Antidepressants Flashcards
Causes of depression
- 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
What was the first class of antidepressants to be developed? And what is their mechanism of action?
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
Give examples of the main MAOIs
- Phenelzine
- Selegiline – also used in Parkinson’s
- Tranylcypromine
What are the main interactions of MAOIs?
- 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)
What are the potential consequences of increasing serotonin to a potentially dangerous level?
- confusion
- hypertension
- tremor
- coma
- possibly death (neuroleptic malignant syndrome)
Give an example of a reversible MAOI and its action
- 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
What is the mechanism of action of tricyclic antidepressants?
- 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
When should tricyclic antidepressants be used with caution?
- Tricyclics should be used with caution in cardiovascular disease due to risk of arrythmias
Uses of tricyclic antidepressants
- Depression
- Anxiety
- PTSD
- Chronic pain (fibromyalgia, reflex sympathetic dystrophy syndrome)
- IBS
- Neuralgia
- OCD
- Nocturnal enuresis
How are tricyclkic antidepressants used for IBS?
Tricyclics have antimuscarinic activity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility
What are the other actions of tricyclic antidepressants?
- They can induce bradycardia followed by tachycardia, reduce bronchial secretions, urinary retention, dry mouth and confusion
What are the common tricyclic antidepressants?
- Amitriptyline
- Clomipramine
- Imipramine
- Lofepramine
- Nortriptyline
What are the concerns associated with using tricyclic antidepressants?
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
What are serotonin receptors known as?
- 5-hydroytyptamine (5-HT)
What is the mechanism of action of selective serotonin reuptake inhibitors (SSRIs)?
- 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
What are the uses of SSRIs?
- Depression
- Anxiety
- OCD
- Panic disorder
- PTSD
- Eating disorders
Where are 5HT receptors found?
- 5HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission
What do 5HT receptors modulate? And what do these pathways influence?
- These receptors modulate the release of many neurotransmitters
- GABA
- Dopamine
- Epinephrine
- Norepinephrine
- Acetylcholine
**They influence aggression, anxiety, cognition, learning memory, mood and sleep
What are the major side effects of SSRIs?
- 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
Describe the SSRIs from most to least toxic
What type of antidepressant is duloxetine?
- SNRI (serotonin norepinephrine up-take inhibitor)
What are the uses of Duloxetine
- Depression
- Neuropathic pain (diabetes, fibromyalgia)
- Stress urinary incontinence
What are the side effects of duloxetine?
- Nausea
- Insomnia
- Dizziness
What type of antidepressant is mirtazipine?
- a presynaptic alpha2-adrenoreceptor antagonist. Also, a noradrenergic and specific serotonergic antidepressant NaSSA
