Tuesday, March 14, 2017

Tricyclic antidepressants (TCAs) - MOA and side effects

This is a fun and concise post on the pharmacology of TCAs. Excited? :D

Cellular effect: Presynaptic serotonin and norepinephrine reuptake inhibition
Clinical consequence: Antidepressant and anxiolytic effects
Extra obvious side note: It is the mechanism of action (MOA)! :D

Cellular effect: Peripheral and central muscarinic acetylcholine receptor antagonism
Clinical consequence: Blurred vision, dry mouth (causes dental caries), urinary retention, constipation
Extra fact: Elderly patients are particularly susceptible to these adverse effects.

Cellular effect: Peripheral alpha adrenergic receptor antagonism
Clinical consequence: Orthostatic hypotension
Extra fact: It is the most common cause of discontinuing TCAs.

Cellular effect: Cardiac fast sodium channels blockade (Like Class IA anti-arrhythmic)
Clinical consequence: Decrease cardiac conduction (causes heart block)
Extra fact: Sodium bicarbonate therapy is indicated in patients with TCA poisoning who develop widening of the QRS interval >100 msec or a ventricular arrhythmia. Sodium bicarbonate increases the extracellular sodium concentration increases the electrochemical gradient across cardiac cell membranes, potentially attenuating the TCA-induced blockade of rapid sodium channels. It also increases serum pH and favors the neutral (ie, non-ionized) form of the drug, making it less available to bind to sodium channels.
Alkalinization of urine to eliminate TCAs is NOT the reason why sodium bicarbonate is used for cardiac toxicity.

Cellular effect: CNS GABA-A receptor antagonism
Clinical consequence: Seizures
Extra: It is therefore logical to treat TCA-induced seizures with GABA agonists such as benzodiazepines such as diazepam rather than sodium channel blocking drugs.

Cellular effect: Histaminic (H1) receptor antagonism
Clinical consequence: Sedation, increased appetite (causes weight gain), confusion, delirium
Extra fact: The sedative properties are sometimes harnessed for patients with insomnia, but more benign options are available.

That's all!

Did you know that TCAs should be discontinued prior to screening for pheochromocytoma?

TCAs act by inhibiting norepinephrine uptake into nerve terminals, with subsequent elevation of its metabolite, normetanephrine. False-positive elevation of plasma free normetanephrine levels can occur with other tricyclic medications or combination SNRIs such as venlafaxine or duloxetine. 


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