Antipsychotics Flashcards
What are antipsychotics also known as?
- Neuroleptics
- Antischizophrenic Drugs
- Major Tranquillisers
What is the common property of antipsychotics?
Common property of antagonizing the actions of dopamine in the brain
When are antipsychotics mainly used?
Mainly used in the treatment of schizophrenia and other psychotic illnesses
What are the clinical features of schizophrenia?
Positive symptoms:
- Delusions
- Hallucinations
- Thought disorders
Negative symptoms:
- Withdrawal from social contact and flattening of emotional responses
Explain the dopamine theory of schizophrenia.
- Amphetamine produces symptoms almost indistinguishable from schizophrenia
- D2- receptor agonists product similar symptoms in animals and exacerbate symptoms in humans
- Strong correlation between clinical potency of antipsychotics and D2 blocking action
- Increase in dopamine content in restricted area of the temporal lone of schizophrenics (amygdala)
- Increase in dopamine synthesis and release in the striatum of schizophrenics
What are the main pathways associated with dopamine in the brain?
- Tuberohypophyseal pathway
- Mesocortical pathway
- Mesolimbic pathway
- Nigrostriatal pathway
Explain the glutamate theory of schizophrenia.
- NMDA receptor antagonists (e.g. phencyclidine and ketamine) produce psychotic symptoms
- Decrease in glutamate and receptor density reported in post-mortem schizophrenic brains
- Transgenic mice with decreased NMDA receptor expression show stereotypic schizophrenic behaviours and decreased social interactions (respond to antipsychotics)
- Glutamate and dopamine exert excitatory and inhibitory effects respectively on GABAergic stratal neurones which 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
Name the first generation or classical antipsychotics with examples.
Phenothiazines:
- Chlorpromazine
- Fluphenazine
- Pipotiazine
Butyrophenones:
- Haloperidol
Thioxanthines:
- Flupentixol
- Zuclopenthixol
Name the second generation or atypical antipsychotics with examples.
Benzamides:
- Amisulpride
Dibenzodiazepines:
- Clozapine
- Olanzapine
Others:
- Risperidone, paliperidone
- Quetiapine
- Aripiprazole
What is the mechanism of action of amisulpride?
(SGA: Benzamide)
Selective D2 and D3 receptor antagonists
What is the mechanism of action of clozapine and olanzapine?
(SGA: Dibenzodiazepine)
Very unselective receptor blocking profile
What is the mechanism of action of Risperidone and Paliperidone?
(SGA)
Mixture of receptor types blocked
What is the mechanism of action of Quetiapine?
(SGA)
a-adrenoreceptor blocker
What is the mechanism of action of Aripiprazole?
(SGA)
Dopamine and 5-HT antagonist
Describe the features of atypical or second generation neuroleptics.
- Overcome some of the problems of the classical neuroleptics
- Show efficacy in treatment-resistant patients
- Improve the negative as well as positive symptoms
(no real evidence that they are more effective than 1st generation in controlling symptoms)
Describe the distinction between typical and atypical groups.
- receptor profile
- incidence of extra-pyramidal side effects (less in SGA)
- efficacy in treatment-resistance group of patients
- efficacy against negative symptoms
What are the behavioural effects of antipsychotics.
- Apathy and reduced initiative
- Display few emotions, drowsy
- Aggressive tendencies inhibited
- Effects are distinct from those produced by hypnotic and anxiolytics
What are the two main disturbances that can occur with antipsychotics?
- Acute, reversible Parkinson-like symptoms : due to block of nigro-striatal dopamine receptors
- Slowly developing tar dive dyskinesia : one of the most serious problems with antipsychotics
Describe tardive dyskinesia associated with antipsychotics.
- Involuntary movement of face and limbs
- Appears after months/years of treatment
- Associated with proliferation of dopamine receptors in the corpus striatum
- Treatment is generally unsuccessful
- Less common with newer antipsychotics
What are the unwanted endocrine action effects associated with antipsychotics?
- Increase in prolactin secretion by blocking D2 receptors in the pituitary
What are the unwanted anti-muscarinic action effects associated with antipsychotics?
- Blurring of vision, dry mouth and eyes, constipation
- Can help attenuate extrapyramidal actions
What are the unwanted a-adrenoreceptor blocking action effects associated with antipsychotics?
- Orthostatic hypotension
What are the unwanted H1-receptor blocking action effects associated with antipsychotics?
- Sedative and anti-emetic actions
List the unwanted effects of antipsychotics.
- Postural hypotension
- Sedation
- Weight gain
- Endocrine actions
- Diabetes
- Autonomic actions (atropine like)
- Extrapyramidal actions
- Jaundice
- Leucopoenia and agranulocytosis
- Skin reactions (itchy rash)
- Neuroleptic malignant syndrome
What antipsychotic drugs can be used to treat acute behavioural emergencies and mania?
Chlorpromazine
Haloperidol
What antipsychotic drugs can be used to treat emesis?
Prochlorperazine
What antipsychotic drugs can be used to treat Huntingdon’s disease?
Olanzapine
Risperidone
Quetiapine
What antipsychotic drug is occasionally used in depression?
Flupentixol
