Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 12e

Chapter 4: Drug Metabolism

You are planning to treat chronic major depression in a 35-year-old patient with recurrent suicidal thoughts. She has several comorbid conditions that require drug therapy, including rifampin for tuberculosis and amiodarone for arrhythmia. You are concerned about drug interactions caused by changes in drug metabolism in this patient.

Drug metabolism in humans usually results in a product that is

(A) Less lipid soluble than the original drug

(B) More likely to distribute intracellularly

(C) More likely to be reabsorbed by kidney tubules

(D) More lipid soluble than the original drug

(E) Less water soluble than the original drug

Biotransformation usually results in a product that is less lipid-soluble. This facilitates elimination of drugs that would otherwise be reabsorbed from the renal tubule. The answer is A.

If therapy with multiple drugs causes induction of drug metabolism in your depressed patient, it will

(A) Be associated with increased smooth endoplasmic reticulum

(B) Be associated with increased rough endoplasmic reticulum

(C) Be associated with decreased enzymes in the soluble cytoplasmic fraction

(D) Require 3–4 months to reach completion

(E) Be irreversible

The smooth endoplasmic reticulum, which contains the mixed-function oxidase drug-metabolizing enzymes, is selectively increased by inducers. The answer is A.

Which of the following factors is likely to increase the duration of action of a drug that is metabolized by CYP3A4 in the liver?

(A) Chronic administration of rifampin during therapy with the drug in question

(B) Chronic therapy with amiodarone

(C) Displacement from tissue-binding sites by another drug

(D) Increased cardiac output

(E) Chronic administration of carbamazepine

Rifampin and carbamazepine can induce drug-metabolizing enzymes and thereby may reduce the duration of drug action. Displacement of drug from tissue may transiently increase the intensity of the effect but decreases the volume of distribution. Amiodarone is recognized as an inhibitor of P450 and may decrease clearance of drugs metabolized by CYP2C9, CYP2D6, and CYP3A4. The answer is B.

Reports of cardiac arrhythmias caused by unusually high blood levels of 2 antihistamines, terfenadine, and astemizole, led to their removal from the market. Which of the following best explains these effects?

(A) Concomitant treatment with rifampin

(B) Use of these drugs by chronic alcoholics

(C) Use of these drugs by chronic smokers

(D) Treatment of these patients with ketoconazole, an azole antifungal agent

Treatment with rifampin and chronic alcohol or tobacco use are associated with increased drug metabolism and lower, not higher, blood levels. Ketoconazole, itraconazole, erythromycin, and some substances in grapefruit juice slow the metabolism of certain older non-sedating antihistamines (Chapter 16). The answer is D.

Which of the following agents, when used in combination with other anti-HIV drugs, permits dose reductions?

(A) Cimetidine

(B) Efavirenz

(C) Ketoconazole

(D) Procainamide

(E) Quinidine

(F) Ritonavir

(G) Succinylcholine

(H) Verapamil

Ritonavir inhibits hepatic drug metabolism, and its use at low doses in combination regimens has permitted dose reductions of other HIV protease inhibitors (eg, indinavir). The answer is F.

Which of the following drugs may inhibit the hepatic microsomal P450 responsible for warfarin metabolism?

(A) Amiodarone

(B) Ethanol

(C) Phenobarbital

(D) Procainamide

(E) Rifampin

Amiodarone is an important antiarrhythmic drug and has a well-documented ability to inhibit the hepatic metabolism of many drugs. The answer is A.

Which of the following drugs, if used chronically, is most likely to increase the toxicity of acetaminophen?

(A) Cimetidine

(B) Ethanol

(C) Ketoconazole

(D) Procainamide

(E) Quinidine

(F) Ritonavir

(G) Succinylcholine

(H) Verapamil

Acetaminophen is normally eliminated by phase II conjugation reactions. The drug’s toxicity is caused by an oxidized reactive metabolite produced by phase I oxidizing P450 enzymes. Ethanol and certain other drugs induce P450 enzymes and thus reduce the hepatotoxic dose. Alcoholic cirrhosis reduces the hepatotoxic dose even more. The answer is B.

Which of the following drugs has higher first-pass metabolism in men than in women?

(A) Cimetidine

(B) Ethanol

(C) Ketoconazole

(D) Procainamide

(E) Quinidine

(F) Ritonavir

(G) Succinylcholine

(H) Verapamil

Ethanol is subject to metabolism in the stomach as well as in the liver. Independent of body weight and other factors, men have greater gastric ethanol metabolism and thus a lower ethanol bioavailability than women. The answer is B.

Which of the following drugs is an established inhibitor of P-glycoprotein (P-gp) drug transporters?

(A) Cimetidine

(B) Ethanol

(C) Ketoconazole

(D) Procainamide

(E) Quinidine

(F) Ritonavir

(G) Succinylcholine

(H) Verapamil

Verapamil is an inhibitor of P-glycoprotein drug transporters and has been used to enhance the cytotoxic actions of methotrexate in cancer chemotherapy. The answer is H.

Which of the following cytochrome isoforms is responsible for metabolizing the largest number of drugs?

(A) CYP1A2

(B) CYP2C9

(C) CYP2C19

(D) CYP2D6

(E) CYP3A4

While CYP2D6 is responsible for metabolizing approximately 25% of drugs, CYP3A4 is involved in almost 50% of such reactions. The answer is E.

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Chapter 4: Drug Metabolism

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