Manifestations and Management of Calcium-Channel Blocker

Introduction:

According to the 1992 annual report of the American Association of Poison Control Centers, there were 6,683 reported toxic exposures to calcium channel blockers and 5,308 exposures to b-adrenergic antagonists. Of the 80 deaths attributed to cardiovascular agents, 16 were due to b-adrenergic-antagonists and 38 were due to calcium-channel blockers, with verapamil producing the greatest number of mortalities in its class.

• Bradyarrhythmias and hypotension are the most common toxic effects associated with calcium-channel-blocker overdose, medicated by inhibition of intracellular movement of calcium ions across voltage-dependent channels.
• A common presenting rhythm of calcium-channel blocker toxicity is a narrow complex junctional bradycardia. Ventricular tachyarrhythmias are unusual.
• b-adrenergic antagonists also impair sinus rhythm and atrioventricular nodal conduction by inhibiting the intracellular flow of calcium ions.
• Sinus bradycardia, with pauses is an early manifestation of b-blocker toxicity. This can progress to various degrees of atrioventricular block and, even intraventricular block.
• Sotalol also has Class III antiarrhythmic properties, and can cause malignant ventricular tachyarrthymias.
• Certain b-adrenergic-blocking agents (e.g., pindolol) exert a partial agonistic effect known as intrinsic sympathomimetic activity (ISA). Early onset of tachycardia and hypertension are frequently the dominant features of significant toxicity.
• The membrane-stabilizing effects of such b-adrenergic blockers as propranolol, pindolol, metoprolol, and acebutolol potentiate decreases in myocardial contractility which, in cases of severe toxicity, lead to impaired cardiac pump function.

• Lethargy, coma, and seizures are more likely to occur with toxicity from b-adrenergic antagonists than from calcium-channel blockers.

• Both b-adrenergic antagonists and calcium-channel blockers can produce clinically detectable alterations in glucose homeostasis
• Hypoglycemia induced by b-adrenergic antagonists is the result of decreased glycogenolysis, lipolysis, and/or gluconeogenesis.
• Hyperglycemia is commonly observed in calcium-channel blocker toxicity and may result from the inhibition of calcium-dependent insulin release.

• The use of non-selective b-adrenergic blockers in patients with asthma and chronic obstructive pulmonary disease can produce significant bronchospasm.

• Nausea and vomiting can occur with both b-adrenergic-antagonist and calcium-channel blocker toxicity.

• Measurement of serum drug levels is rarely necessary in the acute management of patients with either b-adrenergic or calcium-channel blocker overdoses.
• CBC, SMAC obtained.
• Serum acetaminophen and salicylate levels should be obtained in any intentional overdose.
• An electrocardiogram is mandatory to evaluate possible arrhythmias and to characterize conduction disturbances.

• Airway, breathing, and circulation have a large-bore IV line(s) established and placed immediately on continuous cardiac monitoring. Supplemental oxygen is usually necessary for symptomatic patients.

• Orogastric lavage should be considered.
• Activated charcoal (1.0 g/kg) is indicated in all patients who, by history, have ingested toxic amounts of a calcium-channel blocker or b-adrenergic antagonist, regardless of the alleged time of ingestion.
• Repeat dose activated charcoal (0.5 g/kg po q4-6h) may be indicated to enhance drug elimination, and limit additional drug absorption in sustained-release and long-acting preparations.
• Whole bowel irrigation therapy is effective in limiting drug absorption of sustained-release formulations (e.g., Golytely).

• The goal of directed therapy is to maintain a cardiovascular status adequate to support tissue perfusion.
• An IV fluid challenge with normal saline, (10-20 mL/kg) is an appropriate initial measure for augmentation of blood pressure. Although clinically useful, IV fluid therapy should be monitored carefully in order to prevent volume overload and pulmonary edema.
• If Bradycardia is the primary precipitant of hypotension, the heart rate should be normalized before administration of a vasopressor agent.
• Pharmacotherapeutic intervention for bradycardia is indicated only in symptomatic patients. The most useful agents and measures include atropine, glucagon, isoproterenol, epinephrine, and, on occasion, insertion of a temporary venous pacemaker.