Pharmacology of antidepressants Flashcards
Broad mechanism of action for antidepressants?
Block reuptake or monoamine neurotransmitters (5HT, NA, DA)
Prevent breakdown of monoamine neurotransmitters
Leads to short term increased neurotransmitter availability
MAOI examples
Phenelzine
Isocarboxazid
TCA examples
Amitryptilline
Clomipramine
SSRIs?
Fluoxetine
Citalopram
Sertraline
SNRI?
Duloxetine
Noradrenergic and specific serotonergic antidepressants? (NaSSA)
Mirtazapine
Mechanism of action of MAOI
Work in presynpatic nerve terminal ro prevent breakdown of neurotransmitters
Mechanism of TCA?
Work in synaptic cleft to block reuptake of serotonin and norepinephrine
Mechanism of SSRI
Work in presynaptic terminal to prevent reuptake of serotonin
What are 5HT 1a receptors?
Auto receptors, inhibitory, more receptors = more inhibition
They may provide plausible mechanism of delayed antidepressant effect
Antidepressant effect on 5HT 1a receptors?
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.
Which pathway do some SSRI’s (Fluoxetine, Paroxetine) effect to cause interactions with other drugs mtabolised in the same pathway?
CYP450
Adverse effects of SSRIs?
Sexual dysfunction
GI upset
Short term anxiety common
Increase suicide risk of self harm and suicide in young people in first few weeks.
Side effects of TCA?
Constipation Dry mouth Blurred vision Effects on cardiac function Postural hypotension
Why are MAOIs less commonly prescribe?
Anxiety about dietary and drug interactions
MAOI adverse effects?
Hypertensive crisis caused by build up of tyramine
Flushing, headache, increase BP, occasional CVA
Treat with alpha blockade
Extra pyrimidal side effects of Paroxetine?
Tremor
Dystonia
Akathisia
TD
Main inhibitory neurotransmitter in the brain
GABA
How does GABA work?
Binding causes opening of ion channels–> Cl- ions into cell or K+ ions out of cell
Negative change in membrane potential and hyperpolarisation
Anti convulsant drugs used as mood stabilisers?
Carbamazepine
Sodium valproate
Lamotrigine
Atypical antipsychotics used as mood stabilisers?
Risperidone
Olanzapine
Other mood stabilisers?
Lithium carbonate
Mechanism of action of lamotrigine?
Blocking Na+ channels
Suspected action of lithium?
Inhibition of glycogen synthase kinase-3 (GSK-3)
Adverse effects of lithium?
Toxicity
Blood monitoring required
Mechanism of action of typical antipsychotics
Related to affinity for D2 receptor
DA blockade in mesolimbic circuits
Adverse effects of typicals
Movement disorders
Hyperprolactinaemia
Due to DA blockade in nigrostriatal and tuberoinfundibular pathways
Mechanisms of action of atypicals
increased D2 binding affinitiy
Increased 5HT 2a and 2c affinity
Increased 5HT 1a affinity