Antidepressants Flashcards
What are the two general types of depression?
Unipolar and bipolar
Two drugs in favour of the monoamine hypothesis?
Reserpine (treatment in SCZ) - ~15% of users experienced depression (due to breakdown of monoamine stores)
Iproniazid (a TB drug) - sometimes induced euphoria, due to MAO inhibition thus increasing monoamine conc
What are the roles of antidepressants?
To increase amount of monoamine by:
inhibiting breakdown (MAO-Is)
blocking reuptake
What NTs do MAO-A and MAO-B target specifically?
A - 5-HT, NA
B - DA
What did phenelzine interact with?
One of the first antidepressants. Interacted with tyramine in the diet (cheese, red wine), causing amplified sympathetic side effects (sometimes dangerous - hypertensive crisis (fatal)
Why does the ‘cheese effect’ happen?
MAOs are found throughout the body: in the brain, in the GI tract and…
An increase in NA occurs causing vasoconstriction - raised BP
Examples of MAO-A inhibitors? (3)
Clorgyline
Moclobemide
Pirlindole
Examples of MAO-B inhibitors?
Selegiline
Non selective MAO inhibitors
Tranylcypromine
Phenelzine
Iproniazid
What is a RIMA?
Pros?
A selective and Reversible Inhibitor of Mao-A
Don’t need to worry about cheese RXN
Adverse effects of MAO inhibitors?
Postural hypotension, hepatotoxicity, sympathetic effects, CNS effects (insomnia, agitation, convulsions)
Migraine?
Headache caused by postural hypotension (triggered by MAO inhibitors) or because of the hypertensive effects of the cheese effect.
Uptake inhibitors?
a) TCAs
b) selective uptake blockers
Interactions with other receptors with use of TCAs?
mAChRs, alpha-1, muscarinic
Why is clomipramine different from other TCAs?
In vivo, it also blcoks 5-HT reuptake, as well as NA
Side effects of TCAs?
Antimuscarinic, postural hypotension, cardiac dysrhythmias, confusion, convulsions
E.g. TCAs?
imipramine, clomipramine
Selective reuptake blockers?
SSRIs - fluoxetine
NRIs - maprotiline
What is an SNRI? Example?
Serotonin and noradrenaline reuptake inhibitor. Venlafaxine.
Why are selective reuptake inhibitors better than TCAs in some cases?
Fewer antimuscarinic and cardiotoxic effects.
What are atypical antidepressants?
Don’t block monoamine reuptake.
Examples of atypicals?
Mianserin -alpha-2 AR antagonist
iprindole
Adverse effects of atypicals?
EPS, postural hypotension, hepato and renal toxicity
Other examples of antidepressants/?
BDZs (alprazolam)
Multi-action drugs - mirtazepine (alpha 2 antagonist, if these alpha2 receptors are in serotonergic neurones, this enhances 5-HT release)
Trazodone
Problems w the monoamine hypothesis?
Iprindole - no effects on MA
Other reuptake inhibitors (cocaine) aren’t antidepressants [amphetamines INDUCE depression]
Lithium
toxic effects, need large doses, CNS effects, hypothyroidism
