5. Anti-psychotics Flashcards
Other names for antipsychotics?
– Neuroleptics
– Antischizophrenic Drugs
– Major Tranquillisers
Common property of antipsycotics?
Antagonising the actions of dopamine in the brain.
Schizophrenia
Affects ~1% of the population
– Can occur from an early age
– Can be chronic and highly disabling
– Strongly hereditary
Clinical features:
– Positive Symptoms: Delusions, hallucinations, thought disorders
– Negative Symptoms: Withdrawal from social contact and flattening of emotional responses
What is the dopamine theory of schizophrenia?
– 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
– ↑ dopamine content in restricted area of the temporal lobe of schizophrenics (amygdala)
– ↑ dopamine synthesis and release in the striatum of schizophrenics
What are the 4 dopamine pathways?
Nigrostriatal
Mesocortical
Mesolimbic
Tuberohypophyseal
What is the glutamate theory for schizophrenia?
– NMDA receptor antagonists (e.g. phencyclidine and ketamine) produce psychotic symptoms
– ↓ glutamate and receptor density reported in post- mortem schizophrenic brains
– Transgenic mice with ↓ NMDA receptor expression show stereotypic schizophrenic behaviours and ↓ social interactions
• respond to antipsychotics
– Glutamate and dopamine exert excitatory and inhibitory effects respectively on GABAergic striatal 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
What are the 3 classes for first generations or classical antipsychotics?
• Phenothiazines
– chlorpromazine, fluphenazine, pipotiazine
• Butyrophenones
– haloperidol
• Thioxanthines
– flupentixol, zuclopenthixol
What the 3 groups of second generation or “atypical” antipsychotics?
• Benzamides
– Amisulpride (selective D2 and D3 receptor antagonists)
• Dibenzodiazepines
– clozapine and olanzapine (very unselective receptor blocking profile)
• Others
– Risperidone, paliperidone (mixture of receptor types blocked)
– Quetiapine (α adrenoceptor blocker)
– Aripiprazole (Dopamine and 5-HT antagonist)
Purpose 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
Distinction between typical and atypical groups is not clearly defined, but rests on:
– receptor profile
– incidence of extrapyramidal side-effects
– efficacy in treatment-resistant group of patients
– efficacy against negative symptoms
Receptors that have an affinity for anti-psycotics?
D1 and D2 Alpha-1 H-1 mACh 5-HT2
Hence anti-psychotics antagonise the receptors
Pharmacological Effects of Antipsychotics
Behavioural Effects
– 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 two main negative effects of anti-psycotics?
- Tardive Dyskinesia
- Slower progression
• slowly developing tardive dyskinesia
– one of the most serious problems with antipsychotics - Extrapyramidal Motor Disturbances:
• acute, reversible Parkinson-like symptoms
– due to block of nigro-striatal dopamine receptors
Features of tarditive dyskinesia in anti-psycotics?
– Involuntary movements 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
Endocrine effects of anti-psycotics?
↑ prolac n secre on by blocking D2 receptors in the pituitary
Unwanted effects of anti-psycotics:
Anti-muscarinic action?
– Blurring of vision, dry mouth & eyes, constipation – Can help attenuate extrapyramidal actions
Unwanted effects of anti-psycotics:
α-adrenoreceptor blocking actions
– Orthostatic hypotension
Main use for stopping drugs
Unwanted effects of anti-psycotics
H1-receptor blocking actions
– Sedative and anti-emetic actions
Unwanted side 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
Individual variation to chloropromazine?
Different patients experience different effects at the same dose.
i.e. clinical effect is patient dependent
Pharmacological response to first episode schizophrenia?
Choice of antipsychotic 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
–> EFFECTIVE
Continue at established dose
–> NOT EFFECTIVE
Change drug and follow above advice. If not effective give Clozapine
–> NOT TOLERATED OR POOR COMPLIANCE
Depot or compliance aid given
Which antipsychotics are given for:
Schizophrenia
– both classical and atypical depending on side effects
Which antipsychotics are given for:
acute behavioural emergencies and mania?
– chlorpromazine, haloperidol
Which antipsychotics are given for:
Treatment of emesis?
– Prochlorperazine
