Antidepressant drugs

Question 1

What are the types of psychoses

Answer 1

Schizophrenia 
Affective disorders (mania, depression)

Question 2

What are the emotional/psychological symptoms of depression

Answer 2

Misery , apathy, pessimism
Low self-esteem
Loss of motivation
Anhedonia

Question 3

What are the biological symptoms of depression

Answer 3

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

Question 4

Describe unipolar depression/depressive disorder

Answer 4

Mood swings in same direction
Relatively late onset
Drug treatment is the same for both reactive and endogenous depression

Question 5

Compare reactive and endogenous depression

Answer 5

Reactive - stressful life events, non-familial

Endogenous - unrelated to external stresses, familial pattern

Question 6

Describe bipolar depression/manic depression

Answer 6

Oscillating depression/mania
Less common; Early adult onset
Strong hereditary tendency
Drug treatment with lithium

Question 7

Describe the monoamine theory of depression

Answer 7

Depression = functional deficit of centra MA transmission
Mania = functional excess of MA
NA + 5-HT show the same effects

Delayed onset of clinical effect of drugs (adaptive changes?)
Down-regulation: α2, β, 5HT receptors

Question 8

Describe the evidence basis for monoamine theory of depression

Answer 8

Based on pharmacological evidence
Biochemical evidence inconsistent

TCAs block NA and 5HT reuptake - increases mood
MAOis increase NA and 5HT stores - increases mood
Methyldopa - inhibits NA synthesis - decreases mood

Question 9

What is the principal action of tricyclic antidepressants and give and example

Answer 9

Block NA + 5-HT reuptake
Increase mood
Amitriptyline

Question 10

What is the mode of action of tricyclic antidepressants

Answer 10

Neuronal monoamine re-uptake inhibitors
NA and 5-HT reuptake affected
Delayed down-regulation of β-adrenoceptors + 5-HT2 receptors

Question 11

Give examples of other receptors that tricyclic antidepressant might act at

Answer 11

α2
mAChRs
histamine
5-HT

Question 12

Describe the absorptive and metabolic pharmacokinetics of tricyclic antidepressants

Answer 12

Rapid oral absorption

Highly plasma protein bound (PPB) (90 - 95%)

Hepatic metabolism - active metabolites - renal excretion (glucuronide conjugates)

Question 13

What is the plasma half life of tricyclic antidepressants

Answer 13

10-20 hrs

Question 14

What are the unwanted effects of tricyclic antidepressants at therapeutic doses

Answer 14

Atropine - like effects (amitriptyline)

Postural hypotension (vasomotor centre)

Sedation (H1 antagonism)

Question 15

What are the unwanted effects of tricyclic antidepressants in acute toxicity

Answer 15

CNS: excitement, delirium, seizures -> coma, respiratory depression

CVS: cardiac dysrhythmias -> ventricular fibrillation/sudden death

Care - attempted suicide

Question 16

What are the drug interactions of tricyclic antidepressants

Answer 16

PPB: Increases TCA effects (aspirin, phenytoin)

Hepatic microsomal enzymes: Increases TCA effects (neuroleptics; oral contraceptives)

Potentiation of CNS depressants (alcohol)

Antihypertensive drugs (monitor closely)

Question 17

Give an example of a Monoamine oxidase inhibitor and describe their mode of action

Answer 17

Phenelzine

Most are non-selective MAOIs
Irreversible inhibition -> long d.o.a.

Question 18

What are the 2 types of MAO

Answer 18

MAO-A : NA + 5-HT

MAO-B : Dopamine

Question 19

What are the rapid and delayed effects of MAOIs

Answer 19

Rapid: Increase cytoplasmic NA + 5-HT

Delayed effects : clinical response, down-regulation of β-adrenoceptors + 5-HT2 receptors

Question 20

Describe the pharmacokinetics of MAOIs (absorption, half life, metabolism)

Answer 20

Rapid oral absorption
Short plasma t1/2 (few hrs) but longer d.o.a.
Metabolised in liver; excreted in urine

Question 21

What are the unwanted effects of MAOIs

Answer 21

Atropine - like effects (< TCAs)
Postural hypotension (common)
Sedation (Seizures in o.d.) 	
Weight gain (possibly excessive)
Hepatotoxicity (hydrazines; rare)

Question 22

What are the drug interactions of MAOIs

Answer 22

‘Cheese reaction’: Tyramine-containing foods + MAOI -> hypertensive crisis (throbbing headache, increased BP, intracranial haemorrhage)

MAOIs + TCAs -> hypertensive episodes (avoid)

MAOIs + pethidine -> hyperpyrexia, restlessness, coma & hypotension.

Question 23

What is moclobemide

Answer 23

reversible MAO-A inhibitor (RIMA)

↓ Drug interactions ↓ doa.

Question 24

Describe the mode of action of SSRIs and give an example of a drug

Answer 24

Selective 5-HT re-uptake inhibition
Less troublesome side-effects; safer in o.d.
But less effective vs severe depression

Fluoxetine/prozac

Question 25

Describe the pharmacokinetics of SSRIs

Answer 25

oral administration
Plasma t1/2 (18-24 hrs)
Delayed onset of action (2-4 weeks)
Fluoxetine competes with TCAs for hepatic enzymes (avoid co-administration)

Question 26

What are the unwanted effects of SSRIs

Answer 26

Nausea
Diarrhoea
Insomnia
Loss of libido

Question 27

What are the drugs interactions of SSRIs

Answer 27

Interacts with MAOIs (avoid co-admin)