Pharmacology of Antidepressants and Mood Stabilisers Flashcards
What are the clinical uses of antidepressants?
- Moderate to severe depression
- Dysthymia
- Generalised anxiety disorder
- Panic disorder, OCD, PTSD
- Premenstrual dysphoric disorder
- Bulimia nervosa
- Neuropathic pain
Name 3 groups of antidepressant drugs.
- Monoamine oxidase inhibitors.
- Monoamine reuptake inhibitors.
- Atypical drugs (post-synaptic receptor effects).
Give 3 subgroups of monoamine reuptake inhibitors.
- Tricyclics.
- Other non-selective reuptake inhibitors.
- Selective serotonin reuptake inhibitors.
SSRI’s belong to what group?
Monoamine reuptake inhibitors
How many amine groups do monoamines have?
1 lol obvs
How do most antidepressants work?
By altering monoamine neurotransmission in some way
What does depression result from?
A functional problem in the monoamine transmitters
Name 3 main monoamine transmitters.
- Serotonin (5-HT)
- Noradrenaline
- Dopamine
What do drugs that deplete stores of monoamines do?
Cause a low mood
CSF from depressed patients have reduced levels of monoamines or metabolites
TRUE
Most drugs that treat depression act to ________ monoaminergic transmission
INCREASE
What is the life cycle of serotonin?
- Tryptophan is in the presynaptic cleft
- It is converted to 5-OH-tryptophan by tryptophan hydroxyls (enzyme)
- 5-OH-tryptophan is converted to 5-HT by LAA-decarboxylase (enzyme)
- 5-HT leaves presynaptic cleft and is taken up by postsynaptic cleft
- 5-HT is then re-taken by presynaptic cleft
- 5-HT converted to 5-HIAA by MAO’s
What is the life cycle of noradrenaline?
- Tyrosine in presynaptic cleft
2 Tyrosine converted to DOPA by tyrosine hydeoxylase (enzyme) - DOPA converted to DA by LAA-decarboxylase (enzyme)
- DA converted to NA by DA-beta-hydroxylase (enzyme)
- NA leaves presynaptic cleft and is taken up by postsynaptic cleft
- NA is then re-taken by presynaptic cleft
- NA converted to MHPG by MAO’s
Name 2 MAO inhibitors.
- Phenelzine
* Moclobemide
How to MAO inhibitors work?
Inhibit MAO to increase neurotransmitter concentration.
What is the mode of action of MAO inhibitors?
Either irreversible or reversible inhibitors of MAO-A and B
Which MAO inhibitor is reversible and what one is irreversible?
Irreversible – phenelzine.
Reversible – moclobemide.
What are the main side effects of MAO inhibitors?
- ‘Cheese reaction’/Hypertensive crisis.
- Potentiates effects of other drugs (ie. barbiturates) by decreasing their metabolism.
- Insomnia.
- Postural hypotension.
- Peripheral oedema.
What is the ‘cheese reaction’/hypertensive crisis caused by?
Inhibition of MAO-A in the gut (+ liver) by irreversible inhibitors, preventing breakdown of dietary tyramine, and by multiple drugs that potentiate amine transmission (ie. pseudoephedrine, other anti-depressants).
To prevent hypertensive crisis, what should patients be advised?
Don’t eat cheese or gravy :(
How do tricyclic antidepressants work?
Block the re-uptake of NT
Give 4 examples of TCA’s.
Imipramine.
Dosulepin.
Amitriptyline.
Lofepramine.
What is the mode of action of TCA’s?
Block the reuptake of monoamines (mainly noradrenaline and 5-HT) into presynaptic terminals.
What are the common side effects of TCA’s?
- Anticholinergic-
blurred vision, dry mouth, constipation, urinary retention - Sedation
- Weight gain
- Cardiovascular-
Postural hypotension, tachycardia, arrhythmias - Cardiotoxic in overdose
Give 4 examples of SSRI’s.
- Fluoxetine.
- Citalopram/Escitalopram.
- Sertraline.
- (Paroxetine)
What is the mode of action of SSRI’s?
Selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft
What are the common side effects of SSRI’s?
- Nausea
- Headache
- Sweating / vivid dreams
- Worsened anxiety
- Sexual dysfunction
- Hyponatraemia (in elderly)
- Transient increase in self-harm / suicidal ideation in <25 years
Name 2 dual reuptake inhibitors (SNRI’s).
- Venlafaxine
* Duloxetine
How do SNRI’s work?
Block the reuptake of monoamines (noradrenaline AND 5-HT) into presynaptic terminals
What are the side effects of SNRI’s? What is the main advantage to the use of these?
S/E’s are similar to SSRI’s
Lack major receptor-blocking actions so fewer side effects than tricyclics
Mirtazapine
Has mixed receptor affects
What does Mirtazapine block?
alpha2, 5-HT2 & 5-HT3
What are the side effects of a drug like mirtazapine which has mixed receptor effects?
Weight gain + sedation
What can mirtazapine do if given with SSRI’s?
Block serotonergic side-effects.
ie. nausea 5-HT3 antagonists are used as anti-emetics.
Name a dopamine uptake inhibitor.
Bupropion.
What is the onset of action like in most antidepressants?
Delayed - several weeks
There is clearer evidence for the usefulness of antidepressants in what?
More severe depression large placebo response in mild depression
Who should you be cautious of the use of antidepressants in? Why?
Young adults/teenagers due to transient increase in suicidal/aggressive ideas
What is lithium for bipolar normally given as?
Lithium carbonate
Different forms of lithium have different bioavailability so be careful about doses if the type of lithium salt is changed
WARNING
What must be monitored with lithium? Why?
12-hour post-dose blood levels.
- because of narrow therapeutic index.
What are the common side effects of lithium?
- Dry mouth / strange taste
- Polydipsia & polyuria
- Tremor
- Hypothyroidism
- Long term reduced renal function
- Nephrogenic diabetes insipidus
- Weight gain
What are the toxic effects of lithium?
- Vomiting
- Diarrhoea
- Ataxia / coarse tremor
- Drowsiness
- Convulsions
- Coma
Give examples of anticonvulsant drugs which can be used in long term treatment of BPAD.
- Valproic acid.
- Lamotrigine.
- Carbamazepine
What are the side-effects of carbamazepine?
Drowsiness, ataxia, cardiovascular effects, induces liver enzymes
What is the main issue surrounding valproate?
Teratogenicity – neural tube defects
Therefore, don’t give to women of child-bearing age.
Give 4 examples of antipsychotics that can be used as mood stabilisers.
- Quetiapine.
- Aripiprazole.
- Olanzapine.
- Lurasidone.
What is the role of antipsychotics?
Dopamine + 5-HT antagonism
What side effects may be associated with antipsychotics?
- Sedation, weight gain, metabolic syndrome
* Extra-pyramidal side-effects (aripiprazole)
What 5 things are involved in the serotonin pathway of the brain?
- Mood
- Sleep
- Feeding
- Behaviour
- Sensory perception
