The four classes of drugs described in this chapter each stand out as being useful in treating multiple disorders of the cardiovascular system. Core aspects of their mechanisms of action and properties are described here and further details on their use are presented in the chapters dealing specifically with the disorder.

β-Adrenoceptor Antagonists (β-Blockers)

β-Blockers are used to treat angina, cardiac arrhythmias, myocardial infarction and chronic heart failure. Once a first line treatment for hypertension, they are now used only in combination with other antihypertensive drugs if these fail to lower blood pressure sufficiently. Their usefulness derives mainly from their blockade of cardiac β₁-receptors (Figure 35). When stimulated by noradrenaline released from sympathetic nerves, and by blood-borne adrenaline, these receptors increase the rate and force of cardiac contraction, thereby increasing the output, work and O₂ requirement of the heart. Although these responses are important for the normal physiological response to stress, they have the undesirable effect of promoting cardiac ischaemia and its downstream effects if coronary blood flow is compromised by atherosclerotic stenosis or thrombosis (see Chapters 40 and 45). Activation of β₁-receptors also increases atrioventricular (AV) nodal conduction and the excitability of the heart, effects that can sometimes cause or promote cardiac arrhythmias (see Chapters 48 and 51). Chronic activation of the sympathetic system, as in congestive heart failure, causes cardiac fibrosis and remodelling, leading to a progressive deterioration of cardiac function and increasing the occurrence of life-threatening arrhythmias (see Chapters 46 and 48).

β-Blockers have additional useful effects. Importantly, renal afferent arterioles contain renin-producing granular cells which are stimulated by sympathetic nerves to release renin via their β₁-receptors. Thus, the renin–angiotensin–aldosterone (RAA) axis (see Chapter 29) can be stimulated by the sympathetic system, an effect that β-blockers inhibit. β-Blockers also decrease the release of noadrenaline from sympathetic nerves by inhibiting presynaptic β-receptors on sympathetic varicosities that act to facilitate its release.

Propranolol, a ‘first generation’ β-blocker, acts on both β₁ and β₂-receptors, whereas second generation β-blockers (e.g. atenolol, metoprolol, bisoprolol) selectively antagonize β₁-receptors. Third generation β-blockers also cause vasodilatation; for example, carvidelol does this by blocking α-receptors and by releasing nitric oxide. Pindolol belongs to a fourth group of β-blockers with intrinsic sympathomimetic activity; it antagonizes β₁-receptors but stimulates β₂-receptors, thereby causing vasodilatation. Although in all cases the main therapeutic effect of these drugs lies in their effect on β₁

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