TCA antidepressants, tetracyclic and unicyclic, and MAOIs Flashcards
What is are the two main hypotheses about depression.
Amine hypothesis and the neurogenesis hypothesis
- The amine hypothesis of mood postulates that brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood, and a functional decrease of these transmitters results in depression.
- Based on studies showing that many drugs capable of alleviating symptoms of major depressive disorders
enhance the actions of the central nervous system (CNS) neurotransmitters 5-HT and NE.
Difficulties with this hypothesis include the facts that
(1) postmortem studies of patients do not reveal decreases in the brain levels of NE or 5-HT;
(2) although antidepressant drugs may cause changes in brain amine activity
within hours, clinical response requires weeks;
(3) most antidepressants ultimately cause a downregulation of amine receptors;
(4) bupropion has minimal effects on brain NE or 5-HT;
(5) Brain-derived neurotrophic factor (BDNF) is depressed in the brains of depressed patients.
Neurogenesis hypothesis
Depression is a result from impaired hippocampal neurogenesis. Explains the lag time.
List the TCA antidepressants
Imipramine
Desipramine
Amitriptyline
Nortriptyline
Clomipramine
Trimipramine
Doxepin
List the tetracyclic antidepressants
Maprotiline
Amoxapine
What is the unicyclic AD
Buproprion
What are the active metabolites of Imipramine and AMitryptyline
Impiramine –> Desipramine
Amitryptyline –> Nortriptyline.
Actions of the TCAs
Main: inhibit NET and SERT
also:
anti-adrenergic alpha’s
anti-histamine
anti-muscarinic
Actions of the Tetracyclic ADs
same, but Amoxapine also blocks D2 receptors.
Which has the strongest anticholinergic actions?
Which has the least?
Amitryptyline
The secondary amines have the least
Desipramine
Nortryptyline
What are the SEs of the TCAs
General SEs:
- sedation
- antimuscarinic
- orthostatic hypotension
- possible refractory hypotension
- Sexual dysfunction, decreased libido
- anorgasmia
- Impotence
Treatment for TCA overdose
Sodium Bicarbonate i.v.
Increases pH, which decreases TCA ionization and inhibits its Na+ channel binding.
What are the indications for TCAs
1st line for neuropathic or chronic pain syndromes
2nd line for SSRI/SNRI resistant:
- Major depressive disorder
- Panic disorder
- Phobias
Clomipramine 2nd line for SSRI resistant O.C.D.
Amitriptyline 2nd line for migraine prophylaxis.
Doxepine at low doses - H1 inhibition for insomnia.
Indications for the tetracyclic ADs
Maprotiline -
same as the secondary amine TCAs, disipramine and nortriptyline
Amoxapine -
Also inhibits D2 and 5HT2, sometimes used off label as an atypical antipsychotic, otherwise classified as a regular TCA.
Bupropions mechanism and indications
Inhibits NET and DAT.
Mild inhibition of nicotinic receptors
does not have ANY effect on serotonin receptors
Indications:
1) Antidepressant for people that couldn’t tolerate SSRI/SNRI side effects
- Bupropion has no sexual effects or weight gain
2) Quitting Smoking
Buproprion SEs and contraindications
Can increase seizure risk
Contraindicated in anyone with any history of seizures
Also contraindicated in any patients with history of eating disorders, bc these are associated with seizures as well.
No other SEs, its used because it LACKS sexual or weight gain.
List the NON-selective MAO-Is
Tranylcypromine
Phenelezine
Isocarboxazid