anxiety/sedation/depression Flashcards
anti-depressants: explain the mechanism of action of clinically useful anti-depressant drugs and how this contributes to efficacy and side effects; Identify proposed mechanisms underlying the delayed therapeutic effects of antidepressant drugs.
2 groups of psychoses
schizophrenia, affective disorders
2 groups of affective disorders (disorders of mood)
mania, depression
emotional (psychological) symptoms of depression
misery, apathy, pessimism, low self-esteem, loss of motivation, anhedonia (joyment of activities is lost)
biological (somatic) symptoms of depression
slowing of thought and action (psychomotor retardation), loss of libido, loss of appetite, sleep disturbance
2 types of depression
depressive disorder (unipolar depression), manic depression (bipolar depression)
depressive disorder: main feature and onset
mood swings in same direction, relatively late onset
depressive disorder: 2 types of depressive disorder
reactive, endogenous
depressive disorder: what causes reactive depression
stressful life events, non-familial
depressive disorder: what causes endogenous depression
unrelated to external stresses, familial
depressive disorder: treatment type
drug treatment (similar groups for both reactive and endogenous)
manic depression: main feature and onset
oscillating depression/mania, less common with early adult onset
manic depression: cause
strong hereditary tendency
manic depression: treatment type
drug treatment (including oral lithium which stabilises mood, reducing cAMP and IP3, but has narrow therapeutic window)
example of tricyclic antidepressant (TCA)
amitriptyline
method of action of TCA
neuronal monoamine re-uptake inhibitors (NA and 5-HT equally)
4 other possible receptor actions of TCA
a2 (antagonise NA release inhibition), mAChRs, histamine, 5-HT (antagonise 5-HT release inhibition)
what 2 receptors do TCAs cause delayed down-regulation
B-adrenoceptors, 5-HT2 receptors
number of chemical structures of TCAs
2 main classes
pharmacokinetics of TCAs: absorption, plasma protein binding, metabolism, excretion, plasma half life
rapid oral absorption, highly plasma protein binding, undergo hepatic metabolism into active metabolites, renal excretion as glucuronide conjugates, plasma half life of 10-20 hours (relatively long so give once a day)
3 unwanted effects of TCAs at therapeutic dose
atropine-like effects (mACh antagonist e.g. dry mouth, constipation, blurred vision), postural hypotension (vasomoter centre - possibly a2), sedation (H1 antagonism - used to treat insomnia in depressed patients as well)
4 unwanted effects of TCAs at acute toxicity (overdose) in CNS
excitement, delirium, seizures -> coma, respiratory depression
unwanted effect of TCAs at acute toxicity (overdose) in CVS
cardiac dysrhythmias -> ventricular fibrillation and sudden death (NA and mACh)
due to CNS and CVS effects of TCAs, what can patients take an overdose for in care
attempted suicide
2 drug interactions of TCAs which increase TCA effects, with drug examples
plasma protein binding (aspirin, phenytoin, warfarin), hepatic microsomal enzymes (neuroleptics (anti-psychotics), oral contraceptives)
2 other effects of TCA drug interactions
potentiate CNS depressants (e.g. alcohol), potentiate antihypertensive drugs (must monitor closely)
example of monoamine oxidase inhibitor (MAOI)
phenelzine
what do MAO-A preferentially break down
NA and 5-HT
what do MAO-B preferentially break down
DA (relevant to Parkinson’s)
selectivity and duration of action of MAOIs
most are non-selective, and have irreversible inhibition so long duration of action
rapid effects of MAOIs
increased cytoplasmic NA and 5-HT
what receptor down-regulation cause a delayed clinical response with MAOIs
B-adrenoceptors and 5-HT2 receptors
what else can MAOIs inhibit
other enzymes e.g.
how many main chemical structures of MAOIs
3, with single cyclical section (phenalzine is a hydrazine, with hydrazine group being very active)
pharmacokinetics of MAOIs: absorption, plasma half life, metabolism, excretion
rapid oral absorption, short plasma half life (few hours) but longer duration of action, metabolised in liver, excreted in urine
6 unwanted effects of MAOIs
atropine-like effects (some mAChR antagonism but less than TCAs), postural hypotension (common - vasomotor centre), sedation (seizures in overdose), weight gain (increase in appetite; possibly excessive), hepatotoxicity (especially hydrazines, but rare)
drug interaction of MAOIs: “cheese reaction”
tyramine-containing foods (indirectly acting sympathomimetic drug) and MAOI -> high levels of tyramine compete with NA for MAO that’s left, so NA remains high and causes hypertensive crisis (throbbing headache, increased BP, intracranial haemorrhage)
drug interaction of MAOIs: with TCAs
hypertensive episodes so avoid
drug interaction of MAOIs: with pethidine (opioid analgesic)
hyperpyrexia, restlessness, coma, hypotension
what is a reversible MAO-A inhibitor (RIMA), and effect on drug interactions and duration of action (give instead of MAOI)
moclobemide, which decreases MAO-A inhibitor drug interactions (e.g. cheese reaction due to MAO-B being available to break down NA) and duration of action
example of selective serotonin reuptake inhibitors (SSRIs)
fluoxetine (most prescribed anti-depressant drug)
mechanism of action of SSRIs
selective 5-HT reuptake inhibition
relative effectiveness and side effects of SSRIs vs other anti-depressants
less troublesome side effects so safer in overdose, but less effective against severe depression
pharmacokinetics of SSRIs: administation, plasma half life, onset of action, drug interaction with TCAs
oral administration, plasma half life of 18-24 hours (long acting so can take daily), delayed onset of action (2-4 weeks); fluoxetine competes with TCAs for hepatic enzymes, so avoid co-administration
unwanted effects of SSRIs
less than TCAs or MAOIs, but cause nausea, diarrhoea, insomnia, loss of libido, and interact with MAOIs and TCAs (avoid co-administration)
2 other antidepessant drugs
venlafaxine, mirtazapine
mechanism of action of venlafaxine (SNRI - serotonin and noradrenaline reuptake inhibitors)
dose-dependent reuptake inhibitor: 5-HT>Na»DA; 2nd line treatment for severe depression
mechanism of action of mirtazapine
a2 receptor antagonist, increasing NA and 5-HT release; has sedative effect also
when is electroconvulsive therapy (ECT) used (along with suxemethonium as NM blocker)
severe black depression
