ic8 depression & antipsychotic pharmacology

Question 1

types of MAO and their actions respectively?

Answer 1

MAO-A: breaks down serotonin mainly
MAO-A and B (both) break down NE and DA

Question 2

MOA of phenelzine

Answer 2

non-selective MAO inhibitor
irreversible MAO inhibitor

Question 3

adr of MAOI and associated mechanism

Answer 3

1) postural hypotension
due to sympathetic block from DA accumulation in cervical (neck) ganglia

2) restlessness/insomnia
- CNS stimulation

Question 4

MAO with other serotonin drugs ADR?

Answer 4

hyperexcitation
increased muscular tone
myoclonus (jerking, involuntary movements)
LOC

if severe serotonin syndrome:
tremor, hyperthermia, cardiovascular collapse.

Question 5

what drug food interaction occurs with MAO (type of food, effects, and mechanism)

Answer 5

cheese and yeast products (anything fermented)

acute HTN, causing severe migraines (throbbing headache) and possible intracranial haemorrhage

due to accumulation of tyramine (competes with NA in the sympathetic nerves = increases NA in synapse) = sympathomimetic effect (sympathetic nervous system)…

Question 6

risk of drug-food interactions (compare type of MAOIs)

Answer 6

ASSOCIATED with irreversible non-selective MAOIs

less likely with reversible MAO-A selective like MOCLOBEMIDE

Question 7

MOA of TCA and types

Answer 7

effect on serotonin and norepinephrine transporter (SERT and NET)

• NON selective for both: imipramine, nortriptyline, amitryptiline
• selective for NET: desipramine

Question 8

side effects of TCA

Answer 8

sedation
- h1 antagonism
- tolerance 1-2 weeks

postural hypotension
- alpha adreno-receptor block

dry mouth, blurred vision, constipation
- muscarinic receptor antagonism

Question 9

selectivity of SSRIs

Answer 9

SSRI more selectivity for 5HT than TCAs,

SSRI selectivity 5HT > NA

Fluoxetine 50x selectivity for 5HT
Citalopram 1000x selectivity for 5HT

Question 10

ADR for SSRI

Answer 10

insomnia, nausea, sexual dysfunction

Question 11

which SSRI more sedation?

Answer 11

citalopram = some histamine receptor antagonism

Question 12

dopamine pathways in the brain

Answer 12

nigrostriatal pathway:
- substantia nigra –> dorsa striatum
- for voluntary movement; involved in EPSE…

meso-cortical/limbic pathway:
- ventral tegmental area (VTA) –> prefrontal cortex and limbic (emotional) brain
- involved in emotion, cognition, attention.
(cognition and attention for mesocortical; reward and emotion for mesolimbic)

tuberoinfundibular
- hypothalamus –> anterior pituitary

Question 13

what is acute dystonia and causes of it

Answer 13

parkinsonism like
eg cogwheel rigidity and tremors

caused by D2 antagonism

Question 14

what is tardive dyskinesia

Answer 14

repetitive and stereotyped involuntary movement of face, tongue, limbs

associated w/ upregulation or supersentivity of dopamine receptors in nigrostriatal?

Question 15

adr of amisulpride (and explain)

Answer 15

amisulpride has fewer side effects due to selectivity for D2/D3 receptors

and absence of alpha, m1 h1 effects

1) hyperprolactinaemia: increased prolactin secretion due to block of dopamine receptors in anterior pituitary

Question 16

what is considered atypical antipsychotic?

Answer 16

greater affinity at 5HT2 and D4 receptors

mixed antagonism at alpha, h1, m1. 5ht2 receptors

Question 17

why do atypical antipsychotics have less EPSE?

Answer 17

potent 5ht2a > weak D2 = less EPS, more effect over negative sx (CLOZAPINE, OLANZAPINE)

high D3: D2 antagonist (AMISULPRIDE)
- favors action on nucleus accumbens vs striatum

high D4: D2 antaognism (CLOZAPINE)
- favours action on prefrontal cortex vs striatum

high D2: D1 antagonism (AMISULPRIDE, RISPERIDONE)
- reduces impact in the striatum (negative feedback loop)

Question 18

which atypical antipsychotics are better at negative sx, cognitive dysfunction, mood stabilisation vs typical?

Answer 18

clozapine, olanzapine, risperidone