USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 111:

  Which of the following drugs exerts its effects through inhibition of cyclic GMP phosphodiesterase?

  A. hydralazine

  B. minoxidil

  C. nitroprusside

  D. prazosin

  E. sildenafil

  Correct Answer: E

  Section: Pharmacology Vasodilators act by one of three mechanisms: increasing cyclic GMP (cGMP) levels in vascular smooth muscle cells; opening potassium channels; or blocking calcium channels. The organic nitrates and nitroprusside (nitrovasodilators) increase cGMP synthesis by generating nitric oxide (NO), which subsequently activates a soluble form of guanylyl cyclase. Activation of muscarinic receptors on vascular endothelial cells results in formation of NO (earlier identified as endothelium-derived relaxing factor) that diffuses to smooth muscle cells and relaxes them through increased cGMP levels. Erection of the penis involves neuronally regulated formation of NO, increased cGMP levels in the corpus cavernosum, and relaxation of cavernosal and vascular smooth muscle in erectile tissue. Rather than stimulating guanylyl cyclase, sildenafil (Viagra) acts as a selective inhibitor of cGMP phosphodiesterase type 5 to increase the half-life of cGMP in the tissues. The fact that sildenafil acts downstream of NO stimulation of guanylyl cyclase accounts for the toxic interactions between it and nitrovasodilators. The mechanism for relaxation of vascular smooth muscle by hydralazine (choice A) is unknown, but may involve NO. Minoxidil (choice B) is metabolized to minoxidil sulfate, which activates an ATP-sensitive potassium channel in smooth muscle. Nitroprusside (choice C) is a nitrovasodilator that spontaneously releases NO by a mechanism distinct from that of the organic nitrates. Prazosin (choice D) produces vasodilation by inhibiting alpha-1adrenoreceptors on arteriolar smooth muscle.

• Question 112:

  A young boy was treated for 2 years with several antibacterial agents to eradicate tuberculosis. On entering school the following year, his teacher reports that he seems to be retarded. Upon investigation, he is found to have profound hearing loss. Which of the following agents may have been responsible for this hearing loss?

  A. ethambutol

  B. isoniazid

  C. pyrazinamide

  D. rifampin

  E. streptomycin

  Correct Answer: E

  Section: Pharmacology The agents listed are the primary drugs used in the treatment of tuberculosis. Streptomycin (choice E) and other aminoglycosides cause eighth nerve damage, which is often irreversible and may take the form of auditory or vestibular dysfunction. Isoniazid and rifampin are the most efficacious and least toxic, but even when used together are insufficient in many cases to prevent the development of resistance. Therefore, most cases of tuberculosis are treated with three or even four agents in an effort to eradicate the infection before resistance develops. Because each drug has different toxicities, it is sometimes possible to achieve a cure without severe toxicity. Ethambutol (choice A) causes visual dysfunction and possible retinal damage, not hearing loss. Isoniazid (choice B) causes peripheral neuropathies and hepatic damage. Fortunately, hepatitis is uncommon in children treated with this drug. Pyrazinamide (choice C) causes joint pains and swelling, GI upset, and rash. Rifampin (choice D) causes proteinuria, rash, and thrombocytopenia.

• Question 113:

  A patient with AIDS has bacterial meningitis and is being treated with an antimicrobial agent cleared by both hepatic metabolism and renal excretion. The volume of distribution is 10 L and the half-life for elimination is 7 hours in this patient. If the renal contribution to the plasma clearance of the drug is 8.3 mL/ min, approximately what percentage of the drug's elimination can be attributed to hepatic metabolism?

  A. 10%

  B. 25%

  C. 50%

  D. 75%

  E. 90%

  Correct Answer: C

• Question 114:

  Calcium- and aluminum-containing antacids should be avoided by patients taking which of the following antimicrobial drugs?

  A. amoxicillin

  B. erythromycin

  C. isoniazid

  D. minocycline

  E. rifampin

  Correct Answer: D

  Section: Pharmacology Tetracyclines such as minocycline chelate cations, such as aluminum and calcium, and may precipitate in the gut, greatly reducing antibiotic bioavailability. The other drugs listed (choices AC, E) have no significant interactions with antacids.

• Question 115:

  A 60-year-old man reports to the emergency room complaining of shortness of breath and a rapid,

  irregular heart beat. An ECG shows the pattern recorded in below figure, panel A. Adiagnosis of atrial

  fibrillation, heart rate 140, is made. He is treated with an IV drug, which results in a change of the ECG, 1

  hour after drug administration, to the pattern shown in panel B. This ECG was read as atrial fibrillation,

  heart rate 65.

  What drug was used?

  

  A. adenosine

  B. diltiazem

  C. disopyramide

  D. ibutilide

  E. quinidine

  Correct Answer: B

  Section: Pharmacology The initial atrial fibrillation ECG shows a very rapid ventricular rate, which decreases cardiac output and explains the patient's shortness of breath. After administration of the drug, the ventricular rate markedly slowed, but QRS duration and QT interval were not altered. This pattern of effects is observed with drugs that selectively slow AV conduction (i.e., beta blockers [antiarrhythmic group 2] and calcium channel blockers [group 4]). Adenosine (choice A) slows or blocks AV conduction but has a very short duration of action (seconds). Disopyramide (choice C) and quinidine (choice E) are group 1Aantiarrhythmic drugs and prolong the QRS and QT intervals. Ibutilide (choice D) is a group 3 drug and prolongs the QT interval. Cardiac glycosides such as digoxin also slow AV conduction (through their parasympathomimetic action), but have a slower onset of action than parenteral calcium channel blockers or beta blockers.

• Question 116:

  Which of the following substances contains the highest concentration of molecules with estrogenic effects?

  A. ginseng

  B. grapefruit juice

  C. kava

  D. saw palmetto

  E. tomatoes

  Correct Answer: D

  Section: Pharmacology Saw palmetto is promoted by purveyors of herbs and "alternative medicines" as therapy for prostatic hyperplasia and does have weak estrogenic activity. Ginseng (choice A) is known as an adaptogen, which means it increases resistance to physical, chemical, and biological stress and builds up energy and general vitality, including the mental and physical capacity for work. Grapefruit juice (choice B) and tomatoes (choice E) are used therapeutically in a treatment regimen referred to as "raw juice therapy." Raw juices of fruits and vegetables are extremely rich in vitamins, minerals, trace elements, enzymes, and natural sugars. Kava (choice C) is used in herbal therapy to treat anxiety, nervousness, nsomnia, stress, and restlessness. Only saw palmetto is known to have any estrogenic activity.

• Question 117:

  Which of the following correctly describes the mechanism of action of streptokinase?

  A. combines with plasminogen to form an enzymatically active complex

  B. competitively blocks binding of plasminogen to fibrin

  C. converts plasmin to plasminogen

  D. inhibits platelet cyclooxygenase (COX) activity

  E. provides a template for combination of thrombin and antithrombin III

  Correct Answer: A

  Section: Pharmacology Streptokinase has no intrinsic enzymatic activity, but instead forms a stable complex with the patient's plasminogen, making it enzymatically active in cleaving free plasminogen to plasmin. The streptokinaseplasminogen complex is not inhibited by antiplasmin. The other thrombolytic agents-- t-PA, reteplase, tenecteplase, and urokinase-- activate plasminogen directly. Competitive blocking of binding of plasminogen to fibrin (choice B) is a property of aminocaproic acid (AMICAR), a lysine analog used to inhibit fibrinolysis. Conversion of plasmin to plasminogen (choice C) is incorrect; it is plasminogen that is converted to plasmin in the thrombolytic action. Inhibition of cyclooxygenase activity (choice D) is a property of the NSAIDs that contributes to prevention of platelet aggregation and thrombosis. Heparin exerts its anticoagulant actions by providing a template for the combination of thrombin and antithrombin III (choice E).

• Question 118:

  A 17-year-old patient suffers from tonicclonic seizures. This condition has been well controlled with a regimen of phenytoin. Which of the following signs or symptoms indicates phenytoin toxicity?

  A. diplopia and abnormal gait

  B. hyperprolactinemia

  C. polydipsia and polyuria

  D. postural hypotension

  E. rigidity and tremor

  Correct Answer: A

  Section: Pharmacology Diplopia, abnormal gait, and other signs of cerebellar dysfunction are important symptoms of phenytoin toxicity. Other manifestations of toxicity include gingival hyperplasia, nystagmus, and vertigo. Hyperprolactinemia (choice B) is an adverse effect of antipsychotic dopamine antagonists such as the phenothiazines; dopamine inhibits prolactin secretion by the anterior pituitary. Polydipsia and polyuria (choice C) are symptoms of diabetes insipidus. These symptoms may be produced by lithium toxicity during treatment of bipolar depression, and are not associated with phenytoin toxicity. Postural hypotension (choice D) is not an adverse effect of phenytoin but often occurs with levodopa treatment of Parkinson's disease. Rigidity and tremor (choice E) are symptoms of parkinsonism. These symptoms may be produced by dopamine antagonists such as antipsychotic agents, but are not associated with phenytoin toxicity.

• Question 119:

  Exhibit:

  

  Please refer to the exhibit.

  Which of the following is the agent of choice for chronic treatment of simple hypothyroidism (myxedema)?

  A. A

  B. B

  C. C

  D. D

  E. E

  Correct Answer: B

• Question 120:

  A 24-year-old woman presents with hypertension and hypokalemic metabolic alkalosis. Although these symptoms are normally indicative of hyperaldosteronism, this patient's aldosterone levels are undetectable, and no other mineralocorticoid activity is found. A diagnosis of Liddle syndrome is made on the basis of the signs and symptoms and a family history. Liddle syndrome is caused by a genetic defect leading to excessive expression of the apical sodium channel in the principal cells of the cortical- collecting tubule and excess sodium transport in this part of the nephron. Which of the following agents is the best choice for treatment of the hypertension and hypokalemic metabolic alkalosis in this patient?

  A. amiloride

  B. fludrocortisones

  C. hydrochlorothiazide

  D. lisinopril

  E. spironolactone

  Correct Answer: A