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Year 2 - Pharm Lectures 11+ > Antidepressant Drugs > Flashcards

Antidepressant Drugs Flashcards

1
Q

Emotional/psychological symptoms of depression

A
  • Misery, apathy, pessimism
  • Low self-esteem
  • Loss of motivation
  • Anhedonia (loss of enjoyment from activities)
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2
Q

Biological/somatic symptoms of depression?

A
  • Slowing of though & action
  • Loss of libido
  • Loss of appetite, sleep disturbance
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3
Q

2 broad types of depression?

A

(1) Unipolar depression/depressive disorder

(2) Bipolar depression/manic depression

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4
Q

Explain the (1) type of depression

A

Unipolar depression (depressive disorder)

  • Mood swings in SAME direction
  • Relatively LATE onset

Types of unipolar depression:
• Reactive depression - stressful live events, non-familial inheritance

• Endogenous depression - unrelated to external stresses, familial pattern

ALL types of unipolar depression respond in the SAME WAY to the same drug treatments

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5
Q

Explain the (2) type of depression

A

Bipolar depression (manic depression)

  • Oscillating depression/mania
  • LESS common
  • EARLY adult onset
  • STRONG hereditary tendency

Drug treatment includes LITHIUM
• can stabilise swings between mania & depression BUT has a narrow therapeutic window

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6
Q

Define the Monoamine theory of depression

A

Depression is a functional DEFICIT of central MA transmission

Mania is a functional EXCESS of MA transmission

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7
Q

What is MA related to?

A

Related to

• NA & 5-HT (serotonin) deficits/excesses

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8
Q

What evidence supports the MA theory of depression?

A

Pharmacological evidence

onenote table!!

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9
Q

What evidence does NOT support the MA theory of depression and explain why

A

Biological evidence

A reduction in NA metabolites is NOT concurrent with a worse depression

Delayed onset of the clinical effect of drugs (a few weeks sometimes)
– possibly due to adaptive changes and not MA theory:
• there is a downregulation of - alpha2, beta & 5-HT receptors

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10
Q

What other conclusions are made along with the MA theory

A

Could be due to:
• increased CRH (and thus cortisol)?
• hippocampal neurodegeneration?

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11
Q

What drugs provide the pharmacological evidence supporting the MA hypothesis of depression?

A
  • TCAs (tricyclic antidepressants)
  • MAO inhibitors
  • Reserpine
  • alpha-Methyltyrosine
  • Methyldopa
  • ECT
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12
Q

Example of a TCA drug?

A

Amitriptyline

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13
Q

MOA of TCAs?

A

Monoamine re-uptake inhibitor
– NA=5-HT&raquo_space; DA.

Also acts on:
 • alpha2 
  – block pre-synaptic inhibition of NA release)
 • mAChR
 • H2 (histamine) receptors
 • 5-HT receptors

TCAs down-regulate:
• BETA-adrenoceptors
• 5-HT2 receptors

The time-course of this down-regulation correlates well with the clinical onset of symptom relief.

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14
Q

Pharmacokinetics of TCAs?

A

o Oral administration

o Highly PPB – 90-95%

o Hepatic metabolism
– to ACTIVE metabolites –> excreted in the urine (glucuronide conjugates)

o Plasma T1/2 = 10-20 hours
– dose once daily

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15
Q

What are some unwanted effects associated with TCAs?

A

Therapeutic doses:

 Atropine-like effects
– anti-PNS effects such as dry mouth, constipation, etc

 Postural hypotension
– due to effects on vasomotor centre

 Sedation
– due to effects on H1 antagonism

Acute toxicity:

 CNS
– excitement, delirium, seizures –> coma, respiratory depression

 CVS
– cardiac dysrhythmias –> VF & sudden death

Often used for attempted suicide!

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16
Q

TCAs can interact with drugs, causing its effects to increase - explain this

A
  1. PPB
    • INCREASE TCA effects
    • as very PPB, there is a massive increase of bioavailability if co-administered with something that displaces it from the PP
    • e.g. aspirin, phenytoin
  2. Hepatic enzymes
    • INCREASE TCA effects
    • drugs that compete with the metabolising hepatic enzymes
    •e.g. neuroleptics, oral contraceptives
  3. Potentiation
    • drugs that potentiate the effects of the CNS depression
    • e.g. alcohol
  4. Antihypertensive drugs
17
Q

Example MAOI drug?

A

Phenelzine

18
Q

Explain the MOA of MAOI

A

MAO enzymes:
• MAO-A breaks down NA & 5-HT – key MoA!
• MAO-B: breaks down DA – e.g. Selegiline

o Most are non-selective MAOIs
o Irreversible inhibition leads to a long duration of action

Effects:
 Rapid effects
– increase cytoplasmic (not enhanced release but more leakage) NA, 5-HT

 Delayed effects
– delayed clinical response due to down-regulation of beta-adrenoceptors & 5-HT2 receptors
– again, fits with delayed clinical effect

o Inhibits other enzymes – leads to side effects.

19
Q

Pharmacokinetics of MAOI?

A

o Oral absorption

o Short plasma T1/2 but a longer DoA

o Metabolised in the liver, excreted in the urine

20
Q

Unwanted effects associated with MAOI?

A

o Atropine-like effects (anti-PNS effects)
– but less so than TCAs

o Postural hypotension
– common

o Sedation
– causes seizures in OD

o Weight gain
– possibly excessive

o Hepatotoxicity
– hydrazines, rare

21
Q

Why is the drug interactions of MAOI a serious problem?

A

‘Cheese reaction’

Tyramine-containing foods + MAOI = hypertensive crisis

 Tyramine is metabolised by MAO and so high levels of tyramine compete with NA and so higher levels of NA leading to the hypertensive episodes

o MAOIs + TCAs = hypertensive episodes

o MAOIs + pethidine (opioid analgesic) = hyperpyrexia, restlessness, coma & hypotension

22
Q

What are the hypertensive crisis in relation to the ‘cheese reaction’

A
  • Throbbing headache
  • Increase BP
  • Intracranial haemorrhage
23
Q

Example of a MAO-A inhibitor?

A

Moclobemide

Reversible, MAO-A inhibitor (RIMA)
• reduced drug interactions
• reduced DoA

24
Q

SSRIs - example drug?

A

Fluoxetine

25
Q

MoA of SSRIs?

A

• 5-HT re-uptake inhibitor

• Has LESS bad SEs so safer in ODs
- BUT, less effective vs. severe depression

26
Q

Pharmacokinetics of SSRIs?

A

o Oral administration

o Plasma T1/2 = 18-24 hours

o Delayed onset of action
– 2-4 weeks

27
Q

What should we avoid giving fluoxetine with and why?

A

Fluoxetine competes with TCAs for hepatic enzymes so avoid co-administration

28
Q

Unwated effects associated with Fluoxetine?

A

Nausea, diarrhoea, insomnia, loss of libido
• fewer side effects than TCAs/MAOIs (currently the most prescribed antidepressant)

o Interacts with MAOIs
– avoid co-administration
o Increases suicidality in the <18s

29
Q

2 other ADs?

A

(1) Venlafaxine

(2) Mertazapine

30
Q

Explain the (1) AD

A

Venlafaxine

Dose-dependent re-uptake inhibitor
– 5-HT>NA>DA

2nd line for severe depression

31
Q

Explain the (2) AD

A

Mertazapine

a2 receptor antagonist
– inhibits negative inhibition of NA release

o Increases NA and 5-HT release
o Useful in SSRI intolerant patients

32
Q

Tricyclic antidepressant drugs (TCAs) work largely by:

A: Antagonism at 5HT receptors
B: Inhibiting central DA reuptake
C: Blocking VSCCs
D: Inhibition of central NA &amp; 5HT reuptake 
E: Enhancement of the action of GABA
A

D

33
Q

The ‘cheese reaction’ is most likely to be caused by:

A: Tricyclic antidepressants (TCAs)
B: Selective serotonin reuptake inhibitors (SSRIs)
C: Monoamine oxidase inhibitors (MAOIs)
D: Reversible MAO-A inhibitors (RIMAs)
E: α2-Adrenoceptor antagonists
A

C

Year 2 - Pharm Lectures 11+ (23 decks)

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