TCA's

Question 1

TCA’s were derived from…

Answer 1

phenothiazines (antipsychotics)

Question 2

What transporters to TCA’s primarily affect?

Answer 2

SERT and NET (increase both serotonin and norepinephrine) work by blocking re-uptake from SERT and NET (at varying degrees depending on which one you use)
-Some also have antagonist actions at 5HT2A/5HT2C receptors

Question 3

What conditions will TCA’s treat?

Answer 3

They are considered good anti-depressants, also good for OCD, insomnia, some have anti-panic effects @ AD doses; shown efficacy for neuropathic/chronic pain and LBP at low doses

Question 4

Side effect profile limits use of TCAs because…

Answer 4

block muscarinic receptors —> anticholinergic SE (Mad as a hatter, blind as a bat, hot as a hare, red as a beet, dry as a bone, tachycardia)
block H1 histamine receptors —> sedation/wt gain
block alpha1 adrenergic receptors —> can be therapeutic but also causes orthostatic hypotension and dizziness
They also weakly block Na+ ion channels in the heart and brain at therapeutic doses

Question 5

Why are overdoses with TCA’s so lethal?

Answer 5

Blocking of Na+ channels in heart and brain: in OD this can lead to coma/seizures, lethal cardiac arrhythmias and/or cardiac arrest.
A lethal dose is about 30 days-worth of medication (every time you give a refill you’re “handing them a loaded gun”)

Question 6

Agents/Names of TCA’s

Answer 6

Amoxipine Clomipramine
Amitriptyline Desipramine
Nortryptaline Imipramine
Doxepin

Question 7

What’s the most lethal period after OD?

Answer 7

First 6 hours

Question 8

What is a possible benefit from the side effects of TCAs?

Answer 8

The antihistamine effect can cause sedation and ‘dry out’ pts so can be good for bed wetting and insomnia

Question 9

Pharmacokinetic considerations for TCAs

Answer 9

TCA’s metabolized extensively through CYP so check interactions
Some are highly protein-bound so may interact with other similar meds