Depression pharmacological treatment Flashcards

1
Q

what 2 receptors do the most effective anti-depressants work on?

A

5-HT (serotonin) and NA (noradrenaline)

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2
Q

Where are 5HT cell bodies contained in the brain?

A

in the dorsal and median raphe nuclei

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3
Q

Where are NA cell bodies contained in the brain?

A

in the Locus coerulus

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4
Q

what determines the synthesis rate of NA and 5HT?

A
  1. TPH for 5HT (tryptophan hydroxylase)

2. TH for NA (tyrosine hydroxylase)

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5
Q

what determines the breakdown of 5HT and NA?

A

MAO (monoamine oxidase)

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6
Q

what determines the release rate of 5HT and NA?

A

the firing activity of the impulse

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7
Q

what determines the reuptake rate of 5HT and NA?

A

the transporter activity

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8
Q

what part of 5HT, NA and DOPA does MAO act on?

A

the NH2 at the end of the chain

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9
Q

where do MAO act?

A

they break down the monoamine in the cytosol and regulate the vesicle content

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10
Q

How do the monoamine reuptake transporters work?

A

they transport the monoamines from the synaptic cleft to the presynaptic terminal

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11
Q

how can we increase 5HT and NA neurotransmission?

A
  1. reduce their breakdown in the synaptic cleft hence increase their release per impulse
  2. block their reuptake hence increase their duration and concentration in the synaptic cleft.
  3. increase the post-synaptic receptor activation.
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12
Q

what are the two main classes of antidepressant drugs?

A
  1. inhibitors of monoamine metabolism (so they inhibit monoamine oxidase)
  2. inhibitors of monoamine reuptake e.g. (SSRIs, SNRIs and TCAs)
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13
Q

what group of MAO are blocked by monoamine oxidase inhibitors (MAOi)?

A
  1. Monoamine Oxidase A (MAOAa)
    or drugs that block
  2. Monoamine oxidase A and B (MAOA and MAOb)
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14
Q

what are drugs that target just MAOb used for?

A

used for treating Parkinson’s disease.

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15
Q

give an example of only an MAOb inhibitor?

A

Selegiline

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16
Q

Give an example of an MAOa and MAOb inhibitor?

A

Iproniazid

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17
Q

Give an example of a MAOa inhibitor?

A

Clorgyline

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18
Q

Give an example of a TCA?

A

amitriptyline

19
Q

Give an example of a SSRI?

A

citalopram

20
Q

Give an example of a SNRI?

A

Duloxetine and venlafaxine

21
Q

which of these are selective: SSRI, SNRI or TCA?

A

SSRIs

22
Q

what are the side effevts of reuptake inhibitors?

A
  1. GI disturbance
  2. sexual dysfunction
  3. dry mouth
  4. sedation
  5. hypotension
  6. weight gain
  7. skin lashes
  8. anaphylaxis
23
Q

how do MAOIs bind: reversibly or irreversibly?

A

irreversibly

24
Q

what effect do MAOIs have on blood pressure?

A

they lower blood pressure by causing vasoconstriction, hence provoking hypertensive crisis

25
Q

what is the downside of taking other antidepressants alongside the depressant you’re already on?

A

causes serotonin syndrome

26
Q

what happens in serotonin syndrome?

A
  • blocking the reuptake transporter and inhibiting MAO would increase 5HT release and there’ll be a build up of serotonin in the synaptic cleft.
  • This is called serotonin syndrome.
27
Q

what are the symptoms of serotonin syndrome?

A
  1. high temperature
  2. agitation
  3. increased reflexes
  4. tremor
  5. sweating
  6. dilated pupils
  7. diarrhoea
  8. delirium
  9. convulsions
  10. death
28
Q

what is the first line antidepressant treatment?

A

SSRIs

29
Q

what is the last line antidepressant treatment?

A

MAOI

30
Q

how long should you continue to treat after patient has recovered?

A

6months to 2years after recovery

31
Q

What symptoms are experienced in antidepressant discontinuation syndrome?

A

dizziness, headache, nausea and lethargy

32
Q

what is used to treat bipolar disorder?

A
  1. Lithium
  2. Valproate
  3. Atypical antipsychotics
  4. Fluoxetine
33
Q

what causes bipolar disorder?

A

dopamine hyperactivity

  • antagonists of the dopamine receptor reduce mania
  • reducing dopamine synthesis reduces mania
34
Q

where are dopamine cell bodies contained?

A

in the ventral tegmental area (VTA) in the midbrain

35
Q

how is dopamine released?

A

by tonic and phasic release

36
Q

how does lithium work?

A
  1. Decreases DA release
  2. Deceases DA (and 5HT) receptor signalling
  3. Inhibits second messenger IP
37
Q

what is the main use of lithium in Bipolar Disorder (BP)?

A

Acute mania and prophylaxis

38
Q

what is the recommended plasma lithium levels?

A

o.4 to 1 mmol per litre

39
Q

what are the side effects of taking lithium?

A
  1. Dry mouth or metallic taste in the mouth
  2. Mild shaking or fine tremor of the hand(s)
  3. Thirst (polydipsia)
  4. Passing more urine (polyuria)
  5. Dizziness
  6. Mild diarrhoea or nausea
  7. Weight gain
  8. Oedema
40
Q

what does it mean by lithium being ‘teratogenic’?

A

it interferes with fetal development and causes birth defects

41
Q

how does sodium valproate work?

A

it increases GABA transmission

42
Q

when would we use valproate?

A

when lithium is not tolerated

43
Q

what are the side effects of valproate?

A

• Nausea, vomiting

  1. Sedation
  2. Tremor
  3. Hair loss
  4. Weight gain
  5. Pancreatitis
44
Q

is valproate teratogenic?

A

YES!!!! causes fetal valproate syndrome, neural tube defects and intellectual impairment.