Antipsychotics Flashcards
What are the features and clinical uses of Antipsychotics ?
Antipsychotics are also known as;
- Neuroleptics
- Antischizophrenic drugs
- Major tranquillisers
Common property of antagonising the actions of dopamine in the brain
Mainly used in the treatment of schizophrenia and other psychotic illnesses. Some used clinically for other conditions like;
- Emesis
- Huntington’s disease
- Depression
What are the features of Schizophrenia ?
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 symtoms;
- Withdrawal from social contact and flattening of emotional responses
What is the Dopamine Theory behind Schizophrenia ?
Dopamine Theory;
- Amphetamine produces symptoms almost indistinguishable from schizophrenia
- D2 receptor agonists produce similar symptoms in animal 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 (seen in post mortem)
- Increased dopamine synthesis and release in the Striatum of schizophrenics
Dopamine follows the Mesocortical (frontal lobe to the midbrain) and Mesolimbic pathways (from midbrain to Amygdala and hippocampus)
What are the 3 drugs you must know ?!
1st Generation;
- Chlorpromazine (blocks Histamine H1, Cholinergic / muscarinic, alpha adrenergic receptors - pretty much all)
2nd Generation;
- Risperidone (mixture of receptor types blocked, mainly Serotonin)
Dibenzodiazepine;
- Clozapine (blocks Histamine H1 receptor)
How do antipsychotic drugs affect receptors?
They block the dopamine receptor giving a decreased intracellular response
What are the Theories behind Schizophrenia ?
Dopamine Theory & Glutamate Theory
What is the Glutamate Theory ?
Glutamate Theory;
- Glutamate and Dopamine exert excitatory and inhibitory effects respectively on GABAergic striata neurones
- They project to 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 negate symptoms
What are some First Generation (FGA) or ‘Classical’ Antipsychotics ?
First Generation (FGA) or ‘Classical’ Antipsychotics are considered to be Dirty drugs as they don’t just bind to 1 receptor, bind to many other receptors
Examples;
Phenothiazines;
- Chlorpromazine
Butyrophenones;
- Haloperidol
Thioxanthines;
- Flupentixol
- Zuclopenthixol
What are some Second Generation (FGA) or ‘Atypical’ Antipsychotics ?
Second Generation (FGA) or ‘Atypical’ Antipsychotics;
Benzamides;
- Amisulpride (selective D2 and D3 receptor antagonist)
Dibenzodiazepine;
- Clozapine
Others;
- Risperidone, Paliperidone (mixture of receptor types blocked)
- Quetiapine (alpha adrenorecepor blocker)
- Aripiprazole (Dopamine and 5-HT antagonist)
What is the distinction between typical and atypical antipsychotic drugs?
Distinction between typical and atypical groups is not clearly defined but rests on;
- Receptor profile
- Incidence of extrapyramidal side-effects (less in atypical)
- Efficacy in treatment-resistant group of patients
- Efficacy against negative symptoms
What Antipsychotic drugs block which receptors?
Cholinergic (Muscarinic) Receptor;
Particularly;
- Chlorpromazine
- Thioridazine
Alpha Adrenergic Receptor;
Particularly;
- Chlorpromazine
Dopamine Receptor;
All but particularly;
- Thioridazine
- Haloperidol
- Fluphenazine
Serotonin Receptor;
- Clozapine
- Rispiridone
H1 Histamine Receptor;
Particularly;
- Chlorpromazine
- Clozapine
What are some Behavioural Effects of Antipsychotics?
Behavioural effects;
- Apathy and reduced initiative
- Display few emotions, drowsy (can be easily awaken from this)
- Aggressive tendencies inhibited
- Effects are distinct from those produced by hypnotics and anxiolytics
What are common side effects of Antipsychotic drugs?
Side effects;
- Urinary retention
- Weight gain
- Seizure
- Sedation
- Extrapyramidal symptoms
- Postural hypotension
- Sexual dysfunction
- Arrhythmias and sudden cardiac death
- Dry mouth
What are the 2 main types of disturbance side effects you get from Antipsychotic medications ?
- Acute, reversible Parkinson-like symptoms (due to block of nigro-striatal dopamine receptors)
- Slowly developing Tardive Dyskinesia (One of the most serious problems with antipsychotics as they are Irreversible motor base symptoms - Mostly associated with 1st gen)
What are the features of Tardive Dyskinesia?
Tardive Dyskinesia;
- 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
How may anti-psychotic vary in patients ?
Huge difference in individual response to antipsychotics, may have to adjust dose
How do we monitor patients taking Antipsychotic drugs?
At diagnosis we do baseline tests looking at everything then after that patient risk factors affect how often you want to review patients.
How frequently monitor depends on treatment they are on and their risk factors (e.g smoking, etc).
How should you treat a patients First Episode of Schizophrenia ?
- Choice of antipsychotic should consider side-effect profile
- Titrate to minumum effective dose
- Adjust dose according to response and tolerability within BNF limits
- Evaluate over 6-8 weeks
- If effective after 6-8 weeks then continue at established dose
- If not effective after 6-8 weeks then change drug and follow above advice again, review after another 6-8 weeks
- If second drug isn’t effective after 6-8 weeks use Clozapine
- If drug is not tolerated by patient or they have poor compliance either repeat process and pick new drug OR consider a Depot or Compliance aid for patient
