Antipsychotics Flashcards by Alexandra Chan

What are the domains of psychosis

Positive symptoms: hallucinations, delusions, thought disorder
Negative symptoms: alogia, apathy, avolition, associalty, affective blunting
Disorganisation symptoms: bizarre, chaotic and agitated behaviours

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What is the dopamine theory

Dopamine release from the mesolimbic pathway into the nucleus accumbens regulates motivation and facilitates reinforcement and reward

Excessive dopamine → positive symptoms of psychosis

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What are the four dopamine pathways in the brain

Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular

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What is the role of the mesolimbic dopamine pathway in psychosis

Ventral tegmental area → dopaminergic neurons → ventral striatum of basal ganglia
Responsible for positive symptoms

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What is the role of the mesocortical dopamine pathway in psychosis

Ventral tegmental area → dopaminergic neurons → prefrontal cortex
Cognitive control, motivation, emotional response
Negative symptoms

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What is the role of the nigrostriatal dopamine pathway in psychosis

Substantia nigra → dopaminergic neurons → striatum/basal ganglia
Extrapyramidal nervous system, controls motor movement
EPSE

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What is the role of the tuberoinfundibular dopamine pathway in psychosis

Hypothalamus → dopaminergic neurons → anterior pituitary gland
Normally active and inhibits the release of prolactin
Hyperprolactinaemia

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Which area of the brain is associated with aggressive and impulsive symptoms

Orbitofrontal cortex and connections to the amgydala

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What receptors do typical antipsychotics act on and give examples

Widely acts on D2 dopamine receptors

Chlorpromazine (first)
Haloperidol
Zuclopenthixol
Flupentixol

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What receptors do atypical antipsychotics act on and give examples

Selectively acting for dopamine, serotonin and 5-HT2A

Clozapine
Olanzapine
Quetiapine
Risperidone
Aripiprazole

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Why are atypical antipsychotics preferred to typical antipsychotics

Antagonist of the 5HT-2A receptor
Reduces antipsychotic receptor occupancy from 80-60% in the nigrostriatal pathway → reduces risk of EPSEs

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Which antipsychotics have partial agonist activity

aripiprazole
cariprazine
furasidone

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What are the side effects of antipsychotics

Hyperprolactinaemia
QTc prolongation
Extra-pyramidal side effects:
- Parkinsonism
- Dystonia
- Tardive dyskinesia
- Akathisia
Metabolic syndromes
Neuroleptic malignant syndrome

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What are the differentials for hyperprolactinaemia

Physiological: pregnancy, lactation, stress
Antipsychotics - amisulpride, risperidone
Antidepressants
Organic: prolactinoma

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What are the symptoms of hyperprolactinaemia

Often asymptomatic, clinically significant >1000
Women: reduced libido, amenorrhoea, galactorrhoea, osteoporosis, increase breast Ca risk
Men: reduced libido, erectile dysfunction, gynaecomastia, galactorrhoea

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What is the management for hyperprolactinaemia caused by antipsychotics

Switch to a prolactin sparing agent e.g. quetiapine, aripiprazole (dopamine agonist)
Add in aripiprazole
Avoid dopamine agonists e.g. cabergoline, bromocriptine

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What does the QT segment represent, what is classified as prolongation, and why is prolongation a risk

Ventricular depolarisation and repolarisation
Corrected fro heart rate (QTc)
>500ms - risk increases significantly
Increases risk of cardiac arrhythmias e.g. polymorphic ventricular tachycardia (Torsade de Pointes) → loss of cardiac output → unconsciousness → death

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What is the management for QTc prolongation caused by antipsychotics

Switch to a more QTc sparing agent e.g. aripiprazole

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Describe parkinsonism EPSEs from antipsychotics

Occurs when 80-90% of the neurons are lost

Classic symptoms: bradykinesia, rigidity, pill rolling tremor, postural instability
Stooped posture
Shuffling gate, reduced arm swing
Hypomimia
Generally bilateral

What investigations and management should be done for parkinsonism EPSEs from antispychotics

dopamine transporter (DAT) scan

Management: switch medication, add procyclidine (anti-muscarinic)

What is tardive dyskinesia as an EPSE of antipsychotics

Involuntary orofacial dyskinesia associated with long term antipsychotic use
Develops after months/years of treatment
Typically seen as continuous mouth and tongue movements e.g. lip smacking, eye closing, jaw clenching, trunk/extremity movement

What are the the risk factors for developing tardive dyskinesia from antipsychotics

Typical antipsychotics
High dose
Elderly

What is the management for tardive dyskinesia caused by antipsychotics

May be permanent, even when the medication is stopped
Stop the causative agent
Consider tetrabenazine

What is dystonia as an EPSE of antipsychotics

Involuntary muscle spasm/contractions
Develops within hours of starting antipsychotics

Specific types:
- Oculogyric crisis (eyes rolling upward)
- Torticollis (head and neck twisted to one side)
- Laryngeal dystonia (can compromise airway and be life threatening)

What are the risk factors for developing dystonia from antipsychotic use

Antipsychotics naive young males High dose typical antipsychotics

What is the management for dystonia caused by antipsychotics

Anticholinergics e.g. procyclidine

What is akathisia as an EPSE of antipsychotics

A sense of internal restlessness. Occurs within days to weeks of starting/increasing an antipsychotic The patient feels compelled to constantly move, rock, fidget or pace around. Associated with an increased risk of suicide

What is the management for akathisia caused by antipsychotics

Change medication Diphenhydramine Propranolol Low dose benzodiazepines

Describe metabolic syndrome

Schizophrenia reduces life expectancy by 15-20 years, partly mediated by the metabolic side effects: Weight gain Dyslipidaemia Insulin insensitivity Leads to heart disease, lipid problems, HTN, T2DM, dementia, PCOS, cancer, NAFLD

What is the management for metabolic syndrome caused by antipsychotics

Monitor weight, BP, lipid profile, and HbA1c Treat any complications on their merits e.g. statins, anti-glycaemics, anti-hypertensives Promote health eating and exercise

How long does it take for antipsychotic effects to be apparent

Sedation: minutes-hours Antipsychotic effect: 1-2 weeks, max benefit within 6 weeks

What is high dose antipsychotic treatment (HDAT)

total antipsychotic dose >100% BNF maximum dose

What antipsychotics can be used for rapid tranquilisation

IM olanzapine IM haloperidol

What cautions should be taken for antipsychotic use as tranquilisation

Pre-treatment ECG needed with haloperidol due to risk of QTc prolongation IM olanzapine not to be given within 1 hr of IM lorazepam due to risk of respiratory depression No more than 3 days of IM olanzapine to be given in a row due to risk of post-injection syndrome

What is treatment resistance and what can be used

Treatment resistance = If two antipsychotics have been given an adequate trial (6 weeks at a therapeutic dose including one atypical) → consider clozapine (i.e. treatment resistance pathway)

Which medication has evidence towards negative symptoms

Clozapine

What needs to be done before clozapine is started in a patient

FBC and ECG prior Register with national clozapine monitoring service

How often does a patient need to be monitored while on clozapine

Weekly → fortnightly → monthly (after 1 year of treatment)

What is the traffic light system for clozapine monitoring

Green: continue Amber: continue but FBC monitoring increased to twice weekly Red: stop immediately

What are the side effects of clozapine

Lowering of seizure threshold Constipation Agranulocytosis/Neutropenia/leucopenia → regular FBC test monitoring Myocarditis, cardiomyopathy, tachycardia, hypotension Hypersalivation Prothrombotic → DVT/PE Sedation, increased appetite → weight gain (Blocks histamine-H1 receptors)

What are the symptoms of agranulocytosis caused by clozapine

Ulcer development in mucous membranes that line the mouth and GI tract Susceptible to bacterial infections Sepsis occurs to bacterial contamination

How should clozapine be started and stopped

Start at a low dose and titrate slowly Re-titrate if stopped >48 hours Stop slowly - if abruptly stopped there is a high risk of rebound psychosis

What monitoring is done for patients on antipsychotics

6 weeks: weight 12 weeks: weight, pulse, BP, HbA1c//glucose, lipids 1 year: weight, pulse, BP, HbA1c//glucose Annually: - Weight, pulse, BP, waist circumference - HbA1c, U&Es, FBC, lipids, prolactin, LFTs, CK

Describe neuroleptic malignant syndrome

Acute potentially life threatening complication of antipsychotic treatment, seen in <1% of patients A disorder of thermoregulation and neuromotor control Within hours to days of starting an antipsychotic: agitated delirium with confusion pyrexia muscle rigidity Hyporeflexia autonomic lability: hypertension, tachycardia and tachypnoea Diaphoresis Raised CK, AKI, leukocytosis Mortality 10%

What is the management for neuroleptic malignant syndrome

1. stop antipsychotic 2. Admit/transfer to MEDICAL ward 3. IV fluids (prevent renal failure) ± dantrolene ± bromocriptine