Tricyclic acids (TCAs) have been in heavy use for clinical depression since the 1950s.  Despite newer antidepressants, TCAs have a role in major depressive disorder, chronic and neuropathic pain, attention deficit hyperactivity disorder, cyclical vomiting, nocturnal enuresis, and obsessive-compulsive disorders.

Pharmacology

TCAs’ lipophilic structures share a common three-ring subunit and can be classified into tertiary amines and secondary amines.

Antidepressant effects of these drugs are the result of presynaptic reuptake inhibition of serotonin and norepinephrine.  Other pharmacologic effects include competitive muscarinic and alpha-adrenergic antagonism and histamine inhibition, as well as GABA-A antagonism.

TCAs also produce cardiac sodium channel blockade and can be classified as having type IA antiarrhythmic properties. Since these drugs are lipophilic, they bind to plasma proteins and distribute rapidly into tissues (avid to brain and myocardium) with large volumes of distribution and long half-lives of elimination.

Specifically as TCAs undergo rapid absorption from the gastrointestinal system, it follows that TCA overdose onset can occur quickly.

Clinical features of TCA poisoning can be explained via their receptor effects.

Neurologic effects

Occurring via antihistaminic- and anticholinergic-mediated effects, clinical manifestations range of altered mental status range the spectrum from the following (least to most severe):

• Agitation
• Delirium
• CNS depression
• Coma

Cardiac effects

Via the effect of sodium channel blockade due to delayed depolarization, cardiac sequelae include

• Cardiac arrhythmias
• AV conduction disturbances
• Brugada-like pattern
• Hypotension (from decreased vascular resistance)
• Myocardial depression.

 

An R wave in aVR of more than 3 mm has a good predictive value for seizures or arrhythmias (terminal axis deviation of the QRS).

Treatment for Suspected TCA Poisoning

Since there is no specific antidote for TCA poisoning, early supportive care is paramount.  Recognition of vital signs and cardiac rhythm should take place in a critical care setting with observation status at the very least.   

Sodium bicarbonate & Alkalosis

• Sodium bicarbonate may ameliorate hypotension due to volume and sodium loading.  
• It also improves myocardial conduction disturbances via the creation of a sodium load and induction of alkalosis, easily created by hyperventilation.
• Induced hyperventilation may be considered in ventilated patients who cannot tolerate large fluid volumes.
• Alkalosis may alter the charge of the TCA-receptor complex and thus reduce free drug availability so that more is protein bound in the serum.
• Sodium bicarbonate remains the therapy of choice, especially for patients Tricyclic acids (TCAs) have been in heavy use for clinical depression since the 1950s.  Despite newer antidepressants, TCAs have a role in major depressive disorder, chronic and neuropathic pain, attention deficit hyperactivity disorder, cyclical vomiting, nocturnal enuresis, and obsessive-compulsive disorders.

Should Suspected TCA Poisoning be dialyzed?

TCAs are small molecules between 200 and 400 Da and thus, will cross any hemofilter or hemodialyzer.  Numerous publications have looked at describing either a high extraction ratio, a significant reduction in TCA plasma concentrations, or a high plasma clearance during ECTR (extracorporeal treatment). 

Given their large volume of distribution, significant redistribution from deeper compartments into plasma, commonly referred to as “rebound”, would be expected after any extracorporeal session.

For these reasons, according to EXTRIP criteria, the dialyzability of TCAs would be assumed to be poor, whatever extracorporeal modality is used and whatever the specific tricyclic studied.

EXTRIP does not recommend performing ECTR in patients with TCA poisoning.

Click here for EXTRIP Reference

About the author

Kamran Boka, MD MS, is Assistant Professor of Medicine and Attending Physician of Pulmonary & Critical Care Medicine at the University of Texas Health Science Center at Houston. He hosts a blog at BokasNotes.com and despite his ongoing love for Apple, has fully embraced Android. When he's not strutting with the Nephrology Social Media Collective, he's coming up with the next greatest hashtag. #EXTRIP4Life