necessary, glucocorticoid & antihistamine
Cephalosporin
1st Generation Gram (+) Cefalotin, Cefazolin,

Cefradine
2nd Generation Decreasing Gram (+) and Cefuroxime, Cefaclor
Increasing Gram (-)
3rd Generation Gram (+) and Gram (-) Ceftriaxone, Ceftazidime
4th Generation Gram (+) and Gram (-) Cefpirome, Cefepime
Vancomycin
Can be used when following is present:
- Serious, life-threatening infections by Gram-positive bacteria
- Serious infections caused by susceptible organisms resistant to penicillin
(methicillin-resistant Staphylococcus aureus（MRSA） and multi-resistant
Staphylococcus epidermidis (MRSE)
- Individuals with serious allergy to penicillin
Adverse reactions include:

- Nephrotoxicity
- Ototoxicity
27. Inhibitors of protein synthesis
Aminoglycosides
Most commonly used aminoglycosides:
⮚ Streptomycin - for enterococcal and viridians streptococcal endocarditis:
combine with penicillin
⮚ Gentamicin - the drug of first choice for treating Gram-negative bacterial
infections (including P. aeruginosa).
⮚ Tobramycin - More active against P. aeruginosa.
⮚ Amikacin – Has the broadest antibacterial spectrum.
⮚ Netilmicin - Lowest toxicity among aminoglycosides
⮚ Kanamycin - active against G+ and G- bacteria and some mycobacteria
but it has serious toxicity.
⮚ Neomycin - has the most significant nephrotoxicity and ototoxicity.
Antibacterial Activity
⮚ Rapid bactericide
(Bacterial killing is concentration-dependent)
⮚ PAE is long
(Postantibiotic effect (PAE), that is, residual bactericidal activity persisting
after the serum concentration has fallen below the minimum inhibitory
concentration and the duration of this effect is concentration-dependent.)
Antibacterial spectrum
⮚ High activity against aerobic gram-negative rod
⮚ Effective on MRSA netilmicin
⮚ Less active on gram-negative cocci
⮚ P. aeruginosa: tobramycin, gentamicin, amikacin and netilmicin
⮚ Resistant to enterococci and anaerobe
⮚ Mycobacteria: streptomycin, kanamycin
Mechanisms of action
- Inhibition of the synthesis of bacterial protein
3 stages:
⮚ Initiation: interfere with the initiation complex of peptide formation.
⮚ Elongation: induce misreading of mRNA, resulting in non-functional protein.
⮚ Termination: inhibit releasing of peptide chain and the dissociation off 70s
initiation complex.
- Influence the membrane of bacterial cell.
2 stages:
⮚ Influence the function of the membrane.
⮚ The permeability is increased.
Mechanism of resistance
⮚ Produce transferase enzyme
(Adenyl transferase, acetyltransferase or phosphotransferase that
inactivate aminoglycosides by adenylation, acetylation, or
phosphorylation.)
⮚ Decrease the permeability of membrane

Impair the entry of aminoglycoside into the cell by:
- deletion of a porin protein in transport
- decreased oxygen-dependent transport process
⮚ Alter the target site

The receptor protein on the 30S ribosomal subunit may be deleted or
altered
Adverse effects
⮚ Ototoxicity
- Cochlear damage: tinnitus, auditory disturbance, irreversible
deafness
- Vestibular damage: vertigo, ataxia, loss of balance
⮚ Nephrotoxicity
- Alter the structure and function of renal proximal tubular cells
- Mild proteinuria and tubular necrosis may occur rarely
⮚ Neuromuscular blockade
- May take place at high doses or in combination with curariform
drugs
- A curarine-like effect with neuromuscular blockade
⮚ Hypersensitivity
- Skin rash, fever, eosinophilia
- Anaphylactic shock can be seen though infrequently.
- The special attention should be paid to the anaphylactic shock
caused by streptomycin
Macrolides
Most commonly used aminoglycosides:
⮚ Erythromycin - The first choice for mycoplasma pneumonia, legionellosis,
Campylobacteria jejunitis and other Macrolide treated infections
⮚ Clarithromycin - More acid stability, more active against mycobacterium,
M. leprae and Toxoplasma gondii and has a lower frequency of GI
intolerance.
⮚ Azithromycin - less active than erythromycin against staphylococci and
streptococci and slightly more active against H influenzae. Differs from
erythromycin mainly in pharmacokinetic properties.
Both Clarithromycin and Azithromycin are as active against gram-positive
bacteria, but are more active against G- than erythromycin.
⮚ Macrolides typically display bacteriostatic activity, but may be bactericidal
when present at high concentration against very susceptible organisms
⮚ Activity is enhanced at alkaline pH
⮚ Time-dependent activity
⮚ Many G+ bacteria:
- Staphylococcus (β-lactamase-producing)
- Streptococcus
- Pneumococcus
- Diphtheria bacillus
⮚ Some G - bacteria:
- Gonococcus
- Meningococcus
- Brucella
- H. influenza
- Legionella
- Bordetella Pertussis
- Campylobacter
⮚ Other microorganisms
- Spirochete
- Mycoplasma
- Chlamydia
Mechanism of action
Inhibition of bacterial protein synthesis by:
- Binding to the 50s subunit of the bacterial ribosome

- Interfering with the transpeptidation and translocation
Bacterial growth and reproduction are inhibited.
⮚ Reduced permeability of the cell membrane or active efflux (primary in
USA)
⮚ Altered target sites (primary in EU)
⮚ Enzymic inactivation
⮚ Cross-resistance occurs between all macrolides
Adverse effects
⮚ Gastrointestinal reactions - most common with erythron; less with new
agents
⮚ Cholestatic hepatitis (rare) – more than 1 to 2 weeks of erythromycin
estolate
⮚ Thrombophlebitis - dilution of dose or slow administration
⮚ Other:
- ototoxicity (high dose erythro in patients)
- cardiac toxicity: QTc prolongation
- allergy
Clindamycin
Clindamycin is a semisynthetic derivative of lincomycin. Clindamycin is absorbed
better. The first choice for infections of bones and joints caused by cocci.
Clindamycin is used primarily in the treatment of infections caused by gram-
positive organisms, including MRSA and streptococcus, and anaerobic bacteria.
Displays bacteriostatic activity, but may be bactericidal when present at high
concentrations against very susceptible organisms.
⮚ Gram-positive cocci, including penicillin-resistant staphylococci (except
enterococci)
⮚ Anaerobic bacteria
⮚ Gram-negative cocci (Meningococcus and Gonococcus)
Mechanism of action
⮚ Inhibits protein synthesis by binding exclusively to the 50S ribosomal
subunit
⮚ Binds in close proximity to macrolides - competitive inhibition
Adverse effects
⮚ Gastrointestinal disturbance
- Nausea, vomiting and diarrhea are common
- Pseudomembranous colitis: one of worst offenders
- Mild to severe diarrhea, require treatment
Treatment:
Withdrawal before Vancomycin and metronidazole are effective
⮚ Allergic reaction
- skin rashes
- neutropenia
- thrombocytopenia
⮚ Other: Impaired liver and nephrotic function
Tetracyclines
First choice for rickettsia infections (typhus), chlamydial infections, and
Mycoplasma pneumonia.
They are effective for many spirochetal infections, including relapsing fever (first
choice), leptospirosis, Lyme diseases, and syphilis.
They are also effective for treatment of various G+ and G- bacterial infections.
Brucellosis, cholera, and tularemia can be treated with tetracyclines as the first
choice.
⮚ Quickly bacteriostatic drugs, but at high dosage they are also bactericidal.
⮚ Tetracyclines are effective against G+ and G-
⮚ They are weaker than penicillin and cephalosporins against G +
organisms.
⮚ They are weaker than aminoglycosides and chloramphenicol against G-
organisms.
⮚ Broad
⮚ Most G+ and G- bacteria
⮚ Mycoplasma, Rickettsia, Chlamydia and Spirochete
⮚ Some protozoa (amoeba)
Mechanism of action
⮚ Tetracyclines act by inhibiting protein synthesis.
- By binding to the 30s subunit of microbial ribosome
- Blocking the binding of the amino acyl-tRNA to the acceptor site.
⮚ Affect the permeability of bacterial cell membrane

- Allowing the escape of proteins, nucleotides, sugars, amino acids and
others
Bacterial resistance to tetracyclines is mainly due to the follow three
mechanisms:
a) Decreased intracellular accumulation owing to either impaired influx or
increased efflux by an active transport protein pump;
b) Ribosome protection owning to production of proteins that interfere with
tetracycline binding to the target site.
c) Enzymatic inactivation of tetracyclines
Adverse effects
⮚ Gastrointestinal reactions
⮚ Superinfection
⮚ Effects on the bone and teeth of children
⮚ Liver and kidney toxicity: increased during pregnancy
⮚ Phototoxicity
⮚ Local tissue toxicity
Chloramphenicol
Neutral, stable compound, although an effective broad-spectrum antibiotic, its
uses are limited by its serious toxicity. Now is rarely used except for severe
infective diseases. First choice for the treatment: typhoid and paratyphoid.
⮚ Is primarily bacteriostatic, but it may be bactericidal to some strains of
microorganisms even at lower concentration: H. influenza, N. meningitis
and N. gonorrhea
⮚ But, its effects on G- bacteria is better than on G+ bacteria, especially
Salmonella Typha.
⮚ Broad
⮚ Most G- and G+ bacteria. Typhia and paratyphia are more susceptible
⮚ Anaerobic bacteria
⮚ Others: Rickettsia, Spirochete, Mycoplasma and Chlamydia
Mechanism of action
⮚ Acts by inhibiting protein synthesis.
⮚ It binds 50S subunit and block elongation by inhibiting peptidyl
transferase; binding site overlaps with that of macrolides and clindamycin
Adverse effects
⮚ Bone marrow depression
⮚ Toxicity for Newborn Infant
⮚ Gastrointestinal reaction: diarrhea, nausea, vomiting
⮚ Superinfections: such as Oropharyngeal candidiasis and acute
Staphylococcal enterocolitis.
⮚ Hypersensitivity reactions
Tetracycline Chloramphenicol
Spectrum Most G+ and G- bacteria, Most G+ and G- bacteria,
Mycoplasma, Rickettsia, Rickettsia, Chlamydia and
Chlamydia and Mycoplasma
Spirochete
Target 30S subunit 50S subunit
Character Bacteriostatic bacteriostatic
Side effects Superinfection Bone marrow suppression
Bone and teeth Gray baby syndrome
28. Quinolones
Quinolones exert their antibacterial effect by preventing bacterial DNA from
unwinding and duplicating. Specifically, they inhibit the ligase activity of the type
II topoisomerases, gyrase, and topoisomerase IV, which cut DNA to introduce
supercoiling and with their ligase activity disrupted, release DNA with single- and
double-strand breaks that lead to cell death. The majority of quinolones in clinical
use are fluoroquinolones, which have a fluorine atom attached to the central ring
system, typically at the 6-position or C-7 position. Most of them are named with
the -oxacin suffix.
Quinolones are chemotherapeutic bactericidal drugs, eradicating bacteria by

interfering with DNA replication. Quinolones inhibit the bacterial DNA gyrase or
the topoisomerase IV enzyme, thereby inhibiting DNA replication and
transcription. Topoisomerase II is also a target for a variety of quinolone-based
drugs. High activity against the eukaryotic type II enzyme is exhibited by drugs
containing aromatic substituents at their C-7 positions. First- and second-
generation fluoroquinolones selectively inhibit the topoisomerase II ligase
domain, leaving the two nuclease domains intact. This modification, coupled with
the constant action of the topoisomerase II in the bacterial cell, leads to DNA
fragmentation via the nuclease activity of the intact enzyme domains. Third- and
fourth-generation fluoroquinolones are more selective for the topoisomerase IV
ligase domain, thus have enhanced Gram-positive bacteria coverage.
29. Ciprofloxacin
Ciprofloxacin is an antibiotic used to treat bacterial infections including bone and
joint infections, intra-abdominal infections, certain type of infectious diarrhea,
respiratory tract infections, skin infections, typhoid fever, and urinary tract
infections, among others. For some infections it is used in addition to other
antibiotics.
Its spectrum of activity includes most strains of bacterial pathogens responsible
for community-acquired pneumonias, bronchitis, urinary tract infections, and
gastroenteritis. Ciprofloxacin is particularly effective against Gram-negative
bacteria (such as Escherichia coli, Hemophilus influenzae, Klebsiella
pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis,
and Pseudomonas aeruginosa), but is less effective against Gram-positive
bacteria (such as methicillin-sensitive Staphylococcus aureus, Streptococcus
pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones.
Mechanism of action
Ciprofloxacin is a broad-spectrum antibiotic of the fluoroquinolone class. It is
active against some Gram-positive and many Gram-negative bacteria. It
functions by inhibiting a type II topoisomerase (DNA gyrase) and topoisomerase
IV, necessary to separate bacterial DNA, thereby inhibiting cell division.
Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even
during a course of treatment. Numerous pathogens, including enterococci,
Streptococcus pyogenes and Klebsiella pneumoniae (quinolone-resistant) now
exhibit resistance. Widespread veterinary usage of the fluoroquinolones,
particularly in Europe, has been implicated. Meanwhile, some Burkholderia
cepacia, Clostridium innocuum and Enterococcus faecium strains have
developed resistance to ciprofloxacin to varying degrees.
Adverse effects
Adverse effects can involve the tendons, muscles, joints, nerves, and the central
nervous system.
30. Norfloxacin
Norfloxacin is used to treat urinary tract infections, gynecological infections,
inflammation of the prostate gland, gonorrhea and bladder infection. The toxicity
of drugs that are metabolized by the cytochrome P450 system is enhanced by
concomitant use of some quinolones. Quinolones, including norfloxacin, may
enhance the effects of oral anticoagulants, including warfarin or its derivatives or
similar agents. When these products are administered concomitantly,
prothrombin time or other suitable coagulation tests should be closely monitored.
Mechanism of action
Norfloxacin is a broad-spectrum antibiotic that is active against both Gram-
positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type
II topoisomerase, and topoisomerase IV, enzymes necessary to separate
bacterial DNA, thereby inhibiting cell division. Norfloxacin does not bind to DNA
gyrase but does bind to the substrate DNA.
Adverse effects
In general, fluoroquinolones are well tolerated, with most side-effects being mild
to moderate. On occasion, serious adverse effects occur. Common side-effects
include gastrointestinal effects such as nausea, vomiting, and diarrhea, as well
as headache and insomnia.
31. Sulfonamides
Sulfonamide is a functional group that is the basis of several groups of drugs.
The original antibacterial sulfonamides are synthetic (nonantibiotic) antimicrobial
agents. Some sulfonamides are also devoid of antibacterial activity. The
sulfonylureas and thiazide diuretics are newer drug groups based upon the
antibacterial sulfonamides.
In bacteria, antibacterial sulfonamides act as competitive inhibitors of the enzyme

dihydropteroate synthase (DHPS), an enzyme involved in folate synthesis.
Sulfonamides are therefore bacteriostatic and inhibit growth and multiplication of
bacteria, but do not kill them. Humans, in contrast to bacteria, acquire folate
(vitamin B9) through the diet.
Sulfonamides are used to treat allergies and cough, as well as antifungal and
antimalarial functions. The moiety is also present in other medications that are
not antimicrobials, including thiazide diuretics (including hydrochlorothiazide,
metolazone, and indapamide, among others), loop diuretics (including
furosemide, bumetanide, and torsemide), acetazolamide, sulfonylureas (including
glipizide, glyburide, among others), and some COX-2 inhibitors (e.g., celecoxib).
Sulfasalazine, in addition to its use as an antibiotic, is also used in the treatment

of inflammatory bowel disease.
Allergies to sulfonamides are common. including urinary tract disorders,

haemopoietic disorders, porphyria and hypersensitivity reactions. When used in
large doses, they may cause a strong allergic reaction. The most serious of these
are classified as severe cutaneous adverse reactions (i.e. SCARs) and include
the Stevens–Johnson syndrome, toxic epidermal necrolysis (also known as Lyell
syndrome), the DRESS syndrome, and a not quite as serious SCARs reaction,
acute generalized exanthematous pustulosis. Any one of these SCARs may be
triggered by certain sulfonamides.
32. Sulfamethoxazole (SMZ)

Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections
such as urinary tract infections, bronchitis, and prostatitis and is effective against
both gram negative and positive bacteria such as Listeria monocytogenes and E.
coli. Common side effects include nausea, vomiting, loss of appetite, and skin
rashes. It is a sulfonamide and bacteriostatic. It resembles a component of folic
acid. It prevents folic acid synthesis in the bacteria that must synthesize their own
folic acid. Mammalian cells, and some bacteria, do not synthesize but require
preformed folic acid (vitamin B9); they are therefore insensitive to
sulfamethoxazole.
Mechanism of action
Sulfamethoxazole, a sulfanilamide, is a structural analog of para-aminobenzoic
acid (PABA). They compete with PABA to bind to dihydropteroate synthetase
and inhibit conversion of PABA and dihydropteroate diphosphate to dihydro folic
acid, or dihydrofolate. Inhibiting the production of dihydrofolate intermediate
interferes with the normal bacterial synthesis of folic acid (folate). Folate is an
essential metabolite for bacterial growth and replication because it is used in
DNA synthesis, primarily at thymidylate and purine biosynthesis, and amino acids
synthesis, including serine, glycine and methionine. Hence, blockage of folate
production inhibits the folate-dependent metabolic processes for bacterial growth.
Since it inhibits bacterial growth, sulfamethoxazole is considered a bacteriostatic
antibiotic.
Adverse reactions
The most common side effects of sulfamethoxazole are gastrointestinal
disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as
rash and urticaria). There have been rare instances where severe adverse
reactions have resulted in fatalities. These include Stevens–Johnson syndrome
(SJS), toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis,
aplastic anemia, and other blood dyscrasias.
Allergic reactions to Sulfonamides have been shown to include the entire Gel-
Coombs spectrum of hyperactivity reactions. Type 1 reactions include
immunoglobulin E (IgE)-mediated reactions such as urticaria, angioedema, and
anaphylaxis. In contrast, non-type 1 hypersensitivities are believed to be caused
by metabolites of sulfonamides. Therefore, the liver and kidney are the
determining factors of these other hypersensitivity reactions; alterations in kidney
or liver functions may increase or decrease the frequencies of these reactions.
33. Summary
34. BRIEFLY DESCRIBE HOW TO TREAT ARRHYTHMIA BY DRUGS?

Class 1: Block sodium chennels in the cell membrane during an action
potential.sub classes of class I antiarrhythmic drugs.
- Quinidine, depress phase 0 of the action potential and prolong APD.
Procainamide has heart actions similar tothose of quinidine.
- Lidocaine and phenytoin sodium depress somewhat and actually
shorten APD.
- Propafenone (rythmol) markedly depress phase o with a resultant
extreme slowing of conduction.
Class 2) Block beta receptors, causing a depression of phase 4 of the
action potential. Representative drug: Propranolol.
Class 3) Block potassium channels, prolong phase 3of the action
potential. Representative drug: Amiodarane.
Class 4) Block calcium channels in the cell membrane, effect sinus and A
-V node. Representative drug: Verepamil
True or False
- Insulin can be taken orally. (X)
- Biguanide compounds can be used in patients with NIDDM whose pancreas still
has capacity to produce insulin. (✓)
- The principal mechanism of the action of sulfonylureas are to increase the insulin
releasing from pancreatic β cells. (✓)
- Norepinephrine (NE) is the neurotransmitter at most adrenoceptors in organs, as
well as in cardiac and smooth muscle. (✓)
- All direct transmission from the CNS (preganglionic and motor) uses ACh. (✓)
Essay questions
Case 1:
A 17-year-old male high school student is referred to the psychiatry clinic for evaluation
of suspected schizophrenia. After a diagnosis is made, haloperidol is prescribed at a
gradually increasing dose on an outpatient basis. The drug improves the patient’s
positive symptoms but ultimately causes intolerable adverse effects. Although more
costly, risperidone is then prescribed, which, over the course of several weeks of
treatment, improves his symptoms and is tolerated by the patient.
What signs and symptoms would support an initial diagnosis of schizophrenia? In the
treatment of schizophrenia, what benefits do the atypical antipsychotic drugs offer over
the traditional agents such as haloperidol?
In addition to the management of schizophrenia, what other clinical indications warrant

consideration of the use of drugs nominally classified as antipsychotics?
Answer
Schizophrenia is characterized by a disintegration of thought processes and emotional
responsiveness. Symptoms commonly include auditory hallucinations, paranoid or
bizarre delusions, disorganized thinking and speech, and social and occupational
dysfunction. For many patients, typical (ex. haloperidol) and atypical agents (ex.
risperidone) are of equal efficacy for treating positive symptoms. Atypical agents are
often more effective for treating negative symptoms and cognitive dysfunction and have
lower risk of tardive dyskinesia and hyperprolactinemia. Other indications for the use of
selected antipsychotics include bipolar disorder, psychotic depression, Tourette’s
syndrome, disturbed
behavior in patients with Alzheimer’s disease and in the case of older drugs (eg,
chlorpromazine), treatment of emesis and pruritus.
Many drugs used for other purpose also modify emotions and cognition either as part of
their usual actions or as toxic effects of overdosage.
Antipsychotic drugs are able to reduce psychotic symptoms in a wide variety of
conditions, including schizophrenia, bipolar disorder, psychotic depression, senile
psychoses, various organic psychoses, and drug-induced psychoses. They are also able
to improve mood and reduce anxiety and sleep disturbances, but they are not the
treatment of choice when these symptoms are the primary disturbance in nonpsychotic
patients.
Case 2:
A 60-year-old man with a history of moderate chronic obstructive pulmonary disease
presents in the emergency department with a broken hip suffered in an automobile
accident. He complains of severe pain.
What is the most appropriate immediate treatment for his pain? Are any special
precautions needed?
Answer
In this case, the treatment of severe pain should be managed with the administration of
a potent intravenous opioid analgesic such as morphine, hydromorphone, or fentanyl.
Before an additional dose of an opioid analgesic is administered, it is expected that the
patient will require frequent reevaluation of both the severity of his pain and the
presence of potential side effects. Given his history of pulmonary disease, he is also at
increased risk of developing respiratory depression. Frequent reevaluation of his level of
consciousness, respiratory rate, fractional oxygen saturation, and other vital parameters
can help achieve the goal of pain relief and minimize respiratory depression. Concurrent
use of sedative agents such as benzodiazepines should be avoided if possible and
proceed only with great caution.
Case 3:
A 48-year-old man presents with complaints of bilateral morning stiffness in his wrists
and knees and pain in these joints on exercise. On physical examination, the joints are
slightly swollen. The rest of the examination is unremarkable. His laboratory findings are
also negative except for slight anemia, elevated erythrocyte sedimentation rate, and
positive rheumatoid factor. With the diagnosis of rheumatoid arthritis, he is started on a
regimen of naproxen, 220 mg twice daily. After 1 week, the dosage is increased to 440
mg twice daily. His symptoms are reduced at this dosage, but he complains of significant
heartburn that is not controlled by antacids. He is then switched to celecoxib, 200 mg
twice daily, and on this regimen his joint symptoms and heartburn resolve. Two years
later, he returns with increased joint symptoms. His hands, wrists, elbows, feet, and
knees are all now involved and appear swollen, warm, and tender.
What therapeutic options should be considered at this time? What are the possible
complications?
Answer
This patient had good control of his symptoms for 1 year but now has a prolonged flare,
probably denoting worsening disease (not just a temporary flare). In addition to physical
findings and measurement of acute-phase reactants such as sedimentation rate or C-
reactive protein, it would be wise to get hand and feet radiographs to document whether
he has developed joint damage. Assuming such damage is found, the appropriate
approach would be either a combination of nonbiologic DMARDs (ex. adding
sulfasalazine and hydroxychloroquine) or adding a biologic medication, usually a TNF
inhibitor. Follow-up should be every 1-3 months to gauge response and toxicity. Adverse
events requiring caution are an increased risk of infection, possible appearance of
lymphoma and rare liver function test or hematologic abnormalities. Importantly, close
follow-up should ensue, including changing medications every 3-6 months until full
disease control is achieved.
Case 4:
At her annual physical examination, a 53-year-old middle school teacher complains that
she has been having difficulty falling asleep, and after falling asleep, she awakens
several times during the night. These episodes now occur almost nightly and are
interfering with her ability to teach. She has tried various over-the-counter sleep
remedies, but they were of little help and she experienced “hangover” effects on the
day following their use. Her general health is good, she is not overweight, and she takes
no prescription drugs. She drinks decaffeinated coffee but only one cup in the morning;
however, she drinks as many as 6 cans per day of diet cola. She drinks a glass of wine
with her evening meal but does not like stronger spirits.
What other aspects of this patient’s history would you like to know? What therapeutic
measures are appropriate for this patient? What drug, or drugs, (if any) would you
prescribe?
Answer
As described in this chapter, nonpharmacologic factors are very important in the
management of sleep problems: proper diet (and avoidance of snacks before bedtime),
exercise, and a regular time and place for sleep. Avoidance of stimulants is very
important, and the large intake of diet colas reported by the patient should be reduced,
especially in the latter half of the day. If problems persist after these measures are
implemented, one of the newer hypnotics (eszopiclone, zaleplon, or zolpidem) may be
tried on a short-term basis.
Case 5:
A 65-year-old man developed shortness of breath with exertion several weeks after
experiencing a viral illness. This was accompanied by swelling of the feet and ankles
and increasing fatigue. On physical examination he is now found to be mildly short of
breath lying down, but feels better sitting upright. Pulse is 105 bpm and regular, and
blood pressure is 110/70 mm Hg. Crackles are noted at both lung bases, and his jugular
venous pressure is elevated. The liver is enlarged, and there is 3+ edema of the ankles
and feet. An echocardiogram shows a dilated, poorly contracting heart with a left
ventricular ejection fraction of about 20% (normal: 60%). The presumptive diagnosis is
dilated cardiomyopathy secondary to a viral infection with stage C, class III heart failure.
What treatment is indicated?
Answer
The patient has a low ejection fraction with systolic heart failure. He was placed on a low
-sodium diet and treated with a diuretic (furosemide, 40 mg twice daily). On this therapy,
he was less short of breath on exertion and could also lie flat without dyspnea. An
angiotensin-converting enzyme (ACE) inhibitor was added (enalapril, 20 mg twice daily),
and over the next few weeks, he continued to feel better. Because of continued
shortness of breath on exercise, digoxin at 0.25 mg/d was added with a further
improvement in exercise tolerance. Addition of a β blocker and eplerenone is being
considered.
Case 6:
A 65-year-old man has a history of diabetes and chronic kidney disease with baseline
creatinine of 2.8 mg/dL. Despite five different antihypertensives, his clinic blood pressure
is 176/92 mm Hg and he has 2–3+ edema on exam. He has been taking furosemide 80
mg twice a day for one year now. He has mild dyspnea on exertion. At the clinic visit,
hydrochlorothiazide 25 mg daily is added for better blood pressure control and
symptoms/signs of fluid overload. Two weeks later, the patient presents to the
emergency department with symptoms of weakness, anorexia, and generalized malaise.
His blood pressure is now 91/58 mm Hg and he has lost 15 kg in two weeks. His
laboratory tests are significant for a serum creatinine of 10.8.
What has led to the acute kidney injury? What is the reason for the weight loss? What
precautions could have been taken to avoid this hospitalization?
Answer
This patient demonstrates the dramatic diuresis that can be achieved in patients on
chronic loop diuretic therapy after addition of a thiazide diuretic. The drop in systolic
blood pressure and the weight loss are consistent with the rapid diuresis achieved in this
patient. This effect has now led to acute kidney injury in this patient with preexisting
severe kidney disease. This case demonstrates the need for very close monitoring of
patients after addition of thiazide diuretics to chronic loop diuretic therapy (particularly if
they have preexisting chronic kidney disease). This is often best achieved in the
inpatient setting.
Case 7:
A 68-year-old man presents with a complaint of lightheadedness on standing that is
worse after meals and in hot environments. Symptoms started about 4 years ago and
have slowly progressed to the point that he is disabled. He has fainted several times, but
always recovers consciousness almost as soon as he falls. Review of symptoms reveals
slight worsening of constipation, urinary retention out of proportion to prostate size, and
decreased sweating. He is otherwise healthy with no history of hypertension, diabetes,
or Parkinson’s disease. Because of his urinary retention, he was placed on the α1
antagonist tamsulosin but he could not tolerate it because of worsening of orthostatic
hypotension. Physical examination revealed a blood pressure of 167/84 mm Hg supine
and 106/55 mm Hg standing.
Answer
The clinical picture is that of autonomic failure. The best indicator of this is the profound
drop in orthostatic blood pressure without an adequate compensatory increase in heart
rate. Pure autonomic failure is a neurodegenerative disorder selectively affecting
peripheral autonomic fibers. Patients’ blood pressure is critically dependent on whatever
residual sympathetic tone they have, hence the symptomatic worsening of orthostatic
hypotension that occurred when this patient was given the α blocker tamsulosin.
Conversely, these patients are hypersensitive to the pressor effects of α agonists and
other sympathomimetics. For example, the α agonist midodrine can increase blood
pressure significantly at doses that have no effect in normal subjects and can be used to
treat their orthostatic hypotension. Caution should be observed in the use of
sympathomimetics (including over-the-counter agents) and sympatholytic drugs.
Case 8:
A 23-year-old woman presents to the office for consultation
regarding her antiseizure medications. Seven years ago, this
otherwise healthy young woman had a generalized tonic-clonic seizure (GTCS) at home.
She was rushed to the emergency department; at which time she was alert but
complained of headache. A consulting neurologist placed her on levetiracetam, 500 mg
bid. Four days later, EEG showed rare right temporal sharp waves. MRI was normal.
One year after this episode, a repeat EEG was unchanged, and levetiracetam was
gradually increased to 1000 mg bid. The patient had no significant adverse effects from
this dosage. At age 21, she had a second GTCS while in college; further discussion with
her roommate at that time revealed a history of two recent episodes of 1-2 minutes of
altered consciousness with lip smacking (complex partial seizures). A repeat EEG
showed occasional right temporal spikes.
What is one possible strategy for controlling her present symptoms?
Answer
Lamotrigine was gradually added to the regimen to a dosage of 200 mg bid. Since then,
the patient has been seizure-free for almost 2 years but now comes to the office for a
medication review. Gradual discontinuation of levetiracetam is planned if the patient
continues to do well for another year, although risk of recurrent seizures is always
present when medications are withdrawn.
Case 9:
A 35-year-old man presents with a blood pressure of 150/95mm Hg. He has been
generally healthy, is sedentary, drinks several cocktails per day, and does not smoke
cigarettes. He has a family history of hypertension, and his father died of a myocardial
infarction at age 55. Physical examination is remarkable only for moderate obesity. Total
cholesterol is 220, and high-density lipoprotein (HDL) cholesterol level is 40 mg/dL.
Fasting glucose is 105 mg/dL. Chest x-ray is normal. Electrocardiogram shows left
ventricular enlargement.
How would you treat this patient?
Answer
The patient has JNC stage 1 hypertension.
Cardiovascular risk factors in this man include family history of early coronary disease
and elevated cholesterol. Evidence of end-organ impact includes left ventricular
enlargement on EKG. The strong family history suggests that this patient has essential
hypertension. However, the patient should undergo the usual screening tests including
renal function, thyroid function, and serum electrolyte measurements. An
echocardiogram should also be considered to determine whether the patient has left
ventricular hypertrophy secondary to valvular or other structural heart disease as
opposed to hypertension. Initial management in this patient can be behavioral, including
dietary changes and aerobic exercise.
However, most patients like this will require medication. Thiazide diuretics in low doses
are inexpensive, have relatively few side effects, and are effective in many patients with
mild hypertension. Other first-line agents include angiotensin converting enzyme
inhibitors, angiotensin receptor blockers, and calcium channel blockers. Beta blockers
might be considered if the patient had coronary disease or had labile hypertension. A
single agent should be prescribed and the patient reassessed in a month. If a second
agent is needed, one of the two agents should be a thiazide diuretic.
Once blood pressure is controlled, patients should be followed periodically to reinforce
the need for compliance with both lifestyle changes and medications.
Case 10:
A 69-year-old retired teacher presents with a 1-month history of palpitations, intermittent
shortness of breath, and fatigue. She has a history of hypertension. An ECG shows atrial
fibrillation with a ventricular response of 122 beats/min (bpm) and signs of left ventricular
hypertrophy. She is anticoagulated with warfarin and started on sustained-release
metoprolol, 50 mg/d. After 7 days, her rhythm reverts to normal sinus rhythm
spontaneously. However, over the ensuing month, she continues to have intermittent
palpitations and fatigue. Continuous ECG recording over 48-hour period documents
paroxysms of atrial fibrillation with heart rates of 88–114 bpm. An echocardiogram
shows a left ventricular ejection fraction of 38% with no localized wall motion
abnormality.
At this stage, would you initiate treatment with an antiarrhythmic drug to maintain normal
sinus rhythm, and if so, what drug would you choose?
Answer
The patient has significant symptoms during recurrent episodes of atrial fibrillation. The
peak heart rate is not particularly high. Maintenance of sinus rhythm appears to be
important in this patient. The echocardiogram demonstrates impairment of left ventricular
function. Selection of a drug that is tolerated in heart failure and has documented ability
to convert or prevent atrial fibrillation, for example; Dofetilide or Amiodarone would be
appropriate.
Case 11:
A 52-year-old man presents with a history of recent onset chest discomfort when jogging
or swimming vigorously. The pain is substernal and radiates to his jaw but disappears
after 10-15 minutes of rest. He has a history of hyperlipidemia (total cholesterol level of
245 mg/dL and low-density lipoprotein [LDL] of 160 mg/dL one year ago) and admits that
he has not been following the recommended diet. His father survived a “heart attack” at
age 55 and an uncle died of some cardiac disease at age 60. On physical examination,
the patient’s blood pressure is 145/90 mm Hg and his heart rate is 80 bpm. There are no
other significant physical findings and an electrocardiogram is normal except for slight
left ventricular hypertrophy.
Assuming that a diagnosis of stable effort angina is correct,
what medical treatment should be implemented?
Answer
The case described is typical of coronary artery disease in a patient with hyperlipidemia.
His hyperlipidemia should be treated vigorously to slow progression of, and if possible,
reverse, the coronary lesions that are present. Treatment of his acute episodes of
angina should include sublingual tablets or sublingual nitroglycerin spray 0.4-0.6 mg.
Relief of discomfort within 2-4 minutes can be expected. To prevent episodes of angina,
a β blocker such as metoprolol should be tried first. If contraindications to the use of a β
blocker are present, a medium to long-acting calcium channel blocker such as
verapamil, diltiazem, or amlodipine is likely to be effective. Because of this patient’s
family history, an antiplatelet drug such as low-dose aspirin is appropriate. Careful follow
-up is mandatory with repeat lipid panels, repeat dietary counseling, and lipid-lowering
therapy; coronary angiography should also be considered.
Case 12:
Andy, is a 56-year-old construction worker with a 15-year history of hypertension and
ischemic heart disease that was well controlled until 6 months ago. Over the past 2
months, has been seen twice in the ER with chest pain unrelieved by sublingual
nitroglycerin. On a third occasion, he was hospitalized with the same symptoms and was
given a complete workup. He has two severe vessel disease, but refuses angioplasty or
bypass surgery at this time. He also has asthmas.
His current medications include nifedipine, captopril, nitroglycerin, diltiazem, and aspirin.
During the past week, he experienced several anginal attacks each day that were
relieved by nitroglycerin; finally, Andi has decided to seek more definitive treatment.
Tonight, he presents to the ER with chest pain unrelieved by nitroglycerin and is sent to
the critical care until with the diagnosis of unstable angina pectoris. The attending
physician orders IV nitroglycerin and wants to start an IV β-adrenergic blocker to
counteract any tachycardia, but is concerned about its long-term effects on overall
cardiac function.
1. Select the most appropriate β-adrenergic antagonist from the structures

provided. Justify your choice on the basis of the pharmacology:
- NADOLOL
- Isoprenaline
- Metoprolol
- Propranolol
2. One of the structures is contraindicated in the patient. Which one is it, and why is
it contraindicated?
3. Advantages of treatment angina with combination of Nitrates and β-receptor
antagonists.
See antianginal drugs slides
The case described is typical of coronary artery disease in a patient with
hyperlipidemia. His hyperlipidemia should be treated vigorously to slow
progression of, and if possible, reverse, the coronary lesions that are present.
Treatment of his acute episodes of angina should include sublingual tablets or
sublingual nitroglycerin spray 0.4-0.6 mg. Relief of discomfort within 2-4 minutes
can be expected. To prevent episodes of angina, a β blocker such as metoprolol
should be tried first. If contraindications to the use of a β blocker are present, a
medium to long-acting calcium channel blocker such as verapamil, diltiazem, or
amlodipine is likely to be effective. Because of this patient’s family history, an
antiplatelet drug such as low-dose aspirin is appropriate. Careful follow-up is
mandatory with repeat lipid panels, repeat dietary counseling, and lipid-lowering
therapy; coronary angiography should also be considered
Case 13:
A 64-year-old architect complains of left-hand tremor at rest, which interferes with his
writing and drawing. He also notes a stooped posture, a tendency to drag his left leg
when walking, and slight unsteadiness on turning. He remains independent in all
activities of daily living. Examination reveals hypomimia (flat facies), hypophonia, a rest
tremor of the left arm and leg, mild rigidity in all limbs, and impaired rapid alternating
movements in the left limbs. Neurologic and general examinations are otherwise normal.
What is the likely diagnosis and prognosis? He is started on a dopamine agonist, which
he seems to tolerate well, and the dose is gradually built up to the therapeutic range.
About a year later, he and his wife return for follow-up. It now becomes apparent that he
is spending large sums of money, which he cannot afford, on gambling and refuses to
stop, despite his wife’s entreaties.
To what is his condition due and how should it be managed?
Answer
The relation of the tremor to activity (rest tremor) in this case is characteristic of
parkinsonism. Examination reveals the classic findings of Parkinson’s disease—rest
tremor, rigidity, bradykinesia, and a gait disturbance; an asymmetry of the abnormalities
is common in Parkinson’s disease. The prognosis is that symptoms will become more
generalized with time. Pharmacologic treatment would involve a dopamine agonist
(pramipexole or ropinirole) but may not need to be started now unless the patient is
disturbed by his symptoms. The patient developed an impulse control disorder
(gambling) after starting on an agonist, and this may require dose reduction or
discontinuation of the agonist.

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Pharmacology Hacked

2. Which of the following is the inhibitor of protein synthesis of bacteria

7. Which effect of chlorpromazine is comparable to its extrapyramidal action?

8. A major biochemical effect of cardiac glycosides is

9. Common effects of muscarinic stimulant drugs include all of the following

10. A predictably dangerous side effect of propranolol, which constitutes a

14. Which of the following statements about fentanyl is correct?

16. What is drug?

17. Please select all the true statements: (Multiple Choice)

18. ADME equals PK

19. Which one of the following statements is correct regarding benzodiazepines?

20. Which receptor does Cimetidine bind?

21. Which protein does Omeprazole target?

22. A 12-year-old girl with a childhood history of asthma complained of cough,

29. Pilocarpine has the following effects: (Multiple choice)

31. Neostigmine differs from pilocarpine in having effects on:

32. In the presence of naloxone, a higher concentration of morphine is required to

33. A 60-year-old female patient started on a new antihypertensive medication

34. A new antihypertensive drug was tested in an animal model of hypertension.

37. An asthma patient was given a nonselective β agonist to relieve

42. Which of the following drugs is considered to be effective in the treatment of

48. Which of the following effects taken by Ca-antagonists: (Multiple answer)

49. Which one of the following combinations of antiparkinsonian drugs is an

50. Peripheral adverse effects of levodopa, including nausea, hypotension, and

54. Drugs that are highly bound to albumin:

55. Most drugs gain entry to cells by:

57. Urination in the human subject is decreased by:

58. What is the most serious side effects caused by penicillin G?

60. Which microorganisms can penicillin G target?

61. Comparing to penicillin G. Amoxicillin

63. Which microorganism is aminoglycoside not effective against?

64. Where are aminoglycosides mainly distributed?

65. Which one is not the side effect caused by aminoglycosides?

67. Which of the following microorganism is macrolides not effective against?

68. The combination of erythromycin and clindamycin could:

71. Which of the following is not sensitive to tetracycline?

72. Which is NOT correct regarding the side effects of tetracycline?

74. What is the most severe side effect caused by chloramphenicol?

75.Which of the following causes gray-baby syndrome?

78. Which is important to monitor in patients taking digoxin?

80. Suppression of arrhythmias resulting from a reentry focus is most likely to

81. What arrhythmia can be treated with lidocaine?

83. All of the following are adverse effects of amiodarone, except:

88. Activation of postsynaptic M2 receptors on the heart is associated with:

90. Highly ionized drugs tend to accumulate in the:

Adverse drug reaction (ADR)

First pass effect

There are 2 types of resistance:

Thiazide diuretics inhibit sodium re-absorption at the beginning of the distal

A combination of a potassium sparing diuretic with a thiazide diuretic is used to

2. Briefly describe the classification and clinical uses of antithrombotic

An antithrombotic agent is a drug that reduces the formation of blood clots

Different antithrombotic drugs affect different blood clotting processes:

⮚ Antiplatelet drugs limit the migration or aggregation of platelets.

Warfarin: a medication that is used as an anticoagulant (blood thinner). It

- Adverse reactions and antagonist drugs.

4. Classification of antimicrobial agents by their sites of action.

7. What are the final results of biotransformation?

8. What are the pharmacological effects of Atropine?