CHAPTER 2-31: BETA₂-ADRENERGIC STIMULANTS

INTRODUCTION

Beta-adrenergic agonists can be broadly categorized as having beta₁ and beta₂ receptor activity. This section describes the toxicity of beta₂-selective agonists that are commonly available for oral use: albuterol (salbutamol), metaproterenol, and terbutaline (Table II–16). Clenbuterol, a potent beta₂ agonist, is not approved for human use in the United States but is abused for its anabolic effects.

MECHANISM OF TOXICITY

1. Stimulation of beta₂ receptors results in relaxation of smooth muscles in the bronchi, uterus, and skeletal muscle vessels. At high doses, selectivity for beta₂ receptors may be lost, and beta₁ effects may be seen.

2. Pharmacokinetics. These agents are readily absorbed orally or by inhalation. Half-lives and other pharmacokinetic parameters are described in Table II–66.

TOXIC DOSE

Generally, a single ingestion of more than the total usual daily dose (see Table II–16) may be expected to produce signs and symptoms of toxicity. Pediatric ingestion of less than 1 mg/kg of albuterol is not likely to cause serious toxicity. Tonic–clonic seizures were observed 16 hours after ingestion of 4 mg/kg of albuterol in a 3-year old. A 22-year-old woman developed acidosis, rhabdomyolysis, and acute renal failure following ingestion of 225 mg of terbutaline. Dangerously exaggerated responses to therapeutic doses of terbutaline have been reported in pregnant women, presumably as a result of pregnancy-induced hemodynamic changes. Ingestion of 109 mcg of clenbuterol in a 31-year-old man resulted in supraventricular tachycardia and atrial fibrillation lasting 3 days, and ingestion of 5,000 mcg by a 23-year-old male resulted in myocardial infarction.

CLINICAL PRESENTATION

Overdoses of these drugs affect primarily the cardiovascular system. Most overdoses, especially in children, result in only mild toxicity.

1. Vasodilation results in reduced peripheral vascular resistance and can lead to significant hypotension. The diastolic pressure usually is reduced to a greater extent than is the systolic pressure, resulting in a wide pulse pressure and bounding pulse.

2. Tachycardia is a common reflex response to vasodilation and may also be caused by direct stimulation of beta₁ receptors as beta₂ selectivity is lost in high doses. Supraventricular tachycardia or ventricular extrasystoles are reported occasionally.

3. Myocardial ischemia and infarction have been reported after IV administration of albuterol and oral abuse of clenbuterol.

4. Agitation and skeletal muscle tremors are common. Rhabdomyolysis is possible. Seizures are rare.

5. Metabolic effects include ...