The Metabolic Induction Of Losartan By Rofecoxib Cause

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1. A man aged 74 has moderate hypertension controlled with hydrochlorothiazide 12.5 mg once daily and losartan 50 mg once daily. He is prescribed ro-fecoxib 50 mg once daily to control osteoarthritis pain. After 3 months of this therapy, his blood pressure begins to rise. This increase in blood pressure is most likely due to

(A) Inhibition of COX-2 by rofecoxib, which leads to decreased renal blood flow

(B) Increased metabolism of losartan due to induction of CYP2C9 by rofecoxib

(C) Increased excretion of hydrochlorothiazide due to increased renal blood flow caused by rofe-coxib

(D) Arteriolar contraction in the peripheral circulation caused by inhibition of COX-1 by rofecoxib

(E) Weight gain caused by rofecoxib's ability to decrease basal metabolic rate.

2. The use of low-dose methotrexate in the treatment of rheumatoid arthritis is most frequently

(A) Reserved for cases in which NSAIDs no longer adequately control pain and stiffness

(B) Initiated only after significant joint destruction

(C) Contraindicated in individuals being treated with NSAIDs

(D) Used for pregnant women, since it is the DMARD with the least fetal toxicity

(E) Initiated early in the course of moderate to severe forms of the disease

3. A 52-year-old woman with a history of eczema and heavy alcohol use begins taking ibuprofen to control hip and knee pain due to osteoarthritis. Over the course of 6 months, as the pain worsens, she increases her dosage to a high level (600 mg four times daily). What toxicity is most likely to occur, and why?

(A) Abnormal heart rhythms; alcohol induces cy-tochrome P450 isozymes that convert ibuprofen to a cardiotoxic free radical metabolite

(B) Necrotizing fasciitis; eczema predisposes an individual to this toxicity of ibuprofen

(C) Gastric ulceration; heavy alcohol use increases the susceptibility of an individual to ibuprofen-induced GI toxicity

(D) Confusion and ataxia; these CNS toxicities of ibuprofen are additive with those of ethanol

(E) Eosinophilia; this rare complication of ibupro-fen therapy is exacerbated by the immunosuppres-sion frequently seen in alcoholics

4. Etanercept produces its antirheumatic effects by direct

(A) Inhibition of cAMP phosphodiesterase in monocytic lineage leukocytes

(B) Selective inhibition of COX-2

(C) Enhancement of leukotriene synthesis at the expense of prostaglandin synthesis

(D) Reduction of circulating active TNF-a levels

(E) Inhibition of the production of autoantibodies

5. An advantage of celecoxib over most other NSAIDs is

(A) Less inhibition of PGE2 effects on the gastric mucosal

(B) Less risk of bronchospasm and hypersensitivity reactions

(C) Once-daily dosing allows the patient convenience

(D) Less risk of harm to the developing fetus in the third trimester

(E) Greater degree of efficacy in the treatment of rheumatoid arthritis

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