Pharmacology of antidepressants and mood stabilisers Flashcards
What properties do drugs need to have to pass through the BBB?
Lipophilic/ hydrophobic
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
What are the different types of antidepressant drugs?
Monoamine oxidase inhibitors
Monoamine reuptake inhibitors; tricyclics, non-selective reuptake inhibitors, SSRIs, NA reuptake inhibitors
Atypical; post-synaptic receptor effects
What are the monoamine neurotransmitters involved in depression?
NA
5-HT
Dopamine
Is there an excess or deficit of monoamine nTs in depression?
Deficit
What is 5-HT involved in within the brain?
Mood Sleep Feeding behaviour Sensory perception Analgesia
What is the base amino acid of serotonin?
Tryptophan
What enzyme will break up 5-HT into 5-HIAA?
MAO
What are example of monoamine oxidase inhibitors?
Phenelzine
Moclobemide
What are the side effects of monoamine oxidase inhibitors?
Hypertensive crisis due to lack of breakdown of tyramine
Potentiates other drugs such as barbiturates
Insomnia
Postural hypotension
Peripheral oedema
Examples of tricyclic antidepressants
Imipramine
Dosulepin
Amitriptyline
Lofepramine
What is the mode of action of tricyclic antidepressants?
Block reuptake of monoamines (mainly NA and 5-HT) into presynaptic terminals
What are common side effects of tricyclic antidepressants?
Anticholinergic; blurred vision, dry mouth, constipation, urinary retention Sedation Wt gain CV; postural hypotension, tachycardia Cardiotoxic in overdose
Should you give a tricyclic to someone who has ischaemia heart disease or a recent MI?
No
Examples of SSRIs?
Fluoxetine
Citalopram
Escitalopram
Sertraline
Common side effects of SSRIs?
Nausea Headache Sweating Vivid dreams Worsened anxiety Sexual dysfunction Hyponatraemia Transient increase in self-harm/ suicidal ideation in <25 years Discontinuation effects
What is the mode of action of SSRIs?
Selectively inhibit reuptake of serotonin from the synaptic cleft
What is the mode of action of mirtazapine?
Blocks alpha, 5-HT2 and 5-HT3 receptors
SE of mirtzapine
Wt gain
Sedation
What is an example of a dopamine uptake inhibitor?
Bupropion
Should antidepressants be used in mild depression?
No - large placebo response
What is the caution of prescribing antidepressants in young adults/ teenagers?
Transient increase in suicidal ideation
Aggressive ideas
What is the goals of acute treatment in bipolar?
Reduce mood in mania
Increase mood in depression
What is the goal of long term treatment in bipolar disorder?
Stabilise mood and prevent recurrence of both mania and depression (prophylaxis)
What is the mode of action of lithium as a mood stabiliser?
Blocks phosphatidylinositol pathway (second messenger system) or inhibit glycogen synthase kinase 3-beta
Does lithium require therapeutic monitoring?
Yes; 12 hour post dose levels must be monitored due to narrow therapeutic index
Common side effects of lithium that occur at therapeutic levels?
Dry mouth/ strange taste Polydipsia and polyuria Tremor Hypothyroidism Long term reduced renal function Nephrogenic diabetes insipidus Wt gain
What are the toxic effects of lithium overdose?
Vomiting Diarrhoea Ataxia Drowsiness Convulsions Coma
Which anticonvulsants are used as mood stabilisers in bipolar?
Valproic acid
Lamotrigine
Carbamazepine
What are the SE of valproate and carbamazepine?
Drowsiness
Ataxia
CV effects
Induces liver enzymes
Can valproate be given in pregnancy?
No; neural tube defects
What is the risk with lamotrigine?
SJS
Which antipsychotics can be given as mood stabilisers?
Quetiapine
Aripiprazole
Olanzapine
Lurasidone
What is the mode of action of antipsychotics?
Dopamine antagonism + 5-HT antagonism
SE of antipsychotics?
Sedation
Wt gain
Metabolic syndrome
Aripiprazole; extra-pyramidal SE
