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L2 pharmacology > CNS 4 - Antidepressants > Flashcards

CNS 4 - Antidepressants Flashcards

1
Q

What are the 2 classes of depression?

A
  • Unipolar depression
  • Bipolar disorder
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2
Q

What is unipolar depression?

A

Mood swings always in the same direction (negative)

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3
Q

What are the 2 types of unipolar depression?

A
  • Reactive (75%)
  • Endogenous (25%)
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4
Q

What is reactive unipolar depression?

A

Depression brought on by an event

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5
Q

What is endogenous unipolar depression?

A

Can’t identify an underlying cause for the depression

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6
Q

What is bipolar depression?

A

Depression alternates with mania

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7
Q

What are the symptoms of unipolar depression? (7)

A
  • Low mood (anhedonia)
  • Apathy
  • Severe weight loss/gain
  • Low self esteem (worthlessness)
  • Insomnia/excessive sleep
  • Loss of libido
  • Diminished ability to think/concentrate
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8
Q

What is anhedonia?

A

Inability to get pleasure from activities you would usually enjoy

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9
Q

What is apathy?

A

Loss of interest in daily activities

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10
Q

How is depression diagnosed?

A

Patient must be exhibiting depressive symptoms for over 2 weeks and symptoms are disrupting normal daily life

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11
Q

What are the risk factors for developing depression? (3)

A
  • Stressful life event
  • Genetic risk
  • Secondary to illness/drug side effects
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12
Q

Which areas of the brain are involved in depression?

A
  • Cingulate nucleus
  • Nucleus accumbens
  • Amygdala
  • Hippocampus
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13
Q

What happens in the nucleus accumbens which is linked to depression? (2)

A
  • Increased firing of dopaminergic neurons in this region
  • Increased secretion of BDNF
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14
Q

What happens in the hippocampus which is linked to depression? (2)

A
  • Decreased activation of CREB leads to decreased levels of BDNF
  • This is associated with high cortisol levels
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15
Q

What causes the abnormal feeding behaviours seen in depression?

A

Disruption in ghrelin and leptin signalling

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16
Q

How can epigenetic changes cause depression?

A

Children of women with postnatal depression can develop epigenetic changes due to lack of normal interaction with the mother which makes them more susceptible to depression later in life

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17
Q

What animal models are used to study depression? (2)

A
  • Acute stress models
  • Chronic stress models
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18
Q

What is an example of an acute stress model for depression?

A

Forced swimming test:
- Measure how long it takes the animal to give up trying to escape
- Antidepressant treatment reduces the tendency to give up
- Used for assessment of efficacy of antidepressants affecting monoamines

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19
Q

What are chronic stress models for depression?

A
  • Repeated stressors which cause animals to develop a learned helplessness
  • Causes structural, transcriptional and epigenetic changes in several brain regions which mimics those seen in humans
  • E.g. repeated electric shock until the rodent stops trying to get away from the shock
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20
Q

Which neurotransmitters are involved in depression? (2)

A
  • Noradrenaline
  • Serotonin (5HT)
    (Monoamines)
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21
Q

Why does it take several weeks to see an improvement in symptoms with antidepressant treatments?

A

It is believed that noradrenaline and serotonin have long term trophic effects on neurogenesis aswell as short term action

22
Q

Which receptor does BDNF act on?

A

TrkB

23
Q

How is BDNF involved in depression?

A
  • Patients have reduced production of BDNF
  • Reduced activation of TrkB receptors
  • Associated with changes in neurogenesis (changes in brain structure)
24
Q

How is glutamate involved in depression?

A

Overactivation of NMDA receptors is linked to neurodegeneration associated with depression

25
Q

What is the monoamine hypothesis of depression?

A

Depression is caused by a deficiency/imbalance in the monoamine neurotransmitters

26
Q

What is the evidence in support of the monoamine hypothesis of depression? (3)

A
  • The first antidepressant iproniazid is an MAO inhibitor
  • Reserpine depletes monoamine stores and causes depression
  • Tricyclic antidepressants inhibit reuptake of 5-HT and noradrenaline and alleviates symptoms
27
Q

What types of drugs are used to treat depression? (4)

A
  • MAO inhibitors
  • Tricyclic antidepressants
  • SSRIs
  • Monoamine receptor antagonists
28
Q

What are examples of MAO inhibitors? (2)

A
  • Phenelzine (suicide inhibitor)
  • Moclobemide (reversible inhibitor)
29
Q

What is an example of a tricyclic antidepressant?

A

Imipramine

30
Q

How do tricyclic antidepressants work?

A

Block the reuptake of monoamine neurotransmitters

31
Q

What is an example of an SSRI?

A

Fluoxetine

32
Q

What is fluoxetine also known as?

A

Prozac

33
Q

What are the 2 types of MAO?

A
  • Type A
  • Type B
34
Q

Which type of MAO is inhibited causing antidepressant effects?

A

Type A

35
Q

When is it useful to inhibit MAO type B?

A

Treatment of Parkinson’s

36
Q

What is the cheese effect?

A
  • Side effect of MAO inhibitors
  • MAOs in the periphery also inhibited
  • Inability to break down amines from food such as tyramine so taken up into sympathetic neurons and displaces noradrenaline
  • Causes leakage of noradrenaline from sympathetic nerves which leads to hypertensive crisis
37
Q

What are the side effects of the non-selective tricyclic antidepressants (TCAs)? (7)

A
  • Dry mouth
  • Blurred vision
  • Constipation
  • Postural hypotension
  • Sedation
  • Confusion and mania
  • Cardiac dysrhythmias
38
Q

Why are SSRIs preferred over TCAs?

A

More selective and fewer side effects/toxicity

39
Q

Where are dopaminergic neurons mainly located in the brain?

A

Locus coeruleus

40
Q

Where are serotonergic neurons mainly located in the brain?

A

Raphe nuclei

41
Q

What can drugs acting on 5HT transmission be used to treat? (5)

A
  • Depression
  • Anxiety
  • Migraines
  • Anti-emetic
  • Antipsychotic
42
Q

Which amino acid is 5HT made from?

A

Tryptophan

43
Q

What foods are high in tryptophan?

A
  • Chocolate
  • Protein rich foods
44
Q

Which serotonin receptors are involved in depression?

A

5HT1 receptors

45
Q

What kind of receptors are 5HT1 receptors?

A

G protein coupled

46
Q

Which G protein are 5HT1 receptors coupled to?

A

Gi/o (inhibitory)

47
Q

What is the slow working mechanism of action of SSRIs?

A
  • Inhibitory 5HT1A receptors are found on pre and postsynaptic neurones and inhibit serotonin release
  • When initially taking SSRIs, more serotonin = more signalling via 5HT1A inhibitory receptors = worsening of depression
  • Over time, 5HT1 receptors become desensitised and are lost which causes increase in serotonin levels
48
Q

What does BDNF do?

A
  • Released by postsynaptic neurons and acts on the presynaptic neuron to stabilise the synapse
  • Occurs in regularly used synapses
49
Q

How is BDNF linked to depression?

A

Lower neuronal activity means that BDNF is not produced by postsynaptic neurons synapses are lost

50
Q

What alternative methods can be used to treat depression? (4)

A
  • Anti-epileptic drugs
  • Atypical antipsychotics
  • Electroconvulsive shock therapy
  • Deep brain stimulation
51
Q

What is used to treat bipolar disorder?

A

Lithium

52
Q

What is BDNF?

A
  • A growth factor
  • Stimulated by some antidepressants

L2 pharmacology (9 decks)

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