Anti-depressants

Question 1

What are the emotional symptoms of depression?

Answer 1

Apathy, misery, pessimism
Low self esteem
Low motivation
Anhedonism

Question 2

What are the biological symptoms of depression?

Answer 2

Loss of libido
Slowing of thought and action
Loss of appetite and sleep disturbance

Question 3

What are the characteristics of unipolar depression and the two types?

Answer 3

Mood swing is in one direction
Late adult onset
Reactive: response to stressful life events, non-familial
Endogenous: unrelated to external stresses, familial pattern

Question 4

What are the characteristics of bipolar depression?

Answer 4

Alternate between depression and mania
Early adult onset
Often genetic inheritance
Drug treatment e.g. lithium

Question 5

What is the difference between depression and mania?

Answer 5

Depression: functional deficit in central monoamines
Mania: functional excess of MAs

Question 6

What is reserpine known for?

Answer 6

Decreases levels of NA and 5-HT, lowers mood

Used as an anti-psychotic and in high BP

Question 7

What is MOA of Tricyclic antidepressants and the pharmacokinetics?

Answer 7

e.g. Amitriptiline
Neuronal monoamine reuptake inhibitors
Increase levels of NA and 5-HT, slows reuptake
Also act on other receptors;
a2, beta, mAChRs, histamine
Delayed down-regulation of beta and 5-HT receptors.

90-95% PPB
Plasma half life 10-20hrs, long doa
Hepatic metabolism - active metabolites- renal excretion of glucuronide conjugates

Question 8

What are the unwanted effects of TCAs at therapeutic doses and acute toxicity?

Answer 8

Therapeutic doses:
Atropine like effects
Postural hypotension
Sedation

Acute toxicity:
CNS-excitation, delirium, seizures -> coma, respiratory depression
CVS-cardiac arrhythmias, ventricular fibrillations/sudden death

Question 9

What are the possible drug interactions of TCAs?

Answer 9

Drugs which compete for PPB e.g. aspirin, phenytoin
Drugs which increase TCA effects by competing for hepatic metabolic enzymes e.g. neuroleptics, oral contraceptives
Potentiation of CNS depressants
Antihypertensive drugs

Question 10

What is the MOA of monoamine oxidase inhibitors?

Answer 10

e.g. Phenelzine
Non-selective MAO-A (NA + 5-HT) MAO-B (DA) inhibitors
Increase levels of NA and 5-HT in cytoplasm due to leakage of stores in presynaptic terminals
Irreversible inhibition -> long d.o.a
Delayed clinical effects

Question 11

What are the pharmacokinetics of MOAIs?

Answer 11

Oral absorption
Short plasma half-life - long d.o.a
Metabolised in liver, excreted in urine

Question 12

What are the unwanted effects of MAOIs?

Answer 12

Atropine-like effects (less than TCAs)
Postural hypotension
Sedation
Weight gain
Hepatotoxicity (rare)

Question 13

What are the possible drug interactions of MAOIs?

Answer 13

Tyramine ‘cheese reaction’; breakdown of tyramine is blocked, increased NA release -> hypertensive crisis (throbbing headache, increased bp, intracranial haemorrhage).
Avoid co-admin of MAOIs and TCAs
Avoid co-admin of MAOIs and pethidine

Question 14

Name a reversible MOAI

Answer 14

Moclobemide: reversible MAO-A inhibitor
Decreased drug interactions
Decreased duration of action

Question 15

What is the MOA of SSRIs?

Answer 15

e.g. fluoxetine

Serotonin selective reuptake inhibitors

Question 16

What is the pharmacokinetics of SSRIs?

Answer 16

Paraoral
Plasma half-life 18-24hrs
Delayed onset of action 2-4weeks
Less side effects than TCAs or MAOIs
Avoid co-admin with TCAs as is competes for hepatic enzymes

Question 17

What are the unwanted effects of SSRIs?

Answer 17

Nausea, loss of libido, diarrhoea, insomnia
Increased risk of suicidality in <18yrs
Interact with MAOIs

Question 18

What are the two other antidepressant drugs?

Answer 18

Venlofaxane: dose-dependent reuptake inhibitors
NA > 5-HT > DA
2nd line treatment in those with severe depression

Metarzapine: a2 antagonist
Increases levels of NA and 5-HT
Acts on other receptors e.g. H1 receptor contributes to sedative effects
Use in SSRI-intolerant patients