Antidepressant Drugs Flashcards
(33 cards)
Emotional/psychological symptoms of depression
- Misery, apathy, pessimism
- Low self-esteem
- Loss of motivation
- Anhedonia (loss of enjoyment from activities)
Biological/somatic symptoms of depression?
- Slowing of though & action
- Loss of libido
- Loss of appetite, sleep disturbance
2 broad types of depression?
(1) Unipolar depression/depressive disorder
(2) Bipolar depression/manic depression
Explain the (1) type of depression
Unipolar depression (depressive disorder)
- Mood swings in SAME direction
- Relatively LATE onset
Types of unipolar depression:
• Reactive depression - stressful live events, non-familial inheritance
• Endogenous depression - unrelated to external stresses, familial pattern
ALL types of unipolar depression respond in the SAME WAY to the same drug treatments
Explain the (2) type of depression
Bipolar depression (manic depression)
- Oscillating depression/mania
- LESS common
- EARLY adult onset
- STRONG hereditary tendency
Drug treatment includes LITHIUM
• can stabilise swings between mania & depression BUT has a narrow therapeutic window
Define the Monoamine theory of depression
Depression is a functional DEFICIT of central MA transmission
Mania is a functional EXCESS of MA transmission
What is MA related to?
Related to
• NA & 5-HT (serotonin) deficits/excesses
What evidence supports the MA theory of depression?
Pharmacological evidence
onenote table!!
What evidence does NOT support the MA theory of depression and explain why
Biological evidence
A reduction in NA metabolites is NOT concurrent with a worse depression
Delayed onset of the clinical effect of drugs (a few weeks sometimes)
– possibly due to adaptive changes and not MA theory:
• there is a downregulation of - alpha2, beta & 5-HT receptors
What other conclusions are made along with the MA theory
Could be due to:
• increased CRH (and thus cortisol)?
• hippocampal neurodegeneration?
What drugs provide the pharmacological evidence supporting the MA hypothesis of depression?
- TCAs (tricyclic antidepressants)
- MAO inhibitors
- Reserpine
- alpha-Methyltyrosine
- Methyldopa
- ECT
Example of a TCA drug?
Amitriptyline
MOA of TCAs?
Monoamine re-uptake inhibitor
– NA=5-HT»_space; DA.
Also acts on: • alpha2 – block pre-synaptic inhibition of NA release) • mAChR • H2 (histamine) receptors • 5-HT receptors
TCAs down-regulate:
• BETA-adrenoceptors
• 5-HT2 receptors
The time-course of this down-regulation correlates well with the clinical onset of symptom relief.
Pharmacokinetics of TCAs?
o Oral administration
o Highly PPB – 90-95%
o Hepatic metabolism
– to ACTIVE metabolites –> excreted in the urine (glucuronide conjugates)
o Plasma T1/2 = 10-20 hours
– dose once daily
What are some unwanted effects associated with TCAs?
Therapeutic doses:
Atropine-like effects
– anti-PNS effects such as dry mouth, constipation, etc
Postural hypotension
– due to effects on vasomotor centre
Sedation
– due to effects on H1 antagonism
Acute toxicity:
CNS
– excitement, delirium, seizures –> coma, respiratory depression
CVS
– cardiac dysrhythmias –> VF & sudden death
Often used for attempted suicide!
TCAs can interact with drugs, causing its effects to increase - explain this
- PPB
• INCREASE TCA effects
• as very PPB, there is a massive increase of bioavailability if co-administered with something that displaces it from the PP
• e.g. aspirin, phenytoin - Hepatic enzymes
• INCREASE TCA effects
• drugs that compete with the metabolising hepatic enzymes
•e.g. neuroleptics, oral contraceptives - Potentiation
• drugs that potentiate the effects of the CNS depression
• e.g. alcohol - Antihypertensive drugs
Example MAOI drug?
Phenelzine
Explain the MOA of MAOI
MAO enzymes:
• MAO-A breaks down NA & 5-HT – key MoA!
• MAO-B: breaks down DA – e.g. Selegiline
o Most are non-selective MAOIs
o Irreversible inhibition leads to a long duration of action
Effects:
Rapid effects
– increase cytoplasmic (not enhanced release but more leakage) NA, 5-HT
Delayed effects
– delayed clinical response due to down-regulation of beta-adrenoceptors & 5-HT2 receptors
– again, fits with delayed clinical effect
o Inhibits other enzymes – leads to side effects.
Pharmacokinetics of MAOI?
o Oral absorption
o Short plasma T1/2 but a longer DoA
o Metabolised in the liver, excreted in the urine
Unwanted effects associated with MAOI?
o Atropine-like effects (anti-PNS effects)
– but less so than TCAs
o Postural hypotension
– common
o Sedation
– causes seizures in OD
o Weight gain
– possibly excessive
o Hepatotoxicity
– hydrazines, rare
Why is the drug interactions of MAOI a serious problem?
‘Cheese reaction’
Tyramine-containing foods + MAOI = hypertensive crisis
Tyramine is metabolised by MAO and so high levels of tyramine compete with NA and so higher levels of NA leading to the hypertensive episodes
o MAOIs + TCAs = hypertensive episodes
o MAOIs + pethidine (opioid analgesic) = hyperpyrexia, restlessness, coma & hypotension
What are the hypertensive crisis in relation to the ‘cheese reaction’
- Throbbing headache
- Increase BP
- Intracranial haemorrhage
Example of a MAO-A inhibitor?
Moclobemide
Reversible, MAO-A inhibitor (RIMA)
• reduced drug interactions
• reduced DoA
SSRIs - example drug?
Fluoxetine
