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What is the MOA of TCAs?
Block reuptake of NE and serotonin
Discuss the classification of TCAs.
TCAs are classified into two
1. Tertiary Amines (Non-selective antidepressants)
- Block both 5HT and NE transporters
- Relatively more side effects, but more efficatious
2. Secondary Amines (Selective antidepressants)
- Selective to NE
What drugs belong to tertiary TCAs?
1. Amytriptyline (Elavil)
2. Impiramine (Tofranil)
3. Clopiramine (Anafranil)
4. Doxepin (Sinequan)
What drugs belong to secondary TCAs?
1. Nortriptyline (Pamelor)
2. Desipramine (Norpramine)
Contraindications to TCAs?
Why are TCAs not first line?
Due to their severe side effect profile, reserved for treatment resistant depression considered after SSRI or SNRI
What are other indications for TCAs?
1. Phobic disorders
2. Chronic neuropathic pain like peripheral neuropathy 3. Migraine prophylaxis.
4. Clomipramine can be used in the treatment of obsessive-compulsive disorder, or OCD
5. Imipramine is used in the treatment of nocturnal enuresis, which is involuntary urination while asleep.
What are some of the mechanistically relevant side effects of TCAs?
1. Besides serotonin and norepinephrine transporters, TCAs also block histamine H1 receptors, causing sedation; alpha 1 receptors, causing orthostatic hypotension; and muscarinic receptors, causing atropine-like side effects.
2. Atropine-like side effects occur more commonly with tertiary TCAs
They can also cause serotonin syndrome
3. TCAs are also cardiotoxic and can lead to arrhythmias and prolong the QT interval.
Treatment of cardiotoxicity consists of administration of sodium bicarbonate in order to prevent arrhythmias.
4. TCAs inhibit P450
What are the most common causes of death while using TCAs?
They are the 3 Cs (Tri-C)
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