antidepressant drugs Flashcards
What can psychoses be split up into?
- schizophrenia (disorder of thoughts processes)
- affective disorders (disorders of mood)
- affective disorders can be split into depression and mania
what are the emotional/ psychological symtpoms of depression?
- misery
- apathy
- pessimism
- low self esteem
- loss of motivation
- anhedonia (loss of enjoyment from activities)
what are the biological/ somatic symptoms of depression?
- slowing of action/ thoughts
- loss of libido
- loss of appetite
- sleep disturbance
what are the types of depression?
- unipolar depression (depressive disorder)
- bipolar depression (manic depression)
describe unipolar depression
- mood swings only in ONE direction
- relatively late onset
- all types respond in same way to drug treatments
what are the 2 types of unipolar depression?
- reactive depression: stressful life event, non-familial inheritance
- endogenous depression: unrelated to external events, familial pattern
describe bipolar depression
- oscillating b/ depression and mania
- less common
- have early adult onset
- strong hereditary tendency
what treatment can be used for bipolar depression?
- lithium
- can stabilise swings between mania and depression
- but has narrow therapeutic window
what is the monoamine theory of depression?
- depression is a functional deficit of central MA transmission
- mania is a functional excess of MA transmission
- MA = NA and 5-HT
- related to NA and 5-HT deficits/excesses
what is the pharmacological evidence to support this theory?
- TCAs: block NA and 5-HT (inc. mood)
- MAOIs: inc. stores of NA and 5-HT (inc. mood)
- Reserpine: inhibits NA and 5-HT storage (dec mood)
- alpha-methyltyrosine: inhibits NA synthesis (dec. mood, calming of manic pt)
- methyldopa: inhibits NA synthesis (dec. mood)
- ECT: inc. CNS responses to NA and 5-HT (inc. mood)
what is the biological evidence like?
- reduction in NA metabolites not concurrent with worse depression
- delayed onset of clinical effect of drugs
- this maybe due to adaptive changes and not MA theory
- there is downregulation of alpha 2, beta and 5-HT receptors
what is the MoA of TCAs? give an example
monoamine re-uptake inhibitor
e.g. amitriptyline
what receptors do TCAs also act on?
- alpha 2: block pre-synaptic inhibition of NA release
- mAChR
- H2 (histamine) receptors
- 5-HT receptors
- TCAs down regulate beta-adrenoreceptors and 5-HT2 receptors
what are the pharmacokinetics of TCAs?
- oral admin
- highly PPB (90%)
- hepatic metabolism to active metabolites –> excreted in urine
- plasma half life = 10-20 hours
what are the unwanted effects of therapeutic doses of TCAs?
- atropine like effects (TCAs interfere with muscarininc receptors) –> anti-PNS effects (dry mouth, constipation)
- postural hypotension –> effects on vasomotor centre
- sedation: due to effects on H1 antagonism
what are the unwanted effects of acute toxicity of TCAs?
- CNS: excitement, delirium, seizures (= coma, resp depression)
- CVS: cardiac dysrhythmias (= VF and sudden death)
what are drug interactions of TCAs?
- very PPB, so can be a massive inc. in bioavaliability if co-administered with something that displaces it from plasma proteins e.g. aspirin
- hepatic enzymes (drugs that compete w/ metabolizing hepatic enzymes)
- potentiation: drugs that potentiate effects of CNS depression e.g. alcohol
- antihypertensives
what is the MoA of MAOIs?
- INHIBITORS
- MAO-A: breaks down NA and 5-HT
- MAO-B: breaks down DA e.g. Selegiline
- most non-selective
what are the rapid effects of MAOIs?
- inc. cytoplasmic NA, 5-HT
what are the delayed effects of MAOIs?
- delayed clinical respone due to down regulation of beta-adrenoreceptors and 5-HT2 receptors
what are the pharmacokinetics of MAOI?
- oral absorption
- short plasma half life but longer DoA
- metabolised in liver, excreted in urine
what are the unwanted effects of MAOIs?
- atropine-like effects (less than TCAs)
- postural hypotension
- sedation (seizures in OD)
- weight gain (excessive)
- hepatotoxicity
what are the drug interactions of MAOIs?
- cheese reaction
- MAOIs + TCAs = HT episodes
- MAOIs + pethidine = hyperpyrexia, restlessness, coma, HT
describe the cheese reaction
- tyramine found in foods
- tyramine is indirectly acting sympathomimetic (inc. SNS activity)
- goes up into NA neurones, pushes NA out in synapses
- normally tyramine in food broken down by MAO
- pt w/ inhibition not protected against tyramine
- leads to HT crisis, inc. BP
what is meclobemide?
- reversible
- selective MAO-A inhibitor
- reduced drug interactions
- reduced DoA
what is the MoA of SSRIs? give an example
- 5-HT re-uptake inhibitor
- has less bad side effects
- less effective against severe depression
what are the pharmacokinetics against SSRIs?
- oral admin
- plasma half life = 18-24 hours
- delayed onset of action (2-4 weeks)
- fluoxetine competes w/ TCAs for hepatic enzymes –> avoid co admin
what are the unwanted effects of SSRIs?
- nausea
- diarrhoea
- insomia
- loss of libido
- fewer side effects so most prescribed
what is a drug interaction of SSRIs?
- interacts w/ MAOIs so avoid co-admin
what are 2 other anti-depressants?
- venlafaxine
- mertazapine
when is mertazapine useful?
SSRI tolerant patients
What is the MoA of venlafaxine?
dose-dependent re-uptake inhibitor
what is the MoA of mertazapine?
- 2 receptor antagonist
- inhibits negative inhibition of NA release, inc. NA and 5-HT release
