Three alpha-agonist drugs are tested as potential vasoconstrictors. The degree of vasoconstriction is determined by measuring the cross-sectional area of an isolated vessel after application of the drug. The following curves are obtained: Which of the following is the best statement concerning the effects of these drugs?

Question

Three alpha-agonist drugs are tested as potential vasoconstrictors.  The degree of vasoconstriction is determined by measuring the cross-sectional area of an isolated vessel after application of the drug.  The following curves are obtained:  Which of the following is the best statement concerning the effects of these drugs?

Quizplus · Accepted Answer

Efficacy and potency are terms that are commonly used and often confused. In pharmacology, efficacy refers to the intrinsic ability of a drug to elicit an effect, such as receptor activation or dilation of a vessel as described in the question stem. It is a measure of the maximum ceiling of activity [E_max] of a drug with respect to a particular pharmacodynamic end point. For example, loop diuretics such as furosemide or bumetanide will cause greater diuresis or natriuresis than any thiazide diuretic, irrespective of dose. Potency, on the other hand, refers to the dose of drug that is required to produce a given effect. The potency of a drug is primarily affected by the affinity of the drug for its receptor and the amount of drug that is able to reach the target tissues Therefore, drugs that bind their receptors with a higher affinity or are better able to gain access to their target tissues will have greater potency. The potency of different agents can be compared by determining the dose of drug that is required to produce one-half (50%) of the maximum biological response. This dose is known as the ED₅₀. The lower the ED₅₀ of a drug, the more potent it is. For example, among the thiazide diuretics, 25mg of hydrochlorothiazide and 5mg chlorthalidone produce similar drops in blood pressure (similar efficacy), but chlorthalidone requires a lower dose, or lower ED₅₀, than HCTZ to cause a similar effect (higher potency). With respect to the question, drug 2 and drug 3 have similar maximum effects (efficacy). A much lower dose of drug 2 is required to produce the same effect as that seen with drug 3; therefore, drug 2 is more potent than drug 3 and has a lower ED₅₀. To achieve this higher potency, the binding of drug 2 to its receptors (affinity) must be higher than that of drug 3 (Choice B), or drug 2 must be better able to reach its target (penetration) than drug 3. (Choice A) Drug 1 has higher potency than Drug 2 because at low biological activity, it can cause the same effect with much lower concentrations of drug. However, it does not reach the same maximum effect as Drug 2. (Choice C) Drug 1 demonstrates the lowest efficacy (ceiling of biological effect) of the three drugs graphed. Lower efficacy may be a result of partial agonism and other factors. (Choice D) Drugs 2 and 3 exhibit a parallel shift in their relative biological effects exhibiting similar efficacy but different potency (The shapes of their graphs are identical, but at different dose ranges). Drug 3 may contain the same basic pharmocologic agent as Drug 2 but with a competitive antagonist mixed in; thus, the E_max is the same but the ED₅₀ is higher. A competitive antagonist would bind to the same location as the original substance. (Choice E) Drug 2 has a lower ED₅₀ (greater potency) than drug 3. Both have equal efficacy. Educational Objective: Efficacy is a measure of the maximum pharmacodynamic effect achievable with a drug. Potency refers to the dose of drug that is required to produce a given effect. Drugs that bind their receptors with a higher affinity or are better able to gain access to their target tissues will have greater potency (lower ED₅₀).

Three Alpha-Agonist Drugs Are Tested as Potential Vasoconstrictors