Analgesics and Antidepressants

Published on 07/03/2015 by admin

Filed under Critical Care Medicine

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1004 times

Chapter 79 Analgesics and Antidepressants

13 What are the receptor effects and clinical effects of tricyclic antidepressant (TCA) poisoning?

TCAs have seven pharmacologic effects. Understanding these effects is helpful in remembering the associated clinical syndrome of TCA toxicity (Table 79-1).

Table 79-1 Pharmacologic Effects of Tricyclic Antidepressants

Mechanism Effect
Presynaptic biogenic amine reuptake inhibition (norepinephrine and serotonin) Therapeutic antidepressant effect
Early sympathomimesis
Myoclonus
Hyperreflexia
Fast sodium channel influx blockade QRS duration prolonged
PR interval prolonged
Right axis deviation
Bundle branch blockade
Ventricular dysrhythmias
Negative inotropy
Potassium channel efflux blockade QTc prolongation
Muscarinic acetylcholine receptor blockade Tachycardia
Mydriasis
Decreased sweating
Hyperthermia
Flushing
Ileus
Urinary retention
Histaminic receptor blockade Sedation
Alpha receptor blockade Sedation
Orthostatic hypotension
Miosis
Reflex tachycardia
GABA-A receptor blockade Seizures
Status epilepticus

GABA-A, γ-Aminobutyric acid-A.

15 How is cardiovascular toxicity of TCAs treated?

Cardiovascular toxicity of TCAs is treated first with sodium bicarbonate therapy, titrating initial bolus therapy to resolution of QRS prolongation and following this with continuous infusion of bicarbonate solution to alkalinize the serum and provide a loading dose of sodium ions. If the patient continues to have QRS prolongation or significant right axis deviation, despite alkalemia to pH of 7.55, hypertonic saline solution can also be administered. Lidocaine is the historical second-line agent in treating dysrhythmias, but the physician must be aware that lidocaine is also a sodium channel blocker and administration could potentiate seizures. Synchronous cardioversion should be used in patients with TCA overdose on the basis of current advanced cardiac life support guidelines when indicated. Torsades de pointes can be treated with magnesium sulfate infusion. Despite the QTc prolongation associated with TCA use, the tachycardia due to the antimuscarinic effects of TCAs often limits the likelihood of “R-on-T” phenomena. Finally, in recent years, lipid emulsion rescue has emerged as an antidotal treatment in life-threatening poisoning by lipophilic drugs. All TCAs are highly lipophilic, given their therapeutic targets in the CNS, and animal and human data suggest that TCAs and related compounds respond well to lipid rescue. Patients with known or suspected TCA cardiotoxicity and hemodynamic instability or malignant dysrhythmias are candidates for lipid emulsion therapy, discussed in more detail in Chapter 81 on cardiovascular drug toxicity.

Bibliography

1 Bailey B., Buckley N.A., Amre D.K. A meta-analysis of prognostic indicators to predict seizures, arrhythmias or death after tricyclic antidepressant overdose. J Toxicol Clin Toxicol. 2004;42:877–888.

2 Bradberry S.M., Thanacoody H.K., Watt B.E., et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev. 2005;24:195–204.

3 Body R., Bartram T., Azam F., et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the management of tricyclic antidepressant overdose. Emerg Med J. 2011;28:347–368.

4 Engels P.T., Davidow J.S. Intravenous fat emulsion to reverse haemodynamic instability from intentional amitriptyline overdose. Resuscitation. 2010;81:1037–1039.

5 Heard K.J. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008;359:285–292.

6 Higgins R.M., Connolly J.O., Hendry B.M. Alkalinization and hemodialysis in severe salicylate poisoning: comparison of elimination techniques in the same patient. Clin Nephrol. 1998;50:178–183.

7 Johnson M.T., McCammon C.A., Mullins M.E., et al. Evaluation of a simplified N-acetylcysteine dosing regimen for the treatment of acetaminophen toxicity. Ann Pharmacother. 2011;45:713–720.

8 Khandelwal N., James L.P., Sanders C., et althe Acute Liver Failure Study Group. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology. 2011;53:567–576.

9 Kolecki P.F., Curry S.C. Poisoning by sodium channel blocking agents. Crit Care Clin. 1997;13:829–848.

10 O’Malley G.F. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25:333–346.

11 Pentel P.R., Benowitz N.L. Tricyclic antidepressant poisoning. Management of arrhythmias. Med Toxicol. 1986;1:101–121.

12 Pierog J.E., Kane K.E., Kane B.G., et al. Tricyclic antidepressant toxicity treated with massive sodium bicarbonate. Am J Emerg Med. 2009;27:1168. e3-e7

13 Wells K., Williamson M., Holstege C.P., et al. The association of cardiovascular toxins and electrocardiographic abnormality in poisoned patients. Am J Emerg Med. 2008;26:957–959.