This section aims to explore some of the mechanisms related to manipulation of pH in the poisoned patient and in particular tricylic antidepressants and other related psychiatric drugs.

At the end of this section, students should be able to:

• Manage specific psychotropic poisonings
• Understand the aims and therapeutic use of pH manipulation
• Understand syndromes related to specific Central Nervous System receptors

Psychiatric drugs history and overview

• pH manipulation in toxicology
• Tricyclic Antidepressant Problem
• Serotonin Reuptake Inhibitors Problem
• Newer antidepressant agents Problem
• Neuroleptic Problems
• Hypnosedative Problems

The relevant reading for each section is featured in each activity:

1. McCabe JL, Cobaugh DJ, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Emerg Med 1998; 32(3 Pt 1):329-333
2. Bradberry S etal . Management of the cardiovascular complications of tricyclic antidepressant poisoning. Role of sodium bicarbonate . Toxicol reviews 2005 ;24(3) : 195-204
3. Segar D A critical reconsideration of the clinical effects and treatment recommendations for sodium channel blocking drug cardiotoxicity.Toxicol Rev. 2006; 25(4):283-96.
4. Intralipid Outperforms Sodium Bicarbonate in a Rabbit Model of Clomipramine Toxicity. Annals of Emergency Medicine 2007; 49(2): 178-185
5. Blackman K, Brown SGA, Wilkes GJ. Plasma alkalinization for tricyclic antidepressant toxicity: a systematic review. Emergency Medicine 2001;13:204-210.
6. Dawson AH: Cyclic antidepressant drugs. Detailed Monograph from HyperTox dawson_therap_drugs_ch134.pdf [148 KB]
7. Nelson LS. Toxicologic myocardial sensitization. Clinical Toxicology 2002;40(7):867-879.
8. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter serotonin toxicity criteria: simple and accurate diagnostic decision rules for serotonin toxicity. Q J Med 2003;96:635-642. (fulltext)
9. Whyte IM, Dawson AH, Buckley NA. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants. Q J Med 2003;96:369-374.(fulltext)
10. Kelly CA, Dhaun N, Laing WJ, et al. Comparative Toxicity of Citalopram and the Newer Antidepressants After Overdose Clinical Toxicology 2004 42: 67-71.
11. Boyer EW, Shannon M. The serotonin syndrome.N Engl J Med. 2005 Mar 17;352(11):1112-20. http://content.nejm.org/cgi/reprint/352/11/1112.pdf…
12. Proudfoot AT, Krenzelok EP, Vale JA. Position Paper on urine alkalinization.J Toxicol Clin Toxicol. 2004;42(1):1-26. (fulltext)
13. Isbister GK, Hackett LP, Dawson AH, Whyte IM, Smith AJ. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. British Journal of Clinical Pharmacology 2003;56:441-450. (fulltext)
14. Whyte IM, Carter G. Neuroleptic Malignant Syndrome in WikiTox 2004.
15. Balit CR, Isbister GK, Hackett LP, Whyte IM. Quetiapine poisoning: a case study. Annals of Emergency Medicine 2003;42(6):751-758.
16. Burns MJ. The pharmacology and toxicology of atypical antipsychotic agents. Clinical Toxicology 2001;39(1):2001.
17. Buckley NA, Whyte IM, Dawson AH. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. Clinical Toxicology 1995;33(3):199-204.
18. Fritschy JM, Brünig I. Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications. Pharmacology & Therapeutics 2003;98:299-323.
19. Whyte IM. Chapter 133: Monoamine oxidase inhibitors. Detailed monograph in WikiTox
20. Whyte IM. Chapter 140: Miscellaneous anxiolytics, sedatives, and hypnotics. Detailed monograph in WikiTox
21. Gueye PN, Lofaso F, Borron SW, Mellerio F, Vicaut E, Harf A, Baud FJ. Mechanism of respiratory insufficiency in pure or mixed drug-induced coma involving benzodiazepines. Clinical Toxicology 2002;40(1):35-47.
22. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30 (fulltext)

• WikiTox: Tricyclic Antidepressants
• WikiTox: Salicylate monograph
• WikiTox: SSRI monograph
• and Serotonin syndrome
• WikiTox: Venlafaxine monograph
• WikiTox: Monoamine oxidase monograph
• WikiTox: Neuroleptics
• and Neuroleptic Malignant Syndrome
• WikiTox: Benzodiazepines

From Pubmed search: isbister gk, hackett…

• Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal. Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal. Br J Clin Pharmacol 2012;73(3):402-10 …
• The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose. The effect of decontamination procedures on the pharmacokinetics of venlafaxine in overdose. Clin Pharmacol Ther 2009;86(4):403-10 Kumar VV, Oscarsso…
• Olanzapine overdose: a series of analytically confirmed cases. Olanzapine overdose: a series of analytically confirmed cases. Int Clin Psychopharmacol 2007;22(3):183-6 Morgan M, Hackett LP, Isbister GK Ab…
• Pharmacokinetics of quetiapine in overdose and the effect of activated charcoal. Pharmacokinetics of quetiapine in overdose and the effect of activated charcoal. Clin Pharmacol Ther 2007;81(6):821-7 Isbister GK, Friberg LE, Hacket…
• Amisulpride deliberate self-poisoning causing severe cardiac toxicity including QT prolongation and torsades de pointes. Amisulpride deliberate self-poisoning causing severe cardiac toxicity including QT prolongation and torsades de pointes. Med J Aust 2006;184(7):354-6 …
• The population pharmacokinetics of citalopram after deliberate self-poisoning: a Bayesian approach. The population pharmacokinetics of citalopram after deliberate self-poisoning: a Bayesian approach. J Pharmacokinet Pharmacodyn 2005;32(3-4):571-605 …
• Intentional warfarin overdose. Intentional warfarin overdose. Ther Drug Monit 2003;25(6):715-22 Isbister GK, Hackett LP, Whyte IM
• Quetiapine poisoning: a case series. Quetiapine poisoning: a case series. Ann Emerg Med 2003;42(6):751-8 Balit CR, Isbister GK, Hackett LP, Whyte IM
• Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity. Br J Clin Pharmacol 2003;56(4):441-50 Isbister GK, Hackett LP, Dawson AH…
• Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection. Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection. J Toxicol Clin Toxicol 2003;41(2):167-73 Isbister GK, Hackett LP…