Anti depressants Flashcards
What are the symptoms of depression?
- Emotional (Psycho-logical)
* Misery, apathy, pessimism
* Low self-esteem
* Loss of motivation
* Anhedonia (inability to feel pleasure) - Biological (Somatic)
* Slowing of thought & action
* Loss of libido
* Loss of appetite, sleep disturbance
What are the 2 types of depression?
- Unipolar depression
- Bipolar depression
What is the difference between the 2 different types of depression?
- Unipolar
- Mood swings in the same direction
- Relatively late onset
- Bipolar
- Oscillating depression/mania
- Less common
- Early adult onset
- Strong hereditary tendency
What are the 2 subsets of unipolar depression?
- Reactive depression
- stressful life events
- non-familial
- Endogenous depression
- unrelated to external stresses
- familial pattern
What is the monoamine theory of depression and mania?
Depression = Functional deficit in central monoamine transmission (NA and 5-HT)
Minia = functional excess
What’s the evidence for and against the monoamine theory of depression?
- Pharmacological evidence is supportive
- Biochemical evidence is inconsistant
What is the general onset of antidepressant drugs? What could this caused by?
- Delayed onset of action - 1 week
- Could be due to adaptive changes: down-regulation of alpha 2, beta and some subsets of 5HT receptors
What are other theories for depression?
- Increased CRH levels play a role
- Hippocampal neurodegeneration
What is the principal action of the main classes of antidepressant drugs?
- Tricyclic antidepressants
* Block NA & 5-HT reuptake - MAO inhibitors
* Increase stores of NA & 5-HT by preventing metabolism: these eventually leak into synaptic cleft as they build up - SSRIs
* Block 5-HT reuptake
What is the mechanism of action of TCAs? What other receptor actions does it have?
- Neuronal monoamine re-uptake inhibitors (mainly 5HT and NA)
- Delayed down-regulation of β-adrenoceptors & 5-HT2 receptors
- Also block:
- -α2, mAChRs, histamine, 5-HT
- this may lead to the side effects
What are the pharmacokinetics of TCAs?
- Rapid oral absorption
- Highly PPB (90 - 95%)
What’s the half life of TCAs?
10-20 hours
How are TCAs metabolised?
- Hepatic metabolism - active metabolites
- Renal excretion (glucuronide conjugates)
What are the unwanted effects of theraptuic doses of TCAs?
- Atropine - like effects (amitriptyline)
- Postural hypotension (vasomotor centre)
- Sedation (H1 antagonism)
What are the effects of TCA acute toxicity?
- CNS:
* excitement, delirium, seizures -> coma, respiratory depression - CVS:
* cardiac dysrhythmias -> ventricular fibrillation/sudden death
What are the drug interactions of TCAs?
- PPB:
Displace TCA effects (aspirin, phenytoin, warfrin)
- Hepatic microsomal enzymes:
* Competition for enzymes (neuroleptics, oral contraceptives) - Potentiation of CNS depressants (alcohol)
- Antihypertensive drugs (monitor closely)
* Unpredictable rise or fall
What is an example of a TCA?
Amitriptyline
What is an example of a MAO inhibitor?
Phenelzine
What do the MAO preferentially metabolise?
- MAO-A : NA & 5-HT
- MAO-B : DA
What is the mechanism of MAO inhibitors?
- Most are non-selective MAOIs
- Irreversible inhibition -> long d.o.a.
What are the rapid and delayed effects of MAO inhibitors?
Rapid effects :
- increase in cytoplasmic NA & 5-HT
Delayed effects :
- down-regulation of β-adrenoceptors & 5-HT2 receptors
What are the pharmacokinetics of MAO inhibitors?
- 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 the MAO inhibitors?
- Atropine - like effects (< TCAs)
- Postural hypotension (common)
- Sedation (Seizures in o.d.)
- Weight gain (possibly excessive)
- Hepatotoxicity (hydrazines; rare)
What are the other drug interactions of MAO inhibitors?
MAOIs + TCAs = hypertensive episodes (avoid)
MAOIs + pethidine = hyperpyrexia, restlessness, coma & hypotension.
What is the cheese reaction?
Tyramine
- Tyramine is found in food
- Tyramine is a sympathomimmetic drug
- Gains access to the brain and enters NA neurones
- Forces NA out of the pre synaptic terminal
Tyramine + MAOi
- Excessive SNS activation as MAO breaks down tyramine
- Hypertensive crisis - throbbing headaches, increase bp, inracranial haemorrhage
What is Moclobemide?
- reversible MAO-A inhibitor
- ↓ Drug interactions
- ↓ doa.
What are SSRIs? Give an example
- Selective serotonin reuptake inhibitors
- Fluoxetine
What is the mechanism of action of SSRIs?
Selective 5-HT re-uptake inhibition
What are the advantages and disadvantages of SSRIs?
Advantage:
- Less troublesome side-effects; safer in o.d.
Disadvantage:
- Less effective vs severe depression
What are the Pharmacokinetics of SSRIs?
- p.o. 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?
- •Fewer than TCAs/MAOIs
- Nausea, diarrhoea, insomnia & loss of libido
- Interact with MAOIs (avoid co-administration)
What is venlafaxine?
- Anti-depressant drug
- Dose-dependent Reuptake inhibitor
- 5HT > NA >> DA (SNRI)
- 2nd Line treatment for severe depression
What is mirtazapine?
- Anti-depressant
- α2 Receptor antagonist
- ↑ NA & 5HT release
- Other R interactions (sedative)
- Useful in SSRI-intolerant patients
Why might fluoxetine be used over velafaxine?
- Velafaxine can target serotonin > NA > dopamine
- As the more selective drug, the side effect profile of fluoxetine is expected to be lower (a better risk-benefit ratio).
- It is also the most cost-effective solution (i.e. cheapest).
