Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 12e

Chapter 2: Pharmacodynamics

A 55-year-old man is seen in the clinic with hypertension of 150/95 mm Hg (millimeters of mercury). His personal medical history and physical examination are otherwise unremarkable but his family history is positive for early deaths due to cardiovascular disease. A decision is made to treat his hypertension, starting with a calcium channel blocker. Blocker A in a dose of 5 mg produces the same decrease in blood pressure as 500 mg of blocker B. Which of the following predictions is most accurate?

(A) Blocker A will be more efficacious than blocker B

(B) Blocker A will be about 100 times more potent than blocker B

(C) Toxicity of blocker A will be less than that of blocker B

(D) Blocker A will have a wider therapeutic window than blocker B

(E) Blocker A will have a longer half-life than blocker 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 blocker A indicates only 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 analgesic 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 in the population studied. 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

(C) Drug C is most potent

(D) Drug B is more potent than drug C and more effective than drug A

(E) Drug A is more potent than drug B and more effective than drug C

Drug A produces 50% of its maximal effect at a lower dose than either B or C and thus is the most potent; drug C is the least potent. However, drug A, a partial agonist, is less efficacious than drugs B and C. The answer is D.

A study was carried out in isolated intestinal smooth muscle preparations to determine the action of a new drug “novamine,” which in separate studies bound to the same receptors as acetylcholine, an agonist. In the absence of other drugs, acetylcholine caused contraction of the muscle. Novamine alone caused relaxation of the preparation. In the presence of a low concentration of novamine, the EC₅₀ of acetylcholine was unchanged, but the E_max was reduced. In the presence of a high concentration of novamine, extremely high concentrations of acetylcholine had no effect. Which of the following expressions best describes novamine?

(A) A chemical antagonist

(B) An irreversible antagonist

(C) A partial agonist

(D) A physiologic antagonist

(E) A spare receptor agonist

Choices involving chemical or physiologic antagonism are incorrect because novamine is said to act at the same receptors as acetylcholine. When given alone, the novamine effect is opposite to that of acetylcholine; so choice C is incorrect. “Spare receptor agonist” is a nonsense distracter. The answer is B.

Beta adrenoceptors in the heart regulate cardiac rate and contractile strength. Several studies have indicated that in humans and experimental animals, about 90% of β adrenoceptors in the heart are spare receptors. Which of the following statements about spare receptors is most correct?

(A) Spare receptors, in the absence of drug, are sequestered in the cytoplasm

(B) Spare receptors may be detected by finding that the drug-receptor interaction lasts longer than the intracellular effect

(C) Spare receptors influence the maximal efficacy of the drug-receptor system

(D) Spare receptors activate the effector machinery of the cell without the need for a drug

(E) Spare receptors may be detected by finding that the EC₅₀ is smaller than the K_d for the agonist

There is no difference in location between “spare” and other receptors. Spare receptors may be defined as those that are not needed for binding drug to achieve the maximal effect. Spare receptors influence the sensitivity of the system to an agonist because the statistical probability of a drug-receptor interaction increases with the total number of receptors. They do not alter the maximal efficacy. If they do not bind an agonist molecule, spare receptors do not activate an effector molecule. EC₅₀ less than K_d is an indication of the presence of spare receptors. The answer is E.

Two cholesterol-lowering drugs, X and Y, were studied in a large group of patients, and the percentages of the group showing a specific therapeutic effect (35% reduction in low-density lipoprotein [LDL] cholesterol) were determined. The results are shown in the following table.

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Drug Dose (mg)

Percent Responding to Drug X

Percent Responding to Drug Y

100

200

100

Which of the following statements about these results is correct?

(A) Drug X is safer than drug Y

(B) Drug Y is more effective than drug X

(C) The 2 drugs act on the same receptors

(D) Drug X is less potent than drug Y

(E) The therapeutic index of drug Y is 10

No information is presented regarding the safety of these drugs. Similarly, no information on efficacy (maximal effect) is presented; this requires graded dose-response curves. Although both drugs are said to be producing a therapeutic effect, no information on their receptor mechanisms is given. Since no data on toxicity are available, the therapeutic index cannot be determined. The answer is D because the ED₅₀ of drug Y (20 mg/d) is less than that of drug X (50 mg/d).

Sugammadex is a drug that reverses the action of rocuronium and certain other skeletal muscle-relaxing agents (nondepolarizing neuromuscular blocking agents). It appears to interact directly with the rocuronium molecule and not at all with the rocuronium receptor. Which of the following terms best describes sugammadex?

(A) Chemical antagonist

(B) Noncompetitive antagonist

(C) Partial agonist

(D) Pharmacologic antagonist

(E) Physiologic antagonist

Sugammadex interacts directly with rocuronium and not with the rocuronium receptor; therefore, it is a chemical antagonist. The answer is A.

Which of the curves in the graph describes the percentage of binding of a large dose of full agonist to its receptors as the concentration of a partial agonist is increased from low to very high levels?

(A) Curve 1

(B) Curve 2

(C) Curve 3

(D) Curve 4

(E) Curve 5

The binding of a full agonist decreases as the concentration of a partial agonist is increased to very high levels. As the partial agonist displaces more and more of the full agonist, the percentage of receptors that bind the full agonist drops to zero, that is, Curve 5. The answer is E.

Which of the curves in the graph describes the percentage effect observed when a large dose of full agonist is present throughout the experiment and the concentration of a partial agonist is increased from low to very high levels?

(A) Curve 1

(B) Curve 2

(C) Curve 3

(D) Curve 4

(E) Curve 5

Curve 1 describes the response of the system when a full agonist is displaced by increasing concentrations of partial agonist. This is because the increasing percentage of receptors binding the partial agonist finally produce the maximal effect typical of the partial agonist. The answer is A.

Which of the curves in the graph describes the percentage of binding of the partial agonist whose effect is shown by Curve 4 if the system has many spare receptors?

(A) Curve 1

(B) Curve 2

(C) Curve 3

(D) Curve 4

(E) Curve 5

Partial agonists, like full agonists, bind 100% of their receptors when present in a high enough concentration. Therefore, the binding curve (but not the effect curve) will go to 100%. If the effect curve is Curve 4 and many spare receptors are present, the binding curve must be displaced to the right of Curve 4 (K_d > EC₅₀). Therefore, Curve 3 fits the description better than Curve 2. The answer is C.

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Chapter 2: Pharmacodynamics

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Chapter 2: Pharmacodynamics

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