Pharmacology of Mood Disorders Flashcards
Clinical uses of anti depressants
a) Dysthymia - persistent depression
b) Panic disorder, OCD, PTSD
c) Depression (moderate/severe)
d) Generalised anxiety disorder
e) Bulimia nervosa
f) Neuropathic pain
List the classes of anti- depressants
MAO-I Tricyclic antidepressants SSRI SSNRI Others
Examples of MAO-I
Phenelezine (irreversible inhibition)
Moclobemide (reversible inhibition)
MOA of MAO-I
Inhibitors of monoamine oxidase - mitochondrial enzyme responsible for breakdown of monoamine neurotransmitters
Prevents breakdown of these transmitters thereby increasing their availability
Side effects of MAO-I
- “cheese reaction”/ hypertensive crisis
- Postural hypotension
- Peripheral oedema
- Insomnia
Examples of Tricyclic antidepressants (TCA)
Imipramine
Dosulepine
Amitryptiline
Lofepramine
MOA of TCA
Blocks reuptake of monoamines into presynaptic terminals
Mainly NA and 5-HT
Leads to increased concentration of the amines in synaptic cleft in both the CNS and periphery
Pharmacokinetics of TCA
Good oral absorption
Highly protein bound
Metabolised by liver
Metabolites excreted in urine (1-2 wks)
Side effects of TCA
- Anticholinergic: dry mouth, blurred vision, urine retention, constipation, dizziness
- Sedation, confusion, weakness
- Weight gain and increased appetite
- Cardiovascular: Postural hypotension, sweating, palps
CARDIOTOXICITY IN OVERDOSE
Examples of SSRI
sertraline
fluoxetine
Citalopram/escitalopram
MOA of SSRI
Selective inhibition of serotonin uptake (5-HT) from synaptic cleft
Tricyclic antidepressants are the first line drugs for depression - True or False?
False -
SSRIs are the first line drugs as:
a) no cardiotoxicity
b) safe in elderly
Examples of SNRI
Venlafaxine
Duloxetine
MOA of SNRI
Block reuptake of NA and serotonin from synaptic cleft
Side effects of SNRI
Similar to SSRI
Lack major receptor blcoking actions (ex. anticholinergic)
List the atypical antidepressants (MOA + SE)
MIRTAZAPINE
MOA: Blocks 2, 5-HT2 & 5-HT3 - increasing release of 5-HT and NA in brain - antidepressant effect
SE: weight gain, sedation
BUPROPION
MOA: inhibition of dopamine uptake
SE: insomnia, agitation, dry mouth
Which drugs are used as mood stabilisers in treatment of Bipolar Disorder?
- LITHIUM CARBONATE
- Antipsychotics
- Anti-convulsants
Which drug needs consistent monitoring when administered? Why?
Lithium - narrow therapeutic window
MOA of lithium
May block phosphatidylinositol pathway
OR inhibit glycogen synthase kinase 3B
OR modulate NO signalining
Pharmacokinetics of lithium
well absorbed orally (slow)
Neither protein bound nor metabolised
Handled in Kidney
- reabsorption in PCT
- Rapid urinary excretion (10-12 hrs)
Higher levels in older people and those with renal insufficiency
SE of Lithium
Dry mouth/strange taste Tremors Polydipsia and polyuria Hypothyroidism Long term reduced renal function Nephrogenic DI Weight gain
Toxic effects of lithium
Vomiting Diarrhea Ataxia/coarse tremor Drowsiness/altered conscious level Convulsions Coma
List the anticonvulsants used as mood stabilisers
lamotrigine
carbamazepine
MOA of anticonvulsants
unclear
perhaps potentiate GABA transmission thus blocking overactive pathways
SE of anticonvulsant
drowsiness, ataxia, CV effects, induction of liver enzymes
VALPROATE - teratogenictiy
LAMOTRIGINE - Steven Johnson Mary syndrome
List the antipsychotics used as mood stabilisers
Quetiapine
Aripiprazole
Olanzapine
Lurasidone
MOA of antispychotic
Dopamine + 5-HT antagonism
SE of antipsychotic
sedation
weight gain
metabolic syndrome
extrapyramidal effects (aripiprazole)
Which of the following neurotransmitters is NOT a monoamine A. Dopamine B. Glutamate C. Noradrenaline D. 5-Hydroxytryptophan (5-HT
B. Glutamate
Which of the following side-effects is MORE likely to be caused by an SSRI antidepressant than by a Tricyclic?
A. Blurred vision B. Constipation C. Dry Mouth D. Nausea E. Urinary Retention
D. Nausea
Which of the following antidepressants should be avoided in a 57year old man with Ischaemic Heart Disease who has become depressed following an MI 2 months ago?
A. Citalopram B. Fluoxetine C. Imipramine D. Mirtazapine E. Sertraline
C. Imipramine is a TCA - cardiotoxic and easier to cause mortality with overdose
Which of the following side-effects would suggest Lithium levels in the toxic range
A. Ataxia B. Hypothyroidism C. Nausea D. Polyuria E. Tremor
A. Ataxia - symptom of toxicity
A 27 year old woman is diagnosed with Bipolar Disorder. She says that she hopes to get pregnant some time in the foreseeable future. Which mood stabiliser is absolutely to be avoided?
A. Aripiprazole B. Lamotrigine C. Lithium D. Quetiapine E. Valproic Acid
E.
Teratogenic
Side effects of SSRI
Nausea
Headache
Worsened anxiety
Increase in self-harm / suicidal ideation in <25 years
Sweating / vivid dreams
Sexual dysfunction
Hyponatraemia (in elderly)
Discontinuation effects - unsteadiness, increased mood change, restlessness, difficulty sleeping, GI symptoms, paraesthesia
