WBR0902

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::General Principles
Prompt	[[Prompt::A researcher is investigating the effects of two drugs, A and B, for blood pressure reduction in rats. The graph below is the dose-response curve of drug A when administered alone or when co-administered with drug B. Which of the following combinations has similar curve to that of A and B combined? ]]
Answer A	AnswerA::Naloxone and morphine
Answer A Explanation	AnswerAExp::Naloxone is a competitive antagonist of morphine. When a competitive antagonist is present, the potency of the agonist is altered and the curve of the effect of the agonist by increasing dose will be shifted towards the right.
Answer B	AnswerB::Atropine and acetylcholine
Answer B Explanation	AnswerBExp::Atropine is a competitive antagonist of acetylcholine. When a competitive antagonist is present, the potency of the agonist is altered and the curve of the effect of the agonist by increasing dose will be shifted towards the right.
Answer C	AnswerC::Haloperidol and dopamine
Answer C Explanation	AnswerCExp::haloperidol is a competitive antagonist of dopamine. When a competitive antagonist is present, the potency of the agonist is altered and the curve of the effect of the agonist by increasing dose will be shifted towards the right.
Answer D	AnswerD::Ondansetron and serotonin
Answer D Explanation	AnswerDExp::Serotonin is a competitive antagonist of ondansetron. When a competitive antagonist is present, the potency of the agonist is altered and the curve of the effect of the agonist by increasing dose will be shifted towards the right.
Answer E	AnswerE::Noreprinephrine and phenoxybenzamine
Answer E Explanation	AnswerEExp::Phenoxybenzamine is a noncompetitive inhibitor of norepinephrine. An increase in the concentration of norepinephrine is not able to overcome the effect of phenoxybenzamine.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Efficacy is defined as the maximal effect a drug can produce. While a full agonist produces a maximal effect, a partial agonist can only produce a fraction of that effect i.e. has a lower efficacy. The figure demonstrates that when A is administered alone, a maximal response is observed. However, when A and B are combined, the curve is shifted downwards signifying a decrease in efficacy. The dose response curve demonstrates that the response reaches a plateau and does not increase despite an increase in the dose of drug A. This is the classical effect of a non-competitive inhibitor causing an irreversible decrease in efficacy. Phenoxybenzamine is a non-competitive inhibitor of norepinephrine that fits the dose-response curve displayed. Had drug B been a competitive antagonist, the effect would have been observed as a decrease in potency not in efficacy. This signifies a relative decrease in efficacy at a certain dose that can be overcome by increasing the dose. the dose response curve would resemble the one shown below. Educational Objective: Phenoxybenzamine is a noncompetitive inhibitor of norepinephrine that causes a decrease in its efficacy. References: Lambert, DG. Drugs and receptors. Contin Educ Anaesth Crit Care Pain. 2004;4(6): 181-4]]
Approved	Approved::Yes
Keyword	WBRKeyword::Antagonist, WBRKeyword::Competitive antagonist, WBRKeyword::Non-competitive antagonist, WBRKeyword::Phenoxybenzamine, WBRKeyword::Norepinephrine
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