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

Chapter 61: Important Drug Interactions & Their Mechanisms

A 55-year-old patient currently receiving a drug for a psychiatric condition is to be started on diuretic therapy for mild heart failure. Consideration should be given to the fact that thiazides are known to reduce the excretion of which of the following?

(A) Diazepam

(B) Fluoxetine

(C) Imipramine

(D) Lithium

(E) Trifluoperazine

Thiazides reduce the clearance of lithium by about 25%. They do not alter the clearance of the other agents listed. The answer is D.

A hypertensive patient has been using nifedipine for some time without untoward effects. If he experiences a rapidly developing enhancement of the antihypertensive effect of the drug, it is most likely due to which of the following?

(A) Concomitant use of antacids

(B) Foods containing tyramine

(C) Furanocoumarins in grapefruit juice

(D) Induction of drug metabolism

(E) Over-the-counter decongestants

Compounds in grapefruit juice can increase the rate and extent of bioavailability of several dihydropyridine calcium channel blockers, including felodipine and nifedipine. This interaction may be due to inhibition of the metabolism of the dihydropyridines by intestinal wall CYP3A4 or inhibition of the P-glycoprotein transporter in the same location. The answer is C.

A patient suffering from a depressive disorder is being treated with imipramine. If he uses diphenhydramine for allergic rhinitis, a drug interaction is likely to occur because

(A) Both drugs block muscarinic receptors

(B) Both drugs block reuptake of norepinephrine released from sympathetic nerve endings

(C) Diphenhydramine inhibits imipramine metabolism

(D) Imipramine inhibits the metabolism of diphenhydramine

(E) The drugs compete with each other for renal elimination

This is a good example of an additive drug interaction resulting from 2 drugs acting on the same type of receptor. Most tricyclic antidepressants, phenothiazines, and older antihistaminic drugs (those available without prescription) are blockers of muscarinic receptors. Used concomitantly, any pair of these agents will demonstrate a predictable increase in atropine-like adverse effects. The answer is A.

If phenelzine is administered to a patient taking fluoxetine, which of the following is most likely to occur?

(A) A decrease in the plasma levels of fluoxetine

(B) Antagonism of the antidepressant action of fluoxetine

(C) Agitation, muscle rigidity, hyperthermia, seizures

(D) Decreased metabolism of fluoxetine

(E) Priapism

The drug interaction between the inhibitors of monoamine oxidase used for depression and the drugs that selectively block serotonin reuptake (SSRIs) is called the serotonin syndrome. In the case of phenelzine and fluoxetine, the interaction has resulted in a fatal outcome. Key interventions include control of hyperthermia and seizures. The answer is C.

AJ is a 45-year-old homeless man participating in a drug rehabilitation program that supplies daily methadone. AJ reports that he needs more methadone to avoid withdrawal, since he started treatment for his tuberculosis. Which of the following drugs might have caused this scenario?

(A) Ciprofloxacin

(B) Cyclosporine

(C) Erythromycin

(D) Rifampin

(E) Tetracycline

Rifampin is an effective inducer of hepatic P450 isozymes. Cyclosporine and tetracycline have no significant effects on drug metabolism. Ciprofloxacin and erythromycin are inhibitors of drug metabolism. The answer is D.

A 43-year-old woman with type 2 diabetes and hypertension visits your clinic. Her current blood pressure (measured 3 times) is not at target: 155/98 mm Hg, despite the fact that she is taking hydrochlorothiazide and captopril. The antihypertensive effects of captopril can be antagonized (reduced) by which of the following?

(A) Angiotensin II receptor blockers

(B) Loop diuretics

(C) NSAIDs

(D) Sulfonylurea hypoglycemics

(E) Pioglitazone

NSAIDs interfere with the antihypertensive action of angiotensin-converting enzyme inhibitors; the other drugs listed enhance the blood pressure-lowering effects of captopril and other members of the “pril” drug family. Pioglitazone is a hypoglycemic drug used in patients with type 2 diabetes mellitus and has no significant effect on blood pressure. The answer is C.

Which drug has resulted in severe hematotoxicity when administered to a patient being treated with azathioprine?

(A) Allopurinol

(B) Cholestyramine

(C) Digoxin

(D) Lithium

(E) Theophylline

Azathioprine is converted to mercaptopurine, which is responsible for both its immunosuppressant action and its hematotoxicity. Allopurinol inhibits xanthine oxidase, the enzyme that metabolizes mercaptopurine. The answer is A.

The following section consists of a list of lettered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it.

In patients with HIV infection, the inhibitory action of this agent on drug metabolism has clinical value.

(A) Allopurinol

(B) Carbamazepine

(C) Cholestyramine

(D) Cimetidine

(E) Clarithromycin

(F) Cyclosporine

(G) Digoxin

(H) Erythromycin

(I) Fluoxetine

(J) Ibuprofen

(K) Lovastatin

(L) Phenelzine

(M) Rifampin

(N) Ritonavir

(O) Theophylline

Ritonavir inhibits the metabolism of other HIV protease inhibitors and is used in low-dose combinations with indinavir or lopinavir. The answer is N.

The following section consists of a list of lettered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it.

This drug enhances the toxicity of methotrexate by decreasing its renal clearance.

(A) Allopurinol

(B) Carbamazepine

(C) Cholestyramine

(D) Cimetidine

(E) Clarithromycin

(F) Cyclosporine

(G) Digoxin

(H) Erythromycin

(I) Fluoxetine

(J) Ibuprofen

(K) Lovastatin

(L) Phenelzine

(M) Rifampin

(N) Ritonavir

(O) Theophylline

Several NSAIDs, including aspirin, ibuprofen, and piroxicam, increase serum levels of methotrexate by interfering with its renal clearance. The adverse effects of methotrexate, including its hematotoxicity, are predictably increased. The answer is J.

The following section consists of a list of lettered options followed by several numbered items. For each numbered item, select the ONE option that is most closely associated with it.

Concomitant use of St. John’s wort is reported to increase the effectiveness of this drug.

(A) Allopurinol

(B) Carbamazepine

(C) Cholestyramine

(D) Cimetidine

(E) Clarithromycin

(F) Cyclosporine

(G) Digoxin

(H) Erythromycin

(I) Fluoxetine

(J) Ibuprofen

(K) Lovastatin

(L) Phenelzine

(M) Rifampin

(N) Ritonavir

(O) Theophylline

Concomitant use of St. John’s wort enhances the effects of selective serotonin reuptake inhibitors. Note that enhancement is not always positive and too much serotonin is harmful (serotonin syndrome). In contrast, the herb decreases the effectiveness of other drugs (including cyclosporine, estrogens, and protease inhibitors) via its induction of drug-metabolizing enzymes. The answer is I.

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Chapter 61: Important Drug Interactions & Their Mechanisms

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