Antidepressants

Question 1

what are the two types of depression

Answer 1

unipolar and bipolar

Question 2

what are the symptoms of depression

Answer 2

Emotional/Psychological–misery,apathy,pessimism,
low self-esteem, loss of motivation, anhedonia (loss of
enjoyment from activities).

Biological/Somatic – slowing of action/thoughts, loss
of libido, loss of appetite, sleep disturbances.

Question 3

what are the two types of unipolar depression

Answer 3

reactive (eg stress or just life)

endogenous (unrelated to external events)

Question 4

what is the Monoamine theory of depression

Answer 4

Depression is a functional deficit of central Monoamine(MA) transmission

Mania is a functional excess of MA transmission.

Related to NA and 5-HT (serotonin) deficits/excesses.

Question 5

what are the criticisms of the monoamine theory of depression

Answer 5

Good Pharmacological evidence to support it- ie drugs work (and antagonistic drugs worsen mood, ie mania drugs)

POOR BIOLOGICAL EVIDENCE (ie bio evidence is inconsistent) - reduction in NA metabolites is not concurrent with worse depression and delayed onset of clinical effects of drug

could be due to adaptive changes not MA theory (there is downreg of 5-HT receptors and alpha 2, beta 2 receptors)

could be due to increased CRH and thus cortisol or hippocampal neurodegeneration

Question 6

what are the different classes of antidepressants

Answer 6

TCA (tricyclic antidepressants)

Monoamine oxidase inhibitors (MAOIs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

OTHER

Question 7

How do TCAs work (tricyclic antidepressants)

Answer 7

These are Monoamine REUPTAKE inhibitors

they prevent reuptake of NA and 5-HT (much more so than dopamine)

(Other receptor actions on α2 receptors, muscarinic AchRs, histamine receptors and 5-HT receptors)

Question 8

what are the two main groups of TCAs (tricyclic antidepressants)

Answer 8

• dibenzazepines

- dibenzcycloheptene

Question 9

what are the pharmacokinetics of TCAs

Answer 9

rapid oral absorption

Highly plasma protein bound (90 – 95% of TCAs are PPB) – this is important in terms of interactions

Hepatic metabolism: TCAs are metabolised in the liver, and this generates active metabolites (although weaker) then glucuronide conjugation

relatively long half life, so can be given once a day

Question 10

what are the unwanted effects of TCAs

Answer 10

Atropine-like effects with amitriptyline: dry mouth, blurred vision, constipation, urinary retention

Postural hypotension (mediated through the vasomotor centre) – this is a CENTRAL EFFECT

Sedation (TCAs cause H1 antagonism) – patients feel drowsy during the day

Plasma Protein Binding: we see increased TCA effects with co-administration with aspirin, warfarin and phenytoin (anti-convulsant)

Many depressed patients have trouble sleeping, so this can be taken advantage of

drugs metabolised by the same enzyme system (e.g. neuroleptics and oral contraceptives)

Potentiation of CNS depressants with TCAs (alcohol in particular)

interaction with antihypertensive drugs (monitor BP closely) – difficult to predict

Question 11

what are the symptoms of acute toxicity (overdose) of TCAs

Answer 11

CNS: excitement, delirium, seizures –> coma and respiratory depression

CVS: cardiac dysrhythmias –> ventricular fibrillation and sudden death

Question 12

what re the different Monoamine oxidases (MAOs)

Answer 12

MAO-A–breaks down NA & 5-HT – key MoA!

MAO-B– breaks down DA

Question 13

how do Monoamine oxidase inhibitors (MAOIs) work

Answer 13

Most are non-selective MAOIs.

Irreversible (Most) inhibition –> leads to a long duration of action.

Question 14

describe the structure of MAOIs

Answer 14

single ring with carbon side chain

Question 15

what re the different types of MAOIs

Answer 15

Hydrazines
Propargylamines
cyclopropylamines
reversible inhibitors

Question 16

describe the pharmacokinetics of MAOIs

Answer 16

Rapid oral absorption (MAOIs are taken orally, either once a day or every other day)

Short plasma t1/2 (few hours) but longer duration of action due to irreversible inhibition

Metabolised in the liver and excreted in the urine

Question 17

what re the unwanted effects of MAOIs

Answer 17

Atropine-like effects (anti-PNS effects) – but less so than TCAs.

Postural hypotension – common.

Sedation – causes seizures in OD.

Weight gain – due to ^appetite .

Hepatotoxicity – hydrazines, rare.

CHEESE REACTION–Tyramine (also broken down by MAOIs) containing foods (mature cheese, red wine) cause hypertensive crisis when eaten with MAOIs

Question 18

what are the different drug interactions of MAOIs

Answer 18

CHEESE REACTION–Tyramine (also broken down by MAOIs) containing foods (mature cheese, red wine) cause hypertensive crisis when eaten with MAOIs

MAOIs can react with TCAs to produce hypertensive episodes (avoid)

MAOIs can react with pethidine (opioid) to cause hyperpyrexia, restlessness, coma & hypotension

Question 19

how do SSRIs work ? (selective serotonin reuptake inhibitors)

Answer 19

Selective 5-HT re-uptake inhibition

therefore produce less side effects

But they are less effective against severe depression

Question 20

describe the pharmacokinetics of SSRIs

Answer 20

Oral administration of SSRIs

given once a day (t1/2 18-24 hours)

delayed onset of action (2-4 weeks before we see the optimal anti-depressant action of SSRIs)

Fluoxetine competes with TCAs for the hepatic enzymes

Question 21

what re the unwanted effects of SSRIs

Answer 21

There are fewer unwanted effects than TCAs/MAOIs

GI side effects (nausea, diarrhoea) (10%)

insomnia

30% of patients complain of loss of libido

SSRIs can interact with MAOIs

Fluoxetine competes with TCAs for the hepatic enzymes

not effective in all patients, and they are less effective against severe depression

Question 22

describe the structure of SSRIs

Answer 22

couple of rings with aliphatic side chain

Question 23

give an example of an SSRI, a MAOI and a TCA

Answer 23

SSRI- citalopram

MAOI- Phenelzine (hydrazine)

TCA-Amitriptyline

Question 24

what other antidepressant drugs are there (other than SSRIs, MAOIs and TCAs)

Answer 24

SNRIs (serotonin, NA reuptake inhibitors)- Venlafaxine, this is dose dependant, 5HT > NA we can increase the dose to get increase of NA reuptake inhibition

α2 Receptor antagonist- Mirtazapine, It increases NA & 5HT release in the brain