Flashcards in 1.1 Pharmacology of antidepressant drugs and mood stabilisers Deck (32):
What drug class is iproniazid from?
What drug class is imipramine from?
What was lithium initially approved for?
What is the mechanism of action of fluoxetine?
Inhibitor of 5HT reuptake.
What is the mechanism of action of MAOi?
Slows breakdown of:
by inhibiting the mitochondrial enzyme monoamine oxidase.
Is depression simply hyposerotoninsm?
What are the precursor molecules of serotonin?
Tryptophan (from legumes, cheeses, chocolate, red meat)
Which of the 5HT1/2/3 receptor types are inhibitory or excitatory?
What are the key receptor types involved in mood + 5HT?
5HT1A, 5HT1B, 5HT2A, 5HT2C, 5HT4, 5HT6, 5HT7
Which drug groups target the 5HT1A receptors?
Anxiolytics- eg. buspirone
Psychosis - Negative symptoms
Which drug groups target the 5HT1B and 1D receptors?
What drug groups target the 5HT- 2A, 2B, and 2C receptor groups?
Antipsychotics (atypical antipsychotics for 5HT2a)
Which drug groups target the 5HT3 receptors?
some antidepressants and antipsychotics
Which drug groups target the 5HT4 receptors?
GI pro-kinetic drugs, esp in IBS, chronic constipation
What is the long term neurobiological effect of SSRIs?
change relative balance of positive to negative emotional processing, providing platform for subsequent cognitive and psychological consolidation
5HT1a receptors are autoreceptors throughout CNS
With antidepressant treatment, the reuptake of 5HT is inhibited, increased 5HT increases 5HT1A autoreceptor stimulation, which results in inhibition of firing (initially)
Chronic stimulation of the 5HT1a causes it to desensitise. Return of normal firing. Leading to more serotonergic transmission due to reuptake blockade. (later = more serotonin)
Which SSRIs inhibit the CYP450 enzymes?
What are the most coomon adverse effects related to 5HT- SSRIs?
sexual dysfunction - reversed by traxodone
GI: nausea, dyspepsia, constipation, diarrhoea
short term anxiety
What cases may TCAs be preferred for?
Hospitalised or severe depression (maybe)
What three receptor types on the post-synaptic membrane do TCAs act on?
muscarinic acetylcholine receptor
What are the main adverse effects of TCAs?
Effects on cardiac function- do ECG in overdose
What is the mechanism of action of MAOIs?
irreversible inhibitors (phenelzine, isocarboxazid, tranylcypromine) inhibit monoamine oxidase A and B
MAO-A- metabolises NA, 5HT, tyramine
MAO-B- metabolises DA, tyramine and phenylthylamine
This results in increased storage and availability of 5HT and NA for release.
Sympathomimetic effects - esp tranylcypromine
What are the adverse effects of MAOIs?
Hypertensive crisis- tyamine containing foods and drugs cause release of NA.
Foods: cheese, yoghurt, yeast extract, meat, alcohol, broad beans, pickled herring
Drugs: sympathomimetics, OTC cold remedies, pethidine
Symptoms of hypertensive crisis: flushing, headache, increased BP
Treatment: alpha blockade with PENTOLAMINE, CHLORPROMAZINE
What are the dopamine related side effects of some antidepressants?
By blocking dopamine, EPS may occur:
primarily due to antagonism of DA receptors- D2 esp.
What is the action of GABA in adult vs. developing brains?
GABA is the main inhibitory NT in mammalian brains
GABA Is primarily excitatory in developing brains!
binds and allows Cl- into cell or K+ out of cell
= hyper polarisation
Name 4 agonists and 1 antagonist of the GABAa receptor (ligand gated ion channel)
Name 2 agonists of the GABAb receptor - the GPCR that opens ion channels via intermediate G proteins
2. propofol (both GABA a and b)
Name 2 GABA analogues
Which anticonvulsant drugs may be used as a mood stabiliser?
Which atypical or second generation antipsychotics may be used as a mood stabiliser?
How does lamotrigine work in mood stabilising?
-blocks Na+ channels- anticonvulsant activity
-reduces excitability - not via GABA
-may inhibit 5HT, NA, and DA uptake
What is the mechanism of action of lithium?
Not exactly known
-inhibit 5HT(1a?) autoreceptors
-increase anti-apoptotic factor bcl-2
-inbhibit glycogen synthase kinase-3****
-upregulate glutamate re-uptake