USMLE USMLE Certifications USMLE-STEP-1 Questions & Answers

• Question 131:

  Which of the following drugs can be used in rheumatoid arthritis with the lowest probable incidence of GI complications?

  A. aspirin

  B. celecoxib

  C. ibuprofen

  D. misoprostol

  E. naproxen

  Correct Answer: B

  Section: Pharmacology A through C and E are NSAIDs. NSAIDs have long been drugs of first choice in arthritis treatment. Their primary mechanism of action in arthritis appears to be inhibition of COX, an enzyme required for the synthesis of inflammatory and other prostaglandins. Two forms of COX are present in the body: COX-1, which is required for synthesis of several useful prostaglandins (e.g., PGE1, a cytoprotective agent in the stomach), and COX-2, the isoform responsible for synthesis of prostacyclin as well as most of the damaging prostaglandins. Celecoxib is more selective for COX-2 and thus has a lower incidence of adverse GI effects. The older NSAIDs (choices A, C, and E) inhibit both COX-1 and COX-2 with less selectivity and thus reduce protective prostaglandins, resulting in a high incidence of GI disorders, especially peptic ulceration. Misoprostol (choice D) is a PGE1 analog that is used with NSAIDs to reduce peptic ulceration; unfortunately it causes a high incidence of diarrhea.

• Question 132:

  Which of the following drugs is useful in treatment of gout with recurrent renal urate stones because it decreases the excretion of uric acid?

  A. allopurinol

  B. aspirin

  C. colchicines

  D. indomethacin

  E. sulfinpyrazone

  Correct Answer: A

  Section: Pharmacology Allopurinol and its metabolite alloxanthine inhibit xanthine oxidase, thus preventing conversion of xanthine and hypoxanthine to uric acid. Although xanthine and hypoxanthine then accumulate, these compounds are more soluble than uric acid and less likely to deposit in joints or precipitate in the urine. Most doses of aspirin (choice B) increase retention of uric acid, especially low doses. Colchicine (choice C) is an inhibitor of microtubule function that brings relief in an acute gout attack by inhibiting the motility of granulocytes and preventing the formation of mediators of inflammation by leukocytes. Because of its toxicity at higher doses, it is now used chiefly at low doses to prevent acute attacks. Indomethacin (choice D) is an NSAID that inhibits COX and reduces formation of prostaglandins and eicosanoids involved in gouty arthritis. It has no effect on the formation of uric acid and very little on its excretion. Sulfinpyrazone (choice E) and probenecid are uricosuric agents--they increase the excretion of uric acid by the kidney. Renal uric acid excretion is determined by the balance between the amount filtered plus that actively secreted and the amount undergoing passive and active reabsorption. At very low doses, these agents inhibit active secretion and thus promote retention of uric acid. At higher (clinical) doses, both active secretion and active reabsorption are inhibited, with the result that excretion is enhanced.

• Question 133:

  Which of the following is the drug of choice to reverse bronchoconstriction in an acute asthma attack?

  A. albuterol

  B. aminophylline

  C. cromolyn

  D. ipratropium

  E. salmeterol

  Correct Answer: A

  Section: Pharmacology Inhaled albuterol (or other beta-2-selective receptor agonists including bitolterol, metaproterenol, pirbuterol, and terbutaline) are the usual agents of choice for treating bronchoconstriction in an acute asthma attack. These beta-2-selective agonists produce bronchial relaxation by stimulating cyclic AMP (cAMP) formation in bronchiolar smooth muscle and cause less tachycardia than nonselective beta agonists. Unfortunately, they do cause some tachycardia and skeletal muscle tremor. Aminophylline (choice B) and other methylxanthines are rarely used to terminate acute episodes of asthma because they must be administered parenterally for rapid onset of effect. Cromolyn sodium (choice C) must be used prophylactically to prevent acute episodes and probably acts by stabilizing mast cells. It is not a smooth muscle relaxing agent and is not effective in reversing bronchospasm. Inhaled ipratropium (choice D) has less general efficacy in acute attacks than beta agonists. Salmeterol (choice E) is an effective beta-2selective agonist but has a slow onset and long duration of action. Therefore, it is used for prophylaxis, not treatment of acute attacks.

• Question 134:

  Which of the following is used in treating major depression and has the greatest sedative effect?

  A. bupropion

  B. desipramine

  C. fluoxetine

  D. mirtazapine

  E. venlafaxine

  Correct Answer: D

  Section: Pharmacology

  All of the agents listed are useful antidepressants but only mirtazapine has significant sedative effects.

• Question 135:

  Which of the following psychotropic drugs must be monitored for hematotoxic effects?

  A. buspirone

  B. clozapine

  C. haloperidol

  D. lithium carbonate

  E. mirtazapine

  Correct Answer: B

  Section: Pharmacology Clozapine causes agranulocytosis in a small but consistent fraction of patients; monitoring is mandatory. Buspirone (choice A) is an antianxiety agent with minimal sedative action. Haloperidol (choice C) is an older, highly potent antipsychotic drug used in schizophrenia. Lithium carbonate (choice D) is an important antimanic drug. It apparently acts by interfering with inositol phosphate cycling and second messenger synthesis in neurons. Mirtazapine (choice E) is a third-generation antidepressant related to antihistaminics and has significant sedative action.

• Question 136:

  Which of the following describes a possible adverse effect of long-term chronic treatment of schizophrenia with a phenothiazine such as fluphenazine?

  A. diarrhea, nausea, and vomiting

  B. reduced secretion of prolactin

  C. tardive dyskinesia

  D. Tourette syndrome

  E. weight loss

  Correct Answer: C

• Question 137:

  A 13-year-old boy with severe asthma has been treated for 6 months with good control of nocturnal wheezing. His parents now complain that he seems to be very fat around the face and shoulders, bruises easily, and has discolored streaks on his abdomen. Laboratory tests reveal moderate hyperglycemia. He has probably been receiving which of the following drugs?

  A. ipratropium

  B. prednisone

  C. salmeterol

  D. terbutaline

  E. theophylline

  Correct Answer: B

  Section: Pharmacology This patient's presentation is typical of glucocorticosteroid toxicity (iatrogenic Cushing syndrome). Prednisone is an effective corticosteroid frequently used by mouth to control severe asthma that is not responsive to inhaled corticosteroids. High doses of prednisone, given chronically, very predictably cause signs and symptoms of hypercorticism. Ipratropium (choice A) is an antimuscarinic agent used in asthma by inhalation. Salmeterol (choice C) is a long-acting beta-2-selective agonist used by inhalation. Terbutaline (choice D) is a shortacting beta-2-selective agonist, also used by inhalation. Theophylline (choice E) is an oral drug that causes CNS stimulation (including convulsions in toxic overdosage), but not hypercorticism.

• Question 138:

  Which of the following chemotherapeutic agents' mechanisms of action involves inhibition of topoisomerase II and results in DNA strand breakage?

  A. dacarbazine

  B. etoposide

  C. lomustine

  D. prednisone

  E. vincristine

  Correct Answer: B

  Section: Pharmacology Etoposide is a semisynthetic derivative of podophyllotoxin, a constituent of the mandrake plant. Etoposide is an inhibitor of topoisomerase II, an enzyme that relaxes supercoiled DNA by breaking one strand and passing the second strand through the break before closing the break. Etoposide inhibits the closure step and results in an accumulation of DNA strand breaks, leading to cell death. Etoposide is used to treat testicular tumors and small cell carcinoma of the lung in combination with cisplatin. Leukopenia is the dose- limiting toxicity seen with this drug. Dacarbazine (choice A) is a synthetic prodrug activated in the liver to a metabolite that alkylates DNA leading to cytotoxicity. The drug is useful against melanoma and Hodgkin lymphoma. Lomustine (CCNU, choice C) is a lipid-soluble nitrosourea agent that acts as an alkylating agent. The nitrosoureas are unusual in having relatively good access to the CNS and are therefore useful in treating brain tumors. Prednisone (choice D) is a potent, orally active corticosteroid with good lymphotoxic potency. Its mechanism is not fully understood but may involve activation of apoptotic pathways in lymphocytes. Vincristine (choice E) is a natural product isolated from the vinca plant. It is classified as a spindle poison and inhibits mitosis by inhibiting microtubule assembly. This drug is particularly useful in treating acute leukemias in children and Hodgkin lymphoma.

• Question 139:

  Which of the following chemotherapeutic agents' mechanisms of action involve inhibition of thymidylate synthase and incorporation into RNA?

  A. anastrozole

  B. cytarabine

  C. doxorubicin

  D. 5-fluorouracil

  E. imatinib

  Correct Answer: D

  Section: Pharmacology The pyrimidine analog 5-fluorouracil (5-FU) is metabolized by ribosylation and phosphorylation to the nucleotide level (F-UMP). F-UMP is further metabolized to F-dUMP, an inhibitor of thymidylate synthase. Cells then become starved for TTP and incorporate FdUTP and dUTP in its place in DNA. 5- FU also becomes incorporated in RNA, leading to inhibition of RNAprocessing. Anastrozole (choice A) is a nonsteroidal inhibitor of aromatase, an enzyme required for synthesis of estrogens. This drug is useful against advanced estrogen or progesterone receptor-positive breast cancer. Cytarabine (cytosine arabinoside, ara-C, choice B), is an S-phase-specific antimetabolite that is metabolized to the triphosphate form, which blocks DNA synthesis. It is used exclusively in acute myelogenous leukemia. Doxorubicin (choice C) is an anthracycline antibiotic that intercalates into DNA causing strand breakage and blockage of both DNA and RNA synthesis. This agent is widely used in combination regimens for breast, endometrial, ovarian, testicular, and thyroid carcinomas, and several sarcomas and lymphomas. Imatinib (choice E) is an inhibitor of the tyrosine kinase activity of the Bcr-Abl oncogene product. It is a drug of choice in chronic myelogenous leukemia with the Philadelphia chromosome translocation.

• Question 140:

  Which of the following agents used in treating testicular cancer, requires hydration and dieresis to prevent renal toxicity?

  A. bleomycin

  B. cisplatin

  C. cyclophosphamide

  D. 5-fluorouracil

  E. paclitaxel

  Correct Answer: B

  Section: Pharmacology Cisplatin binds to DNA where it forms intra- and interstrand crosslinks. Cisplatin is particularly effective in testicular and ovarian cancers in combination with other antitumor agents. Cisplatin exerts a renal toxicity that may be prevented by the infusion of saline to maintain a high urine flow. Ototoxicity involving high-frequency hearing loss is an effect that is not prevented by hydration. The natural product bleomycin (choice A) binds to DNA and causes single- and double-strand breaks, leading to cytotoxicity. The drug is particularly useful against Hodgkin lymphoma and testicular tumors. Bleomycin has the serious toxicity of pulmonary fibrosis. Cyclophosphamide (choice C) is widely used in combination regimens. Nausea and vomiting are the most common toxicities. Hemorrhagic cystitis may be minimized by hydration and use of the drug mesna. Note that this toxicity is not at the level of the kidney. The pyrimidine analog 5-fluorouracil (5-FU) (choice D) is used to treat a wide variety of carcinomas. Toxicity from 5-FU is expressed as GI disturbances (anorexia, nausea, stomatitis, and diarrhea) and myelosuppression. Paclitaxel (choice E) is particularly useful in treating metastatic breast and ovarian cancer. The primary toxicity of paclitaxel is bone marrow suppression.