Antipsychotic drugs Flashcards
What are the two main classes of drugs?
1) Typical: D2 receptor antagonists but with multiple sites of action
eg. phenothiazines, butyrophenones, cholorpromazine, haloperidol
2) Atypical: serotonin and D2 antagonists
e. g. clozapine, risperidone, aripriprazole
What are the antipsychotic drugs?
- used to control behavioural disorders such as schizophrenia
What are the distinction between typical and atypical antipsychotic drugs?
- not well defined but mainly based on receptor profile, incidence of extrapyramidal side effects (less in the atypical group)
- efficacy against negative symptoms
*other sites of actions may include Alpha1, mAChR, Histamine receptor and other serotonin receptors
What are the symptoms shown from a schizoprenia patient?
1) Positive symptoms: delusions, hallucinations, disorganised thoughts and abnormal behaviours
2) Negative symptoms: blunted emotions, poverty of speech, attention impairment, loss of motivation
3) Mood Symptoms: depression, anxiety, impulse control
4) Cognition: memory, executive functions
What are the causes for schizophrenia?
- not well understood: both environmental and genetic factors
- pregnancy complication: flu? deliver? gestational diabetes?
- stress
- drugs
- disease of hypoglutamatergic or hyperdopaminergic altering input to the cortex
Theory purposed that dopamine might have been the cause leads to schizophrenia
- A disease of hyperdopaminergic dysfuction
- positive correlation seen between D2 receptor blockade and antipsychotic efficacy
Theory purposed that glutamate might have been the cause leads to schizophrenia
- disease of hypoglutamatergic dysfunction
- NMDA antagonists produce psychotic symptoms
- reduced glutamate and glutamate receptor densities found in schizophrenic patients
Theory purposed that 5-HT- DA might have been the cause leads to schizophrenia
- 5-HT2A has important influences on DA pathways
- Atypical antipsychotic drug target serotonin and DA systems= better treatment and side effect profile
-inputs from Raphe (i.e. 5-HT) to dopaminergic cell bodies and terminals
What are the old treatments for schizophrenia?
- insulin induced coma therapy, prefrontal lobotomy, electroconvulsive shock therapy
The main categories of drugs for schizophrenia.
- first generation (typical): chloropromazine, haloperidol, fluphenazine, flupenthixol, clopenthixol
- second generation (atypical): clozapine, risperidone, sertindole, quetiapine, amisulpride, aripiprazole, zotepine
Atypical antipsychotics (D2 and 5HT2 antagonism)
- these are second generation of antipsychotics with improved efficacy and side effects
- antagonise D2 and 5HT2 receptors
Effects of D2 receptor blockade drugs
- mesolimbic: reduces positive symptoms
- mesocortical: increases negative symptoms, cognitive deficits
- nigrostriatal: induces motor side effects (parkinsonism)
- tuberoinfundibular: effects on hormone secretion (hyperprolactinaemia)
= major side effects and high doses can acutely provide behavioural control e.g. haloperidol
Aripiprazole
- partial agonist at D2 receptor and 5-HT2A antagonist
- no mACh receptor efficacy, 5-HT1A and 5-HT2C partial agonists
- moderate affinity for 5-HT transporter, histamine and alpha adrenergic receptors
= partial agonists mean will antagonise D2 receptors when there’s excessive activation (mesolimbic DA hyperactivity); agonise D2 receptors where dopamine is low (mesocortical DA hypoactivity) and prevent total blockade of D2 receptors so conserve some nigrostriatal functionsk
Side Effects from receptor blockade
- D2: prolactin elevation
- M1: anti-muscarinic effects
- H1: sedation, weight gain, dizziness
- alpha 1: hypotension
- 5-HT2C: satiety blockade
What are the extra-pyramidal disturbances of the drugs? (blockade of DA2 receptors in nigrostriatal pathway)
- parkinsonian
- acute dystonia
- akathisia
- tardive dyskinesia
= incidence can be reduced with atypical drugs
