Anti-psychotics Flashcards
List some DDx for schizophrenia?
Organic:
o Vascular: stroke
o Infectious: viral encephalitis, HIV, syphilis, malaria
o Autoimmune: temporal lobe epilepsy, MS, Parkinson’s, Huntington’s, SLE
o Metabolic: hypo/hyperthyroidism, Addison’s disease, hypo/hyperglycaemia, Wilson’s disease,
Cushing’s disease
o Toxin: withdrawal of stimulants, alcohol, cannabis, amphetamines, cocaine, ecstasy, BZDs
o Medication: antidepressants, antiparkinsonian agents, steroids, antihistamines, beta blockers
o Neoplastic: brain tumour
Psychiatric:
o Schizoaffective disorder: meets criteria for schizo and depressive/manic/mixed
o Schizophreniform (schizophrenia < 6 months)
o Brief psychotic disorder
o Bipolar or major depressive disorder with psychotic features
What is the diagnostic criteria for schizophrenia?
Def: chronic debilitating psychotic disorder
Diagnosis: characterised by > 1 month of 2 or more of the following (with at least 1 symptom being delusions, hallucinations or disorganised speech):
o Delusions (fixed false beliefs)
o Hallucinations (sensation without external stimuli)
o Disorganised speech or thought disorder (loss of logical thought process)
o Grossly disorganised behaviours or catatonia
o Negative symptoms: apathy, anhedonia, avolition, blunted affect, and alogia (lack of additional speech content)
Symptoms sometimes categorised into positive (hallucinations, negative (apathy) and cognitive (attention)
Name some risk factors for schizophrenia?
Risk factors:
o Biological relative with schizophrenia
o Obstetric/perinatal complications
o Intrauterine infection
o Inflammation- coeliac disease, thyrotoxicosis, haemolytic anaemia
o Lower socioeconomic class
o Stimulant and hallucinogen drug use
o Family conflict
o Childhood trauma
o Drug use
o Genetic factors: DISC1 (disrupted-in-schizophrenia1), neuregulin-1 (NRG-1),
How is schizophrenia treated?
1st line: atypical (2nd generation) anti-psychotics
- E.g. Amisulpride, Arpiprazole, Olanzapine, Quetiapine, Risperidone, Ziprasidone, Clozapine (not 1st line, used in treatment resistance)
2nd line: typical (1st generation) anti-psychotics
- E.g. Haloperidol, Chlorpromazine
Describe the MOA of 2nd generation anti-psychotics?
Examples: Amisulpride, Arpiprazole, Olanzapine, Quetiapine, Risperidone, Ziprasidone, Clozapine (not 1st line)
• MA: primarily antagonises 5HT2A serotonin receprors and D4 receptors, also block dopamine D2 receptors (weak)
⇒ reduced extrapyramidal SE (by increasing dopaminergic activity in nigrostriatal pathway)
⇒ management of both positive and negative symptoms
• SE: less extrapyramidal SE, more metabolic SE (weight gain, dyslipidaemia, hypercholesterolaemia, hyperglycaemia and T2DM)
- Metabolic SE more common with Olanzapine and Clozapine
• Toxicity: hard to overdose (better safety profile)
Describe the MOA and SE of 1st generation anti-psychotics?
E.g. Haloperidol, Chlorpromazine
o MA: dopamine D2 receptor antagonist -> lowers DA activity -> reduces positive symptoms
o Toxicity: overdose possible (low safety profile)
o SE: extrapyramidal SE prominent (dystonia, akathiasia, pseudo-parkinsonism, tardive dyskinesia), hyperprolactinaemia
What are the general SE of anti-psychotics?
General SE:
- extrapyramidal SE (dystonia, akathisia, pseudo-parkinsonism, tardive dyskinesia/constant movement)
- metabolic syndrome: weight gain, dyslipidaemia, hypercholesterolaemia, hyperglycaemia -> T2DM
- hyper-prolactinaemia (gynaecomastia, glactorrhoea)
- sedation
- cardiac: QT prolongation, orthostatic hypotension
- anti-cholinergic effects with 2nd generation (dry mouth, urinary retention, toxic-confusional state)
- neuroepileptic malignant syndrome (massive DA blockage -> fever, muscle rigidity, autonomic dysfunction)
What SE are of concern with Clozapine use?
Clozapine SE: o Agranulocytosis, neutropaenia o Seizures (lowers threshold) o Myocarditis, tachycardia, cardiomyopathy o Orthostatic hypotension o Anticholingeric o Neurolepileptic Malignant syndrome o Metabolic syndrome
CI: drug-induced agranulocytosis, bone marrow disorders, severe renal/hepatic/cardiac
disease, paralytic ileus, untreated/uncontrolled seizures
Compare Quetiapine with other antipsychotics?
2nd generation antipsychotic
- well tolerated
- metabolic syndrome/weight gain less likely than Olanzapine/Clozapine
- extrapyramidal SE less likely compared to 1st generation
SE (WAACHED mnemonic): weight gain, anti-adrenergic (sedation, hypotension), anti-cholinergic (dry mouth, blurred vision), cardiac (arrhythmia, prolonged QT, cardiomyopathy) hyper-prolactinaemia, extrapyramidal SE (dystonia, parkinsonism), hyperglycaemia, DM, hyperlipidaemia
- Neuroepileptic malignant syndrome (DA blockage, life-threatening)
CI: hepatic disease (reduce dose), elderly (reduce dose)
When is Clozapine used?
Indication: treatment-resistant schizophrenia
(i. e. unresponsive to or intolerant of at least 2 other antipsychotics for 6-12 weeks duration each on optimal doses; development of EPSE).
- Risk: agranulocytosis (1%), neutropenia (2%)
- Epi: used by 12,000 pt in Aus, 19% of pt with schizophrenia
- Prognosis: 50% benefit, esp paranoid and late onset (>20yo) pts
What is agranulocytosis and how do you monitor it?
Definition:
- Granulocyte: white cell with granules (neutrophils, eosinophils, basophils, mast cells)
- Agranulocytosis is acute, severe leukopenia of mostly neutrophils (also include basophils, eosinophils and mast cells) -> increases serious infection risk
Monitoring:
- Bedside: ECG and echo (cardiac function), weight, height, BMI, wast circumference, BP
- FBC (neutrophil count) weekly for 18 weeks, then monthly
- metabolic SE: BSL, fasting lipids
- UEC, LFTs
What are the dopamine pathways?
- Prefrontal cortical: from ventral tegmental area (VTA) to frontal cortex
- Behaviour-related cognition/ executive functions
- Inadequate DA responsible for negative symptoms - Mesolimbic: from ventral tegmental area (VTA) to the nucleus accumbens
- Reward-related cognition
- Aversion-related cognition
- Excessive DA responsible for positive symptoms - Tuberoinfundibular: from arcuate nucleus of hypothalamus to pituitary gland
- Secretion of hormones including prolactin
- Blocked by neuroleptics -> hyperprolactinemia - Nigrostriatal: from substantia nigra pars compacta to the caudate nucleus and putamen
- Motor function
- Reward-related cognition
- Associative learning
- Blocked by neuroleptics, causing extrapyramidal side effect
