Antidepressants Flashcards

1
Q

Describe the monoamine theory and its limitations.

A

Deficits in monoamine neurotransmitters (NA and 5-HT) cause depression.

Limitations:

  • hypothesis originally formulated for NA, but emphasis later shifted to 5-HT
  • studies of monoamine markers in depressed pts yielded inconsistent results
  • MA hypothesis alone is inadequate to explain all the pharmacological actions in depression
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2
Q

Describe unipolar depression.

A

Mood swings always in same direction.

  • Reactive depression (75%): non-familial, associated with life events
  • Endogenous depression (25%): familial, not directly related to external stress
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3
Q

Describe bipolar depression.

A

Depression alternates with mania.

  • periodicity of oscillations in mood usually occur over several weeks
  • strongly familial
  • usually appears in early adulthood
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4
Q

What are the symptoms of depression?

A

Emotional Smx:

  • Misery, apathy and pessimism
  • Low self-esteem
  • Indecisiveness, loss of motivation

Others:

  • Retardation of thoughts and actions
  • Loss of libido
  • Sleep disturbances and loss of appetite
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5
Q

Which form of MAO breaks down 5-HT, NA and dopamine?

A

5-HT mainly by MAO-A, but also MAO-B.

NA and dopamine by both forms.

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6
Q

How do MAOIs work?

A

Inhibit breakdown of MA to increase MA availability in the synapse

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7
Q

List examples of MAOIs.

A

Phenelzine: non-selective, irreversible
Moclobemide: MAO-A selective, reversible

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8
Q

Major adverse effects of MAOIs?

A
  1. Postural hypotension - accumulation of dopamine in cervical ganglia, where it inhibits NA production
  2. Restlessness and insomnia - CNS stimulation
  3. (When combined with other drugs enhancing serotonergic function) Hyperexcitability, increased muscular tone, myoclonus (jerking, involuntary movements), loss of consciousness
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9
Q

Describe the “Cheese Reaction” (drug-food interaction between MAOIs and cheese/concentrated yeast products)

A

Acute hypertension, giving severe throbbing headache and occasionally, intracranial haemorrhage.

MAOIs inhibit breakdown of tyramine, tyramine accumulates and causes sympathomimetic effect. Tyramine competes with NA for reuptake + storage in vesicles ➝ more NA released into synapses.

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10
Q

List some common TCAs.

A

Non-selective for SERT/NET: imipramine, amitriptyline, nortriptyline
Selective for NET: desipramine

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11
Q

Why is nortriptyline preferred to imipramine or amitriptyline?

A

Second gen TCA, milder side effects and improved compliance

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12
Q

Major adverse effects of TCAs

A
  1. Postural hypotension - blocks alpha adrenergic receptors
  2. Sedation - due to H1 histamine receptor antagonism. Tolerance to sedation can develop in 1-2 weeks
  3. Dry mouth, blurred vision, constipation - muscarinic receptor antagonism
  4. DDIs - plasma protein bound; hepatically metabolised
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13
Q

What are the advantages of SSRIs over TCAs?

A

Overall, safer in overdose + better compliance.

  1. Lack of effect at histamine receptors - reduced sedation. (*citalopram can still cause some sedation)
  2. Low affinity for alpha-adrenoceptors - lack of cardiovascular effects, safer in overdose
  3. Low affinity for muscarinic receptors - minimal anticholinergic side effects e.g. dry mouth, constipation
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14
Q

Adverse effects of SSRIs

A
  • Nausea and insomnia (between doses)
  • Sexual dysfunction due to increased stimulation of 5HT2 receptors (can prevent with cyproheptadine or other 5HT2 blockers)
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15
Q

What are the effects of serotonin syndrome?

A
  • Tremor
  • Hyperthermia
  • Cardiovascular collapse
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16
Q

Name the classes of antidepressants.

A
  1. MAOIs
  2. TCA
  3. SSRI
  4. NARI
  5. SNRIs
  6. NaSSa
17
Q

Which NARI has similar adverse effects to TCAs?

A

Maprotiline. Due to alpha adrenoceptor and histamine receptor effects. (Also occasionally caused seizures)

18
Q

Adverse effects of Reboxetine

A

New drug, so adverse effects not well described.

  • Anticholinergic effects: dry mouth mouth, constipation
  • Effects of increased NA: Tachycardia, insomnia
19
Q

SNRIs have similar profile to which class? Similar side effects as which class?

A

Similar profile to non-selective TCAs (dual 5-HT and NA reuptake inhibition). But fewer adverse effects than TCAs.

Similar side effects as SSRIs (nausea, insomnia, sexual dysfunction). Serotonin syndrome when combined with other serotonergic drugs and MAOIs. Withdrawal effects may be more common and stronger than for SSRIs and TCAs.

20
Q

Examples of SNRIs

A

Venlafaxine, desvenlafaxine, duloxetine

21
Q

What is mirtazapine?

A

NaSSA. Alpha2 autoreceptor antagonist and 5HT2C receptor antagonist

22
Q

What is bupropion?

A

NDRI noradrenaline dopamine reuptake inhibitor

23
Q

What is agomelatine?

A

Agonist of melatonin MT1 and MT2 receptors.

24
Q

Advantages and disadvantages of vortioxetine?

A

Novel drug, multimodal serotonergic antidepressant.

May be efficacious in in patients resistant to other antidepressants. Seems to work well in children.

May ↑ risk of suicidal thoughts or actions in children and teens. Close monitoring required in the initial stages.

25
Q

What is ketamine?

A

Glutamate NMDA receptor antagonist used as an anaesthetic, currently evaluated for rapid-onset antidepressant effect.