Schizophrenia Flashcards
Haloperidol
- typical antipsychotics
- preferred for acute schizophrenia
- greater risk of Neuroleptic Malignant Syndrome (NMS)
- D2 > 5HT2A»_space; muscarinic, H1, a-adrenergic
> less epileptogenic
> few autonomic effect
> less jaundice
> does not cause weight gain
- parenteral formulation for IM use in acute case available
Chlopromazine (CPZ)
- typical antipsychotic
- sedative effect promptly, antipsychotic takes weeks
- tolerance to sedative, but not for antipsychotic
- greater risk of Neuroleptic Malignant Syndrome
Chlopromazine
- effect for psychotic & non psychotic
Effect for psychotic:
1. reduce anxiety/ irrational behaviour/ aggressiveness
2. suppress positive symptoms (hallucination/ delusions/ hyperactivity)
3. disturbed thought normalized
Effect for non psychotic:
-> neuroleptic syndrome
- indifference to surrounding/ emotional flattening
- reduction in initiative
- spontaneous movements minimized
- tendency to go off to easily arousable sleep
Name the 3 adverse effects of high potency typical antipsychotics
- exaggeration in negative symptoms - due to dopamine suppression in mesocortical pathway
- extrapyramidal symptoms (EPS) - blockade in nigrostriatal pathway
- Hyperprolactinemia - block tuberoinfundibular pathway (galactorrhea, gynaecomastia, reduced libido, amenorrhea)
State effect of D2 antagonism with typical antipsychotics on prefrontal cortex
- in mesocortical pathway
- VTA to ventromedial PFC
- lack of emotion/ interest/ motivation/ depressed mood - VTA to dorsolateral PFC
- cognitive side effects/ deficient in executive functioning
EPS
- symptoms and treatments
- acute dystonia: muscle spasm
-> anticholinergic (benzatropine) - akathisia: motor restlessness
-> anticholinergic (BZD: clonazepam, diazepam) - Pseudo- Parkinsonism: rigidity, tremor, hypokinesia
-> change to atypical agent, antiparkinsons drug - Tardive dyskinesia: purposeless involuntary facial and limb movements
-> due to upregulation of D2 receptors after chronic receptor blockade
Neuroleptic Malignant Syndrome
- cause
- symptoms
- treatment, drug
- due to high doses of potent agent
- marked rigidity, hyperthermia, immobility, semiconsciousness, confusion
-> syndrome lasts 5 days after drug withdrawal and may be fatal - neuroleptic stopped + symptomatic treatment
- intravenous dantrolene
- large doses of bromocriptine
- greater risk in typical antipsychotics
Advantages of atypical antipsychotics
- lower risk of EPS
- reduce hyperprolactinemia
- improvement on negative symptoms
due to:
- high affinity for 5HT2a/ 5HT2a antagonism
- rapid dissociation from D2 receptors in presence of dopamine
- efficacy in resistant schizophrenia
Clozapine
- most effective drug for refractory schizophrenia
- rare tardive dyskinesia & prolactin not rise
- agranulocytosis / other blood dyscrasias -> weekly monitor of leukocyte needed
- weight gain, hyperlipidemia, precipitation of diabetes
- high dose -> seizure in nonepileptics
Risperidone
- more potent D2 blocker than clozapine
- postural hypotension (a1 & a2 blockade)
- prolactin rise disproportionately
- frequent agitation
- increased risk of stroke in elderly
Olanzapine
- weak D2 blockade
- potent antimuscarinic -> dry mouth and constipation
- more epileptogenic
- metabolic symptoms: wg, impair glucose tolerance/ diabetes, elevate serum triglyceride -> discourage its use
Quetiapine
- new short acting atypical
- twice daily dosing
- low D2 blocking -> EPS and hyperprolactin minimal
- quite sedating, major dose given at night -> help psychotic patient who can’t sleep well
- postural hypotension
- efficacy in acute mania and bipolar depression
- interact with macrolides, anti fungals, anticonvulsants
Aripiprazole
- unique
- partial agonist at D2 and 5HT1a
- antagonist at 5HT2
- long acting
- Eps, hyperprolactinemia, hypotension not significant
- little tendency to wg, rise in blood glucose
- frequent side effects:
- nausea/ dyspepsia/ constipation/ light headedness
Explain weight gain due to antipsychotics
- antagonize H1 -> excessive eating and food craving
- antagonizing muscarinic -> reduce pancreatic insulin
- indirectly affect adrenergic -> hyperglycemia, reduced lipolysis
Name interactions of antipsychotics
- potentiate all CNS depressants - hypnotics, anxiolytics, alcohol, opioids, antihistaminics => overdose symptoms
- block action of levadopa, direct dopamine agonist in parkinsonsm
- enzyme inducers (anticonvulsants, barbiturates) -> reduce blood level of neuroleptics
- antihypertensive action of clonidine, methydopa reduced -> due to central a adrenergic blockade
