ic8 antidepressants and antipsychotics

Question 1

What are the 2 types of MAO

What do they breakdown?

Answer 1

MAO-A, MAO-B

MAO-A breaks down serotonin
MAO-B breaks down dopamine, NA

Question 2

example of MAO-A and MAO-B drugs, nonselective drugs

Answer 2

MAO-A: Moclobemide
MAO-B: Selegiline, Rasagiline

nonselective: Phenelzine

Question 3

Side effects of MAOi (3 points)

Answer 3

Orthostatic hypotension

Restlessness, insomnia

Serotonin syndrome

Question 4

How does postural hypotension occur in MAOi

Answer 4

Increase in dopamine in neck ganglia → sympathetic block
Dopamine acts as inhibitory transmitter and cause sympathetic inactivation / block → counters effect of Adrenaline (which causes sympathetic activation)

Question 5

What causes restlessness and insomnia in MAOi

Answer 5

increase in NE

Question 6

Drug food reaction with MAOi

What are the symptoms

Answer 6

Cheese reaction

acute hypertension, severe headache, occasional intracranial haemorrhage

Question 7

What is the mechanism of the cheese reaction

Answer 7

Tyramine (amino acid) in cheese are broken down by MAO in intestines and liver
MAOi causes accumulation of tyramine, causing sympathomimetic effect
Tyramine will displace NorAdrenaline (NA) in the sympathetic nerve terminal
More NA is released into synapse + MAO are inhibited and cannot breakdown the excess NA that is released
Excess NA → sympathomimetic effect

Question 8

Will the cheese reaction occur more in Moclobemide or Phenelzine

Answer 8

Does not occur in reversible MAO-A selective eg. Moclobemide VS irreversible non-selective MAOIs
MAO-A does not breakdown NA, so inhibition of MAO-A will still be able to breakdown the excess NA released

Question 9

What is the MOA of TCA?

Answer 9

Block reuptake of serotonin and NE, aka Serotonin transporter (SERT) and norepinephrine transporter (NET)

Question 10

What TCA is selective, and for what?

Answer 10

Desipramine, selective for NET

Imipramine, Amitryptyline, Nortriptyline nonselective, inhibit SERT and NET

Question 11

What are the side effects of TCA (3 points)

Answer 11

HAM

Sedation (due to H1 antagonism)

Postural hypotension
Due to alpha-adrenoreceptor sympathetic block

Dry mouth, blurred vision, constipation
Due to Muscarinic receptor antagonism → cause parasympatholytic effect
Muscarinic receptor regulates parasympathetic nervous system
Parasympathetic agonism → rest, relax, digest (salivation, digestion)

Question 12

What is the difference between mechanism of orthostatic hypotension between MAOi and TCA

Answer 12

MAOi is due to build up of dopamine in neck ganglia, causing sympathetic block

TCA is due to a1 adrenoreceptor blockade (the usual mechanism)

Question 13

Why are SSRI better than TCA? (2 points)

Answer 13

Greater serotonin reuptake selectivity than TCA

Fewer adverse effects
Hence SSRI can be administered at therapeutic doses more

Question 14

What is the MOA of SNRI

Answer 14

Inhibit reuptake of serotonin and NE
Same as TCA

Question 15

Examples of SNRI

Answer 15

Duloxetine
Venlafaxine
Desvenlafaxine

Question 16

why atypicals have lesser EPSE?

Answer 16

es, while Atypicals require binding of 5HT2A and D2 to be considered as an atypical antipsychotic, they bind to D3 and D4 also

Nigrostriatum contains D1 and D2 receptors only.

Atypicals bind to D3, D4 more than D2, hence causing lesser D2 antagonism and lesser EPSE

Question 17

between D2 and D1 antagonism, which one blocks dopamine more and hence cause more EPSE?

Answer 17

D1 antagonism is more serious than D2, as there are D2 presynaptic autoreceptors

D2 receptors act as autoreceptors → Blocking D2 will cause blockage of presynaptic autoreceptors → no more negative feedback to stop Dopamine release → Dopamine release not fully inhibited

Question 18

What is the diff between atypical and typical antipsychotics?

Answer 18

typical only have D2

atypical have D2 and 5HT2

Question 19

If Amisulpride has lesser EPSE, what can be said about its Dopamine blockade

Answer 19

More selective for D2, D3 receptors → Lesser EPSE (no D1 blockade in nigrostriatal pathway)

Question 20

Side effect of Amisulpride, caused by?

Answer 20

Increased prolactin secretion
Block Dopamine (D3) receptors in anterior pituitary gland
Breast swelling, pain, lactation
Gynaecomastia in males

Question 21

Benefits of atypical over typical antipsychotics?

Example?

Answer 21

(-) symptoms, mood stabilisation, control over cognitive dysfunction

Clozapine, Risperidone

Question 22

Adverse effects of atypical antipsychotics and example

Answer 22

Muscarinic antagonism, H1 antagonism
Dry mouth, constipation, blurred vision
Example: Clozapine, Olanzapine

A1 antagonism (postural hypotension)
Example: Risperidone

Drug induced diabetes and weight gain
Example: COR