Pharmacology - Anti-depressants Flashcards
What are the different types of psychoses
Psychoses can be split into schizophrenia and affective disorders. Affective disorders can then be split into mania and depression.
What are the emotional symptoms of depression
- Misery, apathy, pessimism
- Low self esteem
- Loss of motivation
- Anhedonia (inability to feel joy)
Somatic symptoms of depression
- Slowing of thoughts and actions
- Loss of libido
- Loss of appetite
- Sleep disturbance
what are the clinical depression calssifications
Unipolar depression
- Mood swings only in one direction
- Realtively late onset
- Reactive depression (stressful life events, non-familial)
- Endogenous depression (unrelated to external stress, familial pattern)
- Drug treatment is the same for all types
Bipolar depression / Manic depression
- Oscillating depression/mania
- Less common
- Early adult onset
- Strong hereditary tendency
- Treated with lithium (mood stabiliser, narrow therapeutic window)
Epidemiology of depression
5-10% of the population will have depression at some point
Describe the mono amine theory of depression
- Depression is a functional deficit of central mono amine transmission; mania is a functional excess
- Functional deficit of noradrenaline and 5-HT in brain
- Down regulation of alpha 2, beta and 5-HT receptors
Why does the response from antidepressants take weeks
This is the time taken for receptors to return to normal after a drop from a huge increase in metabolites suppressing them
How do tricyclic antidepressants work
- Neuronal mono amine reuptake inhibitors
- Binds equally to noradrenaline and 5-HT reuptake carriers
- They also affect a2 receptors, mAChR, histamine receptors and 5-HT receptors
- a2 antagonism leads to increased noradrenaline in the synapse and the other interactions likely lead to unwanted side effects
Pharmacokinetics of TCAs
- Rapidly absorbed via oral route
- Highly plasma protein bound (90-95%)
- Hepatic metabolism -> active metabolites -> renal excretion (glucuronide conjugates)
- Plasma half life of 10-20 hours (one dose daily)
Unwanted effects of TCAs
At therapeutic doses:
- Atropine like effects (amitriptyline - muscarinic receptor antagonism)
- Postural hypotension (vasomotor centre)
- Sedation (H1 antagonism, histamine)
Overdose (acute toxicity)
- CNS : excitement, delirium, seizures -> coma, respiratory depression
- CVS : cardiac dysrhythmias -> ventricular fibrillation/sudden death
- Can be used as attempted suicide route
Drug interactions of TCAs
- Highly plasma bound so other drugs that compete can cause toxicity
- Hepatic enzymes can be competed for causing toxicity
- Potentiation of CNS depression with alcohol
- Unpredictability with anti-hypertensives can raise or decrease BP
What do MAO-A and MAO-B target
MAO-A breaks down NA and 5-HT (key MAO)
MAO-B breaks down dopamine
How do mono amine oxidase inhibitors function
- Most are non-selective MAOIs
- Bind irreversibly - long duration of action
- Rapidly increases cytoplasmic NA and 5-HT
- Delayed effects after 2-3 weeks give clinical response of down regulation of B-adrenoreceptors and 5-HT2 receptors
Pharmacokinetics of MAOIs
- Rapid oral absorption
- Short plasma half-life (few hours, but long duration of action)
- Metabolised in the liver excreted in the urine
Unwanted effects of MAOIs
- Atropine like effects (less than TCAs)
- Postural hypotension (common)
- Sedation (Seizures in OD)
- Weight gain (possibly excessive)
- Hepatotoxicity (hydrazines, rare)
