Anti-depressants part 2 Flashcards
What pharmacological evidence supports the monoamine theory of depression?
Effects of drugs in depressed patients: 1. TCAs block NA, 5-HT re-uptake - increase mood 2. MAO inhibitors increase NA, 5-HT stores - increase mood 3. a-methyltyrosine and methyldopa inhibit NA synthesis - reduce mood 4. Reserpine inhibits NA, 5-HT storage - reduces mood 5. ECT ? increases CNS responses to NA, 5-HT - increases mood
What are the side effects of TCAs?
At Therapeutic dosage: -Atropine-like effects (esp amitriptyline) - parasymp effects ,Postural hypotension (VMC) ,Sedation (H1 antagonism)
Acute toxicity (o.d): CNS: excitement, delirium, seizures which can lead to coma and Resp depression . CVS: cardiac dysrhythmias,which can lead to ventricular fibrillation and sudden death. Care: Attempted suicide by overdosing on TCA
What are the side effects of MAOIs?
- Atropine-like effects (less than TCAs) ,Postural hypotension ,Sedation (seizures -in overdose(od)) ,Weight gain , Hepatotoxicity
Why should fluoxetine (SSRI) not be coadministered with TCAs?
Fluoxetine competes with TCAs for hepatic enzymes. Could accumulate to toxic levels
Classify different psychoses , and describe the emotional and biological symptoms
Differentiate between unipolar and bipolar depression , with alternative names for them
1) Unipolar depression/depressive disorder:
- Mood swings in same direction
- Relatively late onset
- Reactive depression - stressful life events,non-familial
- Endogenous depression - unrelated to external stresses, familial pattern
- Drug treatment
2) Bipolar depression /manic depression
Oscillating depression/mania
Less common; Early adult onset
Strong hereditary tendency
Drug treatment (Lithium; see Fig.
Describe interactions of TCAs with other drugs
Many drug interation
PPB: TCA effects can be increased when other drugs that are highly PPB as it displaces TCA form the PP (aspirin, phenytoin)
Hepatic microsomal enzymes: TCA effects are increase by drugs that are metabolised by the same system therefore increasing it’s effects (neuroleptics; oral contraceptives)
Potentiation of CNS depressants (alcohol)
Antihypertensive drugs (monitor closely), it can affect the blood pressure fo people of these drugs. The chang is unpredictable
SOME PHARMACOKINETICS FOR MAOI
- Rapid oral absorption
- Short plasma t1/2 (few hrs) but longer d.o.a since they are are irreversible inhibitors
- Metabolised in liver; excreted in urine
WHat does Venlafaxin and Mirtazapine do
Venlafaxine: Dose-dependent Reuptake inhibitor
5HT > NA >> DA (SNRI)
2nd Line treatment for severe depression
Mirtazapine: α2 Receptor antagonist
↑ NA & 5HT release
Other R interactions (sedative)
Useful in SSRI-intolerant patients
Explain what is used a last resort to treatment longterm depression
Electrical current across the te,poral lobes of the brain,patients are anastheitized. and ventilated.Give them them a neuromuscular blocker, like succinmethonium. to make sure that we do not get convulsive movements of th earms of the legs and thier limbs will be damaged as a result otherwise. It is a llast resort and is used for chroinic depression, severe depression where they are considering suicide.
What pharmacological evidence doesn’t support the monoamine theory of depression?
Effects of drugs in depressed patients: 1. Amphetamine (releases NA and blocks re-uptake) and cocaine (inhibits NA reuptake) - no effect 2. Tryptophan (increases 5-HT synthesis) - questionable effects on mood 3. Methysergide (5-HT antagonist) - no effect 4. a/B antagonists (block actions of NA) - mood slightly decreased w/B 5. L-dopa (increases NA synthesis) - no effect 6. Iprindole (no effect on amine metabolism) - increases mood
