McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

C lass III antiarrhythmics The class III antiarrhythmics include amiodarone ( Aratac , Cordarone X, Cardinorm ) and sotalol ( Cardol , Sotacor ). Therapeutic actions and indications The class III antiarrhythmics block potassium channels and slow the outward movement of potassium during phase 3 of the action potential, prolonging it (Figure 45.7). All of these drugs are proarrhythmic and have the potential of inducing arrhythmias. Although amiodarone has been associated with such serious and even fatal toxic reactions, in 2005 the American Heart Association issued new guidelines for Advanced Cardiac Life Support (ACLS) that named amiodarone the drug of choice for treating ventricular fibrillation or pulseless ventricular tachycardia in cardiac arrest situations. See Table 45.1 for usual indications for each drug. Pharmacokinetics Amiodarone is available in an oral or intravenous form. Sotalol is administered only in oral form. These drugs are well absorbed after oral administration. Absorption of sotalol is decreased by the presence of food. This drug is metabolised in the liver and excreted in urine. Contraindications and cautions When these drugs are used to treat life-threatening arrhythmias for which no other drug has been effective, there are no contraindications. Because sotalol is known to be proarrhythmic , individuals should be monitored very closely at the initiation of therapy and periodically during therapy. Caution should be used with all of these drugs in the presence of shock, hypotension or respira- tory depression; with a prolonged QTc interval, which could worsen due to the depressive effects on action potentials ; and with renal or hepatic disease, which could alter the biotransformation and excretion of these drugs. Adverse effects The adverse effects associated with these drugs are related to the changes they cause in action potentials. Nausea, vomiting and GI distress; weakness and dizzi- ness; and hypotension, HF and arrhythmia are common. Amiodarone has been associated with a potentially fatal liver toxicity, ocular abnormalities and the development of very serious cardiac arrhythmias. Clinically important drug–drug interactions These drugs can cause serious toxic effects if they are combined with digoxin or quinidine. There is an

increased risk of proarrhythmias if they are combined with antihistamines, phenothiazines or tricyclic anti­ depressants. Sotalol may have a loss of effectiveness if it is combined with non-steroidal anti-inflammatory drugs, aspirin or antacids. Other specific drug–drug interactions have been reported with individual drugs; a drug reference should always be consulted when adding a new drug to a regimen containing any of these agents. Prototype summary: Amiodarone Indications: Treatment of life-threatening ventricular arrhythmias. Actions: Acts directly on heart muscle cells to prolong repolarisation and the refractory period, increasing the threshold for ventricular fibrillation; also acts on peripheral smooth muscle to decrease peripheral resistance. Pharmacokinetics: Route Onset Peak Duration Oral 2–3 days 3–7 hours 6–8 hours IV Immediate 20 mins Infusion T 1/2 : 10 days; metabolised in the liver and excreted in urine. Adverse effects: Malaise, fatigue, dizziness, HF, cardiac arrhythmias, cardiac arrest, constipation, nausea, vomiting, hepatotoxicity, pulmonary toxicity, corneal microdeposits and vision changes. ■■ Class III antiarrhythmics block potassium channels and prolong phase 3 of the action potential. ■■ Amiodarone is the drug recommended for use during life support measures. It is associated with serious to potentially fatal hepatotoxicity. C lass IV antiarrhythmics Class IV antiarrhythmics include two calcium channel blockers: diltiazem ( Cardizem ) and verapamil ( Anpec , Cordilox SR, Isoptin ). Therapeutic actions and indications The class IV antiarrhythmics block the movement of calcium ions across the cell membrane, depressing the generation of action potentials and delaying phases 1 and 2 of repolarisation, which slows automaticity and conduction (see Figure 45.7). Both diltiazem and verapa- mil are used as antihypertensives (see Chapter 43) and to treat angina (see Chapter 46). Table 45.1 describes usual indications for each drug. KEY POINTS