Calcium and Beta Receptor Antagonist Overdose: A Review and Update of Pharmacological Principles and Management

ABSTRACT

Calcium channel and beta-adrenergic receptor antagonists are common pharmaceutical agents with multiple overlapping clinical indications. When used appropriately, these agents are safe and efficacious. In overdose, however, these agents have the potential for serious morbidity. Calcium channel blockers and beta blockers share similar physiological effects on the cardiovascular system, such as hypotension and bradycardia, in overdose and occasionally at therapeutic doses. The initial management for symptomatic overdose of both drug classes consists of supportive care measures. Other therapies including administration of glucagon, calcium, catecholamines, phosphodiesterase inhibitors and insulin have been used with varying degrees of success. In addition, intra-aortic balloon pump and extracorporeal membrane oxygenation techniques have been successfully utilized in refractory cases. This article reviews beta blocker and calcium channel blocker pharmacological principles and updates current management strategies.

KEYWORD

Beta blockers - calcium channel blockers - overdose

REFERENCES

• 1 The United States Pharmacopeial Convention. USPDI: Approved Drug Products and Legal Requirements. 20th ed. Taunton, Mass.: World Color Book Services; 2000
• 2 Litovitz T L, Klein-Schwartz W, White S. 1999 Annual Report of the American Poison Control Centers Toxic Exposure Surveillance System.  Am J Emerg Med . 2000;  18 517-574
• 3 Adams R J, Schwartz A. Comparative mechanisms for contraction of cardiac and skeletal muscle.  Chest . 1980;  78 123-137
• 4 Hartshorne D J. Biochemical basis for contraction of vascular smooth muscle.  Chest . 1980;  78 140-149
• 5 Abernethy D R, Schwartz J B. Calcium-antagonist drugs.  N Engl J Med . 1999;  341 1447-1457
• 6 Levitski A, Marbach I, Bar-Sinai A. The signal transduction between beta receptors and adenyl cyclase.  Life Sci . 1993;  52 2093-2100
• 7 DeRoos F. Calcium channel blockers. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland MA, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies 6th ed. Stamford, Conn.: Appleton & Lange 1998: 829-843
• 8 Buckley C D, Aronson J K. Prolonged half-life of verapamil in a case of overdose: implications for therapy.  Br J Clin Pharmacol . 1995;  39 680-683
• 9 Adams B D, Browne W T. Amlodipine overdose causes prolonged calcium channel blocker toxicity.  Am J Emerg Med . 1998;  16 527-528
• 10 Ramoska E A, Spiller H A, Winter M. A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment.  Ann Emerg Med . 1993;  22 196-200
• 11 Love J N. Beta-blocker toxicity after overdose: when do symptoms develop in adults?.  J Emerg Med . 1994;  12 799-802
• 12 Brubracher J R. Beta-adrenergic antagonists. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland MA, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies 6th ed. Stamford, Conn.: Appleton & Lange 1998: 809-825
• 13 Wiest D. Esmolol: a review of its therapeutic efficacy and pharmacokinetic characteristics.  Clin Pharm . 1995;  28 190-202
• 14 Henry J A, Cassidy S L. Membrane stabilizing activity: a major cause of fatal poisoning.  Lancet . 1986;  8495 1414-1417
• 15 Pritchard B N, Battersby L A, Cruikshank J M. Overdosage with beta adrenergic blocking agents.  Adv Drug React Poison Rev . 1984;  3 91-111
• 16 Reith D M, Dawson A H, Epid D. Relative toxicity of beta blockers in overdose.  Clin Toxicol . 1996;  34 273-278
• 17 Buiumsohn A, Eisenberg E S, Jacob H. Seizures and intraventricular conduction defect in propanolol poisoning: a report of two cases.  Ann Int Med . 1979;  91 860-862
• 18 Frishman W, Jacob H, Eisenberg E, Ribner H. Clinical pharmacology of the new beta-adrenergic blocking drugs, VIII: Self-poisoning with beta-adrenergic blocking agents: recognition and Management.  Am Heart J . 1979;  98 798-811
• 19 Hohnloser S H, Woolsey R L. Sotalol.  N Engl J Med . 1994;  331 31-38
• 20 Krapf R, Gertsch M. Torsade de pointes induced by sotalol despite therapeutic plasma sotalol concentrations.  Br Med J . 1985;  290 1784-1785
• 21 Proano L, Chiang W K, Wang R Y. Calcium channel blocker overdose.  Am J Emerg Med . 1995;  13 444-450
• 22 Ramoska E A, Spiller H A, Myers A. Calcium channel blocker toxicity.  Ann Emerg Med . 1990;  19 649-653
• 23 Lundborg P. The effect of adrenergic blockade on potassium concentrations in different conditions.  Acta Med Scand . 1983;  672 121-126
• 24 Wax P. Intestinal infarction due to nifedipine overdose.  J Toxicol Clin Toxicol . 1995;  33 725-728
• 25 Samniah N, Schlaeffer F. Cerebral infarction associated with oral verapamil overdose.  J Toxicol Clin Toxicol . 1988;  26 365-369
• 26 Devis G, Somers G, Van Obberghen E. Calcium antagonists and islet function: inhibition of insulin release by verapamil.  Diabetes . 1975;  24 547-551
• 27 Brass B J, Winchester-Penny S, Lipper B L. Massive verapamil overdose complicated by noncardiogenic pulmonary edema.  Am J Emerg Med . 1996;  14 459-461
• 28 Pettei M J, Levy J, Abramson S. Nonocclusive mesenteric ischemia associated with propanolol overdose: implications regarding splanchnic circulation.  J Pediatr Gastroenterol and Nutr . 1990;  10 544-547
• 29 Rooney M, Massey K L, Jamali F. Acebutolol overdose treated with hemodialysis and extracorporeal membrane oxygenation.  J Clin Pharmacol . 1996;  36 760-763
• 30 Schofield P M, Beath S V, Mant T K. Recovery after severe oxprenolol overdose complicated by rhabdomyolysis.  Human Toxicol . 1985;  4 57-60
• 31 Thomson D F, Skaehill P A. Drug induced lichen planus.  Pharmacother . 1994;  14 561-571
• 32 Anonymous. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care, VI: Advanced cardiovascular life support, VIIA: Principles and practice of ACLS. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation.  Circulation . 2000;  102 I136-139
• 33 Taboulet P, Cariou A, Berdeaux A. Pathophysiology and management of self-poisoning with beta-blockers.  Clin Toxicol . 1993;  31 531-551
• 34 Lane A S, Woodward A C, Goldman M R. Massive propanolol overdose poorly responsive to pharmacologic therapy: use of the intra-aortic balloon pump.  Ann Emerg Med . 1987;  16 1381-1383
• 35 Haltori V T, Mandel W J, Pete T. Calcium for myocardial depression from verapamil.  N Engl J Med . 1982;  306 238
• 36 Lipman J, Jardine I, Roos C. Intravenous calcium chloride as an antidote to verapamil-induced hypotension.  Intensive Care Med . 1982;  8 55-57
• 37 Love J N, Hanfling D, Howell J M. Hemodynamic effects of calcium chloride in a canine model of acute propanolol intoxication.  Ann Emerg Med . 1996;  28 1-6
• 38 Crump B J, Holt D W, Vale J A. Lack of response to intravenous calcium in severe verapamil poisoning.  Lancet . 1982;  2 939-940
• 39 Luscher T F, Noll G, Sturmer T. Calcium gluconate in severe verapamil intoxication.  N Engl J Med . 1994;  330 718-719
• 40 Nola G T, Pope S, Harrison D C. Assessment of the synergistic relationship between serum calcium and digitalis.  Am Heart J . 1970;  79 499-507
• 41 Yagami T. Differential coupling of glucagon and beta-adrenergic receptors with the small and large forms of the stimulatory G protein.  Mol Pharmacol . 1995;  48 849-854
• 42 Glick G, Parmley W, Weschler A. Glucagon: its enhancement of cardiac performance in the cat and dog and persistence of its inotropic action despite beta receptor blockade with propanolol.  Circ Res . 1968;  22 789-799
• 43 Parmley W W, Glick G, Sonnenblick E. Cardiovascular effects of glucagons in man.  N Engl J Med . 1968;  279 12-17
• 44 Doyon S, Roberts J R. The use of glucagon in a case of calcium channel blocker overdose.  Ann Emerg Med . 1993;  22 1229-1233
• 45 Stone C K, Thomas S H, Koury S I. Glucagon and phenylephrine combination vs glucagon alone in experimental verapamil overdose.  Acad Emerg Med . 1996;  3 120-125
• 46 Walter F G, Frye G, Mullen J T. Amelioration of nifedipine poisoning associated with glucagon therapy.  Ann Emerg Med . 1993;  22 1234-1237
• 47 Lvoff R, Wilken D. Glucagon in heart failure and in cardiogenic shock: experience of 50 patients.  Circulation . 1972;  45 534-542
• 48 Shore E T, Cepin D, Davidson M J. Metoprolol overdose.  Ann Emerg Med . 1981;  10 524-527
• 49 Chimienti M, Previtali M, Medici A. Acute verapamil poisoning: successful treatment with epinephrine.  Clin Cardiol . 1982;  5 219-222
• 50 Lee K C, Cannif P C, Hamel D W. Cardiovascular and renal effects of milrinone in beta adrenoreceptor blocked and non-blocked anesthetized dogs.  Drugs Exp Clin Res . 1991;  18 145-158
• 51 Travill C M, Pugh S, Noble M IM. The inotropic and hemodynamic effects of intravenous milrinone when reflex adrenergic stimulation is suppressed by beta-adrenergic blockade.  Clin Ther . 1994;  16 783-792
• 52 Wolf L R, Spadafora M P, Otten E J. Use of amrinone and glucagon in a case of calcium channel blocker overdose.  Ann Emerg Med . 1993;  22 1225-1228
• 53 Kerns W, Schroeder D, Williams C. Insulin improves survival in a canine model of acute beta-blocker toxicity.  Ann Emerg Med . 1997;  29 748-757
• 54 Kline J A, Leonova E, Raymond R M. Beneficial myocardial metabolic effects of insulin during verapamil toxicity in the anesthetized canine.  Crit Care Med . 1995;  23 1251-1263
• 55 Kline J A, Tomaszewski C A, Schroeder J D, Raymond R M. Insulin is a superior antidote for cardiovascular toxicity induced by verapamil in the anesthetized canine.  J Pharm Exp Ther . 1993;  267 744-750
• 56 Yuan T H, Kerns W P, Tomaszewski, et al. Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning.  J Toxicol Clin Toxicol . 1999;  37 463-474
• 57 Melanson P, Shih R D, DeRoos F. Intra-aortic balloon counterpulsation in calcium channel blocker overdose.  Vet Hum Toxicol . 1993;  35 345
• 58 Mcvey F K, Corke C F. Extracorporeal circulation in the management of massive beta blocker overdose.  Anesthesia . 1991;  46 744-746
• 59 Hendren W G, Schieber R S, Garrettson L K. Extracorporeal bypass for the treatment of verapamil poisoning.  Ann Emerg Med . 1989;  18 984-987