Low mood - psychopharmacology Flashcards
Aetiology of MDD?
- Genes
- environment epigenetic (early life adversity, abuse = stress vulnerability)
- depression/ anxiety
Stages in synapses?
- synthesis
- release
- termination
What does the pre synaptic and post synaptic receptor do?
pre = negative or positive feedback
post = integrated effects on output neurone
What are the different receptor targets?
- ionotropic = ligand gated ion channels mediate fast synaptic transmission eg. NDMA receptor
- metabotropic = couple to second messenger system eg. adrenoceptor, mGLU receptor
Neurotransmitters vs neuromodulators?
- glutamatergic projections - integrate signal
- GABAergic interneurons - local inhibition
- neuromodulatory inputs eg. dopamine, noradrenaline, serotonin, acetylcholine, opioid
- neurotropic mediators - BDNF
Pharmacological evidence for monoamine modulation of mood and cognition?
- amphetamine = NA, DA reuptake and release
- cocaine = DA reuptake
- ecstasy = 5HT reuptake and release
- Ketamine, PCP = NMDA antagonism
- psychedelics = 5HT2A agonism
Monoamine hypothesis?
-MDD arises from functional deficit in monoamine transmission (5HT & NA)
-possible mechanisms:
+deficits in release
+changes in receptor density (pre and post synaptic)
What are some theories behind the time lag in antidepressant action?
- pharmacokinetic (time to reach peak)
- pharmacodynamic (receptor adaptation)
- neurotrophic (hippocampal neurogenesis, synaptogenesis)
- neuropsychological (interaction between drugs and psychological processes)
What are negative biases influenced by?
genetic risk
epigenetic factors
stress
What are the classes of antidepressants?
- first generation (typical antidepressants)
2. second generation (atypical - mixed uptake blockers and receptors blocking drugs)
What are first generation antidepressants?
- Monoamine oxidase inhibitors (MAOI) eg. iproniazid, moclobemide
- tricyclic antidepressants (TCI) eg. imipramine, clomipramine
- selective serotonin reuptake inhibitors (SSRI) eg. fluoxetine, paroxetine
- selective noradrenaline reuptake inhibitors (NARI) eg. reboxetine
What are second generation antidepressants?
- SNRI eg. venlafaxine
- 5HT2 Antagonist + SSRI eg. trazodone
- 5HT2 antagonist + SNRI eg. nefazodone
- alpha2-adrenoreceptor and 5 HT antagonist eg. mianserin
- agomelatine
- mixed 5HT reuptake, 5HT1A agonist, 5HT3 antagonist eg. vortioxetine
Mechanism of MAOI?
- inhibit breakdwon of monoamines
- irreversible and reversible inhibitors of MAO-A and/or B
- MAO found in all tissues eg. GI tract
- A prefers 5HT, B prefers DA and NA
- multiple side effects
moderate therapeutic index
What is the cheese reaction?
- patients taking irreversible MAOI cannot metabolise ingested amines leading to high levels in blood
- tyramine displaces noradrenaline from its terminals leading to a sympathomimetic effect, acute hypertension, intracranial haemorrhage
Mechanism of tricyclic antidepressants?
- block reuptake of monoamines
- some block alpha AR
- active metabolites
- multiple side effects
- cardiotoxicity - low therapeutic index, cause tachycardia, arrythmias and hypotension
