Pharmacology of antidepressants

Question 1

Broad mechanism of action for antidepressants?

Answer 1

Block reuptake or monoamine neurotransmitters (5HT, NA, DA)

Prevent breakdown of monoamine neurotransmitters

Leads to short term increased neurotransmitter availability

Question 2

MAOI examples

Answer 2

Phenelzine

Isocarboxazid

Question 3

TCA examples

Answer 3

Amitryptilline

Clomipramine

Question 4

SSRIs?

Answer 4

Fluoxetine
Citalopram
Sertraline

Question 5

SNRI?

Answer 5

Duloxetine

Question 6

Noradrenergic and specific serotonergic antidepressants? (NaSSA)

Answer 6

Mirtazapine

Question 7

Mechanism of action of MAOI

Answer 7

Work in presynpatic nerve terminal ro prevent breakdown of neurotransmitters

Question 8

Mechanism of TCA?

Answer 8

Work in synaptic cleft to block reuptake of serotonin and norepinephrine

Question 9

Mechanism of SSRI

Answer 9

Work in presynaptic terminal to prevent reuptake of serotonin

Question 10

What are 5HT 1a receptors?

Answer 10

Auto receptors, inhibitory, more receptors = more inhibition

They may provide plausible mechanism of delayed antidepressant effect

Question 11

Antidepressant effect on 5HT 1a receptors?

Answer 11

Reuptake of 5HT inhibited

Increased extracellular 5HT stimulates 5-HT 1a receptor, inhibit firing

Chronic binding desensetizes receptor, normal firing returns, facilitates serotenergic transmission in presence of reupatake blockade.

Question 12

Which pathway do some SSRI’s (Fluoxetine, Paroxetine) effect to cause interactions with other drugs mtabolised in the same pathway?

Answer 12

CYP450

Question 13

Adverse effects of SSRIs?

Answer 13

Sexual dysfunction

GI upset

Short term anxiety common

Increase suicide risk of self harm and suicide in young people in first few weeks.

Question 14

Side effects of TCA?

Answer 14

Constipation
Dry mouth
Blurred vision
Effects on cardiac function
Postural hypotension

Question 15

Why are MAOIs less commonly prescribe?

Answer 15

Anxiety about dietary and drug interactions

Question 16

MAOI adverse effects?

Answer 16

Hypertensive crisis caused by build up of tyramine

Flushing, headache, increase BP, occasional CVA

Treat with alpha blockade

Question 17

Extra pyrimidal side effects of Paroxetine?

Answer 17

Tremor
Dystonia
Akathisia
TD

Question 18

Main inhibitory neurotransmitter in the brain

Answer 18

GABA

Question 19

How does GABA work?

Answer 19

Binding causes opening of ion channels–> Cl- ions into cell or K+ ions out of cell

Negative change in membrane potential and hyperpolarisation

Question 20

Anti convulsant drugs used as mood stabilisers?

Answer 20

Carbamazepine
Sodium valproate
Lamotrigine

Question 21

Atypical antipsychotics used as mood stabilisers?

Answer 21

Risperidone

Olanzapine

Question 22

Other mood stabilisers?

Answer 22

Lithium carbonate

Question 23

Mechanism of action of lamotrigine?

Answer 23

Blocking Na+ channels

Question 24

Suspected action of lithium?

Answer 24

Inhibition of glycogen synthase kinase-3 (GSK-3)

Question 25

Adverse effects of lithium?

Answer 25

Toxicity

Blood monitoring required

Question 26

Mechanism of action of typical antipsychotics

Answer 26

Related to affinity for D2 receptor

DA blockade in mesolimbic circuits

Question 27

Adverse effects of typicals

Answer 27

Movement disorders
Hyperprolactinaemia

Due to DA blockade in nigrostriatal and tuberoinfundibular pathways

Question 28

Mechanisms of action of atypicals

Answer 28

increased D2 binding affinitiy

Increased 5HT 2a and 2c affinity

Increased 5HT 1a affinity