Anti-depressants part 1

Question 1

How do SSRIs work?

Answer 1

Selective 5-HT re-uptake inhibition

Question 2

How do monoamine oxidase inhibitors work?

Answer 2

• Most are non-selective (XCEPT MAO-A: NA, 5-HT -MAO-B: DA )

Irreversible inhibition therore long d.o.a. -

Rapid effects: increaased cytoplasmic NA, 5-HT -

Delayed effects: clinical response, down-regulation of B-adrenoceptors, 5-HT2 receptors -

Inhibit other enzymes

Question 3

Name the different antidepressant drug categories

Answer 3

TCAs, MAOi,SSRI

Question 4

How do TCAs work?

Answer 4

• Neuronal monoamine re-uptake inhibitors - Other receptor actions : a2 (block presynaptic -ve fb), mAchRs, histamine, 5-HT

Delayed down-regulation of B-adrenoceptors and 5-HT2 receptors

Question 5

Some TCA pharmacokinetics

Answer 5

Rapid oral absorption

Highly PPB (90 - 95%)

Hepatic metabolism - active metabolites - renal excretion (glucuronide conjugates)

Plasma t1/2 (10-20 hrs)

Question 6

What is the monoamine theory of depression?

Answer 6

• Depression = functional deficit of central MA(NA & 5-HT) transmission; Mania = functional excess. Down-regulation of a2, B, 5-HT receptors, which corellate deeply with the anti-depressant action.

Question 7

What are the proposed mechanisms underlying the delayed therapeutic effects of antidepressants?

Answer 7

• Their secondary adaptive changes are important - Down-regulation of B and a2-adrenoceptors and 5-HT2 receptors - How this is related to therapeutic effect is unclear

Question 8

What are the side effects of SSRIs?

Answer 8

Fewer than TCAs and MAOIs Nausea, diarrhoea, insomnia, loss of libido

Question 9

Interactions of MAOI with other drugs, and how to solve

Answer 9

•‘Cheese reaction’: Tyramine-containing foods + MAOI ® hypertensive crisis (throbbing headache, ­ b.p., intracranial haemorrhage)

MAOIs + TCAs ® hypertensive episodes (avoid)

•MAOIs + pethidine ® hyperpyrexia, restlessness, coma & hypotension.

serious problem therefore use Moclobemide( reversible MAO-A inhibitor (RIMA). ↓ Drug interactions, however ↓ duraction of actoin (DOA))

Question 10

What is lithium used in

Answer 10

Mania, bipolar disorder