WBR0902
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| Author | [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Serge Korjian)]] |
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| Exam Type | USMLE Step 1 |
| Main Category | Pharmacology |
| Sub Category | 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?
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| Answer A | Naloxone and morphine |
| Answer A Explanation | 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 | Atropine and acetylcholine |
| Answer B Explanation | 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 | Haloperidol and dopamine |
| Answer C Explanation | 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 | Ondansetron and serotonin |
| Answer D Explanation | 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 | Noreprinephrine and phenoxybenzamine |
| Answer E Explanation | 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 | 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.
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| Approved | Yes |
| Keyword | Antagonist, Competitive antagonist, Non-competitive antagonist, Phenoxybenzamine, Norepinephrine |
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