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Clinical Therapeutics > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

What is the first line treatment for sub threshold/mild depression?

A
  • Guided self help
  • Cognitive behavioural therapy (CBT)
  • Behavioural activation (BA)
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2
Q

What are the two types of monoamine neurotransmitters and what is the monoamine theory?

A

Sertotonin (5-HT) and Catecholamines (NA, adrenaline, dopamine)

Depression results from depletion of monoamines in the brain (NA and serotonin)

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3
Q

How is noradrenaline synthesised and stored?

A

Tyrosine (NA precursor) taken up into nerve terminal
Tyrosine -> DOPA (tyrosine hydroxylase)
DOPA -> Dopamine (DOPA decarboxylase) and transferred to synaptic vesicle
Dopamine -> NA (dopamine beta hydroxylase) within synaptic vesicle

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4
Q

How is serotonin synthesised and stored?

A

Tryptophan taken up into nerve terminal
Tryptophan -> 5-HTP (TPH)
5-HTP - 5-HT (decarboxylase) and transferred to synaptic vesicle

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5
Q

What are the two neurotransmitter re-uptake transport proteins?

A

Noradrenaline (norepinephrine) transporter (NET)
Serotonin transporter (SERT)

(both energy dependent)

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6
Q

What two enzymes metabolise NA and 5-HT?

A

Monoamine Oxidase (MAO) - Both
Cathecol-O-methyl transferase (COMT) - NA

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7
Q

Where is MAO found in cells, what are the two types of MAO and what do they break down?

A

Attatched to the mitochondrial membrane

MAOA - NA, 5-HT, dopamine, tyramine
MAOB - dopamine, tyramine

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8
Q

What are some examples of tricyclic antidepressants and what do they inhibit?

A

Amitriptyline and Nortriptyline

Inhibit NET and SERT - increasing concs of NA and 5-HT in the brain

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9
Q

What is the main disadvantage of tricyclic antidepressants and why do they cause this?

A

Poorly tolerated due to side effects

They act as antagonists of alpha, histamine and ((muscadine)) receptors

Oh my god what an idiotic thing to say, it’s muscarinic you ‘basket case’
DO YOU HAVE THE TIME
TO LISTEN TO ME WHINE
ABOUT NOTHING AND EVERYTHING
ALL AT ONCE

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10
Q

What are the side effects of TCAs as a result of alpha, histamine and muscarinic receptor antagonism?

A

Alpha - postural hypotension, sedation
Histamine - sedation and weight gain
Muscarinic - M1 - Dry mouth, blurred vision, constipation, urinary retention
M2 - tachycardia

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11
Q

What are examples of serotonin noradrenaline re-uptake inhibitors (SNRIs), how do they work and what is their advantage over TCAs?

A

Duloxetine and Venlafaxine

Inhibit NET and SERT

less alpha, histamine and muscarinic receptor action

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12
Q

What are examples of selective serotonin re-uptake inhibitors (SSRIs) and how do they work?

A

Citalopram, Sertraline, Fluoxetine, Escitalopram, Paroxetine

Inhibit SERT

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13
Q

What are side effects of SSRIs largely due to, what medication should be reviewed/stopped and why?

A

Raised 5-HT: e.g. nausea, diarrhoea, weight changes, CNS effects

Care with NSAIDS, AVOID WARFARIN (5-HT has an anti-platelet effect - Inc. risk of bleeding)

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14
Q

What are examples of Monoamine oxidase inhibitors and how do they work?

A

Moclobemide (reversible, MAOA selective)
Phenelzine (irreversible, non-selective MAOI)

Inhibits MAO

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15
Q

What is the major issue with MAOIs and what should be avoided and why?

A

Serious interactions with foods, avoid foods containing tyramine (marmite, ripe cheese, picked fish) and for 2 weeks after treatment finished - dangerous rise blood pressure - intracranial haemorrhage

Also avoid OTC decongestants

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16
Q

What other side effects are associated with MAOIs?

A

Postural hypotension, dizziness, anti-choleric effects, liver damage

17
Q

What is an example of a selective NA re-uptake inhibitor (NARI) and how does it work?

A

Reboxetine

Inhibits NET, increases NA concs in brain

18
Q

What is an example of a noradrenergic and specific serotonergic antidepressant (NaSSA) and how does it work?

A

Mirtazapine

Antagonist of alpha-2 Auto and heteroreceptors - Inc conc of 5-HT/NA
antagonist of 5-HT2 and 5-HT3 receptors

19
Q

What is an example of an Na-dopamine disinhibitor (NDDI), how does it work and what it’s main issue?

A

Agomelatine

Melatonin receptor agonist (MT1 and MT2) and 5-HT2c receptor antagonist - inc. NA and dopamine release

Hepatotoxicity

20
Q

What is an example of a weak non-selective NA/5-HT uptake inhibitor and why should it NOT be prescribed for depression?

A

St. John’s Wort

  1. Significant drug interactions
  2. Amount of ingredient varies between preparations
  3. Uncertainty about appropriate dose to be used
21
Q

What is a very dangerous side effect of a patient on two or more serotonergic drugs?

A

Serotonin Syndrome

Clinical Therapeutics (27 decks)

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