Antipsychotics Flashcards
What is the mechanism of action of antipsychotics?
Blocks post-synaptic dopamine D2 receptors
There are 3 dopamine pathways
Blockade of the mesocortical/mesolimbic pathways produce the desired effect
Adverse effects are derived from the blockade of the nigrostriatal (movement) and tuberohypophyseal (HPA axis) pathways.
What are the adverse effects of antipsychotics?
Nigrostriatal
- Early: extrapyramidal SEs (parkinsonism, akathisia, neuroleptic malignant syndrome), acute dystonic reactions including oculogyric crisis
- Late (months/years): tardive dyskinesia (pointless, repetitive and involuntary movements like lip smacking) - disabling and may not resolve on stopping
Tuberohypophyseal
- hyperprolactinaemia (menstrual disturbances, galactorrhoea, breast pain)
Other
- drowsiness, hypotension, QTc prolongation (leading to arrhythmias), weight gainerectile dysfunction
In what situations should typical antipsychotics be avoided?
Dementia (increases risk of death and stroke)
- can be given in the elderly, but at lower doses as they are particularly sensitive to it
Parkinson’s disease due to extrapyramidal effect
What are the indications of antipsychotics?
Urgent treatment of severe psychomotor agitation that is causing dangerous/violent behaviour/to calm patients to permit assessment
Schizophrenia
- typical if metabolic SEs of atypicals problematic
- atypical if extrapyramidal effects of typicals problematic
Bipolar disorder (particularly in episodes of mania or hypomania)
NV (typical antipsychotics) especially in the palliative setting
What are the 2 types of antipsychotics and give examples of each.
Typical (haloperidol, chlorpromazine, prochlorperazine)
Atypical (quetiapine, olanzapine, risperidone, clozapine, aripiprazole)
Compare and contrast typical and atypical antipsychotics
Typical are more likely to cause extrapyramidal side effects, dizziness and sexual dysfuncion
Typical bind more to muscarinic and histaminic receptors
Atypical tend to have more serotonergic activity
Atypical more likely to cause metabolic distrubance leading to wight gain, dyslipidaemia, diabetes mellitus
Both cause QT interval prolongation which could lead to arrhythmias
What is a side effect more specific to risperidone? Why?
Hyperprolactinaemia (breast pain, galactorrhoea, menstrual disturbance)
Due to effects on tuberohypophyseal pathway
What is a severe side effect of clozapine?
Agranulocytosis
Occurs in about 1% of patients
Sometimes causes myocarditis
In which groups of patients should you be cautious when prescribing atypical antipsychotics?
Cardiovascular disease
For clozapine - severe heart disease, neutropenia
What are the important interactions of antipsychotics?
Drugs that prolong the QT interval (macrolides, amiodarone. SSRIs)
How are antipsychotics monitored?
Baseline: FBC, Lipids, LFTs, HbA1c, weight, ECG, BP and pulse
- this is then done again in 3 moths and then yearly
In an ideal world monitor weights weekly as antipsychotics can decrease satiety
What is neuroleptic malignant syndrome?
Rare, but life-threatening reaction to antipsychotics
Characterised by rigidity, confusion, autonomic dysregulation and pyrexia
Death is usually due to rhabdomyolysis, renal failure or seizures
Bloods will show a raised CK and also likely a raised WCC
What are the risk factors for neuroleptic malignant syndrome?
Typical antipsychotics (high potency dopamine antagonists)
Antipsychotic naive
High doses
Young men
What is the treatment for neuroleptic malignant syndrome?
Emergency referral to A&E
Stop antipsychotics
Give BDZ fo acute behavioural disturbance and as a muscle relaxant
Fluid resus
Reduce temperature (cooling blankets)
Oxygen if necessary
For rhabdomyolysis - fluids and sodium bicarb to alkalise the urine
For relaxing muscles - first line is dantrolene/lorazepam and second line is bromocriptine
What drug can be used to treat EPSEs? How is it used?
Anticholinergics
About dopamine:anticholinergic ratio not quantities
Procyclidine is most commonly used, but there is potential for misuse
Others include benzatropine and trihexphenidyl
Not effective for and may exacerbate tardive dyskinesia (difficult to treat)
