Antipsychotics (neuroleptics) Flashcards
What are antipsychotics used for?
Generally - to calm disturbed patients regardless of the underlying pathology:
Schizophrenia, brain damage, mania, toxic delirium, agitated depression
What are they used for in schizophrenia?
Relief of positive symptoms ; less effective on negative symptoms
Aim of the treatment is to reduce the overall suffering and improve social and cognitive functioning
Doses that are effective in acute episodes should be continued as prophylaxis
What affects the choice of antipsychotic?
Informed choice made by service user and healthcare professional together, based on benefits, side effects and current drug history; there is no 1st line per se
What investigations are required before starting antipsychotic medication?
Weight - plotted on a chart Waist circumference Pulse and BP Fasting blood glucose, HbA1c, blood lipid profile, PRL levels Assessment of any movement disorders Assessment of nutritional status, diet and level of physical activity (Smoking status) Offer ECG if CV risk (ie HTN or Hx)
How do first generation (typical) antipsychotics act?
Act by blocking D2 receptors, non-selective for any of the 4 dopamine pathways in the brain
Mesolimbic - Main pathway implicated in the positive symptoms of schizophrenia, reduced pleasure, motivation and the salience of ones life experiences; but as antagonises all pathways, can cause a range of side effects:
Mesocortical - cognitive and negative features of psychosis, affecting cognition and executive function, emotions and affect
Nigrostriatal pathway - extrapyramidal symptoms
Tuberoinfundubular pathway - DA release here tonically inhibits prolactin release, treatment elevates prolactin (sexual dysfunction, galactorrhoea, amenorrhoea, weight gain, demineralisation of bones)
What are some common examples of first generation antipsychotics?
Chlorpromazine hydorchloride (group 1)
Pericyazine (group 2)
Fluphenazine deconate (group 3, EPS common)
Haloperidol (resembles group 3, EPS common)
Flupentixol
Sulpiride
How do second generation (atypical) antipsychotics act?
Serotonin-dopamine D2 receptor antagonists
As well as blocking dopamine at the D2 receptors (though less antagonising than 1st gen), it also antagonises 5-HT2A serotonergic receptors, this reverses the DA antagonism to some extent
Producing a variety of distinct side effect profiles:
Nigrostriatal - reduces EPSs
Tuberoinfundibular - reduces prolactin elevation
What are some common examples of second generation antipsychotics?
Olanzapine Quetiapine Risperidone Ziprasidone Aripiprazole
(clozapine)
What is clozapine?
Second line - treatment resistant schizophrenia, atypical antipsychotic - when 2+ neuroleptics have been used for at least 6-8wks
Requries close monitoring as can cause agranularcytosis (potentially fatal); also constipation, toxic megacolon, cardiac myosotis and cardiomyopathy
Clozapine monitoring system (CPMS) is in place to help regulation and advice - weekly for first 13wks then 4wkly after
If clozapine doses are missed for more than 48 hours the dose will need to be restarted again slowly; if >72hrs, may need more regular blood tests for a short period
Also lowers seizure threshold so may predispose someone to seizures
Consultant prescription only
What are some common side effects of all antipsychotics?
Metabolic - ie weight gain, diabetes, hyperlipidaemia (more common in 2nd gen)
Extrapyramidal symptoms (EPS) - ie akathisia (restlessness), tardative dyskinesia (rhythmic, involuntary movements of face/tongue/jaw, most worrying as can be permanent), acute dystonia (muscle contraction/spasm - acute reaction can occur within hrs of first dose, often facial muscles), bradykinesia, tremor (more common in 1st gen)
Cardiovascular - ie QT prolongation, tachyc, arrhythmias, hypotension
Hormonal - ie increasing plasma prolactin = sexual dysfunction, reduced bone density, menstrual disturbance, breast enlargement, galactorrhoea
Antimuscarinic - ie dry mouth, blurred vision, tachycardia, photophobia, retention, hyperthermia
Other - ie sedation, unpleasant subjective experiences
What is neuroleptic malignant syndrome and how do you manage it?
Thought to originate due to excess dopamine receptor blockade → possible massive glutamate release → catatonia, neurotoxicity and myotoxicity (but not known for sure)
Can be caused by almost any antipsychotic
High potency doses, rapid increase in dose and long acting forms of neuroleptics are risk factors
Onset over a few days - muscle cramps and rigidity, hyporeflexia, tremors, fever, tachycardia, unstable BP, agitation/delirium/coma peaking in 3 days, lasting 8hrs-40 days
Blood test:
Elevated creatinine kinase
Stop antipsychotic, reduce body temp, manage airway if compromised, IV benzos if agitated, IV fluid for dehydration, bromocriptine for D2 agonism, Dantrolene for muscle relaxation
What are depot injections?
Long-acting (1wk-month) antipsychotics, used especially in cases where compliance is unreliable
The depot injection usually be the same as what would be taken PO
Increased risk of EPS, but this risk is lower with 2nd gen depots
How do typical/atypical side effect profiles differ?
Typical - more movement based SEs
Atypical - more metabolic SEs
What is an acute dystonic reaction?
Occurs within hours of taking first dose
Most common with new medication
Blockade of DA leads to excess striatal cholinergic output which leads to symptoms
Possible features:
Acute torticollis - painfully twisted and tilted neck
Oculogyric crisis - backwards and lateral flexion of the neck, widely opened mouth, tongue protrusion (buccolingual crisis), and ocular pain; jaw spasm, breaking tooth
Torticopelvic crisis - abdominal rigidity and pain
Laryngeal dystonia - rare but potentially life threatening - throat pain, dyspnoea, dysphonia
Blepharospasm + other facial spasms e.g. unable to open eyelids
Memory aid:
Acute? Treat it Pro-actively = Procyclidine
(if fails + life threatening - IV diazepam)
Untreated will resolve in a few days
What are Parkinsonian side effects?
Occurs within days
Tremor
Bradykinesia
Rigidity
