22: Anti-Depressants Flashcards
Explain the differnet types of Psychosis
Psychosis is a mental health problem that causes people to perceive or interpret things differently from those around them
Can be split into
- Schizophrenia (thought disorders) and
- Affective disorders (mood disorders)
- Maina
- Depression
What are the symptoms of depression?
Emotional symptoms
- Misery, apathy, pessimism
- Low self-esteem
- Loss of motivation
- Anhedonia (lack of enjoying things)
Biological symptoms
- Slowing of thought & action
- Loss of libido
- Loss of appetite, sleep disturbance
What are the two different types of depression?
What is their characterisitcs?
Depression can be
- Unipolar
- Mood swings in same direction
- Relatively late onset
- (reactive or endogenous)
- Drug treatment for both is the same (TCAs, MAO, SSRIs)
- Bipolar
- early onset (adolescence)
- oscillating episodes of depression and mania
- Strong hereditary tendency
- Treated with lithium (mood stabelising)
What are the different types of unipolar depression?
Reactive depression (75%)
- as reaction to stressful life events
- non-familial pattern
Endogenous depression (25%)
- unrelated to external stresses
- familial pattern
Explain the therapeutic use of lithium
Can be used a mood-stablising agent in the treatment of Bipolar disorders
- MOA unclear but thought to affect downstream mechanism of NA and 5HT release
- Narrow therapeutic window and many side effects
Explain the Monoamine theory of depression
It is an attempt to explain the cause of depression
it says that
- Depression = is due to functional deficit of central MA transmission
- Mania = functional excess of Monoamines
MonoAmines= NA & 5-HT
Evaluate the validity of the monoamine theory of depression
There is some evidence for it but it is not 100% consistet (but best we have at the moment)
- There is strong pharmocological evidence
- Drugs that Increase/decrease central MA levels cause increase in mood/depression respectively
- BUT: though administration of drugs lead to a direct increase in neurotransmitters but only have a delayed onset (possibly due to adaptive changes -> α2 –> less negative feedback in cell (normally inhibits Noradrenaline release) –> if downregulatied: less NA binding –> more release) , β, 5HT receptors)
- Some but limited biochemical evidence
- e.g. cocaine inhibitss reuptake but does not have anti-depressant effect
Explain the possible reasons for the delayed onset of action of anti-depressant drugs
Possible due to adaptive changes in receptors e.g.
- a2 receptors
- normally decrease NA release when binding
- if downregulated: more NA release is possible
- ß receptors
- 5HT receptors
- treatment leading to ? upregulation of cAMP?
What is another name for Serotonin?
5-Hydroxytryptamin (5-HT)
What are TCAs?
Explain thir MOA
TCA=Tricyclic antidepressant
-
Mainly: Neuronal monoamine re-uptake inhibitors (Noradrenaline and Serotonin NA = 5-HT)
- increase the levels of MA in synaptic cleft
- But also: Other receptor actions?
- α2 antagonists –> more NA release
- mAChRs
- histamine
- 5-HT
- Delayed down-regulation of β-adrenoceptors & 5-HT2 receptors –> delayed onset
Name an example of a TCA
Amitriptyline
What kind of drug is Amitriptyline?
A TCA (tricyclic antidepressant)
Summarise the pharmacokinetics of TCAs
- Rapid oral absorption
- Highly PPB (plasma protein bound) (90 - 95%)
- Hepatic metabolism forms active metabolites
- renal excretion (glucuronide conjugates)
- Plasma t1/2 (10-20 hrs) –> OD administration enough
What are the side effects of TCAs at a therapeutic dose?
Some side-effects in use (but very dangerous in overdose)
- Atropine - like effects (amitriptyline)
- Amitripyline inhibiting mAChR
- Postural hypotension (vasomotor centre)
- a2 receptors in vasomotor centre?
- Sedation (H1 antagonism)
What are the side effects of TCAs at a toxic dose?
Acute toxicity (o.d)
- CNS:
- excitement, delirium, seizures, coma, respiratory depression
- CVS: –> increased SNS activity (increased NA release)
- cardiac dysrhythmias, ventricular fibrillation/sudden death
Are often used to attempted suicide
Explain the drug-drug interactions of TCAs
Many drug-drug interactions
- Many due to the fact that TCAs are highly Plasma Protein bound (e.g. asperin)
- If other drugs are also PPB –> they displace TCAs from proteins and might cause toxicity
- Also increase the effects of CNS depressant drugs (e.g. alcohol)
- Monitor patients with antihypertensive drugs closely
What are MAOIs?
Explain their MAO
Monoamineoxidase Inhibitors
- Irreversible block MAO –> that would normally break down NA; 5HT and Dopamine
- Increase rapidly tha cytoplasmic NA+5HT levels
- leading to increased release of MA
- Delayed effects (weeks later) : clinical response down-regulation of β-adrenoceptors and 5-HT2 receptors
- (also inhibit other enzymes)
Name an example of a MAOI
Phenelzine
What kind of drug is Phenelzine
A MOAI
Explain the pharmacokinetics of MAOI
- Rapid oral absorption
- Short plasma t1/2 (few hrs) but longer duration of action
- due to irreversible inhibition of MAOs
- Metabolised in liver; excreted in urine
What are the side effects of MAOI?
- Atropine - like effects (but less than TCAs)
- Postural hypotension (common)
- Sedation (Seizures in overdose )
- Weight gain (possibly excessive)
- increase appetite
- Hepatotoxicity (rare)
- due to reactive hydrazine goups
- Cheese reaction
What is the “Cheese Reaction”?
Explain it in the context of MAOI
It is a reaction leading to
- hypertensive crisis (throbbing headache, b.p., intracranial haemorrhage
Due to
- Tyramine rich foods lead to
- increased tyramine levels in the brain
- tyramine leads to increased release of Noradrenaline
- Normally: boken down by MAO but in MAOI treatment: levels are too high leading to symtoms
What are SSRIs?
What is their MOA?
Selective Serotonin Reuptake inhibitors
•Selective 5-HT re-uptake inhibition
–> increased serotonin levels in synaptiv cleft
What are the advantages and disadvantages of the use of SSRI in comparison to TCA or MAOI
- Less troublesome side-effects; safer in overdose.
- But less effective in severe depression
Summarise the pharmacokinetics of SSRI
- p.o. administration
- Plasma t1/2 (18-24 hrs) (OD perscription)
- Delayed onset of action (2-4 weeks)
- Fluoxetine competes with MAOIs for hepatic enzymes (avoid co-administration)
Explain the side effects of SSRI
- Fewer than TCAs/MAOIs
- GI:
- Nausea, diarrhoea,
- insomnia
- loss of libido
- Interact with MAOIs (avoid co-administration)
- GI:
Name an exaple of a SSRI
Fluoxetine —> (Prozac)
What kind of drug is Fluoxetine?
What is its trade name?
It is a SSRI
Fluoxetine (‘Prozac’): currently most prescribed antidepressant drug
Differentiate between fluoxetine and venlafaxine
- fluoxetine = SSRI, specific for the serotonin transporter
- venlafaxine has variable effects on other monoamine transporters
- low dose: it is more specific for serotonin transporters
- high dose: blocks noradrenaline transporter
- Also: mild effects on dopamine transporters
Why would you prefere using fluoxetine and venlafaxine?
Not sure which one is more effective but NICE guidelines:
- More selective–> fewer expected side-effects
- cheaper
- Might give the ablility to combine the drugs (if not working and make sure patient was adherent)
