McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 4 4 Cardiotonic agents

CARDIOTONIC AGENTS Cardiotonic (inotropic) drugs affect the intracellular calcium levels in the heart muscle, leading to increased contractility. This increase in contraction strength leads to increased cardiac output, which causes increased renal blood flow and increased urine production. Increased renal blood flow decreases renin release, and hence reduces the effects of the renin–angiotensin– aldosterone system, increasing urine output, and leading to decreased blood volume. The result is a decrease in the heart’s workload and relief of HF. Two types of cardio­ tonic drugs are used: the classic cardiac glycosides, which have been used for hundreds of years, and the newer phosphodiesterase inhibitors. Table 44.1 presents a complete list of these agents. Box 44.1 summarises the use of cardiotonic drugs in different age groups. C ardiac glycosides The cardiac glycosides were originally derived from the foxglove or digitalis plant. These plants were once ground up to make digitalis leaf. Today, digoxin ( Lanoxin, Sigmaxin ) is the drug most often used to treat HF. Therapeutic actions and indications Digoxin increases intracellular calcium and allows more calcium to enter myocardial cells during depolarisation (Figure 44.4), causing the following effects: • Increased force of myocardial contraction (a positive inotropic effect). • Increased cardiac output and renal perfusion (which has a diuretic effect, increasing urine output and decreasing blood volume while decreasing renin release and activation of the renin–angiotensin– aldosterone system). • Slowed heart rate, owing to slowing of the rate of cellular repolarisation (a negative chronotropic effect). • Decreased conduction velocity through the atrioventricular node. The overall effect is a decrease in the myocardial workload and relief of HF. Digoxin is indicated for the treatment of HF, atrial flutter, atrial fibrillation and par­ oxysmal atrial tachycardia (see Table 44.1). Digoxin has a very narrow margin of safety (meaning that the thera­ peutic dose is very close to the toxic dose), so extreme care must be taken when using this drug (see Adverse effects and Box 44.3 for information on digoxin antidote). Pharmacokinetics Digoxin is available for oral and parenteral adminis­ tration. The drug has a rapid onset of action and rapid absorption (30 to 120 minutes when taken orally, 5 to

thereby decreasing preload of the heart and helping to improve function (see Chapter 43 for a discussion of ACE inhibitors and Chapter 46 for a discussion of nitrates). Diuretics decrease blood volume, which decreases venous return and blood pressure, resulting in decreased afterload, preload and cardiac workload. (See Chapter 51 for additional information.) • Beta-adrenergic agonists stimulate the beta receptors in the sympathetic nervous system, increasing calcium flow into the myocardial cells and causing increased contraction, a positive inotropic effect. Other sympathetic stimulation effects can cause increased HF because the heart’s workload is increased by most sympathetic activity. (See Chapter 30 for additional information.) • Human B-type natriuretic peptides are normally produced by myocardial cells as a compensatory response to increased cardiac workload and increased stimulation by the stress hormones. They bind to endothelial cells, leading to dilation and resulting in decreased venous return, peripheral resistance and cardiac workload. They also suppress the body’s response to the stress hormones, leading to increased fluid loss and further decrease in cardiac workload. ■■ In HF, the heart pumps blood so ineffectively that blood builds up, causing congestion in the cardiovascular system. ■■ HF can result from damage to the heart muscle combined with an increased workload related to CAD, hypertension, cardiomyopathy, valvular disease or congenital heart abnormalities. As the heart pump fails, the muscle cells can no longer work to move calcium into the cell, and cardiac contractions become weak and ineffective. ■■ Signs and symptoms of HF result from the backup of blood in the vascular system and the loss of fluid in the tissues. Right-sided HF is characterised by oedema, liver congestion, elevated jugular venous pressure and nocturia, whereas left-sided failure is marked by tachypnoea, dyspnoea, orthopnoea, haemoptysis, anxiety and poor oxygenation of the blood. ■■ Treatment agents include vasodilators (to lighten the heart’s workload); diuretics (to reduce blood volume and workload); beta-blockers (to decrease the heart’s workload by activating sympathetic reaction); human B-type natriuretic peptides (to decrease the heart’s workload by vasodilation and suppression of the response to the sympathetic reaction); and cardiotonic (inotropic) agents (to stimulate more effective muscle contractions). KEY POINTS