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MODULE 2 Antidiabetic drugs, analgesics and NSAIDs,Opioids,Methotrexate and Colchicine Objectives At the end of this module, students should be able to: · Understand the mechanisms underlying the toxicity of these agents · Undertake a risk assessment of poisoning · Be aware of agents that have a delayed onset or protracted time course of poisoning and how patients should be monitored · Understand the role and limitations of specific antidotes, where available · Develop an approach for the treatment of these drugs, as single ingestants or co-ingestants
Biguanides, Sulphonylureas and Insulin Objectives - Understand the mechanism of toxicity and clinical effects including time course of hypoglycaemic agents
- Understand the role of antidotes in hypoglycaemic poisoning
- Understand some of the complexities in a medicolegal toxicology case
Reading Biguanides , Sulphonylureas and Insulin Galea M, Jelacin N, Bramham K, White I .Severe lactic acidosis and rhabdomyolysis following metformin and ramipril overdose. Br J Anaesth. 2007 Feb;98(2):213-5.
Lheureux PE, Zahir S, Penaloza A, Gris M .Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide. Crit Care. 2005;9(6):543-9. Epub 2005 Sep 7. Uchida D, Ohigashi S, Hikita S, Kitamura N, Motoyoshi M, Tatsuno I .Acute pulmonary edema caused by hypoglycemia due to insulin overdose. Intern Med. 2004 Nov;43(11):1056-9.
Problems 1 Analgesics and Anti-inflammatory NSAID Poisoning Paracetamol Objectives - To be able to do a risk assessment of a paracetamol poisoning
- Consider variables which may affect the risk assessment
- Understand the limitations of the nomogram
- Understand treatment of paracetamol poisoning
- Discuss the effective methods of gastric decontamination in paracetamol overdose
- Discuss the efficacy of available antidotes based on strength of evidence
- Discuss the problems of management when working in resource poor settings
- Compare the differences in prognosis and management in acute deliberate and accidental paracetamol overdose.
Reading Acetaminophen Teece S, Hogg K .Best evidence topic reports. Gastric lavage in paracetamol poisoning. Emerg Med J. 2004 Jan;21(1):75-6. Penna A, Buchanan N .Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol. 1991 Aug;32(2):143-9. Dargan PI, Jones AL .Acetaminophen poisoning: an update for the intensivist. Crit Care. 2002 Apr;6(2):108-10. Epub 2002 Mar 14. Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, Williams R .Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ. 1991 Oct 26;303(6809):1026-9. Wallace CI, Dargan PI, Jones AL .Paracetamol overdose: an evidence based flowchart to guide management. Emerg Med J. 2002 May;19(3):202-5. Cooper GM, Le Couteur DG, Richardson D, Buckley NA .A randomized clinical trial of activated charcoal for the routine management of oral drug overdose. QJM. 2005 Sep;98(9):655-60. Epub 2005 Jul 22.
Problems 1 , 2 , 3 , 4 , 5 , 6
Anti-inflammatory NSAID Objectives - Understand the mechanism of toxicity of NSAIDs.
- Understand the potential complications of NSAID overdose in general and which agents have specific toxicities.
Reading Analgesics and Anti-inflammatory NSAID Poisoning Alan H. Hall, MD, Susan C. Smolinske, RPh, Kenneth W. Kulig, MD, and Barry H. Rumack, MD .Ibuprofen Overdose—A Prospective Study. West J Med. 1988 June; 148 (6) : 653–656. V Danel, J A Henry, and E Glucksman .Activated charcoal, emesis, and gastric lavage in aspirin overdose. BMJ. 1988 May 28; 296 (6635) : 1507.
D. C. Brown and J. M. Savage .Therapeutic aspirin overdose in a three-year-old boy. Ulster Med J. 1987 April; 56 (1) : 63–65.
Problems 1 , 2 , 3 , 4 Opioids Reading Opioids Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U .Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci. 2005 Mar;30(2):245-52. A Kelly and Z Koutsogiannis .Intranasal naloxone for life threatening opioid toxicity. Emerg Med J. 2002 July; 19 (4) : 375.
Fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine .Safety of codeine during breastfeeding. Can Fam Physician. 2007 January; 53 (1) : 33–35. Problems. 1 , 2 , 3 Methotrexate Reading Methotrexate Noriko IIKUNI1), Sumiko IWAMI1), Shogo KASAI1) and Hitoshi TOKUDA1) . Noncardiogenic Pulmonary Edema in Low-dose Oral Methotrexate Therapy . Internal Medicine Vol. 43 (2004) , No. 9 pp.846-851. Etchells E .Preventing deaths from methotrexate overdose. J Rheumatol. 2005 Oct;32(10):1853-5.
Problems 1 Colchicine Objectives - Understand the mechanism of toxicity
- Be able to make a risk assessment
- Understand the issues underlying the provision of antidotes
Reading Colchicine Weakley-Jones, Barbara M.D.; Gerber, John E. M.D.; Biggs, Gary .Colchicine Poisoning: Case Report of Two Homicides. American Journal of Forensic Medicine & Pathology . 22(2):203-206, June 2001. Baud FJ, Sabouraud A, Vicaut E, Taboulet P, Lang J, Bismuth C, Rouzioux JM, Scherrmann JM. Brief report: treatment of severe colchicine overdose with colchicine-specific Fab fragments. N Engl J Med. 1995 Mar 9;332(10):642-5. M Maxwell, P Muthu, and P Pritty. Accidental colchicine overdose. A case report and literature review. Emerg Med J. 2002 May; 19 (3) : 265–267. Problems 1 , 2
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