====== Module 1 - Cardiovascular Drugs ====== ===== OBJECTIVES ===== At the end of this module, students should be able to:\\ · Understand the mechanisms underlying the toxicity\\ · Undertake a risk assessment of poisoning\\ · Develop an approach for the treatment of mixed cardiovascular drug overdose ===== BETA BLOCKERS AND CALCIUM CHANNEL BLOCKERS ===== ==== Objectives ==== * Understand the mechanism of toxicity of CCBs and beta-blockers. * Understand how this explains differences within each class in the toxicity in overdose. * List the most common clinical manifestations of poisoning with CCBs and beta-blockers. * Recognise situations where the use of antidotes may be indicated. * Recognise situations where a sudden deterioration is likely to occur and steps that may be taken to anticipate and/or prevent such deteriorations. ==== Reading ==== Hantson P, Beauloye C. Myocardial metabolism in toxin-induced heart failure and therapeutic implications. //Clin Toxicol// 2012;50(3):166-71 **[[:wikitox:3.4.3.4.2_beta_blockers|Beta Blockers]]** \\ Reith DM, Dawson AH, Epid D, Whyte IM, Buckley NA, Sayer GP. Relative toxicity of beta blockers in overdose. //J Toxicol Clin Toxicol// 1996;34(3):273-8 [[https://www.ncbi.nlm.nih.gov/pubmed/8667464|PMID8667464]] \\ Boyd R, Ghosh A. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Glucagon for the treatment of symptomatic beta blocker overdose. //Emerg Med J// 2003;20(3):266-7 [[http://www.ncbi.nlm.nih.gov/pubmed/12748150|PMID12748150]] \\ Mansell PI. Glucagon in the management of deliberate self-poisoning with propranolol. //Arch Emerg Med// 1990;7(3):238-40 [[http://www.ncbi.nlm.nih.gov/pubmed/18288073|PMID18288073]] \\ Love JN. Acebutolol overdose resulting in fatalities. //J Emerg Med// 2000;18(3):341-4 [[http://www.ncbi.nlm.nih.gov/pubmed/10729673|PMID10729673]] \\ Pfaender M, Casetti PG, Azzolini M, Baldi ML, Valli A. Successful treatment of a massive atenolol and nifedipine overdose with CVVHDF. //Minerva Anestesiol// 2008;74(3):97-100 [[http://www.ncbi.nlm.nih.gov/pubmed/18288073|PMID18288073]] **[[:wikitox:2.1.6.1.1_calcium_channel_blockers|Calcium Channel Blockers (CCB)]]** \\ Howarth DM, Dawson AH, Smith AJ, Buckley N, Whyte IM. Calcium channel blocking drug overdose: An australian series. //Hum Exp Toxicol// 1994;13(3):161-6 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11296202|Lam YM, Tse HF, Lau CP]]. Continuous calcium chloride infusion for massive nifedipine overdose. Chest 2001;119(4):1280-2 \\ [[http://ccforum.com/content/10/3/212|Philippe ER Lheureux , Soheil Zahir, Mireille Gris, Anne-Sophie Derrey and Andrea Penaloza]] \\ Bench-to-bedside review: Hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. //Critical Care// 2006;10**:**212 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9559422|Oe H, Taniura T, Ohgitani N.]] A case of severe verapamil overdose. \\ [[http://www.ncbi.nlm.nih.gov/pubmed/12101159|Isbister GK]]. Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium. //Emerg Med J// 2002;19(4):355-7 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/8025446|Buckley NA, Whyte IM, Dawson AH]]. Overdose with calcium channel blockers. //BMJ// 1994;308(6944):1639 See: **[[:wikitox:problems_for_discussion_2_beta_blockers_and_calcium_channel_blockers|Problems for Discussion]]** ===== CLONIDINE ===== ==== Objectives ==== * Understand the mechanism of toxicity of clonidine. * Understand the particular risks of clonidine toxicity in children. * Explain the management of cardiovascular toxicity from clonidine overdose. * Detail the role and limitations of any potential antidotes for clonidine toxicity. * Outline the type of preparations that contain imidazoline compounds that can cause an identical poisoning to clonidine. ==== Reading ==== **[[:wikitox:clonidine|Clonidine]]** \\ [[http://file:///C:/Documents%20and%20Settings/Administrator/Application%20Data/Mozilla/Firefox/Profiles/wm5a387v.default/zotero/storage/4798/entrez.html|Romano MJ, Dinh A.]] A 1000-fold overdose of clonidine caused by a compounding error in a 5-year-old child with attention-deficit/hyperactivity disorder. Pediatrics 2001;108(2):471-2 \\ [[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1174908|S N Hunyor, K Bradstock, P J Somerville, and N Lucas.]] Clonidine overdose. //Br Med J// 1975; 4(5987): 23 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/923317|Williams PL, Krafcik JM, Potter BB, Hooper JH, Hearne MJ.]] Cardiac toxicity of clonidine. //Chest// 1977;72(6):784-5 See: **[[:wikitox:problems_for_discussion_2_clonidine|Problems for Discussion]]** ===== ERGOTS ===== ==== Objectives ==== * Understand the mechanism of action of these agents. * Detail the groups of patients at risk of ergot poisoning. * Outline and differentiate acute and chronic ergot poisoning. * Detail the management options, including risks and benefits, of the different agents used to treat ergot poisoning. ==== Reading ==== **[[:wikitox:2.1.11.4.5.1_ergot_alkaloids|Ergots]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10082701|Liaudet L, Buclin T, Jaccard C, Eckert P]]. Severe ergotism associated with interaction between ritonavir and ergotamine. //BMJ// 1999;318(7186):771 \\ Verloes A, Emonts P, Dubois M, Rigo J, Senterre J. Paraplegia and arthrogryposis multiplex of the lower extremities after intrauterine exposure to ergotamine. //J Med Genet// 1990;27(3):213-4 See: **[[:wikitox:problems_for_discussion_2_ergots|Problems for Discussion]]** ===== VASODILATORS ===== ==== Objectives ==== * Understand the mechanism of action of these agents and how these may manifest in overdose. * Outline what additional toxicity may occur with these agents * Detail who are more susceptible to nitrate and nitroprusside toxicity. * Detail the use of specific antidotes for treating some of these agents in overdose. * Understand the supportive management that should be adopted for these agents in overdose, detail which are likely to require treatment with vasopressors and how they should be administered. ==== Reading ==== **[[:wikitox:2.1.6.2.5_vasodilators|Vasodilators]]** \\ Robin ED, McCauley R. Nitroprusside-related cyanide poisoning. Time (long past due) for urgent, effective interventions. Chest 1992;102(6):1842-5 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/1928887|Varon J, Duncan SR.]]Naloxone reversal of hypotension due to captopril overdose. //Ann Emerg Med// 1991;20(10):1125-7 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/1497172|Mortensen ME, Bolon CF, Kelley MT, Walson PD, Cassidy S.]] Encainide overdose in an infant. //Ann Emerg Med// 1992;21(8):998-1001 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/7905816|Kollef MH]]. Labetalol overdose successfully treated with amrinone and alpha-adrenergic receptor agonists. Chest 1994;105(2):626-7 ==== ==== See: **[[:wikitox:problems_for_discussion_2_vasodilators|Problems for Discussion]]** ===== ANTIARRHYTHMICS ===== ==== Objectives ==== * Understand how the presentation of Class 1A agents parallels that of other drugs. * Relate the common clinical presentation and time course of type 1B agents in overdose. * Detail how the acute and chronic presentations of antiarrhythmics poisoning may differ. ==== Reading ==== **[[:wikitox:3.4.3.4_antiarrhythmics|Antiarrhythmics]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9140253|Yasui RK, Culclasure TF, Kaufman D, Freed CR]]. Flecainide overdose: is cardiopulmonary support the treatment? //Ann Emerg Med// 1997;29(5):680-2 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9528738|Katz AM]]. Selectivity and toxicity of antiarrhythmic drugs: molecular interactions with ion channels. //Am J Med// 1998;104(2):179-95 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11726437|Gilbert TB]]. Cardiac arrest from inadvertent overdose of lidocaine hydrochloride through an arterial pressure line flush apparatus. //Anesth Analg// 2001;93(6):1534-6, table of contents \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9825278|Brazil E, Bodiwala GG, Bouch DC.]] Fatal flecainide intoxication. //J Accid Emerg Med// 1998;15(6):423-5 See: **[[:wikitox:problems_for_discussion_2_antiarrhythmics|Problems for Discussion]]** ===== CARDIAC GLYCOSIDES ===== ==== Objectives ==== * To be able to recognise the major sources of poisoning by naturally occurring cardiac glycosides. * To be able to perform a risk assessment following digoxin acute deliberate self-poisoning or accidental paediatric ingestion. * To be able to discuss the risk factors for chronic digoxin intoxication. * To be able to discuss the pharmacokinetics and pharmacodynamics of digoxin. * To be able to recognise the clinical, biochemical and electrocardiographic manifestations of acute and chronic cardiac glycoside intoxication. * To be able to discuss the mechanism of action of digoxin-specific antibodies. * To be able to calculate an appropriate dose of digoxin-specific antibody in a variety of clinical situations. ==== Reading ==== **[[:wikitox:2.1.6.1.2_cardiac_glycosides|Cardiac glycoside]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9727817|Marik PE, Fromm L]].A case series of hospitalized patients with elevated digoxin levels.Am J Med 1998 Aug;105(2):110-5. \\ [[http://www.ncbi.nlm.nih.gov/pubmed/12801736|de Silva HA, Fonseka MM, Pathmeswaran A, Alahakone DG, Ratnatilake GA, Gunatilake SB, Ranasinha CD, Lalloo DG, Aronson JK, de Silva HJ]]. Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial. Lancet 2003;361(9373):1935-8 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10768435|Eddleston M, Rajapakse S, Rajakanthan, Jayalath S, Sjostrom L, Santharaj W et al]]. Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial. Lancet 2000; 355(9208):967-972. \\ [[http://www.ncbi.nlm.nih.gov/pubmed/3094820|Gibb I, Parnham A.]]A star treatment for digoxin overdose? Br Med J (Clin Res Ed) 1986;293(6555):1171-2 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/6409318|Maheswaran R, Bramble MG, Hardisty CA.]]Massive digoxin overdose: successful treatment with intravenous amiodarone. Br Med J (Clin Res Ed) 1983;287(6389):392-3 See: **[[:wikitox:problems_for_discussion_2_cardiac_glycoside|Problems for Discussion]]** ===== ANTICOAGULANT POISONINGS ===== ==== Objectives ==== * Understand the mechanism of toxicity of coumarin anticoagulants. * Understand the different scenarios of anticoagulant poisoning. * Review the literature on the risk of bleeding in patients who are over-anticoagulated. * Understand the treatment options for anticoagulant poisoning: therapeutic, deliberate and unintentional. ==== Reading ==== **[[:wikitox:2.2.7.5.1_anticoagulant|Anticoagulant Poisonings]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/7776988|Cannegieter SC, Rosendaal FR, Wintzen AR, van der Meer FJ, Vandenbroucke JP, Briët E]]. Optimal oral anticoagulant therapy in patients with mechanical heart valves. //N Engl J Med// 1995;333(1):11-7 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11075768|Crowther MA, Julian J, McCarty D, Douketis J, Kovacs M, Biagoni L, Schnurr T, McGinnis J, Gent M, Hirsh J, Ginsberg J.]] Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial. Lancet 2000;356(9241):1551-3 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/12085076|Ingels M, Lai C, Tai W, Manning BH, Rangan C, Williams SR, Manoguerra AS, Albertson T, Clark RF]]. A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination. //Ann Emerg Med// 2002;40(1):73-8 \\ Ramanan AV, Gissen P, Bose-Haider B. Intentional overdose of warfarin in an adolescent: need for follow up. //Emerg Med J// 2002;19(1):90 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/9759690|Chua JD, Friedenberg WR.]]Superwarfarin poisoning. //Arch Intern Med// 1998;158(17):1929-32 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10654963|Mullins ME, Brands CL, Daya MR.]] Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time? Pediatrics 2000;105(2):402-4 See: **[[:wikitox:problems_for_discussion_2_anticoagulant_poisoning|Problems for Discussion]]**