USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 171:

  Which of the following adverse effects of chronic high-dose prednisone administration represents a mineralocorticoid effect?

  A. buffalo hump

  B. easy bruising

  C. edema

  D. moon facies

  E. psychosis

  Correct Answer: C

  Section: Pharmacology Edema and hypertension will occur with any corticosteroid that has mineralocoid properties if given in high dosage over a long period. Prednisone, though much less potent than cortisol as a mineralocorticoid, retains some salt-retaining potency. Newer glucocorticoids, such as dexamethasone and triamcinolone, are much less likely to retain salt and water. Buffalo hump (choice A) and moon facies (choice D) reflect the fat metabolism effects of glucocorticoid activity. Easy bruising (choice B) and striae reflect the catabolic action of glucocorticoids on proteins. The mechanism of central nervous system dysfunction (choice E) is not understood, but it is associated with glucocorticoid, not mineralocorticoid, activity.

• Question 172:

  Which of the following antidiabetic agents acts on the peroxisome proliferator-activated receptor- gamma (PPAR-gamma) nuclear receptor?

  A. acarbose

  B. glyburide

  C. insulin lispro

  D. metformin

  E. pioglitazone

  Correct Answer: E

  Section: Pharmacology The glitazone drugs (pioglitazone, rosiglitazone) reduce insulin resistance in peripheral tissues by activating the PPAR-gamma receptor, which promotes glucose uptake and utilization. Acarbose (choice A) interferes with the action of intestinal alpha-glucosidases and reduces absorption of glucose. Glyburide (choice B) and other sulfonylurea hypoglycemic drugs block the ATP-activated potassium channel in pancreatic cells and cause increased insulin release. Insulin lispro (choice C) is a modified insulin with rapid onset and offset of action. All insulins act by causing insertion of glucose transporters into cell membranes and several other mechanisms. The mechanism of action of metformin (choice D) and similar biguanide antidiabetic drugs is still unclear but may involve reduction of glucagon release, stimulation of glycolysis in peripheral tissues, or decreased hepatic and renal gluconeogenesis.

• Question 173:

  Which of the following agents used to prevent organ transplant rejection is most likely to cause significant decrease in creatinine clearance?

  A. antilymphocyte globulin

  B. cyclosporine

  C. mycophenolate mofetil

  D. prednisone

  E. sirolimus

  Correct Answer: B

  Section: Pharmacology

  Cyclosporine and tacrolimus (not listed) are associated with nephrotoxicity as a major adverse effect.

  Antilymphocyte globulin (choice A) is associated with foreign protein reactions, including anaphylaxis.

  Mycophenolate mofetil (choice C) causes GI disturbances and myelosuppression. Prednisone (choice D)

  causes a variety of chronic toxicities conveniently summarized as "Cushingoid effects" but has little acute

  toxicity. Sirolimus (choice E) is associated with bone marrow suppression.

• Question 174:

  Which of the following is useful in rheumatoid arthritis because it binds tumor necrosis factoralpha (TNFalpha)?

  A. leflunomide

  B. infliximab

  C. methotrexate

  D. paclitaxel

  E. trastuzumab

  Correct Answer: B

  Section: Pharmacology Infliximab is a chimeric monoclonal antibody that binds TNF-alpha and is useful in rheumatoid arthritis, ulcerative colitis, and several other immune diseases. Leflunomide (choice A) inhibits ribonucleotide synthesis and thereby reduces T-cell proliferation. Methotrexate (choice C) is an antimetabolite that inhibits cell proliferation. It is useful in rheumatoid arthritis. Paclitaxel (choice D) is a microtubule-binding agent that is cytotoxic in certain neoplasms and slows restenosis in coronary stents. It is not used in autoimmune diseases. Trastuzumab (choice E) is an antibody to the human epidermal growth factor receptor and is useful in metastatic breast cancer.

• Question 175:

  Which of the following antifungal drugs is strongly associated with drug interactions resulting from inhibition of CYP 3A4?

  A. amphotericin B

  B. caspofungin

  C. fluconazole

  D. ketoconazole

  E. flucytosine

  Correct Answer: D

  Section: Pharmacology Ketoconazole is a potent inhibitor of the cytochrome P450 enzyme, CYP 3A4. Because CYP 3A4 is involved in the metabolism of almost 50% of the drugs in use, ketoconazole is implicated in many pharmacokinetic drug interactions. Amphotericin B (choice A) causes nephrotoxicity and may therefore interfere with the excretion of other drugs. Caspofungin (choice B) appears to be free of most drug interactions. Fluconazole (choice C), although a member of the same (azole) group as ketoconazole, is much less potent as a CYP 3A4 inhibitor and is associated with far fewer drug interactions. Flucytosine (choice E) is associated with few pharmacokinetic drug interactions, but by metabolism to fluorouracil it is toxic to the bone marrow and other rapidly dividing cells.

• Question 176:

  Which of the following drugs is selectively antifungal because of the difference between cholesterol (in mammalian cell membranes) and ergosterol (in fungal membranes)?

  A. amphotericin B

  B. caspofungin

  C. fluconazole

  D. griseofulvin

  E. terbinafine

  Correct Answer: A

  Section: Pharmacology Amphotericin B binds selectively to ergosterol and forms artificial pores in fungal membranes. These pores result in loss of homeostasis and death of the fungal cell. Caspofungin (choice B) is a member of the echinocandins, the newest antifungal antibiotics. These agents disrupt the fungal cell wall by inhibiting the synthesis of beta(1-3) glucan. Fluconazole (choice C) and other azoles (ketoconazole, itraconazole, voriconazole, posaconazole) inhibit ergosterol synthesis. Griseofulvin (choice D) interferes with microtubule function and cell division in fungi. Terbinafine (choice E) inhibits squalene epoxidase in fungi and reduces ergosterol synthesis.

• Question 177:

  Which of the following enzymes is inhibited by drugs of the class to which amoxicillin belongs?

  A. alanine racemase

  B. beta lactamase

  C. enolpyruvate transferase

  D. transglycosylase

  E. transpeptidase

  Correct Answer: E

  Section: Pharmacology All of the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams) inhibit one of the final steps in the synthesis of the bacterial cell wall, cross-linking of peptidoglycan chains by transpeptidase. Alanine racemase (choice A) is inhibited by cycloserine, which is used in the treatment of

  M. tuberculosis. Beta lactamase (choice B) is inhibited by drugs (e.g., clavulanic acid, sulbactam, tazobactam) used to prevent resistance by bacteria that possess it. Enolpyruvate transferase (choice C) is inhibited by fosfomycin, which is used for urinary tract infections. Transglycosylase (choice D), another enzyme important in cell wall cross linking, is inhibited by vancomycin.

• Question 178:

  A known drug abuser is brought to the emergency room by the police. He is in restraints, combative, and hallucinating. His blood pressure, heart rate, and body temperature are elevated. Pupils are dilated and demonstrate both horizontal and vertical nystagmus. Which of the following drugs would cause this presentation?

  A. amphetamine

  B. heroin

  C. LSD

  D. phencyclidine

  E. scopolamine

  Correct Answer: D

  Section: Pharmacology Phencyclidine, an NMDA receptor antagonist, is a more violent hallucinogen than most other drugs in this class (LSD, mescaline, scopolamine). It causes sympathetic discharge and muscle twitching; nystagmus is very common. Amphetamine (choice A) is a sympathomimetic stimulant that can produce hallucinations or toxic psychosis in overdose, but is not usually associated with nystagmus. Heroin (choice B) is a depressant drug and does not present with combative stimulation. Pupils are constricted by opioids. LSD (choice C) is a classical hallucinogen, but does not commonly cause combativeness or nystagmus. Scopolamine (choice E) similarly does not usually cause combativeness or nystagmus. Both LSD and scopolamine cause mydriasis.

• Question 179:

  Which of the following drugs has opioid antagonist actions and also reduces nicotine and alcohol craving in persons dependent on those drugs?

  A. bupropion

  B. flumazenil

  C. nalbuphine

  D. naloxone

  E. naltrexone

  Correct Answer: E

  Section: Pharmacology Naltrexone is a very long-acting opioid antagonist that has also been shown to reduce craving and dependence in smokers and alcoholics. The mechanisms for the latter effects are not fully understood. Bupropion (choice A) is an antidepressant that has some efficacy in tobacco dependence. It is not an opioid antagonist. Flumazenil (choice B) is a benzodiazepine antagonist that is useful in BDZ overdose. It has no opioid antagonist effect. Nalbuphine (choice C) is an opioid partial agonist that has analgesic effects but can also antagonize the actions of strong agonists like morphine. Naloxone (choice D) is a shortacting opioid antagonist but has not been shown to have efficacy in tobacco or alcohol dependence.

• Question 180:

  Methadone has been used in opioid addiction maintenance clinics with partial success. Its ability to reduce the use of heroin and morphine by recovering addicts can be ascribed to which of the following mechanisms?

  A. agonist effects at central dopamine receptors

  B. antidepressant effects at serotonin (5-HT) receptors

  C. antagonist actions at the mu opioid receptor

  D. blockade of the metabolic activation of heroin and morphine to their active forms

  E. long-lasting saturation of the mu opioid receptor and development of tolerance

  Correct Answer: E

  Section: Pharmacology Methadone is a typical strong agonist at opioid mu receptors and differs from morphine chiefly in its long duration of binding to the receptor and long elimination half-life. It therefore produces a prolonged opioid effect that causes tolerance to the euphoric action of short-acting heroin and morphine. Methadone has no opioid antagonist action (choice C), nor does it act on metabolic pathways (choice D), serotonin receptors (choice B), or dopamine receptors (choice E).