Anti-depressants Flashcards
Unipolar depression/depressive disorder
- Mood swings in same direction
- Relatively late onset
- all types respond in the same way to the same drug treatments
Bipolar depression/manic depression
- Oscillation between depression and mania
- Early adult onset
- Less common
- Strong hereditary tendency
- Drug treatment includes Lithium=stabilise swings between depression and mania but lithium has a narrow therapeutic window
Tricyclic antidepressants (TCAs)
Principal action: Blocks NA and 5-HT reuptake
- IMPROVES mood in depressed patients
- Example: Amitriptyline
MAO inhibitors
Principal action: Increases stores of NA and 5-HT
- IMPROVES mood in depressed patients
- Example: Phenelzine
Reserpine
Principal action: Inhibits NA and 5-HT storage
-WORSENS mood in depressed patients
Alpha-Methyltyrosine
Principal action: Inhibits NA synthesis
- WORSENS mood in depressed patients
- CALMING of maniac patients
Methyldopa
Principal action: Inhibits NA synthesis
-WORSENS mood in depressed patients
ECT (Electroconvulsive Therapy)
Principal action: Increases CNS responses to NA and 5-HT
-IMPROVES mood in depressed patients
Tricyclic antidepressants pharmacokinetics
- Oral administration
- Rapid absorption
- highly plasma-protein bound (90%-95%)
- hepatic metabolism gives active metabolites->renal excretion as glucuronide conjugates
- 10-20 hour plasma half life
Tricyclic antidepressants side effects
At therapeutic doses:
-Atropine-like effects
-Postural hypotension (vasomotor centre)
-Sedation (H1 antagonism)
Overdose (acute toxicity):
-CNS: excitement, delirium, seizures leading to coma, respiratory depression
-CVS: cardiac dysrhythmias leading ventricular fibrillation/sudden death
-often used in suicide attempts
Tricyclic antidepressants drug interactions
- PPB=increase TCA effects
- hepatic microsomal enzymes=increase TCA effects
- potentiation of CNS depressants (eg: alcohol)
- antihypertensive drugs (close monitoring)
MAO inhibitors pharmacokinetics
- Oral drug
- Rapid absorption
- few hour plasma half life
- long duration of action
- metabolised in liver -excreted in urine
MAO inhibitors side effects
- Atropine-like effects (less so than TCAs)
- Postural hypotension (common side effect)
- Sedation (seizures in overdose)
- Weight gain (possibly excessive)
- Hepatotoxicity (hydrazines, rare)
MAO inhibitors drug interactions
- ‘Cheese reaction’=tyramine-containing foods and MAO inhibitors leading to hypertensive crisis (throbbing headaches, increased blood pressure, intracranial haemorrhage)
- MAO inhibitors and TCAs leading to hypertensive episodes
- MAO inhibitors and pethidine leading to hyperpyrexia, restlessness, coma and hypotension
SSRIs pharmacokinetics
- Oral administration
- 18-24 hour plasma half life
- delayed onset of action (2-4 weeks)
- Fluoxetine competes with TCAs for hepatic enzymes (avoid co-administration)
SSRIs side effects
Fewer than TCAs and MAO inhibitors
- Nausea, diarrhoea, insomnia and loss of libido
- MAO inhibitor interaction so avoid co-administration
Venlafaxine
- Dose-dependent Reuptake inhibitor
- Second line treatment for severe depression
- serotonin> noradrenaline»dopamine
Mirtazapine
- Alpha-2 receptor antagonist
- Increase NA and 5-HT release
- Useful in SSRI-intolerant patients
Depression symptoms
Emotional/psychological: -misery -apathy -pessimism -low self-esteem -loss of motivation -anhedonia (loss of enjoyment from normally pleasurable activities) Biological/somatic: -slowing of thought and action -loss of libido -loss of appetite -sleep disturbance
Types of unipolar depression
Reactive depression=response to stressful life events, non-familial
Endogenous depression=unrelated to external stresses, familial pattern
Monoamine theory of depression
- depression is a functional deficit of central monoamine transmission
- mania is a functional excess of monoamine transmission
- relation to NA and 5-HT (serotonin) deficits/excesses
Tricyclic antidepressants MOA
- Example: Amitriptyline
- neuronal monoamine re-uptake inhibitor
- TCAs down-regulate beta-adrenoceptors and 5-HT2 receptors
SSRIs MOA
- Example: Fluoxetine (currently most prescribed antidepressant)
- Selective 5-HT re-uptake inhibition
- less troublesome side effects so safer in overdose situation
- less effective vs severe depression
Moclobemide
- Reversible MAO-A inhibitor (RIMA)
- leads to reduced drug interactions and reduced duration of action
MAOI’s MOA
- Example: Phenelzine
- MAO-A break down noradrenaline and serotonin
- MAO-B break down dopamine
- most are non-selective inhibitors
- irreversible inhibition leads to long duration of action
- rapid effects=increased cytoplasmic noradrenaline and serotonin
- delayed effects=clinical response due to down-regulation of beta-adrenoceptors and 5-HT2 receptors
- inhibition of other enzymes
Meclobemide
- reversible MAO-A inhibitor (RIMA)
- reduced drug interactions and reduced duration of action
