Antidepressants Flashcards
Identify the likely biological mechanism behind depression.
Originally thought that low levels of serotonin was the cause
Now not so clear but likely reduction in serotonin receptors in hippocampus
Would help explain why SSRI takes so long to work
Many studies show people with depression having what is assumed to be normal levels of serotonin
Identify the main classes of antidepressants.
- Mono Amine Oxadase Inhibitors MAOI (first class of antidepressants developed, rarely used for depression today)
- Tricyclic antidepressants
- SSRIs (most widely prescribed antidepressants)
- SNRIs
- Presynaptic alpha₂-adrenoreceptor antagonist (Mirtazapine)
Other drugs with antidepressant properties:
- Antipsychotics
- Lithium
Mono Amine Oxadase Inhibitors MAOI
- Mechanism of action
- Examples
- Side effects
MAOIs
-Inhibit the activity of MAO enzymes, which break down norepinephrine/serotonin and dopamine. Inhibiting MAO thereby increases level of all three transmitters.
-Examples: Phenelzine Selegiline – also used in Parkinsons Tranylcypromine Moclobeminde (REVERSIBLE MAOI)
-Side effects: Weakness Headache Weight Gain Dizziness Fatigue Impotence
Describe the main interactions with MAOIs.
1) 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. i.e. neuroleptic malignant syndrome (only way to treat this is to remove cause, give fluids, and possibly diazepam)
Give 14 days washout after stopping MAOI before starting other antidepressants.
2) Foods high in tyramine may also cause a hypertensive crisis (e.g. cheese, venison, alcohol, some grey veggies)
Describe the mechanism of action of Moclobeminde. Describe any differences in interactions with Moclobeminde c.f. othe MAOIs.
Reversible MAOI, 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.
Describe 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.
Identify the main uses of tricyclic antidepressants.
- Depression
- Anxiety
- Chronic pain (i.e. fibromyalgia, reflex sympathetic dystrophy syndrome)
- IBS (reduces peristalsis so slows down gut, so no diarrhea)
- Neuralgia
- OCD
- Nocturnal enuresis
- PTSD
Identify the main cautions for tricyclic antidepressant use.
- Tricyclics should be used with caution in cardiovascular disease due to risk of arrythmias
- Tricyclics have antimuscarinic activity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility
- They can induce bradycardia followed by tachycardia, reduce bronchial secretions, urinary retention, dry mouth and confusion
- Tricyclics are very dangerous in overdose so beware of how much you prescribe for a patient and use with caution in patients at high risk of suicide.
Identify examples of common tricyclics.
Amitriptyline Clomipramine Imipramine Lofepramine Nortriptyline
Identify drugs related to tricyclics. What are the main differences c.f. tricyclics ?
Trazodone
This drug is more sedating (used in elderly ppl with dementia, who are agitated and struggle to sleep).
Describe the mechanism of action of SSRIs.
Believed to work by increasing levels of neurotransmitter serotonin by limiting its re-absorption and pure SSRI have only a weak affinity for norepinephrine and dopamine transmitters (they are, therefore, cleaner with generally fewer side effects and better tolerated by patients)
5-HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission. These receptors modulate the release of many neurotransmitters, including GABA, Dopamine, Epinephrine, Norepinephrine, ACh.
What is the name of Serotonin receptors ?
Serotonin receptors are know as 5-hydroxytryptamine (5-HT)
Identify the main uses of SSRIs.
They influence aggression, anxiety, cognition, learning memory, mood and sleep
Depression Anxiety OCD Panic disorder PTSD Eating disorders
Identify the main side effects of SSRIs.
1) Sexual: dysfunction and reduced libido
2) Cardiac: some, especially citalopram, to be used with caution as can cause QT interval prolongation (which can lead to a life threatening arrhythmia known as torsades de pointes) therefore dose dependant with citalopram
3) Bleeding: affects anticoagulants (i.e. warfarin and aspirin) and also increased risk of GI bleeds.
4) Suicide: possible increased risk of suicide especially in children and adolescents (so should not be started in under 18s)
5) Overdose: safer than other antidepressants
Epilepsy: may reduce fit threshold (more likely to have a seizure)
6) Others include:
-Nausea
-Rash
-Muscle aches
-Insomnia
-Sweating
Identify examples of SSRIs, ranking them by order of overdose toxicity.
MOST TOXIC Citalopram (QT interval) Escitalopram Paroxetine Sertraline Fluoxetine LEAST TOXIC
