Antidepressants

Question 1

What are the two general types of depression?

Answer 1

Unipolar and bipolar

Question 2

Two drugs in favour of the monoamine hypothesis?

Answer 2

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

Question 3

What are the roles of antidepressants?

Answer 3

To increase amount of monoamine by:
inhibiting breakdown (MAO-Is)
blocking reuptake

Question 4

What NTs do MAO-A and MAO-B target specifically?

Answer 4

A - 5-HT, NA

B - DA

Question 5

What did phenelzine interact with?

Answer 5

One of the first antidepressants. Interacted with tyramine in the diet (cheese, red wine), causing amplified sympathetic side effects (sometimes dangerous - hypertensive crisis (fatal)

Question 6

Why does the ‘cheese effect’ happen?

Answer 6

MAOs are found throughout the body: in the brain, in the GI tract and…
An increase in NA occurs causing vasoconstriction - raised BP

Question 7

Examples of MAO-A inhibitors? (3)

Answer 7

Clorgyline
Moclobemide
Pirlindole

Question 8

Examples of MAO-B inhibitors?

Answer 8

Selegiline

Question 9

Non selective MAO inhibitors

Answer 9

Tranylcypromine
Phenelzine
Iproniazid

Question 10

What is a RIMA?

Pros?

Answer 10

A selective and Reversible Inhibitor of Mao-A

Don’t need to worry about cheese RXN

Question 11

Adverse effects of MAO inhibitors?

Answer 11

Postural hypotension, hepatotoxicity, sympathetic effects, CNS effects (insomnia, agitation, convulsions)

Question 12

Migraine?

Answer 12

Headache caused by postural hypotension (triggered by MAO inhibitors) or because of the hypertensive effects of the cheese effect.

Question 13

Uptake inhibitors?

Answer 13

a) TCAs

b) selective uptake blockers

Question 14

Interactions with other receptors with use of TCAs?

Answer 14

mAChRs, alpha-1, muscarinic

Question 15

Why is clomipramine different from other TCAs?

Answer 15

In vivo, it also blcoks 5-HT reuptake, as well as NA

Question 16

Side effects of TCAs?

Answer 16

Antimuscarinic, postural hypotension, cardiac dysrhythmias, confusion, convulsions

Question 17

E.g. TCAs?

Answer 17

imipramine, clomipramine

Question 18

Selective reuptake blockers?

Answer 18

SSRIs - fluoxetine

NRIs - maprotiline

Question 19

What is an SNRI? Example?

Answer 19

Serotonin and noradrenaline reuptake inhibitor. Venlafaxine.

Question 20

Why are selective reuptake inhibitors better than TCAs in some cases?

Answer 20

Fewer antimuscarinic and cardiotoxic effects.

Question 21

What are atypical antidepressants?

Answer 21

Don’t block monoamine reuptake.

Question 22

Examples of atypicals?

Answer 22

Mianserin -alpha-2 AR antagonist

iprindole

Question 23

Adverse effects of atypicals?

Answer 23

EPS, postural hypotension, hepato and renal toxicity

Question 24

Other examples of antidepressants/?

Answer 24

BDZs (alprazolam)
Multi-action drugs - mirtazepine (alpha 2 antagonist, if these alpha2 receptors are in serotonergic neurones, this enhances 5-HT release)
Trazodone

Question 25

Problems w the monoamine hypothesis?

Answer 25

Iprindole - no effects on MA

Other reuptake inhibitors (cocaine) aren’t antidepressants [amphetamines INDUCE depression]

Question 26

Lithium

Answer 26

toxic effects, need large doses, CNS effects, hypothyroidism