Tricyclic antidepressant overdose pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have [[anticholinergic]] effects, cause excessive blockade of [[norepinephrine]] reuptake at the preganglionic [[synapse]], direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having [[quinidine]] like effects on the [[myocardium]].<ref name="EmergMedJ2001-Kerr">{{cite journal | author = Kerr G, McGuffie A, Wilkie S | title = Tricyclic antidepressant overdose: a review | journal = Emerg Med J | volume = 18 | issue = 4 | pages = 236–41 | year = 2001 | pmid = 11435353 | doi = 10.1136/emj.18.4.236 | pmc = 1725608}}</ref> | Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have [[anticholinergic]] effects, cause excessive blockade of [[norepinephrine]] reuptake at the preganglionic [[synapse]], direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having [[quinidine]] like effects on the [[myocardium]].<ref name="EmergMedJ2001-Kerr">{{cite journal | author = Kerr G, McGuffie A, Wilkie S | title = Tricyclic antidepressant overdose: a review | journal = Emerg Med J | volume = 18 | issue = 4 | pages = 236–41 | year = 2001 | pmid = 11435353 | doi = 10.1136/emj.18.4.236 | pmc = 1725608}}</ref> | ||
==Pathophysiology== | |||
===Toxicity=== | |||
Tricyclics have a narrow [[therapeutic index]], ''i.e.'', the therapeutic [[Dose (biochemistry)|dose]] is close to the toxic dose.<ref name="Woolf-2007">{{cite journal |author=Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG |title=Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management |journal=Clin Toxicol (Phila) |volume=45 |issue=3 |pages=203–33 |year=2007 |pmid=17453872 |doi=10.1080/15563650701226192}}</ref> In the medical literature the lowest reported toxic dose is 6.7 mg per kg body weight. Although there are differences in toxicity with the drug class, ingestions of 10 to 20 mg per kilogram of body weight are a risk for moderate to severe poisoning, however, doses ranging from 1.5 to 5 mg/kg may even present a risk. Most [[poison control center]]s refer any case of TCA poisoning (especially in children) to a hospital for monitoring.<ref name="clintox2000-McFee">{{cite journal | author = McFee R, Mofenson H, Caraccio T | title = A nationwide survey of the management of unintentional-low dose tricyclic antidepressant ingestions involving asymptomatic children: implications for the development of an evidence-based clinical guideline |journal = J Toxicol Clin Toxicol | volume = 38 | issue = 1 | pages = 15–9 | year = 2000 | pmid = 10696919 | doi = 10.1081/CLT-100100910}}</ref> Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.<ref name="JClinPsychiatry1982-Preskorn">{{cite journal | author = Preskorn S, Irwin H | title = Toxicity of tricyclic antidepressants--kinetics, mechanism, intervention: a review | journal = J Clin Psychiatry | volume = 43 | issue = 4 | pages = 151–6 | year = 1982 | pmid = 7068546}}</ref> However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.<ref name="NEngJMed1985-Boehnert">{{cite journal | doi = 10.1056/NEJM198508223130804 | author = Boehnert M, Lovejoy F | title = Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants | journal = N Engl J Med | volume = 313 | issue = 8 | pages = 474–9 | year = 1985 | pmid = 4022081}}</ref> TCA levels >1000 ng/ml were associated with QT and QRS prolongation and [[convulsions]]. | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2]
Overview
Most of the toxic effects of TCAs are caused by four major pharmacological effects. TCAs have anticholinergic effects, cause excessive blockade of norepinephrine reuptake at the preganglionic synapse, direct alpha adrenergic blockade, and importantly they block sodium membrane channels with slowing of membrane depolarization, thus having quinidine like effects on the myocardium.[1]
Pathophysiology
Toxicity
Tricyclics have a narrow therapeutic index, i.e., the therapeutic dose is close to the toxic dose.[2] In the medical literature the lowest reported toxic dose is 6.7 mg per kg body weight. Although there are differences in toxicity with the drug class, ingestions of 10 to 20 mg per kilogram of body weight are a risk for moderate to severe poisoning, however, doses ranging from 1.5 to 5 mg/kg may even present a risk. Most poison control centers refer any case of TCA poisoning (especially in children) to a hospital for monitoring.[3] Factors that increase the risk of toxicity include advancing age, cardiac status, and concomitant use of other drugs.[4] However, serum drug levels are not useful for evaluating risk of arrhythmia or seizure in tricyclic overdose.[5] TCA levels >1000 ng/ml were associated with QT and QRS prolongation and convulsions.
References
- ↑ Kerr G, McGuffie A, Wilkie S (2001). "Tricyclic antidepressant overdose: a review". Emerg Med J. 18 (4): 236–41. doi:10.1136/emj.18.4.236. PMC 1725608. PMID 11435353.
- ↑ Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, Wax PM, Manoguerra AS, Scharman EJ, Olson KR, Chyka PA, Christianson G, Troutman WG (2007). "Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management". Clin Toxicol (Phila). 45 (3): 203–33. doi:10.1080/15563650701226192. PMID 17453872.
- ↑ McFee R, Mofenson H, Caraccio T (2000). "A nationwide survey of the management of unintentional-low dose tricyclic antidepressant ingestions involving asymptomatic children: implications for the development of an evidence-based clinical guideline". J Toxicol Clin Toxicol. 38 (1): 15–9. doi:10.1081/CLT-100100910. PMID 10696919.
- ↑ Preskorn S, Irwin H (1982). "Toxicity of tricyclic antidepressants--kinetics, mechanism, intervention: a review". J Clin Psychiatry. 43 (4): 151–6. PMID 7068546.
- ↑ Boehnert M, Lovejoy F (1985). "Value of the QRS duration versus the serum drug level in predicting seizures and ventricular arrhythmias after an acute overdose of tricyclic antidepressants". N Engl J Med. 313 (8): 474–9. doi:10.1056/NEJM198508223130804. PMID 4022081.