IC9 Pharmacology (Antidepressants, Antipsychotics)

Question 1

What is the monoamine theory and what are its 2 limitations?

Answer 1

Theory: Deficits in monoamine ntm (NA and 5-HT) cause depression

Limitations:
- hypothesis originally formulated for NA but later focus shifted to 5-HT
- theory alone is inadequate to explain all pharmacological actions in depression

Question 2

Which neurotransmitters do MAO-A and MAO-B breakdown?

Answer 2

MAO-A 5-HT (mainly) NA
MAO-B: DA (mainly)

Question 3

What are the 3 main adverse effects of MAOIs?

Answer 3

1. Postural hypotension
2. Restlessness and insomnia (due to CNS stimulation)
3. Serotonin syndrome (when combined w drugs that enhance serotonergic fx) (hyperexcitability, increased muscular tone, loss of consciousness)

Question 4

What kinds of foods can precipitate the cheese reaction?

Answer 4

Aged cheeses and meats
Fermented foods
Yeast products like marmite

Question 5

How does the cheese reaction manifest? (3)

Answer 5

1. tremors,
2. acute HTN, giving severe throbbing headaches
3. occasionally intracranial hemorrhage

Question 6

Explain the etiology behind the cheese reaction

Answer 6

MAOIs can lead to an accumulation of tyramine which causes a sympathomimetic effect

Tyramine has a similar structure to NA and is taken up by the NA transporter and displaces NA, leading to an increased release of NA into synapses

Question 7

With which type of MAOI is the cheese reaction less likely to occur with?

Answer 7

Reversible MAO-A selective (eg. moclobemide) (as compared to irreversible non-selective)

Question 8

How do TCAs exert their antidepressive effects?

Answer 8

TCAs are first generation monoamine reuptake inhibitor antidepressants that cause the monoamine ntms to stay in the synapse for longer and exert their effect

Question 9

How do second generation TCAs compare to first generation TCAs?

Answer 9

Less SE hence better compliance

Question 10

What are the 3 main adverse effects of TCAs?

Answer 10

1. Sedation (H1 blockage)
2. Postural hypertension (α1 blockage)
3. Dry mouth, sedation, constipation (muscarinic blockage)

Question 11

What are the advantages of using SSRIs as compared to TCAs? (3)

Answer 11

1. Low affinity for α-adrenoceptors → lack of CV effects, safer in cases of overdose
2. Lack of effect at histamine receptors → reduced sedation
3. Low affinity for muscarininc cholinergic receptors → minimal anticholinergic SE (eg. dry mouth and constipation)

Question 12

What are the main adverse effects of SSRIs?

Answer 12

nausea
vomiting
sexual dysfx

Question 13

Which SSRI has some sedative effect?

Answer 13

Citalopram (some h1 blockage)

Question 14

Compare between withdrawal effects between TCAs, SSRIs and SNRIs

Answer 14

Withdrawal effects may be more common and stronger in SNRIs than with SSRIs and TCAs

Question 15

What are the three neurochemical theories in schizophrenia?

Answer 15

Dopamine, Serotonin and Glutamate theory

Question 16

Describe the dopamine theory

Answer 16

Amphetamines produce symptoms similar to acute schizophrenia

The dopamine pathways of the brain include the nigrostriatal pathways and mesocortical/mesolimbic pathways (DA is increased in schizophrenia via overactivation of the mesocortical/mesolimbic pathways)

Question 17

Describe the serotonin theory

Answer 17

LSD acts primarily as a 5-HT2 agonist and produces symptoms similar to acute schizophrenia

Question 18

Describe the glutamate theory

Answer 18

Drugs which block the NMDA receptor channel produce symptoms similar to acute schizophrenia

Question 19

Which symptoms of schizophrenia are antipsychotics good for controlling?

Answer 19

Positive symptoms

Question 20

FGAs give rise to a lot of side effects from blockages at other receptors. What are the three other receptors that can be implicated and their respective side effects?

Answer 20

M1 (dry mouth, constipation, blurred vision)
H1 (sedation, weight gain)
α1 (postural hypotension, dizziness)

Question 21

Which receptor antagonism results in acute dystonias (EPSE) with antipsychotic use?

Answer 21

D2 antagonism in the nigrostriatal pathway

Question 22

What are the notable side effects of SGAs? (think drug-induced xxx) (2)

Answer 22

1. Drug-induced diabetes (hyperglycemia and diabetes, especially w clozapine, olanzapine and risperidone and diabetes can be irreversible)
2. Drug-induced weight gain (especially clozapine, olanzapine and risperidone, which has led to the experimental use of olanzapine in the treatment of anorexia nervosa)

Question 23

Which antipsychotics are more effective against negative symptoms of schizophrenia?

Answer 23

Clozapine, olanzapine, risperidone

Question 24

Which antipsychotics are good for cognitive dysfunction in schizophrenia?

Answer 24

Clozapine, risperidone

Question 25

Which antipsychotics are better at mood stabilisation?

Answer 25

Clozapine, olanzapine, risperidone