Anti-depressants Flashcards
What are the two categories of depression?
Unipolar and bipolar
What is unipolar depression?
Mood swings in same low direction
Reactive depression due to stress of life or endogenous where there is no cause
What is bipolar depression?
Depression alternates with mania
Characterised by excessive exuberance combined with irritabiility or aggression
Typical unipolar depression symptoms
Low mood, pessimism, anhedonia, apathy…
What is the general diagnosis for depression?
Experience depressed behaviour for more than 2 weeks
Symptoms disrupt normal social and physical life
Subjective qualitative
Name 3 factors increasing risk of depression
- stressful life events
- Genetic components- if depression runs in family more likely to inherit disorder (~40%)
- Side effect of secondary illness due to drug (eg Cushing’s disease)
What does the Nucleus Accumbens do when stimulated?
NAc stimulation has antidepressant effect
NAc uses dopamine transmitter
Increased activity -> increased BDNF
What is BDNF? Where does it exert it’s action?
Brain derived neurotrophic factor
On Track B receptors (TrkB)
What role does the amygdala have in depression?
Important limbic node for processing emotional behaviour
What role does the hippocampus have in depression?
Memory and learning
Increased cortisol -> reduced CREB -> reduced BDNF
What role do Ghrelin and Leptin have in depression?
Both hormones associated with guiding metabolism and appetite
Disruption to these pathways is associated with depression
Explains abnormal feeding behaviour in depression
Explain the ‘forced swimming’ animal model
Put small rodent in water tank
See how long it takes for rodent to give up swimming (hopelessness)
Application of antidepressant = rodent swims for longer
Analgesics have no effect
What is the problem with the animal model?
See a response in animals immediately
In humans drugs take weeks to show response
Explain the ‘learned helplessness’ animal model
Apply mild electric shock to animals feet repeatedly
Animal learns no matter what it does it will get shocked
Application of analgesics has no effect- animal still has learned helplessness
Name 2 monoamine neurotransmitters involved in depression
NA and 5HT (serotonin)
What does BDNF do?
Binds to TrkB receptors
Less BDNF associated with depression therefore less TrkB activated
Over time less TrkB activated effects brain neurogenesis
Creates subtle changes in the brain
What does excessive activation of NMDA receptor do in depressed patients?
Contributes to neurodegeneration
How does iproniazid support the monoamine hypothesis of depression?
MAO inhibitor
Prevents the break down of monoamine transporters
MAs stay in cleft for longer and exert action for longer
How does iproniazid support the monoamine hypothesis of depression?
MAO inhibitor
Prevents the break down of monoamine transporters
MAs stay in cleft for longer and exert action for longer
Name the 4 types of anti-depressants
MAO inhibitors
Tricyclic anti-depressants
Selective serotonin reuptake inhibitors (SSRIs)
Monoamine receptor antagonists
Name a drug example of each anti-depressant (MTSM)
(Must Try Serotonin More)
MAO = Phenylzine
Tricyclic AD = Imipramine
SSRI = Fluoxetine (prozac)
Which type of MAO is selectively targeted by antidepressants and why?
MAO type 1/A
MAO targets breakdown of NA and 5HT
MAO inhibitors cause rapid and sustained increase in 5HT
What side effect does the MAO inhibitor cause?
Cheese effect
Monoamines also used in peripheral nervous system
Their metabolism will also be altered
When combined with high dietary tyramine causes NA leakage from sympathetic neurones
Causing hypertension
What do tricyclic AD do?
Inhibit neuronal reuptake of 5HT and NA
Many different drugs associated with different selectivities of 5HT and NA
What are the side effects of tricyclic AD?
Associated with anticholinergic, adrenergic and anti- histaminergic effects
Anticholinergic- mACH, dry mouth, constipation
Adrenergic- alpha 2 block, postural hypotension
Anti- histaminergic- H1 block, sedation
Why are SSRIs prefered?
Less toxicity and side effects than tricyclic AD
Where is the predominant source of serotonin?
Raphe nuclei
Why are SSRIs used despite the side effects? Name some side effects
They have less anti-muscarinic properties and less sedating (anti- histaminergic) than Tricyclic ADs
Nausea, insomnia and sexual dysfunction
Which 5HT receptor is an important target for anti-depressants?
5HT 1A receptor
Is a Gi (inhibitory) coupled receptor
Where is 5HT1A found and what does this effect?
Found pre synaptically where they inhibit their own serotonin release
Found post synaptically where they inhibit Action Potential firing to consequently inhibit neurotransmitter release
Whats common in the first week of taking an SSRI?
Depression gets acutely worse because serotonin levels drop
What happens after 4-6 weeks of taking SSRIs?
Serotonin receptors become desensitised and these inhibitory receptors are removed
Causing an increase in neuronal activity and consequently increased release of neurotransmitters
What happens to neurotrophins after weeks of taking anti- depressant?
Increased cAMP -> increased PKA -> Increased CREB -> increased BDNF
What happens in a healthy brain when BDNF is released? Compare this to a depressed brain
BDNF released post synaptically and binds to the pre synaptic site and stabilise it
In a depressed brain, less BDNF is secreted and the synapse is lost
