Anti-depressants Flashcards

(34 cards)

1
Q

What are the two categories of depression?

A

Unipolar and bipolar

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2
Q

What is unipolar depression?

A

Mood swings in same low direction
Reactive depression due to stress of life or endogenous where there is no cause

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3
Q

What is bipolar depression?

A

Depression alternates with mania
Characterised by excessive exuberance combined with irritabiility or aggression

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4
Q

Typical unipolar depression symptoms

A

Low mood, pessimism, anhedonia, apathy…

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5
Q

What is the general diagnosis for depression?

A

Experience depressed behaviour for more than 2 weeks
Symptoms disrupt normal social and physical life
Subjective qualitative

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6
Q

Name 3 factors increasing risk of depression

A
  1. stressful life events
  2. Genetic components- if depression runs in family more likely to inherit disorder (~40%)
  3. Side effect of secondary illness due to drug (eg Cushing’s disease)
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7
Q

What does the Nucleus Accumbens do when stimulated?

A

NAc stimulation has antidepressant effect
NAc uses dopamine transmitter
Increased activity -> increased BDNF

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8
Q

What is BDNF? Where does it exert it’s action?

A

Brain derived neurotrophic factor
On Track B receptors (TrkB)

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9
Q

What role does the amygdala have in depression?

A

Important limbic node for processing emotional behaviour

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10
Q

What role does the hippocampus have in depression?

A

Memory and learning
Increased cortisol -> reduced CREB -> reduced BDNF

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11
Q

What role do Ghrelin and Leptin have in depression?

A

Both hormones associated with guiding metabolism and appetite
Disruption to these pathways is associated with depression
Explains abnormal feeding behaviour in depression

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12
Q

Explain the ‘forced swimming’ animal model

A

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

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13
Q

What is the problem with the animal model?

A

See a response in animals immediately
In humans drugs take weeks to show response

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14
Q

Explain the ‘learned helplessness’ animal model

A

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

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15
Q

Name 2 monoamine neurotransmitters involved in depression

A

NA and 5HT (serotonin)

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16
Q

What does BDNF do?

A

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

17
Q

What does excessive activation of NMDA receptor do in depressed patients?

A

Contributes to neurodegeneration

18
Q

How does iproniazid support the monoamine hypothesis of depression?

A

MAO inhibitor
Prevents the break down of monoamine transporters
MAs stay in cleft for longer and exert action for longer

19
Q

How does iproniazid support the monoamine hypothesis of depression?

A

MAO inhibitor
Prevents the break down of monoamine transporters
MAs stay in cleft for longer and exert action for longer

20
Q

Name the 4 types of anti-depressants

A

MAO inhibitors
Tricyclic anti-depressants
Selective serotonin reuptake inhibitors (SSRIs)
Monoamine receptor antagonists

21
Q

Name a drug example of each anti-depressant (MTSM)
(Must Try Serotonin More)

A

MAO = Phenylzine
Tricyclic AD = Imipramine
SSRI = Fluoxetine (prozac)

22
Q

Which type of MAO is selectively targeted by antidepressants and why?

A

MAO type 1/A
MAO targets breakdown of NA and 5HT
MAO inhibitors cause rapid and sustained increase in 5HT

23
Q

What side effect does the MAO inhibitor cause?

A

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

24
Q

What do tricyclic AD do?

A

Inhibit neuronal reuptake of 5HT and NA
Many different drugs associated with different selectivities of 5HT and NA

25
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
26
Why are SSRIs prefered?
Less toxicity and side effects than tricyclic AD
27
Where is the predominant source of serotonin?
Raphe nuclei
28
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
29
Which 5HT receptor is an important target for anti-depressants?
5HT 1A receptor Is a Gi (inhibitory) coupled receptor
30
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
31
Whats common in the first week of taking an SSRI?
Depression gets acutely worse because serotonin levels drop
32
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
33
What happens to neurotrophins after weeks of taking anti- depressant?
Increased cAMP -> increased PKA -> Increased CREB -> increased BDNF
34
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