Antidepressants Flashcards
What is the principle behind most antidepressants?
They inhibit the reuptake of noradrenaline and serotonin (5HT)
What are the commonly used classes of antidepressants?
1) Tricyclic antidepressants
2) Selective Serotonin Reuptake Inhibitors (SSRIs)
N.B SNRIs as well
3) Monoamine Oxidase Inhibitors
4) Receptor blockers
5) Lithium
What are the theories behind depression?
1) The monamine theory - depletion of monoamines from the brain (e.g. by administering reserpine) causes depression. Using drugs to increase their quantity in the brain and synaptic cleft is thought to help treat depression
2) Due to the delay in action of around 2 weeks with most antidepressants it is believed that there may be other mechanisms involved, one of which is though to be hippocampal neurodegeneration
How do tricyclic antidepressants work?
They inhibit amine uptake
Name 4 tricyclic antidepressants
Amitriptyline
Imipramine
Dosulepine
Lofepramine
What are the common side-effects of tricyclics?
They have blocking actions at cholinergic muscarinic, alpha adrenoreceptors, andhistamine receptors.
Side-effects therefore include dry mouth, blurred vision, urinary retention, constipation, tachycardia and hypotension.
They can also increase appetite.
In over-dose they are cardio-toxic and cause arrhythmias.
Who should you not give tricyclic antidepressants to?
Patients with heart disease
What is a specific side-effect of amitriptyline and dosulepin?
They have a sedative effect which can be exploited at night to act as a hypnotic if taken before bed. It also makes these drugs more suitable for agitated and anxious patients.
How do SSRIs work?
It is thought that they cause an increase in extracellular 5HT that initially activates autoreceptors. This action actually inhibits serotonin release and reduces extracellular 5HT to it’s original level.
However, with chronic treatment the inhibitory autoreceptors become desensitized, leading to a maintained increase in forebrain 5HT which gives the therapeutic effect.
What are the common SSRIs used
Citalopram Sertraline Paroxetine Fluoxetine Fluvoxamine
What are the side-effects of SSRIs?
Generally GI, nausea, vomiting, diarrhea and constipation.
SSRIs should not be given to patients under the age of 18 because of the supposed link with suicide.
What is Venlafaxine?
It is an SNRI (higher doses display the noradrenaline reuptake inhibition)
Name 2 receptor blockers and how they work.
Mirtazapine and Trazodone, boht are sedative antidepressants.
Mirtazapine blocks alpha-2-adrenoreceptors, and by blocking the inhibitory alpha-2-autoreceptors on central noradrenergic nerves endings, it may increase the amount of noradrenline in the synaptic cleft.
Trazodone blocks 5HT and H-1-histamine receptors, and also increse 5HT and noradrenaline release.
How do Monoamine oxidase inhibitors work? Give examples + their side-effects
The older MOAIs work by irreversible and non-selectively inhibiting monoamine oxidase. A example is Phenelezine. Rarely used any more because of side-effects and interractions.
SEs - postural hypotension, dizziness, anticholinergic effects and liver damage
Interractions - sympathomimetic amines e.g. ephedrine which is often present in cough syrup and decongestants
- foods containing tyramine e.g. cheese, game and alcoholic drinks (this is because monoamine oxidase in the gut normally metabolises tyramine, and so with its inhibition tyramine reaches the blood where is stimulates the release of noradrenaline from sympathetic nerve endings
More modern reversible and selective MOAIs are Moclobemide, which inhibits monoamine oxidase A. Generally well tolerated fewer side-effects including dizziness, insomnia, nausea.
MOAIs reduce the metabolism of barbituates, opiod analgesics and alcohol. PETHEDINE is a real problem interraction, leading to hyperpyrexia, hypotension and coma.
What is the use of lithium for?
It is used for prophylaxis in manic/depressive illness.
It is used to treat acute mania, though antipsychotics work quicker.
It is also used as an antidepressant when combined with tricyclics in refractory patients.
