Pharmacolog
y Test Prep
PR
1500
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USMLE-
FD
Style
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Questions &
Answers
,Contents
Preface ...................................................................................................................................................................................................................... ix
Section I: General Principles of Pharmacology
Questions
I-1 Pharmacokinetics .................................................................................................................................................................................... 1
I-2 Pharmacodynamics ................................................................................................................................................................................. 7
I-3 Adverse Effects of Drugs ...................................................................................................................................................................... 12
Answers and Explanations
I-1 Pharmacokinetics .................................................................................................................................................................................. 15
I-2 Pharmacodynamics ............................................................................................................................................................................... 21
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I-3 Adverse Effects of Drugs ...................................................................................................................................................................... 26
Section II: Autonomic Nervous System
Questions
II-1 Introduction to Autonomic Pharmacology ......................................................................................................................................... 31
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II-2 Adrenergic Drugs .................................................................................................................................................................................. 34
II-3 Antiadrenergic Drugs ........................................................................................................................................................................... 40
II-4 Cholinergic Drugs ................................................................................................................................................................................. 44
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II-5 Anticholinergic Drugs .......................................................................................................................................................................... 48
Answers and Explanations
II-1 Introduction to Autonomic Pharmacology ......................................................................................................................................... 52
II-2 Adrenergic Drugs .................................................................................................................................................................................. 55
II-3 Antiadrenergic Drugs ........................................................................................................................................................................... 62
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II-4 Cholinergic Drugs ................................................................................................................................................................................. 66
II-5 Anticholinergic Drugs .......................................................................................................................................................................... 71
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Section III: Central Nervous System
Questions
III-1 Introduction to Central Nervous System Pharmacology................................................................................................................... 77
III-2 Sedative and Hypnotic Drugs .............................................................................................................................................................. 80
III-3 General Anesthetics.............................................................................................................................................................................. 84
III-4 Local Anesthetics.................................................................................................................................................................................. 88
III-5 Skeletal Muscle Relaxants ..................................................................................................................................................................... 91
III-6 Antiseizure Drugs ................................................................................................................................................................................. 95
III-7 Drugs for Degenerative Disorders of the Central Nervous System. . 102
III-8 Neuroleptic Drugs .............................................................................................................................................................................. 106
III-9 Drugs for Depressive and Anxiety Disorders .................................................................................................................................. 111
III-10 Drugs for Bipolar Disorders ................................................................................................................................................................ 116
III-11 Drugs for Childhood Behavioral Disorders ....................................................................................................................................... 119
III-12 Opioid Analgesics and Antagonists .................................................................................................................................................... 122
III-13 Drugs of Abuse .................................................................................................................................................................................... 128
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Answers and Explanations
III-1 Introduction to Central Nervous System Pharmacology .............................................................................................................. 134
III-2 Sedative and Hypnotic Drugs ........................................................................................................................................................... 137
III-3 General Anesthetics........................................................................................................................................................................... 141
III-4 Local Anesthetics............................................................................................................................................................................... 145
III-5 Skeletal Muscle Relaxants ................................................................................................................................................................. 148
III-6 Antiseizure Drugs .............................................................................................................................................................................. 152
III-7 Drugs for Degenerative Disorders of the Central Nervous System. . 158
III-8 Neuroleptic Drugs ............................................................................................................................................................................. 162
III-9 Drugs for Depressive and Anxiety Disorders. . 166
III-10 Drugs for Bipolar Disorders .............................................................................................................................................................. 171
III-11 Drugs for Childhood Behavioral Disorders...................................................................................................................................... 174
III-12 Opioid Analgesics and Antagonists .................................................................................................................................................. 177
III-13 Drugs of Abuse ................................................................................................................................................................................... 183
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Section IV: Cardiovascular and Renal Systems
Questions
IV-1 Diuretics.............................................................................................................................................................................................. 191
IV-2 Drugs for Ischemic Heart Disease ................................................................................................................................................... 196
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IV-3 Drugs for Cardiac Failure................................................................................................................................................................... 200
IV-4 Antihypertensive Drugs .................................................................................................................................................................... 206
IV-5 Antiarrhythmic Drugs ....................................................................................................................................................................... 212
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IV-6 Antihyperlipidemic Drugs ................................................................................................................................................................ 218
IV-7 Drugs Affecting Hemostasis............................................................................................................................................................. 222
Answers and Explanations
IV-1 Diuretics.............................................................................................................................................................................................. 227
IV-2 Drugs for Ischemic Heart Disease ................................................................................................................................................... 232
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IV-3 Drugs for Cardiac Failure................................................................................................................................................................... 237
IV-4 Antihypertensive Drugs .................................................................................................................................................................... 245
IV-5 Antiarrhythmic Drugs ....................................................................................................................................................................... 251
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IV-6 Antihyperlipidemic Drugs ................................................................................................................................................................ 257
IV-7 Drugs Affecting Hemostasis............................................................................................................................................................. 261
Section V: Endocrine System
Questions
V-1 Drugs for Hypothalamic and Pituitary Disorders ......................................................................................................................... 267
V-2 Drugs for Thyroid Disorders ............................................................................................................................................................. 271
V-3 Corticosteroids and Antagonists ...................................................................................................................................................... 276
V-4 Drugs for Gonadal Disorders ............................................................................................................................................................. 282
V-5 Drugs for Bone Homeostasis ............................................................................................................................................................. 288
V-6 Drugs for Diabetes Mellitus .............................................................................................................................................................. 292
Answers and Explanations
V-1 Drugs for Hypothalamic and Pituitary Disorders ......................................................................................................................... 298
V-2 Drugs for Thyroid Disorders ............................................................................................................................................................. 303
V-3 Corticosteroids and Antagonists ...................................................................................................................................................... 308
,V-4 Drugs for Gonadal Disorders .............................................................................................................................................................. 315
V-5 Drugs for Bone Homeostasis ............................................................................................................................................................... 321
V-6 Drugs for Diabetes Mellitus ................................................................................................................................................................ 326
Section VI: Respiratory, Gastrointestinal, and Hematopoietic Systems
Questions
VI-1 Drugs for Bronchospastic Disorders ................................................................................................................................................. 333
VI-2 Drugs for Gastrointestinal Disorders ............................................................................................................................................... 338
VI-3 Drugs for Hematopoietic Disorders ................................................................................................................................................. 344
Answers and Explanations
VI-1 Drugs for Bronchospastic Disorders ................................................................................................................................................. 348
VI-2 Drugs for Gastrointestinal Disorders ............................................................................................................................................... 354
VI-3 Drugs for Hematopoietic Disorders ................................................................................................................................................. 359
Section VII: Infammation and Immunomodulation
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Questions
VII-1 Histamine and Serotonin: Agonists and Antagonists . . 363
VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors ......................................................................................................................... 367
VII-3 Nonsteroidal Antiinfammatory Drugs............................................................................................................................................. 370
VII-4 Immunomodulating Drugs ................................................................................................................................................................ 374
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VII-5 Drugs for Arthritis and Gout ............................................................................................................................................................. 378
Answers and Explanations
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VII-1 Histamine and Serotonin: Agonists and Antagonists . . 381
VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors ......................................................................................................................... 385
VII-3 Nonsteroidal Antiinfammatory Drugs............................................................................................................................................. 387
VII-4 Immunomodulating Drugs ................................................................................................................................................................ 392
VII-5 Drugs for Arthritis and Gout ............................................................................................................................................................. 396
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Section VIII: Chemotherapeutic Drugs
Questions
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VIII-1 Bacterial Cell Wall Synthesis Inhibitors ............................................................................................................................................. 400
VIII-2 Bacterial Protein Synthesis Inhibitors............................................................................................................................................... 408
VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function ............................................................................................................. 415
VIII-4 Antimycobacterial Drugs ................................................................................................................................................................... 420
VIII-5 Antifungal Drugs ................................................................................................................................................................................ 423
VIII-6 Antiviral Drugs .................................................................................................................................................................................... 427
VIII-7 Antiprotozoal Drugs ........................................................................................................................................................................... 433
VIII-8 Anthelmintic Drugs ............................................................................................................................................................................ 436
VIII-9 Antineoplastic Drugs ......................................................................................................................................................................... 439
Answers and Explanations
VIII-1 Bacterial Cell Wall Synthesis Inhibitors ............................................................................................................................................. 446
VIII-2 Bacterial Protein Synthesis Inhibitors ............................................................................................................................................... 455
VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function.............................................................................................................. 462
VIII-4 Antimycobacterial Drugs.................................................................................................................................................................... 466
,VIII-5 Antifungal Drugs ................................................................................................................................................................................ 469
VIII-6 Antiviral Drugs ................................................................................................................................................................................... 473
VIII-7 Antiprotozoal Drugs ........................................................................................................................................................................... 478
VIII-8 Anthelmintic Drugs ............................................................................................................................................................................ 481
VIII-9 Antineoplastic Drugs .......................................................................................................................................................................... 484
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,I General Principles of Pharmacology
Questions: I-1 Pharmacokinetics
Difficulty level: Easy Difficulty level: Easy
1. A 22-year-old woman suffering from asthma was prescribed 4. A 12-year-old boy recently diagnosed with type 1 diabetes
albuterol by inhalation. Albuterol is a bronchodilating drug started a therapy with two daily subcutaneous administrations
with a molecular weight of 239 daltons. Which of the fol- of insulin. Which of the following permeation processes best
lowing permeation processes most likely accounted for the explains the absorption of insulin from the site of injection?
transfer of the drug through the bronchial mucosa?
A. Bulk flow transport
A. Aqueous diffusion B. Lipid diffusion
B. Lipid diffusion C. Facilitated diffusion
C. Facilitated diffusion D. Endocytosis
D. Endocytosis E. Active transport
E. Active transport
Difficulty level: Hard
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Difficulty level: Easy
5. An 85-year-old man was recently admitted to a nursing facil-
2. A 34-year-old man on vacation in Mexico was admitted to the ity. Diseases listed in his medical record on admission were
hospital because of vomiting, double vision, and muscular pa- depression with anxiety symptoms, atrial fibrillation, chronic
ralysis. The man reported that he had eaten some canned food obstructive pulmonary disease, and osteoarthritis. Medica-
from a local vendor the previous day. After a physical exam- tions taken orally by the patient included the following:
ination, a presumptive diagnosis of botulism was made. It is
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Sertraline (base, pKa = 9.5)
known that botulinum toxin causes paralysis by getting in-
Diazepam (base, pKa = 3.0)
side the axon terminals of motor nerves, where it inhibits the
Amiodarone (base, pKa = 7.4)
release of acetylcholine. Botulinum toxin is a protein with a
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molecular weight greater than 100,000 daltons. Which of the Theophylline (acid, pKa = 8.8)
following permeation processes most likely accounts for the Ibuprofen (acid, pKa 4.8)
transfer of the toxin through the nerve cell membrane?
Shortly after administration, which of the following drugs was
A. Aqueous diffusion most likely concentrated inside the patient’s gastric cells?
B. Lipid diffusion
A. Sertraline
C. Facilitated diffusion
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B. Diazepam
D. Endocytosis
C. Amiodarone
E. Filtration
D. Theophylline
E. Ibuprofen
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Difficulty level: Easy
3. A 51-year-old woman suffering from hyperthyroidism was Difficulty level: Medium
administered an oral solution of radioactive iodine to destroy
6. A 17-year-old boy took a tablet of naproxen for a headache.
her thyroid gland. Which of the following permeation pro-
Naproxen is a weak acid with a pKa of 5.2. What percentage
cesses most likely accounted for the transfer of the drug across the
of the drug was most likely water soluble in the patient’s
thyroid cell membrane?
plasma?
A. Active transport
A. 1%
B. Lipid diffusion
B. 24%
C. Facilitated diffusion
C. 50%
D. Endocytosis
D. 76%
E. Aqueous diffusion
E. 99%
F. > 99%
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,Difficulty level: Medium Difficulty level: Easy
7. A 69-year-old woman was brought to a local hospital emer- 10. During a phase 1 clinical trial, four different oral dosage
gency department by her son, who reported that his mother forms of the same dose of a drug were administered to a
was found lethargic, disoriented, and combative a few hours healthy volunteer on four separate occasions. The plasma
earlier. Additional history revealed that she had ingested a concentration−time curves are plotted below.
large number of aspirin tablets in a suicide attempt. An ap-
propriate therapy was instituted, which included the admin- W
istration of sodium bicarbonate to increase the elimination of
salicylate. Which of the following best explains the mecha-
nism of this increased elimination?
[Drug]
A. Decreased tubular active transport of salicylate
B. Decreased renal biotransformation of salicylate
C. Decreased bioavailability of salicylate
D. Urinary ion trapping of salicylate
E. Increased glomerular filtration of salicylate
Time
Difficulty level: Medium Which of the following features best explains why formula-
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tion W produces the largest plasma concentration−time curve of
8. A 63-year old man recently diagnosed with hypertension
the drug?
started a therapy with hydrochlorothiazide, one tablet daily.
Hydrochlorothiazide is an acidic drug with a pK a of about 9. A. Highest absorption through gut wall
Which of the following parts of the digestive tract most likely B. Lowest first-pass effect
represents the main site of absorption of that drug? C. Lowest hepatic clearance
D. Highest volume of distribution
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A. Oral mucosa
E. Lowest drug elimination
B. Stomach
C. Small intestine
Difficulty level: Easy
D. Colon
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E. Rectum 11. A 26-year-old man became inebriated after drinking several
glasses of alcoholic beverages at a party. Ethanol is a polar,
Difficulty level: Easy nonionizable drug with an approximate molecular weight of
46 daltons. Which of the following permeation processes
9. The pharmacokinetic properties of five new drugs (P, Q, R, S,
mediated the man’s intestinal absorption of ethanol?
and T) were studied in healthy volunteers. The same dose of
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each drug was administered intravenously (IV) and orally to the A. Aqueous diffusion
same subject on two separate occasions. The results were the B. Bulk flow transport
following: C. Facilitated diffusion
D. Active transport
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Drug AUCOral AUCIV E. Endocytosis
(mg h/L) (mg h/L)
P 50 600 Difficulty level: Hard
Q 200 2000
12. A 44-year-old man took a large dose of acetaminophen in
R 30 400 aqueous solution to treat an excruciating headache. Two
S 100 120 hours later, the pain was not diminished. Because acet-
T 45 90 aminophen should be effective in about 30 minutes after
Abbreviations: AUC, area under the curve; IV, intravenous. its oral administration, which of the following conditions
most likely delayed the oral absorption of the drug in this
Which of the following drugs most likely has the highest oral
patient?
bioavailability?
A. A moderate increase in intestinal peristalsis
A. Drug P
B. The presence of strong pain
B. Drug Q
C. The administration of the drug in aqueous solution
C. Drug R
D. A large volume of distribution of the drug
D. Drug S
E. A very low clearance of the drug
E. Drug T
,Difficulty level: Medium Which of the following statements best explains why several
13. A 22-year-old woman was admitted to the emergency de- drugs, including methotrexate, cannot easily enter the brain?
partment after a car accident. The woman had extensive brain A. Cerebrospinal fluid pressure is lower than cerebral per-
trauma and multiple fractures. She complained of severe fusion pressure.
pain, and the attending physician planned to administer B. The pH of cerebrospinal fluid is lower than plasma pH.
morphine. The physician knew that the dose should be care- C. Many drugs are bound to protein and cannot cross brain
fully titrated because the entry of morphine into the pa- capillaries.
tient’s central nervous system (CNS) was most likely higher D. Endothelial cells of brain capillaries and choroid plexus
than normal. Which of the following factors is most likely to have tight junctions.
have increased morphine entry into the CNS of this patient? E. Most drugs are completely ionized in blood.
A. The high first-pass effect of the drug
Difficulty level: Medium
B. The brain trauma of the patient
C. The young age of the patient 17. The ability of five different drugs (P, Q, R, S, and T) to cross
D. The low clearance of the drug the placenta was studied in laboratory animals. The follow-
E. The high ionization of the drug ing data were obtained.
Difficulty level: Easy Drug Molecular Protein Bound Ionized in
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Weight in Maternal Maternal
14. A 67-year-old woman recently diagnosed with atrial fibril- (daltons) Plasma (%) Plasma (%)
lation started treatment with atenolol, 100 mg/d. With this P 20 0 100
dose, the percentage of atenolol bound to plasma proteins Q 250 99 50
is about 5%. Which of the following would have been the R 4500 25 10
bound percentage of atenolol if a dose of 50 mg/d had been S 500 10 90
administered to the same patient?
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T 2000 15 30
A. 2.5%
B. 5% Which of the following drugs most likely crossed the pla-
C. 10% centa at the fastest rate?
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D. 1.25%
A. Drug P
E. 2% B. Drug Q
C. Drug R
Difficulty level: Hard D. Drug S
15. A 34-year-old man recently diagnosed with grand mal epi- E. Drug T
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lepsy started treatment with valproic acid, an antiseizure
drug with a pK a of 5. What percentage of the drug was most Difficulty level: Medium
likely lipid soluble in the patient’s duodenal lumen (assum-
18. A 52-year-old woman suffering from rheumatoid arthritis
ing pH = 7 in the lumen)?
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started a treatment that included infliximab, a monoclonal
A. 1% antibody against tumor necrosis factor-α (TNF-α). The drug
B. 24% has a volume of distribution of about 3 L. Which of the fol-
C. 50% lowing is most likely the main site of distribution of this
D. 76% drug?
E. 99% A. Fat tissue
B. Plasma
Difficulty level: Easy C. Extracellular fluids
16. A 4-year-old boy suffering from acute lymphoblastic leuke- D. Cell cytosol
mia was about to receive an intrathecal injection of metho- E. Total body water
trexate, a drug that cannot cross the blood−brain barrier.
,Difficulty level: Easy Difficulty level: Medium
19. A 36-year-old woman recently diagnosed with trichomoni- 22. A new drug was studied in a healthy volunteer during a
asis started a treatment with metronidazole. The drug has phase 1 clinical trial. Urine and plasma samples were col-
a hepatic clearance of 4.86 L/h and a renal clearance of lected 1 hour after the intravenous administration of a test
0.54 L/h. On the assumption that only the liver and kidney dose. Drug concentration was 40 mg/mL in urine and 1 mg/mL in
are involved in the elimination of this drug, what percentage plasma. The urine output of this subject was 1.44 L/d. Which
of the administered drug will be eliminated by the liver? of the following was most likely the renal clearance of the drug,
A. 20% in mL/min?
B. 40% A. 40
C. 50% B. 30
D. 60% C. 20
E. 70% D. 50
F. 90% E. 60
F. 10
Difficulty level: Medium
Difficulty level: Easy
20. The pharmacokinetic properties of five new drugs (P, Q, R, S,
and T) were studied in laboratory animals. The drugs were 23. A 10-mg dose of a new drug that follows first-order, one--
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given orally, and the results are shown below. compartment model kinetics was given intravenously to
healthy subjects in a phase 1 clinical trial. The volume of dis-
Drug Percentage of Hepatic tribution (Vd) of the drug turned out to be 80 L. Which of the
Drug Reaching Clearance
the Portal Vein (mL/min) following would have been the volume of distribution of the
P 90 20
drug (in liters) if the administered dose were 20 mg?
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Q 86 1000 A. 40
R 50 450 B. 80
C. 240
S 2 100
D. 160
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T 10 30
E. 120
Which of the following drugs most likely has the highest oral
bioavailability? Difficulty level: Medium
A. Drug P 24. A 45-year-old man suffering from epilepsy had been receiv-
ing carbamazepine, one tablet daily. The drug has a total
B. Drug Q
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clearance of 63 L/h and a hepatic clearance of 62 L/h. The
C. Drug R
man was recently diagnosed with a skin infection due to
D. Drug S
Mycobacterium marinum, and treatment with rifampin and
E. Drug T
ethambutol was started. Knowing that rifampin is a potent
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inducer of microsomal enzymes, which of the following
Difficulty level: Medium
changes most likely occurred to the pharmacokinetics of
21. When studied in healthy volunteers, the oral bioavailability
carbamazepine?
of a new drug turned out to be 20%. Knowing that in this case
the entire administered drug reached the portal circulation, A. The hepatic clearance of the drugs decreased.
which of the following will be the hepatic clearance (in mL/ B. The first-pass loss of the drug decreased.
min) of the drug? C. The renal clearance of the drug decreased.
D. The volume of distribution of the drug increased.
A. 500
E. The half-life of the drug decreased.
B. 800
C. 1200
Difficulty level: Medium
D. 1500
E. 2000 25. A 59-year-old Japanese man with atrial fibrillation pre-
sented to his physician complaining of red urine. The man
had been receiving a standard dose of warfarin, which is an
anticoagulant drug biotransformed by CYP2C9 isozyme.
Which of the following was the most likely cause of the pa-
tient’s disorder?
, A. Increased protein binding of warfarin Difficulty level: Easy
B. Decreased renal excretion of warfarin
29. A 22-year-old man suffering from adult autism and violent
C. Genetic polymorphism of CYP2C9 behavior started a treatment that included buspirone, a drug
D. Decreased metabolism of CYP2C9 with a large first-pass effect. Which of the following phar-
E. Increased CYP2C9 synthesis in a person of Asian origin macokinetic properties of the drug was most likely affected by
this large first-pass effect?
Difficulty level: Easy
A. Volume of distribution
26. The pharmacokinetics of a new drug was studied in labora-
B. Oral bioavailability
tory animals. The drug was given orally, and the following C. Renal clearance
results were obtained: D. Sublingual bioavailability
Percent reaching the portal circulation: 40% E. Intramuscular bioavailability
Liver clearance: negligible
Difficulty level: Easy
Liver blood flow in the animal was 1000 mL/min. Which of
the following would be the oral bioavailability of the drug? 30. A 47-year-old man recently diagnosed with systolic heart
failure started a treatment that included furosemide. The
A. 1.0
drug has a total clearance of about 136 mL/min, and about
B. 0.4
66% of the drug is excreted as such in the urine. On the as-
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C. 0.1
sumption that, in this case, only the liver and kidneys are in-
D. 2.2
volved in drug elimination, which of the following was most
E. 0.6
likely the renal clearance of furosemide (in mL/min)?
F. 0.8
A. 90
B. 70
Difficulty level: Medium
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C. 110
27. A 35-year-old Caucasian man complained to his physician of
D. 25
tingling sensation in his limbs and noted that his arms some-
E. 81
times felt heavy. The man, recently diagnosed with pulmo-
F. 16
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nary tuberculosis, had been receiving isoniazid and rifampin
for 2 months. He was diagnosed with peripheral neuropathy,
Difficulty level: Hard
a known adverse effect of isoniazid. Which of the following
events most likely caused the patient’s symptoms and signs? 31. The pharmacokinetics of a new drug that followed first-order,
one-compartment model kinetics was studied in a healthy
A. Rifampin-induced inhibition of isoniazid metabolism
volunteer. A 20-mg dose was given intravenously. The plasma
B. Worsening of the disease, despite the therapy
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concentration of the drug turned out to be 2 mg/L initially and
C. Allergic reaction to rifampin
1 mg/L 2 hours later. Which of the following was most likely
D. Inherited deficiency of N-acetyltransferase
the total clearance of the drug (in L/h)?
E. Allergic reaction to isoniazid
A. 2.5
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B. 8.4
Difficulty level: Medium
C. 5.5
28. A 49-year-old obese man recently diagnosed with vasospas-
D. 6.7
tic angina started a treatment with nifedipine. The drug has
E. 3.5
a volume of distribution (Vd) of about 55 L in a 70-kg person,
F. 4.9
but in this obese patient, the Vd turned out to be 110 L. The
standard loading dose of nifedipine for a patient weighing
70 kg is 30 mg. Which of the following should be the thera-
peutic loading dose administered to this patient (in mg) in
order to achieve the same target concentration?
A. 20
B. 40
C. 60
D. 90
E. 120
F. 150
y Test Prep
PR
1500
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USMLE-
FD
Style
O
C
Questions &
Answers
,Contents
Preface ...................................................................................................................................................................................................................... ix
Section I: General Principles of Pharmacology
Questions
I-1 Pharmacokinetics .................................................................................................................................................................................... 1
I-2 Pharmacodynamics ................................................................................................................................................................................. 7
I-3 Adverse Effects of Drugs ...................................................................................................................................................................... 12
Answers and Explanations
I-1 Pharmacokinetics .................................................................................................................................................................................. 15
I-2 Pharmacodynamics ............................................................................................................................................................................... 21
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I-3 Adverse Effects of Drugs ...................................................................................................................................................................... 26
Section II: Autonomic Nervous System
Questions
II-1 Introduction to Autonomic Pharmacology ......................................................................................................................................... 31
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II-2 Adrenergic Drugs .................................................................................................................................................................................. 34
II-3 Antiadrenergic Drugs ........................................................................................................................................................................... 40
II-4 Cholinergic Drugs ................................................................................................................................................................................. 44
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II-5 Anticholinergic Drugs .......................................................................................................................................................................... 48
Answers and Explanations
II-1 Introduction to Autonomic Pharmacology ......................................................................................................................................... 52
II-2 Adrenergic Drugs .................................................................................................................................................................................. 55
II-3 Antiadrenergic Drugs ........................................................................................................................................................................... 62
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II-4 Cholinergic Drugs ................................................................................................................................................................................. 66
II-5 Anticholinergic Drugs .......................................................................................................................................................................... 71
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Section III: Central Nervous System
Questions
III-1 Introduction to Central Nervous System Pharmacology................................................................................................................... 77
III-2 Sedative and Hypnotic Drugs .............................................................................................................................................................. 80
III-3 General Anesthetics.............................................................................................................................................................................. 84
III-4 Local Anesthetics.................................................................................................................................................................................. 88
III-5 Skeletal Muscle Relaxants ..................................................................................................................................................................... 91
III-6 Antiseizure Drugs ................................................................................................................................................................................. 95
III-7 Drugs for Degenerative Disorders of the Central Nervous System. . 102
III-8 Neuroleptic Drugs .............................................................................................................................................................................. 106
III-9 Drugs for Depressive and Anxiety Disorders .................................................................................................................................. 111
III-10 Drugs for Bipolar Disorders ................................................................................................................................................................ 116
III-11 Drugs for Childhood Behavioral Disorders ....................................................................................................................................... 119
III-12 Opioid Analgesics and Antagonists .................................................................................................................................................... 122
III-13 Drugs of Abuse .................................................................................................................................................................................... 128
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Answers and Explanations
III-1 Introduction to Central Nervous System Pharmacology .............................................................................................................. 134
III-2 Sedative and Hypnotic Drugs ........................................................................................................................................................... 137
III-3 General Anesthetics........................................................................................................................................................................... 141
III-4 Local Anesthetics............................................................................................................................................................................... 145
III-5 Skeletal Muscle Relaxants ................................................................................................................................................................. 148
III-6 Antiseizure Drugs .............................................................................................................................................................................. 152
III-7 Drugs for Degenerative Disorders of the Central Nervous System. . 158
III-8 Neuroleptic Drugs ............................................................................................................................................................................. 162
III-9 Drugs for Depressive and Anxiety Disorders. . 166
III-10 Drugs for Bipolar Disorders .............................................................................................................................................................. 171
III-11 Drugs for Childhood Behavioral Disorders...................................................................................................................................... 174
III-12 Opioid Analgesics and Antagonists .................................................................................................................................................. 177
III-13 Drugs of Abuse ................................................................................................................................................................................... 183
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Section IV: Cardiovascular and Renal Systems
Questions
IV-1 Diuretics.............................................................................................................................................................................................. 191
IV-2 Drugs for Ischemic Heart Disease ................................................................................................................................................... 196
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IV-3 Drugs for Cardiac Failure................................................................................................................................................................... 200
IV-4 Antihypertensive Drugs .................................................................................................................................................................... 206
IV-5 Antiarrhythmic Drugs ....................................................................................................................................................................... 212
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IV-6 Antihyperlipidemic Drugs ................................................................................................................................................................ 218
IV-7 Drugs Affecting Hemostasis............................................................................................................................................................. 222
Answers and Explanations
IV-1 Diuretics.............................................................................................................................................................................................. 227
IV-2 Drugs for Ischemic Heart Disease ................................................................................................................................................... 232
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IV-3 Drugs for Cardiac Failure................................................................................................................................................................... 237
IV-4 Antihypertensive Drugs .................................................................................................................................................................... 245
IV-5 Antiarrhythmic Drugs ....................................................................................................................................................................... 251
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IV-6 Antihyperlipidemic Drugs ................................................................................................................................................................ 257
IV-7 Drugs Affecting Hemostasis............................................................................................................................................................. 261
Section V: Endocrine System
Questions
V-1 Drugs for Hypothalamic and Pituitary Disorders ......................................................................................................................... 267
V-2 Drugs for Thyroid Disorders ............................................................................................................................................................. 271
V-3 Corticosteroids and Antagonists ...................................................................................................................................................... 276
V-4 Drugs for Gonadal Disorders ............................................................................................................................................................. 282
V-5 Drugs for Bone Homeostasis ............................................................................................................................................................. 288
V-6 Drugs for Diabetes Mellitus .............................................................................................................................................................. 292
Answers and Explanations
V-1 Drugs for Hypothalamic and Pituitary Disorders ......................................................................................................................... 298
V-2 Drugs for Thyroid Disorders ............................................................................................................................................................. 303
V-3 Corticosteroids and Antagonists ...................................................................................................................................................... 308
,V-4 Drugs for Gonadal Disorders .............................................................................................................................................................. 315
V-5 Drugs for Bone Homeostasis ............................................................................................................................................................... 321
V-6 Drugs for Diabetes Mellitus ................................................................................................................................................................ 326
Section VI: Respiratory, Gastrointestinal, and Hematopoietic Systems
Questions
VI-1 Drugs for Bronchospastic Disorders ................................................................................................................................................. 333
VI-2 Drugs for Gastrointestinal Disorders ............................................................................................................................................... 338
VI-3 Drugs for Hematopoietic Disorders ................................................................................................................................................. 344
Answers and Explanations
VI-1 Drugs for Bronchospastic Disorders ................................................................................................................................................. 348
VI-2 Drugs for Gastrointestinal Disorders ............................................................................................................................................... 354
VI-3 Drugs for Hematopoietic Disorders ................................................................................................................................................. 359
Section VII: Infammation and Immunomodulation
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Questions
VII-1 Histamine and Serotonin: Agonists and Antagonists . . 363
VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors ......................................................................................................................... 367
VII-3 Nonsteroidal Antiinfammatory Drugs............................................................................................................................................. 370
VII-4 Immunomodulating Drugs ................................................................................................................................................................ 374
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VII-5 Drugs for Arthritis and Gout ............................................................................................................................................................. 378
Answers and Explanations
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VII-1 Histamine and Serotonin: Agonists and Antagonists . . 381
VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors ......................................................................................................................... 385
VII-3 Nonsteroidal Antiinfammatory Drugs............................................................................................................................................. 387
VII-4 Immunomodulating Drugs ................................................................................................................................................................ 392
VII-5 Drugs for Arthritis and Gout ............................................................................................................................................................. 396
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Section VIII: Chemotherapeutic Drugs
Questions
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VIII-1 Bacterial Cell Wall Synthesis Inhibitors ............................................................................................................................................. 400
VIII-2 Bacterial Protein Synthesis Inhibitors............................................................................................................................................... 408
VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function ............................................................................................................. 415
VIII-4 Antimycobacterial Drugs ................................................................................................................................................................... 420
VIII-5 Antifungal Drugs ................................................................................................................................................................................ 423
VIII-6 Antiviral Drugs .................................................................................................................................................................................... 427
VIII-7 Antiprotozoal Drugs ........................................................................................................................................................................... 433
VIII-8 Anthelmintic Drugs ............................................................................................................................................................................ 436
VIII-9 Antineoplastic Drugs ......................................................................................................................................................................... 439
Answers and Explanations
VIII-1 Bacterial Cell Wall Synthesis Inhibitors ............................................................................................................................................. 446
VIII-2 Bacterial Protein Synthesis Inhibitors ............................................................................................................................................... 455
VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function.............................................................................................................. 462
VIII-4 Antimycobacterial Drugs.................................................................................................................................................................... 466
,VIII-5 Antifungal Drugs ................................................................................................................................................................................ 469
VIII-6 Antiviral Drugs ................................................................................................................................................................................... 473
VIII-7 Antiprotozoal Drugs ........................................................................................................................................................................... 478
VIII-8 Anthelmintic Drugs ............................................................................................................................................................................ 481
VIII-9 Antineoplastic Drugs .......................................................................................................................................................................... 484
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,I General Principles of Pharmacology
Questions: I-1 Pharmacokinetics
Difficulty level: Easy Difficulty level: Easy
1. A 22-year-old woman suffering from asthma was prescribed 4. A 12-year-old boy recently diagnosed with type 1 diabetes
albuterol by inhalation. Albuterol is a bronchodilating drug started a therapy with two daily subcutaneous administrations
with a molecular weight of 239 daltons. Which of the fol- of insulin. Which of the following permeation processes best
lowing permeation processes most likely accounted for the explains the absorption of insulin from the site of injection?
transfer of the drug through the bronchial mucosa?
A. Bulk flow transport
A. Aqueous diffusion B. Lipid diffusion
B. Lipid diffusion C. Facilitated diffusion
C. Facilitated diffusion D. Endocytosis
D. Endocytosis E. Active transport
E. Active transport
Difficulty level: Hard
PR
Difficulty level: Easy
5. An 85-year-old man was recently admitted to a nursing facil-
2. A 34-year-old man on vacation in Mexico was admitted to the ity. Diseases listed in his medical record on admission were
hospital because of vomiting, double vision, and muscular pa- depression with anxiety symptoms, atrial fibrillation, chronic
ralysis. The man reported that he had eaten some canned food obstructive pulmonary disease, and osteoarthritis. Medica-
from a local vendor the previous day. After a physical exam- tions taken orally by the patient included the following:
ination, a presumptive diagnosis of botulism was made. It is
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Sertraline (base, pKa = 9.5)
known that botulinum toxin causes paralysis by getting in-
Diazepam (base, pKa = 3.0)
side the axon terminals of motor nerves, where it inhibits the
Amiodarone (base, pKa = 7.4)
release of acetylcholine. Botulinum toxin is a protein with a
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molecular weight greater than 100,000 daltons. Which of the Theophylline (acid, pKa = 8.8)
following permeation processes most likely accounts for the Ibuprofen (acid, pKa 4.8)
transfer of the toxin through the nerve cell membrane?
Shortly after administration, which of the following drugs was
A. Aqueous diffusion most likely concentrated inside the patient’s gastric cells?
B. Lipid diffusion
A. Sertraline
C. Facilitated diffusion
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B. Diazepam
D. Endocytosis
C. Amiodarone
E. Filtration
D. Theophylline
E. Ibuprofen
C
Difficulty level: Easy
3. A 51-year-old woman suffering from hyperthyroidism was Difficulty level: Medium
administered an oral solution of radioactive iodine to destroy
6. A 17-year-old boy took a tablet of naproxen for a headache.
her thyroid gland. Which of the following permeation pro-
Naproxen is a weak acid with a pKa of 5.2. What percentage
cesses most likely accounted for the transfer of the drug across the
of the drug was most likely water soluble in the patient’s
thyroid cell membrane?
plasma?
A. Active transport
A. 1%
B. Lipid diffusion
B. 24%
C. Facilitated diffusion
C. 50%
D. Endocytosis
D. 76%
E. Aqueous diffusion
E. 99%
F. > 99%
1
,Difficulty level: Medium Difficulty level: Easy
7. A 69-year-old woman was brought to a local hospital emer- 10. During a phase 1 clinical trial, four different oral dosage
gency department by her son, who reported that his mother forms of the same dose of a drug were administered to a
was found lethargic, disoriented, and combative a few hours healthy volunteer on four separate occasions. The plasma
earlier. Additional history revealed that she had ingested a concentration−time curves are plotted below.
large number of aspirin tablets in a suicide attempt. An ap-
propriate therapy was instituted, which included the admin- W
istration of sodium bicarbonate to increase the elimination of
salicylate. Which of the following best explains the mecha-
nism of this increased elimination?
[Drug]
A. Decreased tubular active transport of salicylate
B. Decreased renal biotransformation of salicylate
C. Decreased bioavailability of salicylate
D. Urinary ion trapping of salicylate
E. Increased glomerular filtration of salicylate
Time
Difficulty level: Medium Which of the following features best explains why formula-
PR
tion W produces the largest plasma concentration−time curve of
8. A 63-year old man recently diagnosed with hypertension
the drug?
started a therapy with hydrochlorothiazide, one tablet daily.
Hydrochlorothiazide is an acidic drug with a pK a of about 9. A. Highest absorption through gut wall
Which of the following parts of the digestive tract most likely B. Lowest first-pass effect
represents the main site of absorption of that drug? C. Lowest hepatic clearance
D. Highest volume of distribution
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A. Oral mucosa
E. Lowest drug elimination
B. Stomach
C. Small intestine
Difficulty level: Easy
D. Colon
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E. Rectum 11. A 26-year-old man became inebriated after drinking several
glasses of alcoholic beverages at a party. Ethanol is a polar,
Difficulty level: Easy nonionizable drug with an approximate molecular weight of
46 daltons. Which of the following permeation processes
9. The pharmacokinetic properties of five new drugs (P, Q, R, S,
mediated the man’s intestinal absorption of ethanol?
and T) were studied in healthy volunteers. The same dose of
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each drug was administered intravenously (IV) and orally to the A. Aqueous diffusion
same subject on two separate occasions. The results were the B. Bulk flow transport
following: C. Facilitated diffusion
D. Active transport
C
Drug AUCOral AUCIV E. Endocytosis
(mg h/L) (mg h/L)
P 50 600 Difficulty level: Hard
Q 200 2000
12. A 44-year-old man took a large dose of acetaminophen in
R 30 400 aqueous solution to treat an excruciating headache. Two
S 100 120 hours later, the pain was not diminished. Because acet-
T 45 90 aminophen should be effective in about 30 minutes after
Abbreviations: AUC, area under the curve; IV, intravenous. its oral administration, which of the following conditions
most likely delayed the oral absorption of the drug in this
Which of the following drugs most likely has the highest oral
patient?
bioavailability?
A. A moderate increase in intestinal peristalsis
A. Drug P
B. The presence of strong pain
B. Drug Q
C. The administration of the drug in aqueous solution
C. Drug R
D. A large volume of distribution of the drug
D. Drug S
E. A very low clearance of the drug
E. Drug T
,Difficulty level: Medium Which of the following statements best explains why several
13. A 22-year-old woman was admitted to the emergency de- drugs, including methotrexate, cannot easily enter the brain?
partment after a car accident. The woman had extensive brain A. Cerebrospinal fluid pressure is lower than cerebral per-
trauma and multiple fractures. She complained of severe fusion pressure.
pain, and the attending physician planned to administer B. The pH of cerebrospinal fluid is lower than plasma pH.
morphine. The physician knew that the dose should be care- C. Many drugs are bound to protein and cannot cross brain
fully titrated because the entry of morphine into the pa- capillaries.
tient’s central nervous system (CNS) was most likely higher D. Endothelial cells of brain capillaries and choroid plexus
than normal. Which of the following factors is most likely to have tight junctions.
have increased morphine entry into the CNS of this patient? E. Most drugs are completely ionized in blood.
A. The high first-pass effect of the drug
Difficulty level: Medium
B. The brain trauma of the patient
C. The young age of the patient 17. The ability of five different drugs (P, Q, R, S, and T) to cross
D. The low clearance of the drug the placenta was studied in laboratory animals. The follow-
E. The high ionization of the drug ing data were obtained.
Difficulty level: Easy Drug Molecular Protein Bound Ionized in
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Weight in Maternal Maternal
14. A 67-year-old woman recently diagnosed with atrial fibril- (daltons) Plasma (%) Plasma (%)
lation started treatment with atenolol, 100 mg/d. With this P 20 0 100
dose, the percentage of atenolol bound to plasma proteins Q 250 99 50
is about 5%. Which of the following would have been the R 4500 25 10
bound percentage of atenolol if a dose of 50 mg/d had been S 500 10 90
administered to the same patient?
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T 2000 15 30
A. 2.5%
B. 5% Which of the following drugs most likely crossed the pla-
C. 10% centa at the fastest rate?
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D. 1.25%
A. Drug P
E. 2% B. Drug Q
C. Drug R
Difficulty level: Hard D. Drug S
15. A 34-year-old man recently diagnosed with grand mal epi- E. Drug T
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lepsy started treatment with valproic acid, an antiseizure
drug with a pK a of 5. What percentage of the drug was most Difficulty level: Medium
likely lipid soluble in the patient’s duodenal lumen (assum-
18. A 52-year-old woman suffering from rheumatoid arthritis
ing pH = 7 in the lumen)?
C
started a treatment that included infliximab, a monoclonal
A. 1% antibody against tumor necrosis factor-α (TNF-α). The drug
B. 24% has a volume of distribution of about 3 L. Which of the fol-
C. 50% lowing is most likely the main site of distribution of this
D. 76% drug?
E. 99% A. Fat tissue
B. Plasma
Difficulty level: Easy C. Extracellular fluids
16. A 4-year-old boy suffering from acute lymphoblastic leuke- D. Cell cytosol
mia was about to receive an intrathecal injection of metho- E. Total body water
trexate, a drug that cannot cross the blood−brain barrier.
,Difficulty level: Easy Difficulty level: Medium
19. A 36-year-old woman recently diagnosed with trichomoni- 22. A new drug was studied in a healthy volunteer during a
asis started a treatment with metronidazole. The drug has phase 1 clinical trial. Urine and plasma samples were col-
a hepatic clearance of 4.86 L/h and a renal clearance of lected 1 hour after the intravenous administration of a test
0.54 L/h. On the assumption that only the liver and kidney dose. Drug concentration was 40 mg/mL in urine and 1 mg/mL in
are involved in the elimination of this drug, what percentage plasma. The urine output of this subject was 1.44 L/d. Which
of the administered drug will be eliminated by the liver? of the following was most likely the renal clearance of the drug,
A. 20% in mL/min?
B. 40% A. 40
C. 50% B. 30
D. 60% C. 20
E. 70% D. 50
F. 90% E. 60
F. 10
Difficulty level: Medium
Difficulty level: Easy
20. The pharmacokinetic properties of five new drugs (P, Q, R, S,
and T) were studied in laboratory animals. The drugs were 23. A 10-mg dose of a new drug that follows first-order, one--
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given orally, and the results are shown below. compartment model kinetics was given intravenously to
healthy subjects in a phase 1 clinical trial. The volume of dis-
Drug Percentage of Hepatic tribution (Vd) of the drug turned out to be 80 L. Which of the
Drug Reaching Clearance
the Portal Vein (mL/min) following would have been the volume of distribution of the
P 90 20
drug (in liters) if the administered dose were 20 mg?
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Q 86 1000 A. 40
R 50 450 B. 80
C. 240
S 2 100
D. 160
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T 10 30
E. 120
Which of the following drugs most likely has the highest oral
bioavailability? Difficulty level: Medium
A. Drug P 24. A 45-year-old man suffering from epilepsy had been receiv-
ing carbamazepine, one tablet daily. The drug has a total
B. Drug Q
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clearance of 63 L/h and a hepatic clearance of 62 L/h. The
C. Drug R
man was recently diagnosed with a skin infection due to
D. Drug S
Mycobacterium marinum, and treatment with rifampin and
E. Drug T
ethambutol was started. Knowing that rifampin is a potent
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inducer of microsomal enzymes, which of the following
Difficulty level: Medium
changes most likely occurred to the pharmacokinetics of
21. When studied in healthy volunteers, the oral bioavailability
carbamazepine?
of a new drug turned out to be 20%. Knowing that in this case
the entire administered drug reached the portal circulation, A. The hepatic clearance of the drugs decreased.
which of the following will be the hepatic clearance (in mL/ B. The first-pass loss of the drug decreased.
min) of the drug? C. The renal clearance of the drug decreased.
D. The volume of distribution of the drug increased.
A. 500
E. The half-life of the drug decreased.
B. 800
C. 1200
Difficulty level: Medium
D. 1500
E. 2000 25. A 59-year-old Japanese man with atrial fibrillation pre-
sented to his physician complaining of red urine. The man
had been receiving a standard dose of warfarin, which is an
anticoagulant drug biotransformed by CYP2C9 isozyme.
Which of the following was the most likely cause of the pa-
tient’s disorder?
, A. Increased protein binding of warfarin Difficulty level: Easy
B. Decreased renal excretion of warfarin
29. A 22-year-old man suffering from adult autism and violent
C. Genetic polymorphism of CYP2C9 behavior started a treatment that included buspirone, a drug
D. Decreased metabolism of CYP2C9 with a large first-pass effect. Which of the following phar-
E. Increased CYP2C9 synthesis in a person of Asian origin macokinetic properties of the drug was most likely affected by
this large first-pass effect?
Difficulty level: Easy
A. Volume of distribution
26. The pharmacokinetics of a new drug was studied in labora-
B. Oral bioavailability
tory animals. The drug was given orally, and the following C. Renal clearance
results were obtained: D. Sublingual bioavailability
Percent reaching the portal circulation: 40% E. Intramuscular bioavailability
Liver clearance: negligible
Difficulty level: Easy
Liver blood flow in the animal was 1000 mL/min. Which of
the following would be the oral bioavailability of the drug? 30. A 47-year-old man recently diagnosed with systolic heart
failure started a treatment that included furosemide. The
A. 1.0
drug has a total clearance of about 136 mL/min, and about
B. 0.4
66% of the drug is excreted as such in the urine. On the as-
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C. 0.1
sumption that, in this case, only the liver and kidneys are in-
D. 2.2
volved in drug elimination, which of the following was most
E. 0.6
likely the renal clearance of furosemide (in mL/min)?
F. 0.8
A. 90
B. 70
Difficulty level: Medium
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C. 110
27. A 35-year-old Caucasian man complained to his physician of
D. 25
tingling sensation in his limbs and noted that his arms some-
E. 81
times felt heavy. The man, recently diagnosed with pulmo-
F. 16
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nary tuberculosis, had been receiving isoniazid and rifampin
for 2 months. He was diagnosed with peripheral neuropathy,
Difficulty level: Hard
a known adverse effect of isoniazid. Which of the following
events most likely caused the patient’s symptoms and signs? 31. The pharmacokinetics of a new drug that followed first-order,
one-compartment model kinetics was studied in a healthy
A. Rifampin-induced inhibition of isoniazid metabolism
volunteer. A 20-mg dose was given intravenously. The plasma
B. Worsening of the disease, despite the therapy
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concentration of the drug turned out to be 2 mg/L initially and
C. Allergic reaction to rifampin
1 mg/L 2 hours later. Which of the following was most likely
D. Inherited deficiency of N-acetyltransferase
the total clearance of the drug (in L/h)?
E. Allergic reaction to isoniazid
A. 2.5
C
B. 8.4
Difficulty level: Medium
C. 5.5
28. A 49-year-old obese man recently diagnosed with vasospas-
D. 6.7
tic angina started a treatment with nifedipine. The drug has
E. 3.5
a volume of distribution (Vd) of about 55 L in a 70-kg person,
F. 4.9
but in this obese patient, the Vd turned out to be 110 L. The
standard loading dose of nifedipine for a patient weighing
70 kg is 30 mg. Which of the following should be the thera-
peutic loading dose administered to this patient (in mg) in
order to achieve the same target concentration?
A. 20
B. 40
C. 60
D. 90
E. 120
F. 150
