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Pharmacology > Anti-depressants > Flashcards

Anti-depressants Flashcards

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
Q

What are the side effects of tricyclic AD?

A

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
Q

Why are SSRIs prefered?

A

Less toxicity and side effects than tricyclic AD

27
Q

Where is the predominant source of serotonin?

A

Raphe nuclei

28
Q

Why are SSRIs used despite the side effects? Name some side effects

A

They have less anti-muscarinic properties and less sedating (anti- histaminergic) than Tricyclic ADs
Nausea, insomnia and sexual dysfunction

29
Q

Which 5HT receptor is an important target for anti-depressants?

A

5HT 1A receptor
Is a Gi (inhibitory) coupled receptor

30
Q

Where is 5HT1A found and what does this effect?

A

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
Q

Whats common in the first week of taking an SSRI?

A

Depression gets acutely worse because serotonin levels drop

32
Q

What happens after 4-6 weeks of taking SSRIs?

A

Serotonin receptors become desensitised and these inhibitory receptors are removed
Causing an increase in neuronal activity and consequently increased release of neurotransmitters

33
Q

What happens to neurotrophins after weeks of taking anti- depressant?

A

Increased cAMP -> increased PKA -> Increased CREB -> increased BDNF

34
Q

What happens in a healthy brain when BDNF is released? Compare this to a depressed brain

A

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

Pharmacology (12 decks)

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