Antidepressant drugs Flashcards
What are the types of psychoses
Schizophrenia Affective disorders (mania, depression)
What are the emotional/psychological symptoms of depression
Misery , apathy, pessimism
Low self-esteem
Loss of motivation
Anhedonia
What are the biological symptoms of depression
Slowing of thought and action
Loss of libido
Loss of appetite, sleep disturbance
Describe unipolar depression/depressive disorder
Mood swings in same direction
Relatively late onset
Drug treatment is the same for both reactive and endogenous depression
Compare reactive and endogenous depression
Reactive - stressful life events, non-familial
Endogenous - unrelated to external stresses, familial pattern
Describe bipolar depression/manic depression
Oscillating depression/mania
Less common; Early adult onset
Strong hereditary tendency
Drug treatment with lithium
Describe the monoamine theory of depression
Depression = functional deficit of centra MA transmission
Mania = functional excess of MA
NA + 5-HT show the same effects
Delayed onset of clinical effect of drugs (adaptive changes?)
Down-regulation: α2, β, 5HT receptors
Describe the evidence basis for monoamine theory of depression
Based on pharmacological evidence
Biochemical evidence inconsistent
TCAs block NA and 5HT reuptake - increases mood
MAOis increase NA and 5HT stores - increases mood
Methyldopa - inhibits NA synthesis - decreases mood
What is the principal action of tricyclic antidepressants and give and example
Block NA + 5-HT reuptake
Increase mood
Amitriptyline
What is the mode of action of tricyclic antidepressants
Neuronal monoamine re-uptake inhibitors
NA and 5-HT reuptake affected
Delayed down-regulation of β-adrenoceptors + 5-HT2 receptors
Give examples of other receptors that tricyclic antidepressant might act at
α2
mAChRs
histamine
5-HT
Describe the absorptive and metabolic pharmacokinetics of tricyclic antidepressants
Rapid oral absorption
Highly plasma protein bound (PPB) (90 - 95%)
Hepatic metabolism - active metabolites - renal excretion (glucuronide conjugates)
What is the plasma half life of tricyclic antidepressants
10-20 hrs
What are the unwanted effects of tricyclic antidepressants at therapeutic doses
Atropine - like effects (amitriptyline)
Postural hypotension (vasomotor centre)
Sedation (H1 antagonism)
What are the unwanted effects of tricyclic antidepressants in acute toxicity
CNS: excitement, delirium, seizures -> coma, respiratory depression
CVS: cardiac dysrhythmias -> ventricular fibrillation/sudden death
Care - attempted suicide
What are the drug interactions of tricyclic antidepressants
PPB: Increases TCA effects (aspirin, phenytoin)
Hepatic microsomal enzymes: Increases TCA effects (neuroleptics; oral contraceptives)
Potentiation of CNS depressants (alcohol)
Antihypertensive drugs (monitor closely)
Give an example of a Monoamine oxidase inhibitor and describe their mode of action
Phenelzine
Most are non-selective MAOIs
Irreversible inhibition -> long d.o.a.
What are the 2 types of MAO
MAO-A : NA + 5-HT
MAO-B : Dopamine
What are the rapid and delayed effects of MAOIs
Rapid: Increase cytoplasmic NA + 5-HT
Delayed effects : clinical response, down-regulation of β-adrenoceptors + 5-HT2 receptors
Describe the pharmacokinetics of MAOIs (absorption, half life, metabolism)
Rapid oral absorption
Short plasma t1/2 (few hrs) but longer d.o.a.
Metabolised in liver; excreted in urine
What are the unwanted effects of MAOIs
Atropine - like effects (< TCAs) Postural hypotension (common) Sedation (Seizures in o.d.) Weight gain (possibly excessive) Hepatotoxicity (hydrazines; rare)
What are the drug interactions of MAOIs
‘Cheese reaction’: Tyramine-containing foods + MAOI -> hypertensive crisis (throbbing headache, increased BP, intracranial haemorrhage)
MAOIs + TCAs -> hypertensive episodes (avoid)
MAOIs + pethidine -> hyperpyrexia, restlessness, coma & hypotension.
What is moclobemide
reversible MAO-A inhibitor (RIMA)
↓ Drug interactions ↓ doa.
Describe the mode of action of SSRIs and give an example of a drug
Selective 5-HT re-uptake inhibition
Less troublesome side-effects; safer in o.d.
But less effective vs severe depression
Fluoxetine/prozac
Describe the pharmacokinetics of SSRIs
oral administration
Plasma t1/2 (18-24 hrs)
Delayed onset of action (2-4 weeks)
Fluoxetine competes with TCAs for hepatic enzymes (avoid co-administration)
What are the unwanted effects of SSRIs
Nausea
Diarrhoea
Insomnia
Loss of libido
What are the drugs interactions of SSRIs
Interacts with MAOIs (avoid co-admin)
