NERVOUS SYSTEM: ANTIDEPRESSANTS, TCAs + RELATED DRUGS

Question 1

TCAs + RELATED DRUGS: INDICATIONS

Answer 1

• 2nd line tx for moderate to severe depression where 1st line SSRIs are ineffective
• Tx option for neuropathic pain - not licensed

Question 2

TCAs + RELATED DRUGS: MOA

Answer 2

• Inhibit neuronal uptake of Serotonin (5-HT) and NA, therefore increasing its avaliability for Neurotransmission
• Block a wide array of receptors - muscarinic, alpha-adrenergic (a1+2), dopamine (D2)

Question 3

TCAs + RELATED DRUGS: IMPORTANT ADVERSE EFFECTS

Answer 3

• Blockade of antimuscarinic receptors causes dry mouth, constipation, urinary retention and blurred vision
• Blockade of H1 and α1 receptors causes sedation and hypotension
• Cardiac adverse effects (multiple mechanisms) include arrhythmias and ECG changes (including prolongation of the QT and QRS durations)
• In the brain, more serious effects include convulsions, hallucinations and mania
• Blockade of dopamine receptors can cause breast changes and sexual dysfunction and rarely causes extrapyramidal symptoms (tremor and dyskinesia)
• Tricyclic antidepressants are extremely dangerous in overdose, causing severe hypotension, arrhythmias, convulsions, coma and respiratory failure, which can be fatal.
• Sudden withdrawal of tricyclic antidepressants can cause gastrointestinal upset, neurological and influenza-like symptoms and sleep disturbance.

Question 4

TCAs + RELATED DRUGS: WARNINGS

Answer 4

• elderly
• people with cardiovascular disease or epilepsy
• people with constipation, prostatic hypertrophy or raised intraocular pressure, which may be worsened by antimuscarinic effects

Question 5

TCAs + RELATED DRUGS: IMPORTANT INTERACTIONS

Answer 5

• Monoamine oxidase inhibitors as both drug classes increase serotonin and noradrenaline levels at the synapse and together they can precipitate hypertension and hyperthermia or serotonin syndrome (see Antidepressants, selective serotonin reuptake inhibitors)
• Can augment antimuscarinic, sedative or hypotensive adverse effects of other drugs.

Question 6

TCAs + RELATED DRUGS: EXAMPLES

Answer 6

• Amitryptiline

- Lofepramine