5: Pharmacology of antidepressants and mood stabilisers Flashcards
Are antidepressants only given for depression?
No
eating disorders, anxiety, chronic pain as well
What is dysthymia?
Persistent low-grade depression
What are some examples of monoamine neurotransmitters?
Noradrenaline (excitatory)
Dopamine (excitatory)
5-HT / Serotonin (inhibitory)
What is 5-HT?
Serotonin
NA, 5-HT and dopamine are examples of ____ neurotransmitters.
monoamine
Serotonin is widely distributed in the brain.
What are its functions
a) superiorly
b) at the nucleus raphe magnus?
a) Mood, sleep, appetite, perception
b) Analgesia
What effects does NA produce in the brain specifically?
Arousal
Emotional response
fight or flight in the brain
Which part of the brain releases NA in response to signals from the periaqueductal grey?
What general effect does this cause?
Locus caeruleus
Analgesia
Which enzyme metabolises monoamine neurotransmitters to clear them out of the pre-synaptic terminal?
Monoamine oxidase
What happens if you inhibit monoamine oxidase?
Neurotransmitter isn’t cleared up
It sticks around in the synapse for longer
Increased excitation
What are two examples of monoamine oxidase inhibitors?
Phenelzine (irreversible)
Moclobemide (reversible)
Which monoamine oxidase inhibitor is
a) reversible
b) irreversible?
a) Moclobemide
b) Phenelzine
What is a major side effect, involving diet, of monoamine oxidase inhibitors?
If you eat products containing lots of tyramine e.g cheese, gravy you’ll have a hypertensive crisis
Why aren’t monoamine oxidase inhibitors e.g phenelzine, moclobemide widely used?
Side effects
What are some side effects of monoamine oxidase inhibitors?
Hypertensive crisis w/ high tyramine diet
Postural hypotension
Peripheral oedema
Insomnia
How do tricyclic antidepressants work?
Block re-uptake of monoamine neurotransmitter into pre-synaptic terminal
What are some examples of tricyclic antidepressants?
Imipramine
Dosulepin
Amitriptyline
Lofepramine
What are some side effects of TCAs?
Anticholinergic effects - reduce smooth muscle activity; blurred vision (can’t accomodate), dry mouth, constipation, urinary retention
Cardiovascular problems - tachycardia, postural hypotension, (fatal) arrhythmia
Sedation
Weight gain
What are some anticholinergic effects of TCAs?
Dry mouth and eyes
Blurred vision (failure of accommodation)
Constipation
Urine retention
What are some cardiovascular side effects of TCAs?
Postural hypotension
Tachycardia
Arrhythmia (fatal in overdose)
bad for the heart in general
What can patients suffer if they overdose on TCAs?
Fatal arrhythmias
How do SSRIs work?
Same action as TCAs, prevent reuptake of monoamine neurotransmitter into pre-synaptic terminal
but act selectively on 5-HT
SSRIs act selectively on ___.
5-HT (serotonin)
What are some examples of selective serotonin reuptake inhibitors?
Fluoxetine
Citalopram
Sertraline
What are some side effects of SSRIs?
N&V (opposite: anti-emetics which INHIBIT a type of 5-HT)
Headache (opposite: triptans which INHIBIT a type of 5-HT)
Sweating
Sexual dysfunction
The nausea and headache typically caused by SSRIs is ___.
transient
meaning it goes away after a while
Which symptoms are
a) 5-HT1
b) 5-HT3
receptors responsible for?
a) Headache (antagonists are the -triptans, for migraine)
b) Nausea (antagonists are -setrons, or anti-emetics)
SSRIs may initially ___ the symptoms of anxiety or depression.
worsen
especially in young people
In young people, what do SSRIs increase the risk of?
Thoughts of self-harm / suicide
Why shouldn’t SSRIs be given to patients under 25?
Increase in thoughts of self-harm / suicidal ideation
SSRIs can cause a degree of ___ dysfunction.
sexual dysfunction
Which class of antidepressant has a similar mode of action to SSRIs but less side effects?
SNRIs
duloxetine
blocks uptake of NA AND 5-HT
Which antidepressant can be added alongside an SSRI to block its nausea and headache side effects?
Mirtazapine
look at receptors to see why
In the treatment of depression, you don’t combine drugs because you get more side effects without more benefit.
What is the one exception to this?
Addition of mirtazapine to SNRI (duloxetine) therapy to reduce side effects
What is the onset of action of antidepressants?
2 - 6 weeks
What should you ask about in the drug history of someone with a mood disorder?
Drugs they’ve been on previously
They may help again
The more severe a patient’s depression is, the (more / less) effective antidepressants tend to be.
more severe > more effective
Which mood stabiliser is the gold standard treatment for bipolar disorder?
Lithium
Lithium has a narrow ___ ___.
narrow therapeutic index
effective dose is v close to toxic dose
Lithium has a lot of ___ side effects.
renal
Lithium may cause renal impairment when given with which class of drug?
NSAIDs
Which mood stabiliser is toxic when given in high doses?
Lithium
Which class of antidepressant can cause fatal arrhythmias when an overdose occurs?
TCAs
imipramine, amitriptyline, dosulepin
Which drugs, used in epilepsy, can also be given to stabilise mood in bipolar disorder?
Anticonvulsants
sodium valproate
lamotrigine
carbamazepine
remember sodium valproate is teratogenic and carbamazepine makes myoclonic epilepsy worse
Which class of antidepressant drug can cause a fatal hypertensive crisis when the patient eats mature cheese?
Why?
Monoamine oxidase inhibitor (phenelzine, moclobemide)
Tyramine is a substrate of monoamine oxidase, accumulation causes noradrenaline release - BP skyrockets > pulmonary oedema, palpitations, subarachnoid haemorrhage
