McKenna's Pharmacology for Nursing, 2e

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P A R T 8  Drugs acting on the cardiovascular system

Heart, Lung and Blood Institute looked at the mortality rate of people with asymptomatic, non-life-threatening arrhythmias being treated with antiarrhythmics. The results showed that long-term use of some antiarrhyth- mics was associated with an increased risk of death. In fact, the risk of death for some people was two to three times greater than that for untreated individuals. These results prompted more clinical trials to look at the effec- tiveness of long-term use of antiarrhythmics. It was found that antiarrhythmics may block some reflex arrhythmias that help to keep the cardiovascular system in balance, or they may precipitate new, deadly arrhythmias. Therefore, it is important to document the arrhythmia being treated and the rationale for treat- ment and to monitor a person regularly when using these drugs. C lass I antiarrhythmics Class I antiarrhythmics (Table 45.1) are drugs that block the sodium channels in the cell membrane during an action potential. These drugs are further broken down into three subclasses, reflecting the manner in which their blockage of sodium channels affects the action potential. These subclasses include the following: • Class Ia antiarrhythmics: disopyramide ( Rythmodan ) • Class Ib antiarrhythmics: lignocaine ( Xylocaine and others) • Class Ic antiarrhythmics: flecainide ( Flecatab , Tambocor ) and propafenone ( Rytmonorm [available in NZ]) Therapeutic actions and indications The class I antiarrhythmics stabilise the cell membrane by binding to sodium channels, depressing phase 0 of the action potential and changing the duration of the action potential (Figure 45.6). Class Ia drugs depress phase 0 of the action potential and prolong the duration of the action potential. Class Ib drugs depress phase 0 somewhat and actually shorten the duration of the action potential. Class Ic drugs markedly depress phase 0, with a resultant extreme slowing of conduction, but have little effect on the duration of the action potential.

These drugs are local anaesthetics or membrane- stabilising agents. They bind more quickly to sodium channels that are open or inactive—ones that have been stimulated and are not yet repolarised. This character- istic makes these drugs preferable in conditions such as tachycardia, in which the sodium gates are open fre- quently. These drugs are indicated for the treatment of potentially life-threatening ventricular arrhythmias and should not be used to treat other arrhythmias because of the risk of a proarrhythmic effect. See Table 45.1 for usual indications for each class I antiarrhythmic agent. Pharmacokinetics These drugs are widely distributed after injection or after rapid absorption through the gastrointestinal (GI) tract. They undergo extensive hepatic metabolism and are excreted in urine. These drugs cross the placenta and are found in breast milk (see Contraindications and cautions). Disopyramide is available in oral form. Lignocaine is administered by the IM or IV route, and can also be given as a bolus injection in emergencies when monitor- ing is not available to document the exact arrhythmia. Flecainide is available in oral form. Contraindications and cautions Class I antiarrhythmics are contraindicated in the presence of allergy to any of these drugs; with brady- cardia or heart block unless an artificial pacemaker is in place, because changes in conduction could lead to complete heart block ; with heart failure (HF), hypoten- sion or shock, which could be exacerbated by effects on the action potential ; and with electrolyte disturbances, which could alter the effectiveness of these drugs. Caution should be used in people with renal or hepatic dysfunction, which could interfere with the biotrans­ formation and excretion of these drugs. These drugs cross the placenta, and although no specific adverse effects have been associated with their use, it is suggested that they be used in pregnancy only if the benefits to the mother clearly outweigh the poten- tial risks to the fetus. Class I antiarrhythmics enter breast milk, and because of the potential for adverse effects on the neonate , they should not be used during

TABLE 45.1

DRUGS IN FOCUS Antiarrhythmic agents

Drug name

Dosage/route

Usual indications

Class I antiarrhythmics Class Ia disopyramide (Rythmodan)

Adult: 400–800 mg/day PO in divided doses q 6–12 hours; use lower doses with older people Paediatric: 6–30 mg/kg per day PO in divided doses q 6 hours, base dose on age

Treatment of life-threatening ventricular arrhythmias