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

Christopher R. H. Newton; Joao H. Delgado; Hernan F. Gomez

doi:10.1055/s-2002-20585

Seminars in Respiratory and Critical Care Medicine, Table of Contents

Semin Respir Crit Care Med 2002; 23(1): 019-026
DOI: 10.1055/s-2002-20585

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

Christopher R.H. Newton¹ , Joao H. Delgado² , Hernan F. Gomez¹

¹Department of Emergency Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
²Rocky Mountain Poison Control Center, Denver, Colorado

Abstract

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

Full Text

References

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