Chapter 2: Pharmacodynamics
A 55-year-old woman with hypertension is to be treated with a thiazide diuretic. Thiazide A in a dose of 5 mg produces the same decrease in blood pressure as 500 mg of thiazide B. Which of the following statements best describes these results?
(A) Thiazide A is more efficacious than thiazide B
(B) Thiazide A is about 100 times more potent than thiazide B
(C) Toxicity of thiazide A is less than that of thiazide B
(D) Thiazide A has a wider therapeutic window than thiazide B
(E) Thiazide A has a longer half-life than thiazide B
No information is given regarding the maximal antihypertensive response to either drug. Similarly, no information about half-life or toxicity is provided. The fact that a given response is achieved with a smaller dose of thiazide A indicates that A is more potent than B in the ratio of 500:5. The answer is B.
Graded and quantal dose-response curves are being used for evaluation of a new antiasthmatic drug in the animal laboratory and in clinical trials. Which of the following statements best describes graded dose-response curves?
(A) More precisely quantitated than quantal dose-response curves
(B) Obtainable from isolated tissue preparations but not from the study of intact subjects
(C) Used to determine the maximal efficacy of the drug
(D) Used to determine the therapeutic index of the drug
(E) Used to determine the variation in sensitivity of subjects to the drug
Precise quantitation is possible with both types of dose-response curves. Quantal dose-response curves show the frequency of occurrence of a specified response, which may be therapeutically effective (ED) or toxic (TD). Thus, quantal studies are used to determine the therapeutic index and the variation in sensitivity to the drug. Graded (not quantal) dose-response curves are used to determine maximal efficacy (maximal response). The answer is C.
Prior to clinical trials in patients with heart failure, an animal study was carried out to compare two new positive inotropic drugs (A and B) to a current standard agent (C). The results of cardiac output measurements are shown in the graph below.
Which of the following statements is correct?
(A) Drug A is most effective
(B) Drug B is least potent