Anti-depressants

Question 1

What is the overall classification of psychoses?

Answer 1

2 types of psychoses: schizophrenia and affective disorders. There are 2 types of affective disorders which are mania and depression.

Question 2

List some symptoms of depression?

Answer 2

Misery, apathy, pessimism
Low self-esteem
Loss of motivation
Anhedonia (not enjoying things you normally enjoy)
Slowing of thought & action
Loss of libido
Loss of appetite, sleep disturbance

Question 3

What are the 2 types of depression?

Answer 3

Unipolar and bipolar

Question 4

Describe unipolar depression?

Answer 4

You get mood swings in one direction and generally late onset. 2 types:
Reactive- in response to a stressful event and not familial
Endogenous- no external stress and familial

Question 5

Describe bipolar depression?

Answer 5

Oscillating between depression and mania, early adult onset, strong hereditary link, treat wit lithium

Question 6

Describe monoamine theory of depression?

Answer 6

Depression results in fucntional defcits in central monoamine transmission…later expanded to include 5HT (seratonin).

Question 7

Describe evidence for MOA theory?

Answer 7

Pharmacological evidence: TCAs, MAO inhibitors increase NA and 5HT and subsequently increase mood. Methyldopa inhibits NA production so decreases mood.

Biochemical evidence is inconsistent: changes to NA or 5HT levels due to drugs are not reflected in changing concentrations within urine.

Question 8

What are two other possible theories?

Answer 8

The HPG axis is involved…e.g. in chronic depression, there’s an increase in CRH.

Hippocampus degenerates in chronic depression

Question 9

Describe the mechanism of action of TCAs and give example?

Answer 9

Amitriptyline

Inhibit monoamine and 5HT reuptake in synapses in CN. Also interact with alpha 2 receptors (antagonists) muscarinic (antagonists) and histamines (antagonists)

Question 10

Describe pharmacokinetics of TCAs?

Answer 10

Rapid oral absorption
Highly PPB (90 - 95%)
Hepatic metabolism - active metabolites - renal excretion
Plasma t1/2 (10-20 hrs)

Question 11

Describe side effects of TCAs?

Answer 11

Atropine -like effects (amitriptyline). due to muscarinic antagonism…e.g. dry mouth, GI disurbance and blurred vision.
Postural hypotension (vasomotor centre)
Sedation (H1 antagonism)

At toxic levels can cause excitation, seizures and respiratory depression. Effects CVS too can cause dysarrythmias and ventricular fibrillation.

Question 12

Describe interactions of TCAs?

Answer 12

Drgs tat compete for plasma protein binding e.g. aspirin will increase free plasma levels.
Drugs that use same microsmomal liver enzymes will also increase TCAs.
Synergises with alchol in depressing CNS.

Question 13

Describe the mechanism of action of monoamine inhibitors and give an example?

Answer 13

Phenelzine

Most are non-selective MAOIs- target MAO A and B
Irreversible inhibition so have long d.o.a.
Rapid effects : cytoplasmic NA & 5-HT spike quickly
Delayed effects : due to beta recptor and 5HT2 receptor downregulation

Question 14

What are the two types of monoamine oxidase?

Answer 14

MAO A mettabolises NA and 5HT, MAO B mettabolises dopamine.

Question 15

Describe pharmacokinetcs of MAO inhibitors?

Answer 15

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

Question 16

Describe unwanted effects and interactions of MAO inhibitors?

Answer 16

Atropine - like effects (< TCAs)
Postural hypotension (common)
Sedation (Seizures in o.d.) due to antagonism of H1 receptors
Weight gain (possibly excessive)
Hepatotoxicity (hydrazines; rare)

Question 17

Describe interactions of MAOIs?

Answer 17

Cheese raction (tyramine)
MAOIs + TCAs leads to hypertensive episodes (avoid)
MAOIs + pethidine leads to hyperpyrexia, restlessness, coma & hypotension

Question 18

Descrbe usage of revesible MAOIs?

Answer 18

Have fewer interactions but lower duration of action.

Question 19

Describe method of action of SSRIs and givean example?

Answer 19

Fluoxetine

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

Question 20

Describe pharmacokinetics of SSRIs?

Answer 20

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 21

Describe unwanted efects of SSRIs?

Answer 21

Nausea, diarrhoea, insomnia & loss of libido

Interact with MAOIs (avoid co-administration)

Question 22

Describe 2 other antidepressant drugs?

Answer 22

Venlafaxine: Dose-dependent Reuptake inhibitor. Targets 5HT > NA&raquo_space; DA (SNRI). 2nd Line treatment for severe depression

Mirtazapine: α2 Receptor antagonist. ↑ NA & 5HT release. Sedative effects due to H1 antagonism. Useful in SSRI-intolerant patients