Potency—Drugs A and B are said to be more potent than drugs C and D because of the relative positions of their dose-response curves along the dose axis of Figure 2–15. Potency refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug’s maximal effect. Thus, the pharmacologic potency of drug A in Figure 2–15 is less than that of drug B, a partial agonist because the EC50 of A is greater than the EC50 of B. Potency of a drug depends in part on the affinity (Kd) of receptors for binding the drug and in part on the efficiency with which drug-receptor interaction is coupled to response. Note that some doses of drug A can produce larger effects than any dose of drug B, despite the fact that we describe drug B as pharmacologically more potent. The reason for this is that drug A has a larger maximal efficacy (as described below).
For therapeutic purposes, the potency of a drug should be stated in dosage units, usually in terms of a particular therapeutic end point (eg, 50 mg for mild sedation, 1 mcg/kg/min for an increase in heart rate of 25 bpm). Relative potency, the ratio of equi-effective doses (0.2, 10, etc), may be used in comparing one drug with another.
2.
Maximal efficacy—This parameter reflects the limit of the dose-response relation on the response axis. Drugs A, C, and D in Figure 2–15 have equal maximal efficacy, and all have greater maximal efficacy than drug B. The maximal efficacy (sometimes
FIGURE 2–15 Graded dose-response curves for four drugs, illustrating different pharmacologic potencies and different maximal efficacies. (See text.) referred to simply as efficacy) of a drug is obviously crucial for making clinical decisions when a large response is needed. It may be determined by the drug’s mode of interactions with receptors (as with partial agonists) * or by characteristics of the receptor-effector system involved.
Thus, diuretics that act on one portion of the nephron may produce much greater excretion of fluid and electrolytes than diuretics that act elsewhere. In addition, the practical efficacy of a drug for achieving a therapeutic end point (eg, increased cardiac contractility) may be limited by the drug’s propensity to cause a toxic effect (eg, fatal cardiac arrhythmia) even if the drug could otherwise produce a greater therapeutic effect.
B. Shape of Dose-Response Curves
Although the responses depicted in curves A, B, and C of Figure 2–15 approximate the shape of a simple Michaelis-Menten relation (transformed to a logarithmic plot), some clinical responses do not. Extremely steep dose-response curves (eg, curve D) may have important clinical consequences if the upper portion of the curve represents an undesirable extent of response (eg, coma caused by a sedative-hypnotic). Steep dose-response curves in patients can result from cooperative interactions of several different actions of a drug (eg, effects on brain, heart, and peripheral vessels, all contributing to lowering of blood pressure).
* Note that “maximal efficacy,” used in a therapeutic context, does nothave exactly the same meaning that the term denotes in the more specialized context of drug-receptor interactions described earlier in this chapter.In an idealized in vitro system, efficacy denotes the relative maximalefficacy of agonists and partial agonists that act via the same receptor. Intherapeutics, efficacy denotes the extent or degree of an effect that can beachieved in the intact patient. Thus, therapeutic efficacy may be affectedby the characteristics of a particular drug-receptor interaction, but it alsodepends on a host of other factors as noted in the text.
C. Quantal Dose-Effect Curves