Antipsychotics Flashcards
What are antipsychotics also known as?
- Neuroleptics
- Antischizophrenic drugs
- Major tranquillisers
What can antipsychotics be used to treat?
- Schizophrenia
- Emesis
- Huntington’s disease
- Depression
What is the most common property of antipsychotics?
Antagonising the actions of dopamine in the brain
What does the dopamine theory involve which causes schizophrenia (i.e what evidence points towards this theory)?
- Amphetamine produces symptoms almost indistinguishable from schizophrenia
- D2-receptor agonists produce similar symptoms in animals and exacerbate symptoms in humans
- Strong correlation between clinical potency of antipsychotics and D2 blocking action
- Increased dopamine content in restricted area of the temporal lobe of schizophrenics (amygdala)
- Increased dopamine synthesis and release in the striatum of schizophrenics
What is the evidence to support the Glutamate theory?
- NMDA receptor antagonist (e.g. phencyclidine and ketamine) produce psychotic symptoms
- Decreased glutamate and receptor density reported in post-mortem schizophrenia brains
- Transgenic mice with decreased NMDA receptor expression show stereotypic schizophrenic behaviours and decreased socialinteractions (respond to antipsychotics)
What is the theory that glutamate and dopamine work together to cause schizophrenia?
- Glutamate and dopamine exert excitatory and inhibitory effects respectively on GABAergic striatal neurons (project to the thalamus and constitute a sensory ‘gate’)
- Too little glutamate or too much dopamine disables the ‘gate’ allowing uninhibited sensory input to reach the cortex
- Excess dopamine could be responsible for the positive symptoms and reduced glutamate for the negative symptoms
What are the different classes of first generation or ‘classical’ antipsychotics?
- Penothiazines (chlorpromazine, fluphenazine, piptiazine)
- Butyrophenones (haloperidol)
- Thioxanthines (flupentixol, zuclopenthixol)
What are the different classes of second generation or ‘atypical’ antipsychotics?
- Benzamides (amisulpide) (selective D2 and D3 receptor antagonist)
- Dibenzodiazepines (clozapine and olanzapine) (very unselective receptor blocking profile)
Others: - Risperidone, paliperidone (mixture of receptor types blocked)
- Quetiapine (alpha adrenoceptor blocker)
- Aripiprazole (Dopamine and 5-HT antagonist)
What is clozapine?
A second generation benzamide antipsychotic (very unselective receptor blocking profile)
How do atypical second generation neuroleptics work / differ from first generation?
- Overcome some of the problems of the classical neuroleptics
- Show efficacy in treatment-resistance patients
- Improve the negative as well as positive symptoms
- No real evidence that they are more effective than first generation at treating positive symptoms
In what generation of antipsychotics are extrapyramidal side-effects more common?
First generation
Distinction between typical and atypical (first and second generation) is based on what?
- Receptor profile
- Incidence of extrapyramidal side-effects
- Efficacy in treatment-resistant group of patients
- Efficacy against negative symptoms
What are the behavioural effects of antipsychotics?
- Apathy and reduced initiative
- Display few emotions, drowsy (can be easily stirred from this)
- Aggressive tendencies inhibited
- Effects are distinct from those produced by hypnotics and anxiolytics
What are common effects of antipsychotics?
- Urinary retention
- Weight gain
- Seizure
- Sedation
- Extrapyramidal symptoms
- Postural hypotension
- Sexual dysfunction
- Arrhythmias and sudden cardiac death
- Dry mouth
What are the two main types of tardive dyskinesia and extrapyramidal motor disturbances?
- Acute, reversible Parkinson-like symptoms (due to block of nigro-striatal dopamine receptors) (regidity)
- Slowly developing tardive dyskinesia (one of the most serious problems with antipsychotics)
What is tardive dyskinesia?
- Involuntary movements of face and limbs
- Appears after onths/years of treatment
- Associated with proliferation of dopamine receptors in the corpus striatum
- Treatment is generally unsuccessful
- Less common with newer antipsychotics
What is an endocrine side-effect associated with antipsychotics?
Increased prolactin secretion by blocking D2 receptors in the pituitary
What are the anti-muscarinic side-effects of antipsychotics?
- Blurring of vision, dry mouth and eyes, constipation
- Can help attenuate extrapyramidal actions
What are the alpha-adrenoreceptor bocking side-effects?
Orthostatic hypotension
What are the H1-receptor blocking side-effects?
Sedative and ant-emetic actions
What are other unwanted side-effects of antipsychotics?
- Neuroleptic malignant syndrome
- Jaundice (chlorpromazine)
- Leukopoenia and agranulocytosis (clozapine usually)
- Diabetes (tubo-hypophyseal pathway disruption)
- Skin reactions (itchy rash)
What is neuroleptic malignant syndrome?
- Antipsychotic side effect
- Rare, but life threatening
- Fever, muscle rigidity, altered mental status, autonomic dysfunction
- Often occurs upon initiation or change of dose
Why is there a huge individual variation to antipsychotics?
- Variety of drug metabolising enzymes and receptors associated with transport of the drug that vary in terms of patient
- Interact with other medications
- Makes it difficult to choose a drug that is both tolerable and effective to patient
What does a high peak plasma concentration of a drug correlate with?
Side-effects (not nessisarily what dose)
How is antipsychotic chosen after a first-episode of schizophrenia?
- Choice of drug should consider side-effect profile
- Titrate to minimum effective dose
- Adjust dose according to response and tolerability within BNF limits
- Evaluate over 6 - 8 weeks
What drug is useful in treating treatment-resistant schizophrenia?
Clozapine
If compliance is an issue how can an antipsychotic be administered?
Compliance aid (injected subdermally or IM or subcutaneously) - drug slowly leaches out into patients plasma
