Antidepressants Flashcards
what are the two types of depression
unipolar and bipolar
what are the symptoms of depression
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.
what are the two types of unipolar depression
reactive (eg stress or just life)
endogenous (unrelated to external events)
what is the Monoamine theory of depression
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.
what are the criticisms of the monoamine theory of depression
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
what are the different classes of antidepressants
TCA (tricyclic antidepressants)
Monoamine oxidase inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
OTHER
How do TCAs work (tricyclic antidepressants)
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)
what are the two main groups of TCAs (tricyclic antidepressants)
- dibenzazepines
- dibenzcycloheptene
what are the pharmacokinetics of TCAs
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
what are the unwanted effects of TCAs
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
what are the symptoms of acute toxicity (overdose) of TCAs
CNS: excitement, delirium, seizures –> coma and respiratory depression
CVS: cardiac dysrhythmias –> ventricular fibrillation and sudden death
what re the different Monoamine oxidases (MAOs)
MAO-A–breaks down NA & 5-HT – key MoA!
MAO-B– breaks down DA
how do Monoamine oxidase inhibitors (MAOIs) work
Most are non-selective MAOIs.
Irreversible (Most) inhibition –> leads to a long duration of action.
describe the structure of MAOIs
single ring with carbon side chain
what re the different types of MAOIs
Hydrazines
Propargylamines
cyclopropylamines
reversible inhibitors
describe the pharmacokinetics of MAOIs
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
what re the unwanted effects of MAOIs
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
what are the different drug interactions of MAOIs
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
how do SSRIs work ? (selective serotonin reuptake inhibitors)
Selective 5-HT re-uptake inhibition
therefore produce less side effects
But they are less effective against severe depression
describe the pharmacokinetics of SSRIs
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
what re the unwanted effects of SSRIs
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
describe the structure of SSRIs
couple of rings with aliphatic side chain
give an example of an SSRI, a MAOI and a TCA
SSRI- citalopram
MAOI- Phenelzine (hydrazine)
TCA-Amitriptyline
what other antidepressant drugs are there (other than SSRIs, MAOIs and TCAs)
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
