Pharmacology Test Prep E-Book

Mario Babbini

• Herausgeber: Thieme Medical Publishers
• Kategorie: Fachliteratur
• Sprache: Englisch

Veröffentlichungsjahr: 2014

Beschreibung

A high-yield Q&A pharmacology review…

Pharmacology Test Prep is an outstanding collection of 1500 clinical multiple-choice questions written according to USMLE® guidelines and classified by learning objective and difficulty. The questions and answers in this book cover all the areas that are included in topic-based and organ system-based courses in the first two years of medical school. This book provides medical students preparing to take the USMLE® with a thorough review of pharmacology concepts and is an excellent review book for those needing to brush up on pharmacology for their rotations.

Key Features:

• Questions require students to analyze information before choosing the best answer
• Full explanations are included with answers, giving students a comprehensive USMLE® review tool
• Organized along clinical as well as pharmacological lines, making it suitable for both Step 1 and Step 2 exam preparation

Leseprobe

Pharmacology Test Prep

1500 USMLE-Style Questions & Answers

Mario Babbini, MD, PhDProfessorDepartment of PharmacologyRoss Medical School

Mary Thomas, PhDProfessor EmeritusDepartment of PharmacologyUniversity of Texas Medical Branch at Galveston

ThiemeNew York · Stuttgart · Delhi · Rio

Vice President and Editorial Director, Educational Products: Anne VinnicombeDevelopmental Editor: Julie O’MearaEditorial Assistant: Huvie WeinreichSenior Vice President, Editorial and Electronic Product Development: Cornelia SchulzeProduction Editor: Barbara A. ChernowInternational Production Director: Andreas SchabertInternational Marketing Director: Fiona HendersonDirector of Sales, North America: Mike RosemanInternational Sales Director: Louisa TurrellVice President, Finance and Accounts: Sarah VanderbiltPresident: Brian D. ScanlanCompositor: Carol Pierson, Chernow Editorial Services, Inc.

Library of Congress Cataloging-in-Publication Data

Babbini, Mario, author.

Pharmacology test prep: 1500 USMLE-style questions & answers/Mario Babbini, Mary Thomas.

p. ; cm.

ISBN 978-1-62623-041-5 (alk. paper) — ISBN 978-1-62623-042-2 (eISBN)

I. Thomas, Mary (Professor of pharmacology), author. II. Title.

[DNLM: 1. Pharmacological Phenomena—Examination Questions. QV 18.2]

RS97

615.1076—dc23                                      2014027117

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ISBN 978-1-62623-041-5

Also available as an e-book:eISBN 978-1-62623-042-2

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Nevertheless, this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect to any dosage instructions and forms of applications stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statements made in the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user’s own risk and responsibility. The authors and publishers request every user to report to the publishers any discrepancies or inaccuracies noticed. If errors in this work are found after publication, errata will be posted at www.thieme.com on the product description page.

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Contents

Preface

Section I: General Principles of Pharmacology

Questions

I-1 Pharmacokinetics

I-2 Pharmacodynamics

I-3 Adverse Effects of Drugs

Answers and Explanations

I-1 Pharmacokinetics

I-2 Pharmacodynamics

I-3 Adverse Effects of Drugs

Section II: Autonomic Nervous System

Questions

II-1 Introduction to Autonomic Pharmacology

II-2 Adrenergic Drugs

II-3 Antiadrenergic Drugs

II-4 Cholinergic Drugs

II-5 Anticholinergic Drugs

Answers and Explanations

II-1 Introduction to Autonomic Pharmacology

II-2 Adrenergic Drugs

II-3 Antiadrenergic Drugs

II-4 Cholinergic Drugs

II-5 Anticholinergic Drugs

Section III: Central Nervous System

Questions

III-1 Introduction to Central Nervous System Pharmacology

III-2 Sedative and Hypnotic Drugs

III-3 General Anesthetics

III-4 Local Anesthetics

III-5 Skeletal Muscle Relaxants

III-6 Antiseizure Drugs

III-7 Drugs for Degenerative Disorders of the Central Nervous System

III-8 Neuroleptic Drugs

III-9 Drugs for Depressive and Anxiety Disorders

III-10 Drugs for Bipolar Disorders

III-11 Drugs for Childhood Behavioral Disorders

III-12 Opioid Analgesics and Antagonists

III-13 Drugs of Abuse

Answers and Explanations

III-1 Introduction to Central Nervous System Pharmacology

III-2 Sedative and Hypnotic Drugs

III-3 General Anesthetics

III-4 Local Anesthetics

III-5 Skeletal Muscle Relaxants

III-6 Antiseizure Drugs

III-7 Drugs for Degenerative Disorders of the Central Nervous System

III-8 Neuroleptic Drugs

III-9 Drugs for Depressive and Anxiety Disorders

III-10 Drugs for Bipolar Disorders

III-11 Drugs for Childhood Behavioral Disorders

III-12 Opioid Analgesics and Antagonists

III-13 Drugs of Abuse

Section IV: Cardiovascular and Renal Systems

Questions

IV-1 Diuretics

IV-2 Drugs for Ischemic Heart Disease

IV-3 Drugs for Cardiac Failure

IV-4 Antihypertensive Drugs

IV-5 Antiarrhythmic Drugs

IV-6 Antihyperlipidemic Drugs

IV-7 Drugs Affecting Hemostasis

Answers and Explanations

IV-1 Diuretics

IV-2 Drugs for Ischemic Heart Disease

IV-3 Drugs for Cardiac Failure

IV-4 Antihypertensive Drugs

IV-5 Antiarrhythmic Drugs

IV-6 Antihyperlipidemic Drugs

IV-7 Drugs Affecting Hemostasis

Section V: Endocrine System

Questions

V-1 Drugs for Hypothalamic and Pituitary Disorders

V-2 Drugs for Thyroid Disorders

V-3 Corticosteroids and Antagonists

V-4 Drugs for Gonadal Disorders

V-5 Drugs for Bone Homeostasis

V-6 Drugs for Diabetes Mellitus

Answers and Explanations

V-1 Drugs for Hypothalamic and Pituitary Disorders

V-2 Drugs for Thyroid Disorders

V-3 Corticosteroids and Antagonists

V-4 Drugs for Gonadal Disorders

V-5 Drugs for Bone Homeostasis

V-6 Drugs for Diabetes Mellitus

Section VI: Respiratory, Gastrointestinal, and Hematopoietic Systems

Questions

VI-1 Drugs for Bronchospastic Disorders

VI-2 Drugs for Gastrointestinal Disorders

VI-3 Drugs for Hematopoietic Disorders

Answers and Explanations

VI-1 Drugs for Bronchospastic Disorders

VI-2 Drugs for Gastrointestinal Disorders

VI-3 Drugs for Hematopoietic Disorders

Section VII: Inflammation and Immunomodulation

Questions

VII-1 Histamine and Serotonin: Agonists and Antagonists

VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors

VII-3 Nonsteroidal Antiinflammatory Drugs

VII-4 Immunomodulating Drugs

VII-5 Drugs for Arthritis and Gout

Answers and Explanations

VII-1 Histamine and Serotonin: Agonists and Antagonists

VII-2 Eicosanoids: Agonists, Antagonists, and Inhibitors

VII-3 Nonsteroidal Antiinflammatory Drugs

VII-4 Immunomodulating Drugs

VII-5 Drugs for Arthritis and Gout

Section VIII: Chemotherapeutic Drugs

Questions

VIII-1 Bacterial Cell Wall Synthesis Inhibitors

VIII-2 Bacterial Protein Synthesis Inhibitors

VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function

VIII-4 Antimycobacterial Drugs

VIII-5 Antifungal Drugs

VIII-6 Antiviral Drugs

VIII-7 Antiprotozoal Drugs

VIII-8 Anthelmintic Drugs

VIII-9 Antineoplastic Drugs

Answers and Explanations

VIII-1 Bacterial Cell Wall Synthesis Inhibitors

VIII-2 Bacterial Protein Synthesis Inhibitors

VIII-3 Inhibitors of Bacterial Nucleic Acid Synthesis or Function

VIII-4 Antimycobacterial Drugs

VIII-5 Antifungal Drugs

VIII-6 Antiviral Drugs

VIII-7 Antiprotozoal Drugs

VIII-8 Anthelmintic Drugs

VIII-9 Antineoplastic Drugs

Preface

This book is a collection of multiple choice questions (MCQs) to promote the learning of pharmacology in the framework of preclinical and clinical disciplines. The main features of the book are the following:

• The MCQs are all of the type that is used for the step 1 medical board exams in the United States and are written according to United States Medical Licensing Examination (USMLE) guidelines (i.e., patient-centered vignettes). All questions are “one best answer”; in most cases, there are five answer choices, but in some cases six or seven answer choices are given.

• Because the MCQs are about pharmacology, each question mentions a drug or a drug class either in the stem or as the answer choices.

• Each MCQ is provided with a level of difficulty, a learning objective, the correct answer, and an explanation.

• There are three levels of difficulty: easy, medium, and hard.

• The learning objective is a brief behavioral statement written using an action verb. If a student can perform that action, then he or she should be able to answer the question correctly. The explanation includes both the reasons why a given answer is correct and why the distractors are wrong.

• Many questions are related to the highest levels of Bloom’s taxonomy (e.g., interpretation of data and solution of problems) rather than being simple recall questions.

• For each drug or drug class, the concepts asked by the MCQs are related to mode of action, pharmacokinetics, pharmacodynamics, adverse effects, interactions, or clinical uses.

• Most MCQs are integrated questions, and a good knowledge of the relevant human physiology, biochemistry, pathology, microbiology, and/or elementary clinical medicine is a necessary prerequisite to determine the right answer to the question. Therefore, the question with its answer explanation can also be used as a powerful tool for reviewing and integrating the medical science disciplines.

• The MCQs are grouped in chapters covering most topics presented in standard pharmacology textbooks. There are 20 to 50 MCQs in each chapter, totaling over 1500 questions.

MCQs are the learning tool most frequently used by medical students. This book is intended as an integrated tool for both course study and board exam preparation. Because the book is organized along clinical rather than strictly pharmacological lines, it should be useful for both step1 and step 2 exam preparation.

Pharmacology is a fast-evolving discipline. The authors have checked sources believed to be reliable, in order to provide information that is in accordance with the currently accepted standards. However, the authors are aware that in several instances the pharmacotherapy of disease is still controversial. They have tried, as much as possible, to avoid questions addressing controversial issues.

This book is not intended to be a substitute for pharmacology textbooks. Students are strongly advised to consult their textbooks of pharmacology for more in-depth coverage of the subject matter.

Mario Babbini, MD, PhDMary Thomas, PhD

I General Principles of Pharmacology

Questions: I-1 Pharmacokinetics

Difficulty level: Easy

1. A 22-year-old woman suffering from asthma was prescribed albuterol by inhalation. Albuterol is a bronchodilating drug with a molecular weight of 239 daltons. Which of the following permeation processes most likely accounted for the transfer of the drug through the bronchial mucosa?

A. Aqueous diffusion

B. Lipid diffusion

C. Facilitated diffusion

D. Endocytosis

E. Active transport

Difficulty level: Easy

2. A 34-year-old man on vacation in Mexico was admitted to the hospital because of vomiting, double vision, and muscular paralysis. The man reported that he had eaten some canned food from a local vendor the previous day. After a physical examination, a presumptive diagnosis of botulism was made. It is known that botulinum toxin causes paralysis by getting inside the axon terminals of motor nerves, where it inhibits the release of acetylcholine. Botulinum toxin is a protein with a molecular weight greater than 100,000 daltons. Which of the following permeation processes most likely accounts for the transfer of the toxin through the nerve cell membrane?

A. Aqueous diffusion

B. Lipid diffusion

C. Facilitated diffusion

D. Endocytosis

E. Filtration

Difficulty level: Easy

3. A 51-year-old woman suffering from hyperthyroidism was administered an oral solution of radioactive iodine to destroy her thyroid gland. Which of the following permeation processes most likely accounted for the transfer of the drug across the thyroid cell membrane?

A. Active transport

B. Lipid diffusion

C. Facilitated diffusion

D. Endocytosis

E. Aqueous diffusion

Difficulty level: Easy

4. A 12-year-old boy recently diagnosed with type 1 diabetes started a therapy with two daily subcutaneous administrations of insulin. Which of the following permeation processes best explains the absorption of insulin from the site of injection?

A. Bulk flow transport

B. Lipid diffusion

C. Facilitated diffusion

D. Endocytosis

E. Active transport

Difficulty level: Hard

5. An 85-year-old man was recently admitted to a nursing facility. Diseases listed in his medical record on admission were depression with anxiety symptoms, atrial fibrillation, chronic obstructive pulmonary disease, and osteoarthritis. Medications taken orally by the patient included the following:

Ibuprofen (acid, pKa 4.8)

Shortly after administration, which of the following drugs was most likely concentrated inside the patient’s gastric cells?

A. Sertraline

B. Diazepam

C. Amiodarone

D. Theophylline

E. Ibuprofen

Difficulty level: Medium

6. A 17-year-old boy took a tablet of naproxen for a headache. Naproxen is a weak acid with a pKa of 5.2. What percentage of the drug was most likely water soluble in the patient’s plasma?

A. 1%

B. 24%

C. 50%

D. 76%

E. 99%

F. > 99%

Difficulty level: Medium

7. A 69-year-old woman was brought to a local hospital emergency department by her son, who reported that his mother was found lethargic, disoriented, and combative a few hours earlier. Additional history revealed that she had ingested a large number of aspirin tablets in a suicide attempt. An appropriate therapy was instituted, which included the administration of sodium bicarbonate to increase the elimination of salicylate. Which of the following best explains the mechanism of this increased elimination?

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

Difficulty level: Medium

8. A 63-year old man recently diagnosed with hypertension started a therapy with hydrochlorothiazide, one tablet daily. Hydrochlorothiazide is an acidic drug with a pKa of about 9. Which of the following parts of the digestive tract most likely represents the main site of absorption of that drug?

A. Oral mucosa

B. Stomach

C. Small intestine

D. Colon

E. Rectum

Difficulty level: Easy

9. The pharmacokinetic properties of five new drugs (P, Q, R, S, and T) were studied in healthy volunteers. The same dose of each drug was administered intravenously (IV) and orally to the same subject on two separate occasions. The results were the following:

Drug

AUCOral (mg h/L)

AUCIV (mg h/L)

P

50

600

Q

200

2000

R

30

400

S

100

120

T

45

90

Abbreviations: AUC, area under the curve; IV, intravenous.

Which of the following drugs most likely has the highest oral bioavailability?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Easy

10. During a phase 1 clinical trial, four different oral dosage forms of the same dose of a drug were administered to a healthy volunteer on four separate occasions. The plasma concentration−time curves are plotted below.

Which of the following features best explains why formulation W produces the largest plasma concentration−time curve of the drug?

A. Highest absorption through gut wall

B. Lowest first-pass effect

C. Lowest hepatic clearance

D. Highest volume of distribution

E. Lowest drug elimination

Difficulty level: Easy

11. A 26-year-old man became inebriated after drinking several glasses of alcoholic beverages at a party. Ethanol is a polar, nonionizable drug with an approximate molecular weight of 46 daltons. Which of the following permeation processes mediated the man’s intestinal absorption of ethanol?

A. Aqueous diffusion

B. Bulk flow transport

C. Facilitated diffusion

D. Active transport

E. Endocytosis

Difficulty level: Hard

12. A 44-year-old man took a large dose of acetaminophen in aqueous solution to treat an excruciating headache. Two hours later, the pain was not diminished. Because acetaminophen should be effective in about 30 minutes after its oral administration, which of the following conditions most likely delayed the oral absorption of the drug in this patient?

A. A moderate increase in intestinal peristalsis

B. The presence of strong pain

C. The administration of the drug in aqueous solution

D. A large volume of distribution of the drug

E. A very low clearance of the drug

Difficulty level: Medium

13. A 22-year-old woman was admitted to the emergency department after a car accident. The woman had extensive brain trauma and multiple fractures. She complained of severe pain, and the attending physician planned to administer morphine. The physician knew that the dose should be carefully titrated because the entry of morphine into the patient’s central nervous system (CNS) was most likely higher than normal. Which of the following factors is most likely to have increased morphine entry into the CNS of this patient?

A. The high first-pass effect of the drug

B. The brain trauma of the patient

C. The young age of the patient

D. The low clearance of the drug

E. The high ionization of the drug

Difficulty level: Easy

14. A 67-year-old woman recently diagnosed with atrial fibrillation started treatment with atenolol, 100 mg/d. With this dose, the percentage of atenolol bound to plasma proteins is about 5%. Which of the following would have been the bound percentage of atenolol if a dose of 50 mg/d had been administered to the same patient?

A. 2.5%

B. 5%

C. 10%

D. 1.25%

E. 2%

Difficulty level: Hard

A. 1%

B. 24%

C. 50%

D. 76%

E. 99%

Difficulty level: Easy

16. A 4-year-old boy suffering from acute lymphoblastic leukemia was about to receive an intrathecal injection of methotrexate, a drug that cannot cross the blood−brain barrier.

Which of the following statements best explains why several drugs, including methotrexate, cannot easily enter the brain?

A. Cerebrospinal fluid pressure is lower than cerebral perfusion pressure.

B. The pH of cerebrospinal fluid is lower than plasma pH.

C. Many drugs are bound to protein and cannot cross brain capillaries.

D. Endothelial cells of brain capillaries and choroid plexus have tight junctions.

E. Most drugs are completely ionized in blood.

Difficulty level: Medium

17. The ability of five different drugs (P, Q, R, S, and T) to cross the placenta was studied in laboratory animals. The following data were obtained.

Which of the following drugs most likely crossed the placenta at the fastest rate?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Medium

18. A 52-year-old woman suffering from rheumatoid arthritis started a treatment that included infliximab, a monoclonal antibody against tumor necrosis factor-α (TNF-α). The drug has a volume of distribution of about 3 L. Which of the following is most likely the main site of distribution of this drug?

A. Fat tissue

B. Plasma

C. Extracellular fluids

D. Cell cytosol

E. Total body water

Difficulty level: Easy

19. A 36-year-old woman recently diagnosed with trichomoniasis started a treatment with metronidazole. The drug has a hepatic clearance of 4.86 L/h and a renal clearance of 0.54 L/h. On the assumption that only the liver and kidney are involved in the elimination of this drug, what percentage of the administered drug will be eliminated by the liver?

A. 20%

B. 40%

C. 50%

D. 60%

E. 70%

F. 90%

Difficulty level: Medium

20. The pharmacokinetic properties of five new drugs (P, Q, R, S, and T) were studied in laboratory animals. The drugs were given orally, and the results are shown below.

Drug

Percentage of Drug Reaching the Portal Vein

Hepatic Clearance(mL/min)

P

90

20

Q

86

1000

R

50

450

S

2

100

T

10

30

Which of the following drugs most likely has the highest oral bioavailability?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Medium

21. When studied in healthy volunteers, the oral bioavailability of a new drug turned out to be 20%. Knowing that in this case the entire administered drug reached the portal circulation, which of the following will be the hepatic clearance (in mL/min) of the drug?

A. 500

B. 800

C. 1200

D. 1500

E. 2000

Difficulty level: Medium

22. A new drug was studied in a healthy volunteer during a phase 1 clinical trial. Urine and plasma samples were collected 1 hour after the intravenous administration of a test dose. Drug concentration was 40 mg/mL in urine and 1 mg/mL in plasma. The urine output of this subject was 1.44 L/d. Which of the following was most likely the renal clearance of the drug, in mL/min?

A. 40

B. 30

C. 20

D. 50

E. 60

F. 10

Difficulty level: Easy

23. A 10-mg dose of a new drug that follows first-order, onecompartment model kinetics was given intravenously to healthy subjects in a phase 1 clinical trial. The volume of distribution (Vd) of the drug turned out to be 80 L. Which of the following would have been the volume of distribution of the drug (in liters) if the administered dose were 20 mg?

A. 40

B. 80

C. 240

D. 160

E. 120

Difficulty level: Medium

24. A 45-year-old man suffering from epilepsy had been receiving carbamazepine, one tablet daily. The drug has a total clearance of 63 L/h and a hepatic clearance of 62 L/h. The man was recently diagnosed with a skin infection due to Mycobacterium marinum, and treatment with rifampin and ethambutol was started. Knowing that rifampin is a potent inducer of microsomal enzymes, which of the following changes most likely occurred to the pharmacokinetics of carbamazepine?

A. The hepatic clearance of the drugs decreased.

B. The first-pass loss of the drug decreased.

C. The renal clearance of the drug decreased.

D. The volume of distribution of the drug increased.

E. The half-life of the drug decreased.

Difficulty level: Medium

25. A 59-year-old Japanese man with atrial fibrillation presented 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 patient’s disorder?

A. Increased protein binding of warfarin

B. Decreased renal excretion of warfarin

C. Genetic polymorphism of CYP2C9

D. Decreased metabolism of CYP2C9

E. Increased CYP2C9 synthesis in a person of Asian origin

Difficulty level: Easy

26. The pharmacokinetics of a new drug was studied in laboratory animals. The drug was given orally, and the following results were obtained:

Percent reaching the portal circulation: 40%

Liver clearance: negligible

Liver blood flow in the animal was 1000 mL/min. Which of the following would be the oral bioavailability of the drug?

A. 1.0

B. 0.4

C. 0.1

D. 2.2

E. 0.6

F. 0.8

Difficulty level: Medium

27. A 35-year-old Caucasian man complained to his physician of tingling sensation in his limbs and noted that his arms sometimes felt heavy. The man, recently diagnosed with pulmonary tuberculosis, had been receiving isoniazid and rifampin for 2 months. He was diagnosed with peripheral neuropathy, a known adverse effect of isoniazid. Which of the following events most likely caused the patient’s symptoms and signs?

A. Rifampin-induced inhibition of isoniazid metabolism

B. Worsening of the disease, despite the therapy

C. Allergic reaction to rifampin

D. Inherited deficiency of N-acetyltransferase

E. Allergic reaction to isoniazid

Difficulty level: Medium

28. A 49-year-old obese man recently diagnosed with vasospastic angina started a treatment with nifedipine. The drug has a volume of distribution (Vd) of about 55 L in a 70-kg person, 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 therapeutic 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

Difficulty level: Easy

29. A 22-year-old man suffering from adult autism and violent behavior started a treatment that included buspirone, a drug with a large first-pass effect. Which of the following pharmacokinetic properties of the drug was most likely affected by this large first-pass effect?

A. Volume of distribution

B. Oral bioavailability

C. Renal clearance

D. Sublingual bioavailability

E. Intramuscular bioavailability

Difficulty level: Easy

30. A 47-year-old man recently diagnosed with systolic heart failure started a treatment that included furosemide. The drug has a total clearance of about 136 mL/min, and about 66% of the drug is excreted as such in the urine. On the assumption that, in this case, only the liver and kidneys are involved in drug elimination, which of the following was most likely the renal clearance of furosemide (in mL/min)?

A. 90

B. 70

C. 110

D. 25

E. 81

F. 16

Difficulty level: Hard

31. The pharmacokinetics of a new drug that followed first-order, one-compartment model kinetics was studied in a healthy volunteer. A 20-mg dose was given intravenously. The plasma con centration of the drug turned out to be 2 mg/L initially and 1 mg/L 2 hours later. Which of the following was most likely the total clearance of the drug (in L/h)?

A. 2.5

B. 8.4

C. 5.5

D. 6.7

E. 3.5

F. 4.9

Difficulty level: Easy

32. The pharmacokinetic properties of five new drugs (P, Q, R, S, and T) were studied in laboratory animals. A 100-mg dose of each drug was administered intravenously to the same animal on five separate occasions. The plasma concentration− time curves for each drug are depicted in the figure below:

Which of the following drugs has the largest volume of distribution?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Easy

33. The pharmacokinetics of a new drug was studied in healthy volunteers. It was found that the drug followed first-order, one-compartment model kinetics and had a volume of distribution of 100 L. After the oral administration of 200 mg, the theoretical plasma concentration at time 0 turned out to be 1 mg/L. Which of the following was most likely the oral bioavailability of the drug?

A. 0.1

B. 0.5

C. 0.8

D. 1.0

E. 2.3

F. 1.6

Difficulty level: Hard

34. A 32-year-old male cocaine addict was brought unconscious to the emergency department. A friend stated that the man had intravenously self-injected an unknown dose of cocaine 2 hours earlier. An immediate lab analysis indicated that the plasma level of cocaine was 0.75 mg/L. Cocaine has a volume of distribution of about 130 L and a half-life of about 1 hour. Which of the following was most likely the injected dose of cocaine (in mg)?

A. 250

B. 390

C. 420

D. 315

E. 180

F. 115

Difficulty level: Hard

35. A 23-year-old healthy male volunteer received an intravenous dose of 2 mg of a new drug during a clinical trial. The drug followed a first-order, one-compartment model kinetics and had a volume of distribution of 10 L. After 6 hours the plasma concentration of the drug was 50 µg/L. Which of the following was most likely the half-life of the drug (in hours)?

A. 1

B. 2

C. 3

D. 4

E. 5

F. 6

Difficulty level: Medium

36. The figure below depicts the plasma concentration−time curves for four drugs (W, X, Y, and Z) given by IV infusion to the same laboratory animal on four separate occasions.

Which of the following drugs has the shortest half-life?

A. Drug W

B. Drug X

C. Drug Y

D. Drug Z

Difficulty level: Hard

37. The pharmacokinetics of a new drug was studied in a healthy volunteer. The drug was given by intravenous infusion at a rate of 30 mg/h. The plasma concentration−time curve of the drug is depicted below.

Which of the following is most likely the total clearance of the drug (in L/h)?

A. 4

B. 6

C. 2

D. 10

E. 14

F. 16

Difficulty level: Easy

38. The pharmacokinetics of a new drug following zero-order kinetics was studied in a healthy volunteer. Three hours after the intravenous administration of a test dose, the plasma concentration of the drug was 8 mg/L, and 1 hour later it was 7 mg/L. Which of the following was most likely the plasma con centration of the drug (in mg/L) immediately after drug administration?

A. 9

B. 32

C. 11

D. 16

E. 64

F. 5

Difficulty level: Medium

39. The figure below depicts the concentration−time curve of a new drug after a single intravenous dose of 20 mg was administered to a laboratory animal.

Which of the following drugs does the new agent most resemble?

A. Atropine

B. Propranolol

C. Ethanol

D. Phenylephrine

E. Clonidine

F. Dobutamine

Difficulty level: Hard

40. The pharmacokinetics of a new drug was studied in a healthy volunteer. The drug followed first-order, one-compartment model kinetics and had a half-life of 3 hours. An intravenous infusion of the drug was started at 8:00 a.m. A blood sample taken at 2:00 p.m. of the same day showed a plasma drug concentration of 60 µg/mL. Which of the following was most likely the plasma concentration of that drug (in µg/mL) at the steady state?

A. 100

B. 60

C. 80

D. 30

E. 40

F. 120

Questions: I-2 Pharmacodynamics

Difficulty level: Medium

1. A 68-year-old man recently diagnosed with atrial fibrillation started therapy with atenolol, a β-receptor blocker. Which of the following changes most likely occurred in cardiac myocytes during the first 2 weeks of therapy?

A. Spare β receptors became activated.

B. The G-protein number decreased.

C. The β-receptor number increased.

D. Most β receptors became phosphorylated.

E. The ability to respond to intracellular cyclic adenosine monophosphate (cAMP) declined.

Difficulty level: Easy

2. A new drug was tested in an in vitro system. It was found that only one enantiomer of the racemic pair bound substantially to a specific receptor, whereas the other enantiomer showed negligible binding. Which of the following terms best defines this property?

A. Intrinsic activity

B. Affinity

C. Stereoselectivity

D. Potency

E. Variability

F. Maximal efficacy

Difficulty level: Easy

3. A 14-year-old girl suffering from seasonal rhinitis started a therapy with loratadine, a drug that binds to H1 histamine receptors. Which of the following terms describes a characteristic of loratadine binding to the H1 receptor?

A. Intrinsic activity

B. Potency

C. Maximal efficacy

D. Affinity

E. Receptor activation

Difficulty level: Easy

4. Two new drugs were tested in laboratory animals. Which of the following drug parameters was most likely recorded to estimate the relative potency of both drugs?

A. The therapeutic index of both drugs

B. The maximal responses produced by each drug

C. The graded log dose−response curve of both drugs

D. The volume of distribution of both drugs

E. The clearance of both drugs

Difficulty level: Medium

5. A 65-year-old man suffering from osteoarthritis has been taking naproxen, 500 mg daily for 1 month. The drug was effective, but the patient suffered from nausea and heartburn. The physician decided to try another nonsteroidal antiinflammatory drug (NSAID) and prescribed celecoxib, a drug ~5 times more potent than naproxen, with negligible gastrointestinal side effects. Which of the following would be the most appropriate daily dose of celecoxib (in mg) to prescribe to the patient?

A. 50

B. 1000

C. 10

D. 25

E. 100

F. 75

Difficulty level: Easy

6. A 2-year-old boy was admitted to the emergency department after a generalized tonic-colonic seizure. His mother reported that the boy apparently ingested several tablets of propranolol, a β-blocker, which he had found in his father’s dresser drawer. Vital signs on admission were blood pressure 85/50 mm Hg, heart rate 40 beats per minute (bpm), respiratory rate 20/min. The boy received an intramuscular injection of glucagon, a hormone that activates glucagon receptors in the heart, causing a significant increase in heart contractility. Which of the following terms best defines the antagonism between glucagon and β-blockers?

A. Chemical

B. Functional

C. Competitive

D. Pharmacokinetic

E. Pharmacological

Difficulty level: Medium

7. The effect of a new autonomic drug was tested on a healthy volunteer during a clinical trial. The subject was treated with saline or with the drug, and cardiac rate was recorded at rest or after exercise. The results are reported below.

Treatment

Heart Rate (bpm)

At Rest

After Exercise

Saline

70

150

Drug

85

100

Abbreviation: bpm, beats per minute.

Which of the following terms best defines the tested drug?

A. Noncompetitive antagonist

B. Competitive antagonist

C. Partial agonist

D. Physiologic antagonist

E. Full agonist

F. Chemical antagonist

Difficulty level: Easy

8. A 65-year-old woman suffering from atrial fibrillation had been taking a drug to treat this condition for 6 months. The drug had no intrinsic activity and bound reversibly to β1 receptors. Which of the following terms best defines this drug?

A. Partial agonist

B. Functional antagonist

C. Inverse agonist

D. Noncompetitive antagonist

E. Competitive antagonist

F. Full agonist

Difficulty level: Medium

9. A new β-blocker was tested in healthy volunteers. The cumulative frequency distribution of subjects showing a decrease of 10 bpm in the heart rate was plotted against the log dose. Which of the following drug parameters can be determined from this cumulative frequency distribution?

A. Receptor affinity

B. Median effective dose

C. Therapeutic index

D. Therapeutic window

E. Maximal efficacy

Difficulty level: Easy

10. In the figure below, curve X depicts the in vitro log dose− response curve for a full α1 agonist on contraction of vascular smooth muscle. Which of the curves best depicts the log dose−response curve of that agonist when a fixed dose of a competitive α1 antagonist is given concomitantly?

A. Curve P

B. Curve Q

C. Curve R

D. Curve S

E. Curve T

Difficulty level: Medium

11. The figure below depicts the in vitro log dose−response curves of five different drugs (P, Q, R, S, and T). Which of the following pairs of drugs can fully activate the same receptors?

A. Drugs P and Q

B. Drugs P and R

C. Drugs P and S

D. Drugs Q and T

E. Drugs Q and S

F. Drugs R and S

Difficulty level: Easy

12. The figure below depicts the in vitro log dose−response curves of five different drugs (P, Q, R, S, and T) acting on the same receptor.

Which of the following drugs has the highest ED50?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Easy

13. A 65-year-old woman who had been admitted to the hospital with a myocardial infarction developed ventricular tachycardia and received an intravenous injection of lidocaine. Her cardiologist knew that the dose given must be within the range of doses that have a high probability of therapeutic success. Which of the following terms best defines this range?

A. Intrinsic activity

B. Efficacy

C. Potency

D. Therapeutic index

E. Therapeutic window

F. Response variability

Difficulty level: Medium

14. A 67-year-old man suffering from terminal cancer started analgesic treatment with an opioid drug. Knowing that tolerance to opioids is pronounced, which of the following drug parameters was most likely increased after a few days of treatment?

A. Maximal efficacy

B. Median effective dose

C. Therapeutic index

D. Potency

E. Half-life

Difficulty level: Medium

15. A 17-year-old girl started smoking 1 month ago, and now she is smoking 5 to 10 cigarettes daily. She has noticed that the first cigarette of the day often causes mild tachycardia, which does not usually occur with the following cigarettes. Which of the following terms best defines this tolerance pattern?

A. Cross-tolerance

B. Tachyphylaxis

C. Pharmacokinetic tolerance

D. Innate tolerance

E. Sensitization

Difficulty level: Medium

16. A 64-year-old man with terminal cancer had been suffering from continuous pain and started treatment with morphine. After a few days of treatment, the initial dose was no longer effective, and the physician gradually increased the dose, knowing that pharmacodynamic tolerance most likely had occurred. Which of the following best explains the mechanism of tolerance in this patient?

A. Accelerated morphine metabolism

B. Increased affinity of receptors to morphine

C. Decreased binding of morphine to plasma proteins

D. Decreased morphine receptor density

E. Decreased concentration of morphine in the brain

Difficulty level: Medium

17. A 17-year-old boy drank increasing amounts of alcohol when attending parties. He noticed that lately he was able to better tolerate alcohol effects and asked his physician the reason for this. The physician said that pharmacodynamic tolerance had probably occurred. Which of the following actions most likely mediated this tolerance?

A. Decreased concentration of the drug at the site of action

B. Homeostatic adaptive changes that counteract the drug effect

C. Decreased bioavailability of the drug

D. Increased biotransformation of the drug

E. Increased number of drug receptors

Difficulty level: Easy

18. A 46-year-old woman complained to her physician that the sedative effect of the drug she was taking had increased substantially. The woman, who was suffering from generalized anxiety disorder, had been taking diazepam, one tablet daily. A few days earlier, she had started taking cimetidine to treat her heartburn. Cimetidine is an inhibitor of the cytochrome P-450 system in the liver. Which of the following terms best defines this cimetidine−diazepam interaction?

A. Additive effect

B. Potentiation

C. Synergism

D. Sensitization

E. Reverse tolerance

Difficulty level: Easy

19. A 45-year-old woman recently diagnosed with a urinary tract infection started therapy with a trimethoprim−sulfamethoxazole combination. Both trimethoprim and sulfamethoxazole are bacteriostatic drugs when given alone. However, a bactericidal effect is obtained when the two drugs are given in combination. Which of the following terms best defines this drug interaction?

A. Additive effect

B. Potentiation

C. Synergism

D. Reverse tolerance

E. Sensitization

Difficulty level: Easy

20. A 2-year-old girl was rushed to the emergency department after ingesting several tablets of a medication containing iron. An emergency treatment was started that included the intravenous administration of deferoxamine. This drug is able to combine with iron in plasma to form an inactive complex and therefore to antagonize iron effects. Which of the following terms best defines this antagonism?

A. Competitive

B. Noncompetitive

C. Functional

D. Chemical

E. Pharmacokinetic

Difficulty level: Easy

21. A new drug was tested in an in vitro system. The relationship between the concentration of the drug and the association and dissociation of the drug−receptor complex was evaluated. Which of the following factors regulates this relationship?

A. The pharmacological response

B. The volume of distribution of the drug

C. The total clearance of the drug

D. The law of mass action

E. The rate of signal transduction

Difficulty level: Easy

22. An 83-year-old woman suffering from overflow urinary incontinence started a therapy with a cholinergic drug that was able to relieve leaking. Which of the following best defines the molecular event initiated by drug−receptor binding and ending with the therapeutic effect in this patient?

A. Receptor upregulation

B. Drug efficacy

C. Signal transduction pathway

D. Drug−receptor interaction

E. Drug potency

Difficulty level: Easy

23. A 9-year-old boy suffering from mild asthma used a β2 agonist “as needed” by inhalation. Which of the following was most likely the immediate consequence of the activation of β2 receptors?

A. Opening of ligand-gated K+ channels

B. Increased synthesis of cAMP

C. Decreased synthesis of cAMP

D. Conformational change of a G protein

E. Phosphorylation of a G protein

Difficulty level: Easy

24. A 57-year-old man who was in the hospital after a surgical procedure complained of a severe abdominal pain. The physician decided to start analgesic treatment with an opioid. The drugs he was considering were morphine (10 mg IM) and buprenorphine (0.3 mg IM). Morphine is a full agonist at mu (μ) opioid receptors, whereas buprenorphine is a partial agonist at the same receptors. The above-mentioned doses of the two drugs are equieffective. Which of the following pairs of statements correctly defines the potency and efficacy of morphine and buprenorphine?

A. Morphine is more potent. Buprenorphine is more effective.

B. Morphine is more potent. Buprenorphine is less effective.

C. Morphine is less potent. Buprenorphine is more effective.

D. Morphine is less potent. Buprenorphine is less effective.

Difficulty level: Easy

25. A series of new β agonists was tested in laboratory animals. Heart rate was measured after treatment with different doses of each drug. The results are given below:

Drug

ED50 (mg)

Maximal Increase in Heart Rate (bpm)

A

2

+15

B

10

+22

C

15

+30

D

5

+40

E

20

+55

Abbreviations: bpm, beats per minute; ED50, effective dose that produces a response in 50% of subjects.

Which of the following drugs was the most potent?

A. Drug A

B. Drug B

C. Drug C

D. Drug D

E. Drug E

Difficulty level: Easy

26. Two new diuretics were tested in healthy volunteers. They were given singly or together on separate occasions. The results are given below:

Drug

Dose (mg)

Daily Urine Output (L)

A

20

5

B

5

3

A + B

20 (A) + 5 (B)

8

Which of the following terms best defines the type of drug− drug interaction that has occurred?

A. Synergism

B. Potentiation

C. Additive

D. Functional antagonism

E. Pharmacokinetic antagonism

Difficulty level: Medium

27. A 45-year-old woman recently diagnosed with lupus erythematosus started a treatment with a synthetic steroid. Which of the following is the most likely time lapse expected between receptor activation and therapeutic response?

A. Few milliseconds

B. Few seconds

C. Few minutes

D. One or 2 hours

E. Several hours or days

Difficulty level: Medium

28. The figure below depicts the in vitro log dose−response curves of different drugs acting on the same receptor.

Which of the drugs has the highest affinity for the receptor?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Easy

29. Some new drugs acting on the same receptor were studied in laboratory animals. It was found that

• Drug X was able to decrease the constitutive level of activity of the receptor.

• Drug Y was able to increase the constitutive level of activity of the receptor.

• Drug Z was able to antagonize the effects of both drug X and drug Y.

Which of the following terms best defines drug X?

A. Competitive antagonist

B. Partial agonist

C. Inverse agonist

D. Irreversible antagonist

E. Full agonist

Difficulty level: Medium

30. A clinical trial was conducted by orally administering a new analgesic drug to a group of patients suffering from arthritic pain. One hour after administration, the patients were questioned about pain relief, and a sample of blood was collected from each patient to measure plasma drug levels. Pain relief generally correlated well with plasma levels, but three patients whose plasma levels were equal to zero reported good pain relief. Which of the following is the most likely explanation of the analgesic effect of the drug in those three patients?

A. High bioavailability of the drug

B. Small volume of distribution of the drug

C. Very low clearance of the drug

D. Poor patient compliance

E. Placebo effect

Questions: I-3 Adverse Effects of Drugs

Difficulty level: Easy

1. A 23-year-old woman complained to her physician that the diphenhydramine she used to prevent motion sickness when traveling by boat was effective in preventing vomiting but caused drowsiness and dry mouth. Which of the following terms best explains the underlying cause of these drug-related adverse effects?

A. Genetic predisposition

B. Nonspecific cytotoxicity

C. Drug−receptor interaction

D. Immunologic response

E. Preexisting pathology

Difficulty level: Medium

2. Five new anticonvulsant drugs (P, Q, R, S, and T) were tested in laboratory animals. It was found that all of the drugs had approximately the same lethal dose that produces death in 50% of subjects (LD50). The median effective dose of each drug is reported below:

Drug

Median Effective Dose (mg)

P

3

Q

10

R

24

S

35

T

50

Which of the drugs most likely has the highest risk of overdose toxicity?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Easy

3. A 51-year-old man reported to his physician that in the morning he noticed his urine was cloudy and red. The man had been taking an oral anticoagulant for 3 weeks to treat a deep venous thrombosis. If the patient’s symptoms were caused by the anticoagulant, which of the following adverse drug reactions was most likely involved?

A. Overdose toxicity

B. Autoimmune reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Immediate allergic reaction

Difficulty level: Hard

4. A 23-year-old woman scheduled for surgical dilation and curettage was anesthetized with thiopental. Shortly after recovery from the anesthesia, the woman had generalized seizures followed by a deep coma. Further information given by her husband indicated that the patient’s mother had suffered from acute intermittent porphyria. If the coma was caused by thiopental, which of the following drug reactions was most likely involved?

A. Type II allergic reaction

B. Delayed allergic reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Overdose toxicity

Difficulty level: Medium

5. A 28-year-old woman who had had a mitral valve replacement for rheumatic heart disease 2 years ago had her suspected pregnancy confirmed by a positive pregnancy test. Her current medications include the anticoagulant warfarin (U.S. Food and Drug Administration [FDA] category for teratogenic risk D) and amoxicillin (FDA category B). Which of the following would be the best course of action to be implemented by her family physician?

A. Stop all medications throughout pregnancy

B. Suspend warfarin for the first trimester of pregnancy

C. Replace warfarin with heparin and continue amoxicillin

D. Continue warfarin and replace amoxicillin with penicillin G

E. Reduce the dose of warfarin and continue amoxicillin

Difficulty level: Medium

6. Five new antihypertensive drugs were tested in healthy volunteers. All of the drugs were found to be equally effective in controlling hypertension. The minimum effective plasma concentrations and the minimum toxic plasma concentrations were determined for each drug. The results are reported below:

Drug

Plasma Concentration (mg/L)

Minimum effective

Minimum toxic

P

5

20

Q

1

10

R

30

60

S

0.6

3

T

20

80

Which of the drugs has the highest probability of therapeutic success?

A. Drug P

B. Drug Q

C. Drug R

D. Drug S

E. Drug T

Difficulty level: Medium

7. A 32-year-old African American man who worked as a Peace Corps volunteer in Ghana presented with weakness, fatigue, yellowing of his skin and sclera, and slight fever. He recently was given chloroquine as a prophylaxis for malaria. Laboratory findings confirmed the diagnosis of hemolytic anemia likely due to chloroquine treatment. This patient’s disease was most likely mediated by genetic polymorphism of which of the following enzymes?

A. N-acetyltransferase

B. Glucose-6-phosphate dehydrogenase

C. Reduced form of nicotinamide adenine dinucleotide (NADH)−methemoglobin reductase

D. Pseudocholinesterase

E. Glucuronosyltransferase

Difficulty level: Medium

8. A 61-year-old woman complained to her physician of a burning sensation when she urinated. Past history of the patient was significant for serious hypersensitivity to sulfa drugs. Urinalysis revealed abundant gram-negative bacteria, and a sensitivity test showed that they were sensitive to amikacin, piperacillin, trimethoprim-sulfametoxazole, ciprofloxacin, and ceftriaxone. A diagnosis of urinary tract infection was made, and an antibiotic therapy was prescribed. Which of the following antibiotics should be avoided in this patient?

A. Trimethoprim-sulfamethoxazole

B. Piperacillin

C. Amikacin

D. Ciprofloxacin

E. Ceftriaxone

Difficulty level: Easy

9. A new hypnotic drug was tested in laboratory animals. It was found that the ED50 for inducing sleep was 2 mg/kg. Which of the following best explains the meaning of that dose?

A. The mean dose able to elicit sleep induction

B. The dose with a 50% probability of causing sleep

C. The dose that elicits sleep in 50% of animals

D. The mean dose with a good probability of sleep induction

E. The dose that elicits a median therapeutic sleep response in most animals

Difficulty level: Medium

10. A newborn boy whose mother had epilepsy presented with microcephaly, a broad nasal bridge, short nose, cleft palate, and hypoplasia of the distal phalanges. Drugs used by the mother during pregnancy included phenytoin for seizures, methyldopa for pregnancy-induced hypertension, and erythromycin for an upper respiratory infection during the first trimester. During the delivery, the woman was treated with diazepam and had epidural anesthesia with lidocaine. Which of the drugs taken by the mother most likely caused the baby’s presenting syndrome?

A. Methyldopa

B. Phenytoin

C. Erythromycin

D. Lidocaine

E. Diazepam

Difficulty level: Medium

11. A 75-year-old woman complained to her physician of increased need to urinate during the night. The woman had been receiving gentamicin for 2 months to treat a urinary tract infection. Lab tests revealed a serum creatinine level of 5 mg/dL (normal 0.5−1.2 mg/dL). Serum gentamicin concentration obtained just before the last dose was 9 mg/dL (normal < 2 mg/dL). The patient was most likely suffering from which of the following adverse drug reactions?

A. Type II allergic reaction

B. Type III allergic reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Overdose toxicity

Difficulty level: Medium

12. A 34-year-old man was admitted to the hospital because of sudden onset of fever (102.2°F, 39.0°C), oliguria, and a skin rash. The man had been receiving ampicillin for primary syphilis. Laboratory findings showed eosinophiluria, proteinuria, and increased serum levels of urea nitrogen and creatinine. A diagnosis of drug-induced tubulointerstitial nephritis was made. Which of the following adverse drug reactions best explains the disease of this patient?

A. Overdose toxicity

B. Tachyphylactic reaction

C. Idiosyncratic reaction

D. Allergic reaction

E. Pseudoallergic reaction

Difficulty level: Medium

13. A 15-year-old boy was admitted to the hospital with fever (103.1°F, 39.5°C), a morbilliform skin eruption, lymphadenopathy, angioedema, and arthralgia. The boy had been receiving ampicillin for a pulmonary infection for 2 weeks. Lab data revealed elevated circulating immune complexes. Which of the following adverse drug reactions best explains the patient’s disorder?

A. Overdose toxicity

B. Anaphylactoid reaction

C. Idiosyncratic reaction

D. Autoimmune reaction

E. Serum sickness

Difficulty level: Hard

14. A 69-year-old man presented to the hospital with a skin eruption over his neck, arms, and legs. The patient reported that he was diagnosed with senile pruritus 3 week earlier, and he had been applying a topical doxepin cream to relieve itching. Physical examination revealed red, swollen skin covered with blisters, and a patch test confirmed that the skin eruption was due to doxepin. Which of the following adverse drug reactions best explains the patient’s disorder?

A. Type I allergic reaction

B. Type II allergic reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Type IV allergic reaction

Difficulty level: Hard

15. A 38-year-old woman went to her physician because of a bluish discoloration of her lips. Medical history was significant for an inherited deficiency of the reduced form of nicotinamide adenine dinucleotide (NADH)−methemoglobin reductase. One week earlier, she had started therapy with trimethoprim-sulfamethoxazole to treat a urinary tract infection. Physical examination showed cyanosis of the oral mucosa, and a blood test revealed a high level of methemoglobinemia. The physician suspected that sulfamethoxazole was the cause of the patient’s cyanosis. Which of the following adverse drug reactions best explains the patient’s disorder?

A. Type I allergic reaction

B. Type IV allergic reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Overdose toxicity

Difficulty level: Easy

16. A 32-year-old woman complained to her physician of urticaria. Three days earlier, the woman had started therapy with amoxicillin for infectious tonsillitis. The physician suspected an allergic reaction to the drug. Which of the following was most likely the main determinant of that drug reaction?

A. Dose of the drug

B. Chemical structure of the drug

C. Oral bioavailability of the drug

D. Genetic pedigree of the patient

E. Liver and kidney functions of the patient

Difficulty level: Easy

17. An 85-year-old woman was admitted to the hospital with an infected decubitus ulcer. Cultures revealed Staphylococcus aureus that was sensitive to some β-lactam antibiotics, namely, oxacillin, cephalexin, and imipenem. Which of the following would be the first procedure to undertake in order to minimize the risk of an allergic reaction to these antibiotics?

A. Start the therapy with a very small dose

B. Perform a skin sensitivity test

C. Pretreat the patient with an antiallergic drug

D. Use another β-lactam antibiotic active against S. aureus

E. Get a detailed drug history

Difficulty level: Medium

18. A 32-year-old pregnant woman was found to have a red blood cell count of 3.2 × 106/mm3 (normal 3.5−5.5 × 106) and a positive direct Coombs test during a regular clinic visit. The woman had started a treatment with methyldopa 4 months earlier because of stage 1 hypertension. Which of the following mechanisms most likely mediated the drug-induced reaction of this patient?

A. Deficiency of the reduced form of nicotinamide adenine dinucleotide (NADH)−methemoglobin reductase

B. Production of autoantibodies against red blood cells

C. Drug-induced deficiency of folic acid

D. Drug-induced bone marrow suppression

E. Deficiency of glucose-6-phosphate dehydrogenase

Difficulty level: Easy

19. A 64-year-old man was hospitalized for treatment of Staphylococcus aureus bacteremia and was given an intravenous infusion of vancomycin. A few minutes later he developed symptoms of an anaphylactic-like reaction. The patient was not aware of previous exposure to vancomycin, and a search for antibodies to the suspected drug was negative. Which of the following types of drug reaction was most likely experienced by the patient?

A. Type I allergic reaction

B. Autoimmune reaction

C. Genetically mediated reaction

D. Pseudoallergic reaction

E. Overdose toxicity

Difficulty level: Medium

20. A 43-year-old man had to undergo surgery to remove a biliary calculus. The anesthesiologist chose to supplement the anesthesia with succinylcholine, a paralyzing agent that has a rapid onset and a short duration of action. In this patient, however, the drug-induced paralysis lasted several hours, necessitating the anesthesiologist to continue the anesthesia and continue artificial respiration. Which of the following adverse drug reactions best explains the patient’s disorder?

A. Type II allergic reaction

B. Immediate allergic reaction

C. Idiosyncratic reaction

D. Pseudoallergic reaction

E. Overdose toxicity

Answers and Explanations: I-1 Pharmacokinetics

Learning objective: Describe the main features of lipid diffusion of drugs across cell membranes.

1. B Lipid diffusion is by far the most common transport system of drugs across cell membranes. Because albuterol has a low molecular weight, lipid diffusion most likely accounts for the transfer of albuterol through the bronchial mucosa.

A, C−E See correct answer explanation.

Learning objective: Identify the mechanism of permeation of botulinum toxin through nerve cell membranes.

2. D Very large molecules cannot permeate cell membranes by diffusion or filtration. The only way they can cross cell membranes is by endocytosis, a process by which a substance is bound to the cell surface, engulfed by the cell membrane, and carried into the cytosol, where the substance can be released by breakdown of the vesicle membrane.

A–C, E See correct answer explanation.

Learning objective: Describe the main features of active transport of drugs across cell membranes.

3. A About one fifth of the iodides ingested with foods are selectively removed from the circulating blood by the Na+-dependent secondary active transport system that concentrates iodide in thyroid cells 30 to 100 times its concentration in the blood. Because radioactive iodine is essentially the same as iodide taken with foods, it is transported into the thyroid cells by the same secondary active transport system.

B−E See correct answer explanation.

Learning objective: Describe the main features of bulk flow transport of drugs across cell barriers.

4. A A drug administered subcutaneously will initially be located primarily in the extracellular fluid. In order to be absorbed, the drug must enter the general circulation; that is, it must cross the capillary wall. Capillaries have very wide fenestrae that permit the passage of molecules with a molecular weight as high as 30,000 daltons (D). Therefore, most drugs given by the subcutaneous or intramuscular routes will enter the general circulation by bulk flow transport (or filtration; also known as solvent drag) through capillary fenestrae. Moreover, insulin is a protein with a molecular weight of about 6000 D, so it cannot cross the capillary wall by lipid or aqueous diffusion through aquaporins (water channels) of cell membranes. Bulk flow transport is a passive process and is directly proportional to the pressure gradient across the capillary wall. It does not depend on the structure of the drug but only on its molecular size (both lipid- and water-soluble drugs can be filtered provided the molecule is not too large).

B See correct answer explanation.

C−E Facilitated diffusion, endocytosis, and active transport do not seem to be involved in the absorption of insulin from the site of injection.

Learning objective: Explain the main mechanistic features of ion trapping.

5. E The Henderson-Hasselbalch equation predicts that a weak acid will be more nonionized, and therefore more lipid soluble, when pKa is greater than pH. Because the pH of the stomach lumen is less than 2, ibuprofen, an acid drug with a pKa of 4.8, will be mainly nonionized in the gastric lumen and will readily penetrate the gastric mucosal cell membranes. Inside the mucosal cells, however, the pH is about 7, and the drug will become mainly ionized because now the pKa is less than the pH. Consequently, the concentration gradient of the nonionized, lipid-soluble form will remain high, and the drug will continue crossing cell membranes. At equilibrium, the concentration of the nonionized moiety of the drug will be the same on both sides, but the concentration of the ionized moiety inside the cell can be 15 to 20 times higher than that in the gastric lumen, as the ionized moiety is “trapped” inside the cell (ion-trapping mechanism). Therefore, the total drug concentration inside the cell will be high.

A−C Basic drugs are mainly ionized when the pKa is higher than the pH; therefore, most of the drug will stay in the stomach lumen.

D Theophylline, an acidic drug with a pKa of 8.8, is mainly nonionized in the stomach lumen and therefore can readily penetrate the gastric cell membranes. Inside the gastric cells, however, the drug remains mainly non-nonionized (i.e., lipid soluble) because the pKa is greater than the pH. Therefore, the drug will be able to diffuse through the basolateral membrane of the cell, thus reaching the extracellular fluids. No ion trapping occurs, and the drug will not concentrate inside the cells.

Learning objective: Explain why the lipid and water solubilities of a drug are related to their pKa and to the pH of the solvent.

6. F An acidic drug is mainly water soluble when its pKa is lower than the pH of the medium. The amount of water solubility is proportional to the difference between pH and pKa, according to the following table

Because the pH of plasma is about 7.4, the drug will be greater than 99% water soluble in the patient’s plasma.

A−E See correct answer explanation.

Learning objective: Describe the ion-trapping mechanism of drugs.

7. D Aspirin is an acidic drug. As a rule, the excretion of an acidic drug can be accelerated by alkalinizing the urine, because an acidic drug dissociates to its charged, polar form in alkaline solution. This form, being water soluble, is “trapped” in the tubular lumen and cannot be transported back into the blood across the renal tubular cells. Conversely, the urinary excretion of a weak base may be accelerated by acidifying the urine.

A Salicylates do not undergo active transport.

B Salicylate biotransformation by the kidney is negligible.

C Aspirin was already absorbed, so bioavailability is not relevant.

E Glomerular filtration of a drug is strictly related to the renal glomerular filtration rate (GFR). It is very rare for drugs to significantly increase GFR.

Learning objective: Identify the main site of absorption of drugs administered by the oral route.

8. C All drugs given by the oral route are primarily absorbed by the small intestine. This is because of the very large surface area of the small intestine, which is about 250 m2 and represents about 80% of the total area of the gastrointestinal tract. Hydrochlorothiazide is an acidic drug with a pKa of about 9, so it will be more lipid soluble in the stomach (where the pH is less than 2) than in the small intestine (where the pH is around 7). Nevertheless, absorption will take place mainly in the small intestine because of its enormous absorptive surface area.

A Because a drug given orally is swallowed, the oral mucosa does not contribute to absorption.

B, D, E See correct answer explanation.

Learning objective: Calculate the oral bioavailability of a drug, given sufficient data.

9. D Oral bioavailability is measured by the ratio AUCOral/AUCIV. Drug S gives an oral bioavailability of 0.83, the highest of all the listed drugs.

A−C, E See correct answer explanation.

Learning objective: Explain why the dosage form of a drug formulation can affect the oral bioavailability of that drug.

10. A The amount of drug reaching the portal circulation after oral administration can be strongly influenced by the dosage formulation. Because only single molecules of the drug can pass through the gut wall, the drug must be in solution in order to enter the intestinal epithelial cells. For example, a tablet must be disintegrated and dissolved before reaching the portal circulation. The efficiency of this process depends on several factors, including the way the tablet is manufactured and the excipients used. Once in the portal circulation, the drug can be metabolized by the liver, but the hepatic clearance will be the same, regardless of the different dosage forms. Because in this case the same dose of the drug was administered, the concentration of the drug in the portal vein will be directly proportional to the oral bioavailability of the different formulations, which is indicated by the different AUCs depicted in the figure.

B−D See correct answer explanation.

Learning objective: Describe the main characteristics of drug permeation across cell membranes.

11. A Being a polar drug, ethanol is readily water soluble. Because its molecular weight is small, it can cross cell membranes by aqueous diffusion through aquaporins.

B−E See correct answer explanation.

Learning objective: List the main factors affecting the absorption of drugs administered by the oral route.

12. B Strong pain can substantially decrease gastric emptying, likely because of the activation of the sympathetic nervous system. Because the absorption of drugs by the stomach is very small, gastric emptying is a major factor influencing the rate of intestinal drug absorption, and its decrease can significantly delay this absorption.

A, C These factors usually speed up, not delay, the intestinal absorption of drugs.

D, E The distribution and elimination (clearance) of drugs have nothing to do with absorption.

Learning objective: Describe the main factors that can increase the entry of drugs into the central nervous system.

13. B The permeability of the blood−brain barrier can be increased by several factors. Damage to the brain by any cause (trauma, infections, tumors, metabolic disorders, cerebrovascular disorders) is one of the most common causes of increased blood−brain barrier permeability.

A, D The first-pass effect is related to the bioavailability of a drug. Clearance is related to the elimination of a drug. Passage into the brain is related to the distribution of the drug. Bioavailability, distribution, and elimination are independent processes.

C The permeability of the blood−brain barrier is physiologically increased only in the fetus and the newborn.

E The high ionization of the drug decreases, not increases, the drug entry into the brain.