Antidepressants

Question 1

What is the monoamine oxidase theory of depression and what is the evidence behind it?

Answer 1

a. Depression is caused by a deficit of monoamines in the synapse (noradrenaline and serotonin)
a. Mania is caused by an excess
b. Pharmacological evidence - all antidepressant targeting MA’s work
a. Methyldopa inhibits NA synthesis which dec mood
c. But delayed onset of clinical effects suggests it may be downstream changes such as downregulation of alpha2, beta and serotonin receptors
d. Amphetamine inc release NA, depleting stores which shld cause depression but it doesn’t hence contradicts the theory

Question 2

How do TCA’s work

Answer 2

a. Neuronal monoamine reuptake inhibits so slows down transporter on presynaptic membrane
b. Also has an effect on alpha 2, muscarinic Ach, histamine and serotonin receptors
c. Delayed down-regulation of beta adrenoceptos and serotonin receptors

Question 3

TCA PK

Answer 3

a. Rapid oral absorption
b. Highly plasma protein bound
c. Hepatic metabolism -> active metabolites -> renal excretion
Long half life

Question 4

TCA unwanted effects

Answer 4

a. Atropine like due to muscarinic effects
b. Postural hypotension (vasomotor centre)
c. Sedations (H1 antagonism)
d. Toxicity leading to seizure, coma, respiratory depression, cardiac dysrhythmias, ventricular fibrillation

Question 5

f. Interactions

of TCAs

Answer 5

a. Plasma protein bound drugs inc TCA effects due to displacing TCA (aspirin, phenytoin, warfarin)
b. Drugs metabolised by hepatic microsomal enzymes inc TCA effects (neuroleptics, contraceptives)
c. Potentiation of CNS depressants (alcohol)
d. Antihypertensive drugs

Question 6

eg TCA

Answer 6

Amitriptyline

Question 7

How do Monoamine Oxidase Inhibitors work,

Answer 7

a. MAO-A = NA and serotonin
b. MAO-B = dopamine
c. Most inhibitors are non selective
d. Irreversible inhibition so long lasting
e. Inc cytoplasmic NA and serotonin
f. Down regulation of b adrenoceptors and serotonin receptors

Question 8

MAOi’s PK

Answer 8

a. Rapid oral absorption
b. Short plasma half life but long duration of action
c. Metabolised in liver, excreted in urine

Question 9

MAOi Unwanted effects

Answer 9

a. Atropine like but less than Tcas
b. Postural hypotension
c. Sedation but seizures in OD
d. Weight gain
e. Hepatotoxicity

Question 10

MAOi drug interactions

Answer 10

a. Cheese (tyramine containing -> release of NA leading to hypertensive crisis)
b. Hypertensive episodes with TCA’s
c. + pethidine -> hyperpyrexia, restlessness, coma, hypotension

Question 11

MAOi eg

Answer 11

Phenelzine

Question 12

PK SSRIs

Answer 12

acokinetics 
		a. Oral administration
		b. Long half life
		c. Delayed onset of action 
Hepatic metabolism ( avoid with TCA's)

Question 13

Unwanted effects of SSRIs

Answer 13

a. Nausea, diarrhoea, insomnia, loss of libido

Question 14

drug interactions SSRIs

Answer 14

MAOSIs

Question 15

eg SSRI

Answer 15

fluoxetine