Pharmacology for Anaesthesia and Intensive Care

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17 Central nervous system

Table 17.2.Effects of various antidepressants.

Anticholinergic

effects Sedation

Postural

hypotension

TCA

Amitriptyline ++++ ++++ ++

Imipramine ++ ++ +++

Nortriptyline ++ ++ +

Desipramine +++

SSRI

Fluoxetine + nil +

Mechanism of action

They competitively block neuronal uptake (uptake 1) of noradrenaline and sero-

tonin (5-HT). In doing so they increase the concentration of transmitter in the

synapse. However, the antidepressant effects do not occur within the same time

frame, taking up to 2 weeks to work. They also block muscarinic, histaminergic and

α-adrenoceptors, and have non-specific sedative effects (Table17.2).

Effects


Central nervous system – sedation and occasionally seizures in epileptic patients.


Anticholinergic effects – dry mouth, constipation, urinary retention and blurred

vision.


Cardiovascular – postural hypotension especially in the elderly.

Kinetics

TCAs are well absorbed from the gut reflecting their high lipid solubility. They are

highly plasma protein bound and have a high volume of distribution. Metabolism,

which shows large interpatient variability, occurs in the liver and often produces

active metabolites (e.g. imipramine to desipramine and nortriptyline).

TCA overdose

This is not uncommon in depressed patients. The features of tricyclic overdose

include a mixture of:


Cardiovascular effects – sinus tachycardia is common and there is a dose-related

prolongation of the QT interval and widening of the QRS complex. Ventricular

arrhythmias are more likely when the QRS complex is longer than 0.16 seconds.

Right bundle branch block is also seen. The blood pressure may be high or low but

in serious overdose hypotension may be refractory to treatment and culminate in

pulseless electrical activity.