McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

C alcium channel blockers Calcium channel blockers include amlodipine ( Norvasc ), diltiazem ( Cardizem ), nifedipine ( Adalat , Nyefax ), perhexiline ( Pexsig ), and verapamil ( Cordilox SR , Isoptin ). Therapeutic actions and indications Calcium channel blockers inhibit the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction. A loss of smooth muscle tone, vasodilation and decreased peripheral resistance occur. Subsequently, preload and afterload are decreased, which in turn decreases cardiac workload and oxygen consumption. Calcium channel blockers are indicated for the treat- ment of variant angina, chronic angina, effort-associated angina and hypertension. In variant angina, these agents relieve coronary artery vasospasm, increasing blood flow to the muscle cells. Research also indicates that these drugs block the proliferation of cells in the endothelial layer of the blood vessel, slowing the progress of the atherosclerosis. Verapamil is also used to treat cardiac tachyarrhythmias because it slows conduction more than the other calcium channel blockers do. The drug of choice depends on the person’s diagnosis and ability to tolerate adverse drug effects. See Table 46.1 for usual indications for each of these drugs. Pharmacokinetics These drugs are generally well absorbed after oral administration, metabolised in the liver and excreted in urine. They have an onset of action of 20 minutes and duration of action of 2 to 4 hours. These drugs cross the placenta and enter breast milk. Contraindications and cautions Calcium channel blockers are contraindicated in the presence of allergy to any of these drugs to avoid hypersensitivity reactions and with pregnancy or breast- feeding because of the potential for adverse effects on the fetus or neonate. Caution should be used with heart block or sick sinus syndrome, which could be exacerbated by the conduction-slowing effects of these drugs ; with renal or hepatic dysfunction, which could alter the metabolism and excretion of these drugs ; and with heart failure, which could be exacerbated by the decrease in cardiac output that could occur. People with diabetes should be careful when taking perhexiline as this drug can cause hypoglycaemia and dose adjustment may be necessary in the first few days.

Adverse effects The adverse effects associated with these drugs are related to their effects on cardiac output and on smooth muscle. CNS effects include dizziness, light-headedness, headache and fatigue. GI effects can include nausea and hepatic injury related to direct toxic effects on hepatic cells. Cardiovascular effects include hypotension, brady- cardia, peripheral oedema and heart block. Skin effects include flushing and rash. Clinically important drug–drug interactions Drug–drug interactions vary with each of the calcium channel blockers. Potentially serious effects to keep in mind include increased serum levels and toxicity of cyclosporin if they are taken with diltiazem and increased risk of heart block and digoxin toxicity if they are combined with verapamil (because verapamil increases digoxin serum levels). Both verapamil and digoxin depress myocardial conduction. If any combina- tions of these drugs must be used, the individual should be monitored very closely and appropriate dose adjust- ments made. Verapamil has also been associated with Prototype summary: Diltiazem Indications: Treatment of variant angina, effort- associated angina and chronic stable angina; also used to treat essential hypertension and paroxysmal supraventricular tachycardia. Actions: Inhibits the movement of calcium ions across the membranes of myocardial and arterial muscle cells, altering the action potential and blocking muscle cell contraction, which depresses myocardial contractility; slows cardiac impulse formation in the conductive tissues, and relaxes and dilates arteries, causing a fall in blood pressure and a decrease in venous return; decreases the workload of the heart and myocardial oxygen consumption; relieves the vasospasm of the coronary artery, increasing blood flow to the muscle cells (variant angina). Pharmacokinetics: Route Onset Peak Oral 30–60 mins 2–3 hours SR, extended release (ER) 30–60 mins 6–11 hours IV Immediate 2–3 mins T 1/2 : 3.5 to 6 hours (SR), 5 to 7 hours (ER); metabolised in the liver and excreted in urine. Adverse effects: Dizziness, light-headedness, headache, asthenia, peripheral oedema, bradycardia, atrioventricular block, flushing, rash, nausea.