ic8 antidepressants and antipsychotics Flashcards
What are the 2 types of MAO
What do they breakdown?
MAO-A, MAO-B
MAO-A breaks down serotonin
MAO-B breaks down dopamine, NA
example of MAO-A and MAO-B drugs, nonselective drugs
MAO-A: Moclobemide
MAO-B: Selegiline, Rasagiline
nonselective: Phenelzine
Side effects of MAOi (3 points)
Orthostatic hypotension
Restlessness, insomnia
Serotonin syndrome
How does postural hypotension occur in MAOi
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)
What causes restlessness and insomnia in MAOi
increase in NE
Drug food reaction with MAOi
What are the symptoms
Cheese reaction
acute hypertension, severe headache, occasional intracranial haemorrhage
What is the mechanism of the cheese reaction
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
Will the cheese reaction occur more in Moclobemide or Phenelzine
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
What is the MOA of TCA?
Block reuptake of serotonin and NE, aka Serotonin transporter (SERT) and norepinephrine transporter (NET)
What TCA is selective, and for what?
Desipramine, selective for NET
Imipramine, Amitryptyline, Nortriptyline nonselective, inhibit SERT and NET
What are the side effects of TCA (3 points)
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)
What is the difference between mechanism of orthostatic hypotension between MAOi and TCA
MAOi is due to build up of dopamine in neck ganglia, causing sympathetic block
TCA is due to a1 adrenoreceptor blockade (the usual mechanism)
Why are SSRI better than TCA? (2 points)
Greater serotonin reuptake selectivity than TCA
Fewer adverse effects
Hence SSRI can be administered at therapeutic doses more
What is the MOA of SNRI
Inhibit reuptake of serotonin and NE
Same as TCA
Examples of SNRI
Duloxetine
Venlafaxine
Desvenlafaxine
why atypicals have lesser EPSE?
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
between D2 and D1 antagonism, which one blocks dopamine more and hence cause more EPSE?
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
What is the diff between atypical and typical antipsychotics?
typical only have D2
atypical have D2 and 5HT2
If Amisulpride has lesser EPSE, what can be said about its Dopamine blockade
More selective for D2, D3 receptors → Lesser EPSE (no D1 blockade in nigrostriatal pathway)
Side effect of Amisulpride, caused by?
Increased prolactin secretion
Block Dopamine (D3) receptors in anterior pituitary gland
Breast swelling, pain, lactation
Gynaecomastia in males
Benefits of atypical over typical antipsychotics?
Example?
(-) symptoms, mood stabilisation, control over cognitive dysfunction
Clozapine, Risperidone
Adverse effects of atypical antipsychotics and example
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
