Page 181 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 10 Adrenoceptor Antagonist Drugs 167

These effects may contribute to the clinical benefits of the drug in with either a diuretic or a vasodilator. Despite the short half-life
chronic heart failure (see Chapter 13). of many β antagonists, these drugs may be administered once or
Esmolol is an ultra-short–acting β -selective adrenoceptor twice daily and still have an adequate therapeutic effect. Labetalol,
1
antagonist. The structure of esmolol contains an ester link- a competitive α and β antagonist, is effective in hypertension,
age; esterases in red blood cells rapidly metabolize esmolol to a although its ultimate role is yet to be determined. Use of these
metabolite that has a low affinity for β receptors. Consequently, agents is discussed in greater detail in Chapter 11. There is some
esmolol has a short half-life (about 10 minutes). Therefore, dur- evidence that drugs in this class may be less effective in the elderly
ing continuous infusions of esmolol, steady-state concentrations and in individuals of African ancestry. However, these differences
are achieved quickly, and the therapeutic actions of the drug are are relatively small and may not apply to an individual patient.
terminated rapidly when its infusion is discontinued. Esmolol Indeed, since effects on blood pressure are easily measured, the
may be safer to use than longer-acting antagonists in critically therapeutic outcome for this indication can be readily detected
ill patients who require a β-adrenoceptor antagonist. Esmolol is in any patient.
useful in controlling supraventricular arrhythmias, arrhythmias
associated with thyrotoxicosis, perioperative hypertension, and Ischemic Heart Disease
myocardial ischemia in acutely ill patients. Beta-adrenoceptor blockers reduce the frequency of anginal epi-
Butoxamine is a research drug selective for β receptors. Selec- sodes and improve exercise tolerance in many patients with angina
2
tive β -blocking drugs have not been actively sought because there (see Chapter 12). These actions are due to blockade of cardiac
2
is no obvious clinical application for them; none is available for β receptors, resulting in decreased cardiac work and reduction in
clinical use.
oxygen demand. Slowing and regularization of the heart rate may
contribute to clinical benefits (Figure 10–7). Multiple large-scale
■ CLINICAL PHARMACOLOGY OF prospective studies indicate that the long-term use of timolol,
propranolol, or metoprolol in patients who have had a myocar-
THE BETA-RECEPTOR–BLOCKING dial infarction prolongs survival (Figure 10–8). At present, data
DRUGS are less compelling for the use of other than the three mentioned
β-adrenoceptor antagonists for this indication. It is significant
Hypertension that surveys in many populations have indicated that β-receptor
antagonists are underused, leading to unnecessary morbidity and
The β-adrenoceptor–blocking drugs have proved to be effective mortality. In addition, β-adrenoceptor antagonists are strongly
and well tolerated in hypertension. Although many hypertensive indicated in the acute phase of a myocardial infarction. In this set-
patients respond to a β blocker used alone, the drug is often used ting, relative contraindications include bradycardia, hypotension,

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110

Heart rate 90

70

50
10 30 50 70 90 110
Time (min)
FIGURE 10–7 Heart rate in a patient with ischemic heart disease measured by telemetry while watching television. Measurements were
begun 1 hour after receiving placebo (upper line, red) or 40 mg of oxprenolol (lower line, blue), a nonselective β antagonist with partial agonist
activity. Not only was the heart rate decreased by the drug under the conditions of this experiment, it also varied much less in response to
stimuli. (Adapted, with permission, from Taylor SH: Oxprenolol in clinical practice. Am J Cardiol 1983;52:34D. Copyright Elsevier.)