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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor= {{Rim}} (Reviewed by Serge Korjian)
|Prompt=A researcher is investigating the effects of two drugs A and B on blood pressure in rats.  The graph below shows the maximal effect of A in decreasing blood pressure when administered alone or when administered in combination with B. Which of the following combinations has an interaction similar to that of A and B?
|ExamType=USMLE Step 1
|Explanation=Efficacy is defined as the maximal effect a drug can produce. While a full agonist produces maximal effect, a partial agonist only leads to less effect when compared to a full agonist.
|MainCategory=Pharmacology
Potency is defined effect is produced for a given concentration of a drug. The lower the concentration of a substance to produce an effect, the higher the affinity of the substance to the receptor and hence the higher the potency.
|SubCategory=General Principles
According to the figure, when A is alone, a maximal effect is produced. However, when A and B are combined the curve is shifted downwards depicting decreased efficacy.  An increase in the concentration of A was not able to overcome the effect of B on the efficacy. Hence B is a non-competitive inhibitor.  Phenoxybenzamine is a noncompetitive inhibitor of norepinephrine.
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|SubCategory=General Principles
|MainCategory=Pharmacology
|MainCategory=Pharmacology
|SubCategory=General Principles
|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?


Educational objective:  
[[File:WBR0902.png|450px]]
|AnswerA=[[Naloxone]] and [[morphine]]
|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.
 
[[Image:Dose-responseNCA.png|450px]]
|AnswerA=Naloxone and morphine
|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.
|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.
|AnswerB=[[Atropine]] and [[acetylcholine]]
|AnswerB=Atropine and acetylcholine
|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.
|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.
|AnswerC=[[Haloperidol]] and [[dopamine]]
|AnswerC=Haloperidol and dopamine
|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.
|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.
|AnswerD=[[Ondansetron]] and [[serotonin]]
|AnswerD=Ondansetron and serotonin
|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.
|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.
|AnswerE=[[Noreprinephrine]] and [[phenoxybenzamine]]
|AnswerE=Noreprinephrine and phenoxybenzamine
|AnswerEExp=Phenoxybenzamine is a noncompetitive inhibitor of norepinephrine.  An increase in the concentration of norepinephrine is not able to overcome the effect of phenoxybenzamine .
|AnswerEExp=Phenoxybenzamine is a noncompetitive inhibitor of norepinephrine.  An increase in the concentration of norepinephrine is not able to overcome the effect of phenoxybenzamine.
|EducationalObjectives=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
|RightAnswer=E
|RightAnswer=E
|Approved=No
|WBRKeyword=Antagonist, Competitive antagonist, Non-competitive antagonist, Phenoxybenzamine, Norepinephrine,
|Approved=Yes
}}
}}

Latest revision as of 02:02, 28 October 2020

 
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
Linked Question Linked::
Order in Linked Questions LinkedOrder::