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 MedicineVol. 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