Antidepressants Flashcards

1
Q

Causes of depression

A
  • Originally thought that low levels of serotonin were the cause
  • Now not so clear but likely reduction in serotonin receptors in hippocampus
  • Would explain why SSRI takes so long to work
  • Many studies show people with depression having what is assumed to be normal levels of serotonin
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2
Q

What was the first class of antidepressants to be developed? And what is their mechanism of action?

A

Mono Amine Oxadase Inhibitors (MAOI)

Inhibit the activity of MAO enzymes

**MAO breaks down norepinephrine/serotonin and dopamine so inhibiting MAO increases the levels of all three neurotransmitters

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3
Q

Give examples of the main MAOIs

A
  • Phenelzine
  • Selegiline – also used in Parkinson’s
  • Tranylcypromine
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4
Q

What are the main interactions of MAOIs?

A
  • Should not be used in combination with SSRI/Tricyclic as well as some analgesics such as morphine/Tramadol as they will increase serotonin to potentially dangerous levels causing confusion, hypertension, tremor, coma and possibly death (neuroleptic malignant syndrome)
  • Give 14 days washout after stopping MAOI before starting another antidepressant
  • Foods high in tyramine may also cause a hypertensive crisis: cheese, certain meats such as venison, alcohol and some green vegetables (broad beans)
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5
Q

What are the potential consequences of increasing serotonin to a potentially dangerous level?

A
  • confusion
  • hypertension
  • tremor
  • coma
  • possibly death (neuroleptic malignant syndrome)
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6
Q

Give an example of a reversible MAOI and its action

A
  • Moclobemide  reported to act by reversible inhibition of MAO type A
    • Therefore, called RIMA
    • Tyramine has less of an effect
    • Short acting so medications can be changed with only one-week washout period
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7
Q

What is the mechanism of action of tricyclic antidepressants?

A
  • Act by inhibiting re-uptake of norepinephrine and serotonin by blocking the transporters responsible for re-uptake of these neurotransmitters
  • Increasing concentration of neurotransmitters in the synapses and triggering further neurotransmission
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8
Q

When should tricyclic antidepressants be used with caution?

A
  • Tricyclics should be used with caution in cardiovascular disease due to risk of arrythmias
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9
Q

Uses of tricyclic antidepressants

A
  • Depression
  • Anxiety
  • PTSD
  • Chronic pain (fibromyalgia, reflex sympathetic dystrophy syndrome)
  • IBS
  • Neuralgia
  • OCD
  • Nocturnal enuresis
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10
Q

How are tricyclkic antidepressants used for IBS?

A

Tricyclics have antimuscarinic activity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility

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11
Q

What are the other actions of tricyclic antidepressants?

A
  • They can induce bradycardia followed by tachycardia, reduce bronchial secretions, urinary retention, dry mouth and confusion
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12
Q

What are the common tricyclic antidepressants?

A
  • Amitriptyline
  • Clomipramine
  • Imipramine
  • Lofepramine
  • Nortriptyline
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13
Q

What are the concerns associated with using tricyclic antidepressants?

A

tricyclics are very dangerous in overdose so beware of how much you describe for a patient and use with caution in patients at high risk of suicide

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14
Q

What are serotonin receptors known as?

A
  • 5-hydroytyptamine (5-HT)
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15
Q

What is the mechanism of action of selective serotonin reuptake inhibitors (SSRIs)?

A
  • Believed to work by increasing levels of neurotransmitter serotonin by limiting its reabsorption and pure SSRI have only a weak affinity for norepinephrine and dopamine transmitters
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16
Q

What are the uses of SSRIs?

A
  • Depression
  • Anxiety
  • OCD
  • Panic disorder
  • PTSD
  • Eating disorders
17
Q

Where are 5HT receptors found?

A
  • 5HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission
18
Q

What do 5HT receptors modulate? And what do these pathways influence?

A
  • These receptors modulate the release of many neurotransmitters
    • GABA
    • Dopamine
    • Epinephrine
    • Norepinephrine
    • Acetylcholine

**They influence aggression, anxiety, cognition, learning memory, mood and sleep

19
Q

What are the major side effects of SSRIs?

A
  • Sexual: dysfunction and reduced libido
  • Cardiac: some, especially citalopram, to be used with caution as can cause QT interval prolongation therefore dose dependent with citalopram
  • Bleeding: affects anticoagulants (warfarin and aspirin) and also increased risk of GI bleeds
  • Suicide: possible increased risk of suicide especially in children and adolescents
  • Overdose: safer than other antidepressants
  • Epilepsy: may reduce fit threshold
  • Others include:
    • Nausea
    • Rash
    • Muscle aches
    • Insomnia
    • Sweating
20
Q

Describe the SSRIs from most to least toxic

A
21
Q

What type of antidepressant is duloxetine?

A
  • SNRI (serotonin norepinephrine up-take inhibitor)
22
Q

What are the uses of Duloxetine

A
  • Depression
  • Neuropathic pain (diabetes, fibromyalgia)
  • Stress urinary incontinence
23
Q

What are the side effects of duloxetine?

A
  • Nausea
  • Insomnia
  • Dizziness
24
Q

What type of antidepressant is mirtazipine?

A
  • a presynaptic alpha2-adrenoreceptor antagonist. Also, a noradrenergic and specific serotonergic antidepressant NaSSA
25
Q

What are the uses of mirtazipine?

A
  • Depression
  • Anxiety
  • PTSD
26
Q

What are the side effects of mirtazpine?

A
  • Low doses cause drowsiness so best taken at night
  • Higher dose more stimulant effect
27
Q

What type of antidepressant is venlaflaxine?

A

serotonin-norepinephrine re-uptake inhibitor (SNRI)

28
Q

What are the main uses of venlaflaxine?

A
  • Major depressive disorder
  • Anxiety
  • Panic
  • Social phobia
  • Metabolised in the body to desvenlafaxine (by cytochrome P205 isoenzyme in the liver)
29
Q

What are the main OTHER drugs that can be used to treat depression?

A
  • Antipsychotics such as risperidone
  • Lithium used in bipolar/mania mood stabilisation possible adverse effects on kidney and thyroid function
30
Q

What antidepressants are commonly used to treat pain and why?

A
  • Tricyclics work by blocking the re-uptake of noradrenaline and serotonin (5-HT) into the nerve endings and increasing their levels in the pain control pathways
  • Their benefit arises: by their direct effect on pain, and also through beneficial effects on sleep
  • Commonly used antidepressants:
    • Amitriptyline
    • Nortriptyline
    • Duloxetine
  • Duloxetine is also licensed for diabetic neuropathy
31
Q

What can prolongation of the QT interval cause?

A
  • Prolongation of the QT interval can lead to a life threatening arrhythmia known as torsades de pointes
  • Recent warnings have highlighted the risk of OT prolongation with citalopram
32
Q

Who are more at risk for QTc prolongation?

A
  • People who have more risk factors for QTc prolongation than the general population are particularly vulnerable to drug induced LQTS
    • Major psychiatric disorders
    • Cardiovascular disease
    • The elderly
    • Women