Pharmacology of anti-depressants and mood stabilisers Flashcards
What are some conditions that anti-depressants are indicated in?
- Moderate-severe depression
- Dysthymia
- Generalised anxiety disorder
- Panic disorder, OCD, PTSD
- Premenstrual dysphoric disorder
- Bulimia nervosa
- Neuropathic pain
What are the 2 main classes of antidepressant drugs?
Monoamine oxidase inhibitors
Monoamine re-uptake inhibitors
What are some examples of monoamine re-uptake inhibitors?
SSRIs
SNRIs other non-selective re-uptake inhibitors
Tricyclics
Noradrenaline re-uptake inhibitors
What is the general basis for antidepressant use?
In depression, there are usually lower levels of monoamines, and so antidepressants are used to increase monoaminergic transmission
However, depression is not CAUSED by monoamine deficiency, in the same way that ACE deficiency is not the cause of hypertension, but ACE inhibitors treat hypertension
What are the 2 main serotonin (5-HT) pathways in the brain?
Rostral - Mood, sleep, feeding behaviour, sensory perception
Caudal raphe - Analgesia
Formation of 5-HT at the synapse:
Tryptophan -> 5-OH-tryptophan -> 5-HT
What happens to 5-HT once it is released into the synapse?
It stimulates the post-synaptic neurone
It is then taken back in via a specific 5-HT transporter where it is either re-excreted or converted into 5-HIAA by monoamine oxidase (MAO), which leaves the cell
What produces MAO (Monoamine oxidase)
Mitochondria
What are the 2 noradrenaline pathways in the brain?
Locus ceruleus - Arousal, emotion
Lateral tegmental area
Formation of noradrenaline at the synapse:
Tyrosine → DOPA → Dopamine → Noradrenaline
What happens to noradrenaline once it is released into the synapse
It stimulates the post-synaptic neurone
It is then taken back in via a specific NA transporter where it is either re-excreted or converted into MHPG by monoamine oxidase (MAO), which leaves the cell
MOA - Monoamine oxidase inhibitors
These block monoamine oxidase action, preventing the recycling of NA and 5-HT, and therefore increasing the levels of it that is reused and sent back out into the synapse
What are the 2 types of MAO inhibitors
Irreversible
Reversible
Example of an irreversible MAO inhibitor
Phenelzine
Example of a reversible MAO inhibitor
Moclobemide
What are some side effects of MAO inhibitors?
Hypertensive crisis (Cheese reaction)
- Potentiates effects of other drugs (E.g. barbituates)
- Insomnia
- Postural hypotension
- Peripheral oedema
What causes hypertensive crisis in MAO inhibitors?
Inhibition of MAO-A in the gut and liver prevents breakdown of dietary tyramine (Lots in cheese), which causes hypertension which may be fatal
MOA of tricyclic antidepressants
These inhibit the re-uptake of monoamine neurotransmitters (Mainly NA and 5-HT) by blocking the specific transporters, meaning there are higher levels in the synapse to stimulate the post-synaptic neurones
What are some examples of tricyclic antidepressants
- Imipramine
- Amitriptyline
- Dosulepin
- Lofepramine
What are some side effects of tricyclic antidepressants?
Anti-cholinergic side effects
Sedation
Weight gain
Cardiovascular side effects
Cardiotoxic in OD
What are some anti-cholinergic side effects of tricyclic antidepressants?
- Blurred vision
- Dry mouth
- Constipation
- Urinary retention
What are some cardiovascular side effects of antidepressants?
- Postural hypotension
- Tachycardia
- Arrhythmia
MOA of SSRIs
Selectively inhibit the 5-HT specific transporter, decreasing reuptake and therefore increasing the amount in the synapse for stimulation of the post-synaptic neurone
Examples of SSRIs
- Fluoxetine
- Citalopram
- Escitalopram
- Sertraline
- Paroxetine
Short term (1 week) side effects of SSRIs and SNRIs
- Nausea
- Headache
- Worsened anxiety
- Transient increase in self-harm or suicidal ideation in those <25
Long term side effects of SSRIs and SNRIs
- Sweating
- Vivid dreams
- Sexual dysfunction
- Hyponatraemia (Elderly)
MOA of SNRIs
These inhibit both the 5-HT and noradrenaline specific transporters, (As opposed to all other monoamine transporters in tricyclics) preventing reuptake and increasing levels in the synapse
What does SSRI stand for
Selective Serotonin Re-uptake Inhibitor
What does SNRI stand for
Serotonin-Noradrenaline Re-uptake Inhibitor
What are some examples of SNRIs?
- Venlafaxine
- Duloxetine
MOA mirtazipine
Blocks a2, 5-HT2 and 5-HT3 receptors
Side effects of mirtazipine
Weight gain
Sedation
Positives of mirtazipine
Help with sleep
Block serotenergic side-effects of SSRIs
What are the risks of discontinuing antidepressants?
Sudden discontinuation of antidepressants can result in unpleasant physical and mental effects, which can be difficult to distinguish from depressive relapse, so advise to avoid stopping suddenly
What are some discontinuation effects of antidepressants?
- Restlessness.
- Trouble sleeping.
- Unsteadiness.
- Sweating.
- Stomach problems.
- Feeling as if there’s an electric shock in your head.
- Changes to your mood, such as low mood or feeling irritable, anxious or confused.
MOA of Lithium (Carbonate)
This is thought to block the phosphatidylinositol pathway or inhibit glycogen synthase kinase 3ß or modulated nitric oxide signalling
How is Lithium treatment monitored?
12 hour post-dose blood levels must be taken as lithium has a narrow therapeutic index (0.4-1 mmol/L)
Side effects of lithium
- Dry mouth and strange taste
- Polydipsia and polyuria
- Tremor
- Hypothyroidism
- Long-term reduced renal function
- Nephrogenic DI
- Weight gain
What are some of the toxic effects of lithium?
- Vomiting
- Diarrhoea
- Ataxia/Coarse tremor
- Drowsiness
- Convulsions
- Coma
Why is lithium stopped in dehydration?
It is renally excreted and is indistinguishable to sodium by the renal tubules of the kidneys, so during dehydration, Na+ is taken back into the blood in the kidneys to draw water back into the blood, and lithium is drawn in with it, therefore increasing blood concentration to dangerous levels
MOA of anti-psychotics
Antagonise dopamine and 5-HT in the synapses to stabilise mood
Examples of antipsychotics
- Quetiapine
- Aripiprazole
- Olanzapine
- Lurasidone
Side effects of antipsychotics?
- Sedation
- Weight gain
- Metabolic syndrome
- Aripiprazole - Extra-pyramidal side effects
