This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong. ====== Module 3 - Anticonvulsants and Other Centrally Acting Drugs ====== ===== FULL TEXT READING ===== Jones AL, Proudfoot AT. Features and management of poisoning with modern drugs used to treat epilepsy. QJM 1998;325-332[[http://qjmed.oxfordjournals.org/content/91/5/325.full.pdf+html|(Fulltext)]]\\ [[http://www.ncbi.nlm.nih.gov/pubmed/20376593|Clinical effects and toxicokinetic evaluation following massive topiramate ingestion.]] Lynch MJ, Pizon AF, Siam MG, Krasowski MD. J Med Toxicol 2010;6(2):135-8\\ [[http://www.ncbi.nlm.nih.gov/pubmed/19043374|Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion.]] Eyer F, Felgenhauer N, Pfab R, Thürmel K, Zilker T. Med Sci Monit 2008;14(12):CS145-8\\ [[http://www.ncbi.nlm.nih.gov/pubmed/18855540|Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations.]]\\ Ferrell PB Jr, McLeod HL. Pharmacogenomics 2008;9(10):1543-6\\ [[http://www.ncbi.nlm.nih.gov/pubmed/17711961|Chronic valproic acid intoxication: reversal by naloxone.]] Thanacoody HK. Emerg Med J 2007;24(9):677-8 PMID17711961Free PMC Article\\ [[http://www.ncbi.nlm.nih.gov/pubmed/17409271|Possible bioactivation pathways of lamotrigine.]] Lu W, Uetrecht JP. Drug Metab Dispos 2007;35(7):1050-6 Epub 2007 Apr 4\\ [[http://www.ncbi.nlm.nih.gov/pubmed/17057142|Toxicology case of the month: Carbamazepine overdose.]] Soderstrom J, Murray L, Little M, Daly FF. Emerg Med J 2006;23(11):869-71\\ [[http://www.ncbi.nlm.nih.gov/pubmed/16277730|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;9(5):431-40 Epub 2005 Jun 10. Review\\ ===== VALPROATE ===== ==== Reading ==== **[[:wikitox:3.4.2.2_sodium_valproate|Valproate]]** \\ [[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884232/|Isbister GK, Balit CR, Whyte IM, Dawson A.]] Valproate overdose: a comparative cohort study of self poisonings.Br J Clin Pharmacol 2003;55(4):398-404\\ [[http://www.ncbi.nlm.nih.gov/pubmed/18082799|Sikma MA, Mier JC, Meulenbelt J]].Massive valproic acid overdose, a misleading case. Am J Emerg Med 2008;26(1):110.e3-6. See: **[[:wikitox:problems_for_discussion_2_anticonvulsants_valproate|Problems for Discussion]]** ===== 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 ==== **[[:wikitox:2.1.11.2.1_phenytoin|Phenytoin]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/14718732|Privitera MD, Welty T.]]Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Neurology 2004;62(1):161; author reply 161\\ [[http://www.ncbi.nlm.nih.gov/pubmed/11206048|Mamiya K, Kojima K, Yukawa E, Higuchi S, Ieiri I, Ninomiya H, Tashiro N]].Phenytoin intoxication induced by fluvoxamine.Ther Drug Monit 2001;23(1):75-7 See: **[[:wikitox:problems_for_discussion_2_anticonvulsants_phenytoin|Problems for Discussion]]** ===== 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 ==== **[[:wikitox:3.4.2.3_carbamazepine|Carbamazepine]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/14762040|LaRoche SM, Helmers SL]].The new antiepileptic drugs: scientific review. JAMA 2004;291(5):605-14 See: **[[:wikitox:problems_for_discussion_2_anticonvulsants_carbamazepine|Problems for Discussion]]** ===== 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 ==== **[[:wikitox:quinine|Quinine]] and [[:wikitox:chloroquine|]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/8400953|Wilkinson R, Mahatane J, Wade P, Pasvol G.]]Chloroquinine poisoning.BMJ 1993;307(6902):504\\ [[http://books.google.com/books?hl=en&id=qDf3AO8nILoC&dq=medical+toxicology&printsec=frontcover&source=web&ots=pUNi90ot1s&sig=j_Lgktu6Vjisb9X2Sm5ZsA2ENRw&sa=X&oi=book_result&resnum=8&ct=result|Wyte IM]]. Chapter 94: Antimalarial agents. In: Dart RC et al (Eds). MedicalToxicology. Third Edition. Philadelphia: Lippincott Williams and Wilkins; 2004. p.466-474 See: **[[:wikitox:problems_for_discussion_2_quinine_and_the_antimalarial_agents|Problems for Discussion]]** ===== 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 ==== **[[:wikitox:2.1.11.4.1_anticholinergics|Anticholinergics]] and [[:wikitox:2.1.11.4.2_antihistamines|Antihistamines]]** \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11719751|Isbister GK, Oakley P, Whyte I, Dawson A]].Treatment of anticholinergic-induced ileus with neostigmine. Ann Emerg Med 2001;38(6):689-93 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/12902007|Suchard JR]]. Assessing physostigmine's contraindication in cyclic antidepressant ingestions. J Emerg Med 2003;25(2):185-91 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11174251|Oakley P]]. Physostigmine versus diazepines for anticholinergic poisoning. Ann Emerg Med 2001;37(2):239-41 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10234644|Francis PD, Clarke CF]]. Angel trumpet lily poisoning in five adolescents: clinical findings and management. J Paediatr Child Health 1999 Feb;35(1):93-5 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10750216|Craig-McFeely PM, Freemantle SL, Pearce GL, Shakir SA]].QT lengthening and life-threatening arrhythmias associated with fexofenadine. Br J Gen Pract 2000;50(451):148 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/1564131|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;32(3):267-71 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/10215756|de Abajo FJ, RodrÃguez LA]].Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs. Br J Clin Pharmacol 1999;47(3):307-13 \\ [[http://www.ncbi.nlm.nih.gov/pubmed/11318079|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;23(3):451-66 See: **[[:wikitox:problems_for_discussion_2_anticholinergics_and_antihistamines|Problems for Discussion]]** ===== 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 ==== **[[:wikitox:2.1.11.4.6_xanthines|Xanthines]]** \\ [[http://www.annals.org/cgi/content/full/133/11/922|Okada S, Teramoto S, Matsuoka R]].Recovery from theophylline toxicity by continuous hemodialysis with filtration. Ann Intern Med 2000;133(11):922 See: **[[:wikitox:problems_for_discussion_2_xanthines|Problems for Discussion]]** CKG Edit