MODULE 3
Anticonvulsants and Other Centrally Acting Drugs




FullTextReading

Jones AL, Proudfoot AT. Features and management of poisoning with modern drugs used to treat epilepsy. QJM;1998:325-332.(Fulltext)



Clinical effects and toxicokinetic evaluation following massive topiramate ingestion.
Lynch MJ, Pizon AF, Siam MG, Krasowski MD.
J Med Toxicol. 2010 Jun;6(2):135-8.




Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion.
Eyer F, Felgenhauer N, Pfab R, Thürmel K, Zilker T.
Med Sci Monit. 2008 Dec;14(12):CS145-8.



Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations.
Ferrell PB Jr, McLeod HL.
Pharmacogenomics. 2008 Oct;9(10):1543-6.



Chronic valproic acid intoxication: reversal by naloxone.
Thanacoody HK.
Emerg Med J. 2007 Sep;24(9):677-8.
PMID: 17711961 [PubMed - indexed for MEDLINE]Free PMC Article


Possible bioactivation pathways of lamotrigine.
Lu W, Uetrecht JP.
Drug Metab Dispos. 2007 Jul;35(7):1050-6. Epub 2007 Apr 4.



Toxicology case of the month: Carbamazepine overdose.
Soderstrom J, Murray L, Little M, Daly FF.
Emerg Med J. 2006 Nov;23(11):869-71.



Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence?
Lheureux PE, Penaloza A, Zahir S, Gris M.
Crit Care. 2005 Oct 5;9(5):431-40. Epub 2005 Jun 10. Review.







Valproate


Reading

Valproate

Isbister GK, Balit CR, Whyte IM, Dawson A. Valproate overdose: a comparative cohort study of self poisonings.Br J Clin Pharmacol. 2003 Apr;55(4):398-404.
Sikma MA, Mier JC, Meulenbelt J.Massive valproic acid overdose, a misleading case.Am J Emerg Med. 2008 Jan;26(1):110.e3-6.

Problems

1 , 2




Phenytoin


Objectives

  • Understand the complex pharmacokinetics of phenytoin and how these influence the risk for phenytoin toxicity.
  • Compare and contrast the differences between oral and intravenous phenytoin toxicity.

Reading

Phenytoin

Privitera MD, Welty T.Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction.Neurology. 2004 Jan 13;62(1):161; author reply 161.
Mamiya K, Kojima K, Yukawa E, Higuchi S, Ieiri I, Ninomiya H, Tashiro N.Phenytoin intoxication induced by fluvoxamine.Ther Drug Monit. 2001 Feb;23(1):75-7.


Problems

1



Carbamazepine


Objectives

  • Understand the mechanisms of toxicity and the clinical effects seen in carbamazepine poisoning.
  • Realise the potential importance and methods of GI decontamination following massive carbamazepine overdose
  • Understand the methods of enhanced elimination that may be used to increase carbamazepine clearance in severe poisoning.

Reading

Carbamazepine

LaRoche SM, Helmers SL.The new antiepileptic drugs: scientific review. JAMA. 2004 Feb 4;291(5):605-14.


Problems

1 , 2




Quinine and the Antimalarial agents


Objectives

  • To be able to discuss the important adverse effects of chloroquine and quinine in therapeutic doses.
  • To be able to perform a risk assessment following acute deliberate self-poisoning and accidental paediatric ingestion of quinine, chloroquine and hydroxychloroquine.
  • To be able to discuss the clinical manifestations of quinine intoxication, including cinchonism, CNS effects, cardiovascular effects and quinine blindness (amblyopia).
  • To be able to discuss the clinical manifestations of chloroquine and hydroxychloroquine intoxication.
  • To be able to discuss the role of gastrointestinal decontamination and intravenous diazepam in antimalarial poisoning.

Reading

Quinine and the antimalarial agents

Wilkinson R, Mahatane J, Wade P, Pasvol G.Chloroquinine poisoning.BMJ. 1993 Aug 21;307(6902):504.



Wyte IM. Chapter 94: Antimalarial agents. In: Dart RC et al (Eds). MedicalToxicology. Third Edition. Philadelphia: Lippincott Williams and Wilkins; 2004. p.466-474.


Problems

1, 2



Anticholinergics and Antihistamines


Objectives- Antihistamines

  • To understand the differences in antihistamine toxicity
  • To review the effects of P450 metabolism on drug toxicity
  • To review the effects of the potassium efflux pump (ie, potassium channel)


Objectives- Anticholinergics

  • To understand the diagnostic features of the anticholinergic syndrome
  • To understand the role of cholinergic agents in its treatment and the background to the controversy

Reading

Anticholinergics and Antihistamines

Isbister GK, Oakley P, Whyte I, Dawson A.Treatment of anticholinergic-induced ileus with neostigmine.Ann Emerg Med. 2001 Dec;38(6):689-93.
Suchard JR.Assessing physostigmine's contraindication in cyclic antidepressant ingestions.J Emerg Med. 2003 Aug;25(2):185-91.
Oakley P.Physostigmine versus diazepines for anticholinergic poisoning.Ann Emerg Med. 2001 Feb;37(2):239-41.
Francis PD, Clarke CF.ngel trumpet lily poisoning in five adolescents: clinical findings and management.J Paediatr Child Health. 1999 Feb;35(1):93-5.

Craig-McFeely PM, Freemantle SL, Pearce GL, Shakir SA.QT lengthening and life-threatening arrhythmias associated with fexofenadine.Br J Gen Pract. 2000 Feb;50(451):148.
Eller MG, Walker BJ, Westmark PA, Ruberg SJ, Antony KK, McNutt BE, Okerholm RA.Pharmacokinetics of terfenadine in healthy elderly subjects. J Clin Pharmacol. 1992 Mar;32(3):267-71.
de Abajo FJ, Rodríguez LA.Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs. Br J Clin Pharmacol. 1999 Mar;47(3):307-13.
Gupta S, Banfield C, Kantesaria B, Marino M, Clement R, Affrime M, Batra V.Pharmacokinetic and safety profile of desloratadine and fexofenadine when coadministered with azithromycin: a randomized, placebo-controlled, parallel-group study.Clin Ther. 2001 Mar;23(3):451-66.




Problems

1



Xanthines


Objectives

  • Understand the mechanism of toxicity and clinical effects.
  • Understand treatment of theophylline overdose, in particular the theory behind the use of multi-dose charcoal.

Reading

Xanthines

Okada S, Teramoto S, Matsuoka R.Recovery from theophylline toxicity by continuous hemodialysis with filtration.Ann Intern Med. 2000 Dec 5;133(11):922.


Problems

1 , 2