Psychosis Flashcards
Definition
Clinical state of mind characterised by loss of contact with reality
Clinical signs
Patients might experience perceptual disturbances e.g. hallucinations that are generally auditory as well as disturbances of thought content i.e. delusions
Negative symptoms- blunting of affect, avolition, alogia
Social or occupational dysfunction
clear sensorium
Delirium with acute confusion and aggression - clinical signs
Impaired awareness, confusion, disorientation
Others : restlessness, agitation and hallucinations, ANS symptoms, aggressiveness etc
Causes of delirium can be due to
DIMTOP (drugs, infection, metabolic, trauma, oxygen, psychological)
Pathogenesis of psychosis
UNKNOWN
Dopamine hypothesis of schizophrenia
Excessive dopaminergic activity
Neuroanatomy of psychosis
Mesolimbic-mesocortical - behaviour
Nigrostrial-coordination of voluntary movement
Tuberoinfindibular-inhibition of prolactin secretion
Causes of psychosis
Functional psychosis (Schizophrenia, Bipolar mood disorder)
Psychotic disorders due to medical conditions (Medical conditions e.g. epilepsy, Alzheimer’s dementia, HIV, neurosyphilis and Drugs - Illicit drugs –cannabis, mandrax, cocaine, amphetamines; prescription drugs- steroids, antiparkinsonism drugs, atropine)
Other- e.g. postpartum psychosis
Management depends on…
Aetiology
Onset of the psychosis
Acute management (agitated or acutely disturbed pt)
Goals of therapy is to calm pt down and achieve containment
Antipsychotic and/or benzodiazepine of your choice
Chronic management
Goal of therapy is to prevent relapse of acute psychotic symptoms i.e. delusions, hallucination so as to maintain functionality
Antipsychotic drugs
Supportive psychotherapy for patient and family
Classes of classical neuroleptics
Dopamine 2 receptor antagonists
Tendency to cause extrapyramidal side effects
Classes of atypical neuroleptics
D2 & D3 receptor antagonists
D2 & serotonin receptor antagonist
Primary indications for neuroleptics
Schizophrenia
Mania
Organic psychosis
Other indications for neuroleptics
Nausea and vomiting Intractable hiccups Tourette’s syndrome Behaviour disorders Anaesthesia
name 3 classes of Traditional neuroleptics
Phenothiazines (side chain)
Butyrophenones
Thioxanthenes
3 classe of phenothiazines and examples of each
Aliphatic e.g. chlorpromazine
Piperazine e.g. prochloperazine, fluphenazine
Piperidine e.g. thioridazine*, pericyazine
name 2 examples of Butyrophenones
Haloperidol, droperidol
name 2 examples of thioxanthenes
Flupenthixol, zuclopenthixol
Formulations
oral
Injectables- usually IM (Short acting- acute management; long acting depot preparations- preferred if compliance a problem)
MOA of typical antipsychotics
Blocks D2 and D1, preventing dopamine-receptor interaction
MOA of adverse effects of typical antipsychotics
Blocks H1 and 5-HT2 receptors
MOA of atypical antipsychotics
block D1
MOA of adverse effects atypical antipsychotics
Block 5-HT2 and alpha adrenergic receptors
Oldest neuroleptic of low potency
Chlorpromazine (Piperazine phenothiazine)
Indications for chlorpromazine
Schizophrenia
Mania
Organic psychosis etc
Tranquillization in emergency aggressive behavioural disturbances
Onset of action of Chlorpromazine
Onset 30-60min after oral ingestion and 15min after injection
Half-life of Chlorpromazine
30 hrs
Contraindications for Chlorpromazine
coma, severe mental depression, severe liver impairment, significant cardiac disorders, glaucoma, bone marrow depression
Adverse effects of chlorpromazine
EPSEs, sedation, postural hypotension, anticholinergic side effects, epileptogenic, photosensitivity ,jaundice, agranulocytosis
Drug interactions Chlorpromazine
anticholinergics, antiepileptics, antihypertensives, antiparkinsonism drugs, CNS depressants , enzyme inducers
Doses: Chlorpromazine
initially 25mg tds but maintenance range 75-300mg.
IM 25-50mg ,can be repeated 3-4 times in 24hrs as necessary
USE THE LOWEST EFFECTIVE DOSE
EPSE-complications of antipsychotics
Acute dystonic reaction Parkinsonism akathisia Tardive dyskinesia Neuroleptic malignant syndrome
Explain acute dystonic reaction
Acute dystonic reaction- spasm of muscles of tongue, face, neck, and back (torticollis, protrusion of the tongue, facial grimacing, oculogyric crisis, opisthotonus, truncal dystonia and laryngeal spasm) vs seizure
Onset 24-48hrs
Risk factor- young male
Rx –biperiden 2mg IM/IV, benzodiazepine if necessary, if c/o pain analgesia
Stop neuroleptic until symptoms full resolution
Explain parkinsonism
Parkinsonism –bradykinesia, rigidity, tremor
Onset-weeks or months
Common in older pts
Rx - reduce dose- lowest effective dose
Prescribe anticholinergic orphenadrine 50-150mg
Explain akathisia
Akathisia-motor restlessness vs anxiety
Onset days-weeks
Rx - Reduce dose, Add anticholinergic if necessary
Explain tardive dyskinesia
Tardive dyskinesia- syndrome of choreoathetoid and or other involuntary movements, usually of face, lips and tongue +/- arms legs and trunk
Onset-usually >6/12
MOA-? Excess dopamine
Rx- PREVENTION N.B. lowest effective dose for the shortest time - Gradually withdraw , Consider changing to atypical antipsychotics (less tendency for EPSEs)
explain Neuroleptic malignant syndrome
Neuroleptic malignant syndrome-Rare BUT mortality >10%
Aetiology unknown-?dopamine blockade in hypothalamus
Onset –usually weeks but can occur after 1st dose
Risk- ↑ambient temp, dehydration, intercurrent mildly febrile illness, catatonia
Presents with
-Hyperpyrexia
-Sweating
-Unstable blood pressure
-Changes in LOC (stupor or catatonia like state)
-Muscle rigidity
Lasts 5-7 days, longer if depot prep used
Advantages and disadvantage of atypical neuroleptics & uses
Newer and expensive
Less EPSEs (not devoid of EPSEs), prolactin effects, ↑weight gain
Clozapine EDL- reserved for treatment resistant psychosis
Major s/e agranulocytosis & neutropenia
Associated with QT prolongation
Special populations
Pregnancy or lactation
- No randomised controlled trials
- All neuroleptics cross the placenta
- Phenothiazines are excreted in breast milk-behavioural changes in infants
Children
- Use only if necessary as EPSEs can occur after first dose
Elderly
- More susceptible to cardiovascular side effects and anticholinergic side effects
Hepatic diseases
- dose adjustment may be needed
Causes of treatment failure
Low efficacy rate!!!!! 40-60%
Inter and intraindividual variability
Under dosing- lowest EFFECTIVE dose
Malabsorption- change to depot preparation
Drug interactions
Wrong diagnosis- Rx underlying cause e.g. brain tumours
Non-compliance
- Lack of insight-consider depot preparation vs tablets
- Adverse effects- consider changing classes
