McKenna's Pharmacology for Nursing, 2e

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P A R T 5  Drugs acting on the autonomic nervous system

TABLE 31.1

DRUGS IN FOCUS Non-selective adrenergic blocking agents

Drug name

Dosage/route

Usual indications

amiodarone (Cordarone X )

200 mg PO t.d.s. initially, reduced for maintenance to 200 mg/day; 5 mg/ kg IV diluted in 5% glucose over 20 minutes–2 hours to maximum 1200 mg/24 hours 6.25–12.5 mg PO b.d. for hypertension; 3.125–6.25 mg PO b.d. for heart failure 100 mg PO b.d. initially, maintenance 200–400 mg PO b.d.; 20 mg IV, slowly with additional doses given at 10-minute intervals to a maximum dose of 300 mg for severe hypertension

Treatment of life-threatening ventricular arrhythmias

carvedilol (Dilatrend, Vedilol)

Treatment of hypertension and heart failure in adults, alone or as part of combination therapy Treatment of hypertension, hypertension associated with phaeochromocytoma, and clonidine withdrawal

labetalol (Presolol, Trandate)

reaction ; and women who are breastfeeding because of the potential adverse effects on the neonate. These drugs should be used with caution in indi- viduals with diabetes because the disorder could be aggravated by the blocked sympathetic response and because the usual signs and symptoms of hypogly­ caemia and hyperglycaemia are masked with the SNS blockade. Caution also should be used in people with bronchospasm, which could progress to respiratory distress due to the loss of noradrenaline’s broncho­ dilating actions ; and in pregnancy because there are no well-defined studies to evaluate the potential risk to the fetus. The drugs should only be used if the benefit to the mother clearly outweighs the potential risk to the fetus . Adverse effects The adverse effects associated with the use of non- selective adrenergic blocking agents are usually associ- ated with the drug’s effects on the SNS. These effects can include dizziness, paraesthesias, insomnia, depres- sion, fatigue and vertigo, which are related to the blocking of noradrenaline’s effect in the CNS . Nausea, vomiting, diarrhoea, anorexia and flatulence are associ­ ated with the loss of the balancing sympathetic effect on the gastrointestinal (GI) tract and increased parasym­ pathetic dominance. Cardiac arrhythmias, hypotension, HF, pulmonary oedema and cerebrovascular accident or stroke, are related to the lack of stimulatory effects and loss of vascular tone in the cardiovascular (CV) system. Bronchospasm, cough, rhinitis and bronchial obstruction are related to loss of bronchodilation of the respiratory tract and vasodilation of mucous membrane vessels. Other effects reported include decreased exercise tolerance, hypoglycaemia and rash related to the sym­ pathetic blocking effects. Abruptly stopping these drugs after long-term therapy can result in MI, stroke and arrhythmias related to an increased hypersensitivity to catecholamines that develops when the receptor sites

have been blocked. Carvedilol has been associated with hepatic failure related to its effects on the liver. Clinically important drug–drug interactions There is increased risk of excessive hypotension if any of these drugs is combined with general anaesthet- ics in volatile liquid form such as enflurane, halothane or isoflurane. The effectiveness of diabetic agents is increased, leading to hypoglycaemia when such agents are used with these drugs; individuals should be moni­ tored closely and dose adjustments made as needed. In addition, carvedilol has been associated with poten- tially dangerous conduction system disturbances when combined with verapamil or diltiazem; if this combina- tion is used, the person requires continuous monitoring. Prototype summary: Labetalol Indications: Hypertension, alone or in combination with other drugs; off-label uses—control of blood pressure in phaeochromocytoma, clonidine- withdrawal hypertension. Actions: Competitively blocks alpha- and beta- receptor sites in the SNS, leading to lower blood pressure without reflex tachycardia and decreased renin levels. Pharmacokinetics: Route Onset Peak Duration Oral Varies 1–2 hours 8–12 hours IV Immediate 5 mins 5.5 hours T 1/2 : 6 to 8 hours, with hepatic metabolism and excretion in the urine. Adverse effects: Dizziness, vertigo, fatigue, gastric

pain, flatulence, impotence, bronchospasm, dyspnoea, cough, decreased exercise tolerance.