5.7 TCAs

Question 1

What are the features of a tricyclic antidepressant (TCA) drug poisoning?

CVS

Answer 1

1. Cardiovascular

• Palpitations, chest pain, tachycardia, hypotension
• ECG changes include nonspecific ST or T wave changes,

prolongation of QT, PR and QRS interval,

right bundle branch block, right axis deviation, atrioventricular block,

Brugada wave
(ST elevation in V1–V3 and right bundle branch block)

Question 2

What are the features of a tricyclic antidepressant (TCA) drug poisoning?

CNS

Autonomic

Answer 2

2. Central nervous system

• Agitation,
  hallucinations,
  blurred vision,
  convulsions,
  hyperreflexia,
  myoclonus,
  coma in severe cases

3. Peripheral autonomic system

• Dry mouth,
  dry skin,
  urinary retention,
  pyrexia

Question 3

What is the mechanism of action of TCA drugs?

Answer 3

The pharmacological effects of tricyclic antidepressant drugs
at therapeutic
doses are complex and include:

• Anticholinergic effects
• Competitive antagonism of H1 and H2 receptors
• Blockade of presynaptic uptake of amines
  (norepinephrine, dopamine,
  and serotonin)
• Antagonism of α1 adrenergic receptors
• Blockade of the cardiac fast sodium channel
• Blockade of the cardiac delayed rectifier potassium channel

Question 4

Describe the pharmacokinetics of TCA drugs.

Answer 4

Absorption:
TCA drugs are well absorbed from the gastrointestinal tract,
and peak plasma levels occur 2 to 4 hours after ingestion.

Distribution:
The large volume of distribution
reflects high concentrations in tissues.

Less than 10% of TCA circulates as free drug;
the rest is bound to circulating proteins
(albumin and α1 acid glycoprotein)

or dissolved in circulating free fatty acids.

Metabolism:
TCA drugs are metabolised in the liver by
hydroxylation and methylation.

Many TCAs have active metabolites.

Both the parent drug and the active metabolites
may undergo enterohepatic circulation.

Excretion:
Renal excretion is low and is usually less than 10%.

Question 5

Why do tcA drugs cause arrhythmias and ?

Answer 5

Tricyclic antidepressants

slow phase 0 of cardiac depolarisation

by inhibiting sodium channels.

=

The resulting delay in propagation of
depolarisation in the atrioventricular node,
His-Purkinje fibres,
and ventricular myocardium
leads to prolongation of the PR and QRS interval.

Abnormal atrial and ventricular repolarisation
may give rise to ECG changes mimicking
myocardial infarction
(ST segment elevation and T wave inversion).

Question 6

Why do TCAs cause hypotension

Answer 6

The blood pressure may be elevated in the early stages after overdose,

presumably due to the inhibition of norepinephrine uptake.

Subsequently, the blood pressure is reduced,
often to very low levels and may be due to a number of causes.

TCAs themselves can cause

direct myocardial depression
or it relates to
relative volume depletion

and α receptor blockade induced vasodilatation.

Thus, it usually responds rapidly to intravenous fluids.

Question 7

What is the management of acute TCAD overdose?

Answer 7

ABC approach specific measures

1. • Preventing gastric absorption with activated charcoal
2. • Induced alkalemia with sodium bicarbonate
     as this reduces the amount
     of free drug in circulation
3. • Treatment of arrhythmias:
     Ventricular tachyarrhythmias are treated with
     blockade and severe bradyarrhythmias may need pacing
4. • Treatment of seizures with benzodiazepines
     Supportive care in a HDU/ICU setting.
     Ventilation may be required for a low GCS.

ECG monitoring is recommended for the first 24 hours.