Antipsychotics Flashcards
Haloperidol
Acts mainly on D2 receptors
Some effects on 5HT2 and alpha-1 receptors.
Negligible effects on D1.
Chlorpromazine and Thioridazine
Block alpha 1 more potently than D2
Block Serotonin 5HT2 receptors relatively strongly.
Affinity for D1 is relatively weak.
Pimozide and Amisulpride
Acts mainly on D2 receptors.
Clozapine
Binds more to D4,5HT2,alpha1, and H1 receptors than D2 or D1 receptors.
Risperidone
Potent in blocking D2 and 5HT2 receptors.
Olanzepine
More potent as 5HT2 receptors antagonists. Lesser potency at D1, D2 and alpha 1.
Quetiapine
Lower potency compound with relatively similar antagonism of 5HT2, D2, alpha 1 and 2 receptors.
Similarity between olanzepine, clozapine and quetiapine?
Inhibits H1 histamine receptors.
Consistent with their sedative properties.
Aripiprazole
Partial agonist effects at D2 and 5HT1a receptors.
All effective antipsychotics block _____
D2 receptors.
Advantages of atypical antipsychotics
Lower doses, reduced side effects, higher effectiveness especially on negative symptoms, better compliance.
Less chance of extra pyramidal side effects.
Discuss metabolic effects of atypical agents
Aripiprazole 1kg/yr
Olanzepine and Clozapine >6kg/yr
Risperidone and Quetiapine >6kg/yr
Amisulpride 1.5kg/yr
Discuss disadvantages of atypical agents
Risperidone and olanzepine increase risk of stroke when used for behavioral control in dementia.
Olanzepine + Prediabetes increases risk of conversion to type 2 diabetes by 6 fold. From a former 10% chance. Stopping Olanzepine causes 70% to reconvert.
Idiosyncratic toxicity.
Nigrostriatal system
Motor control : difficulty in urinating, rigidity, as seen in Parkinson’s disease.
Mesolimbic system
Behavioral effects - over activity leads to abnormal behaviour in rats.
Tubero-infundibular system
Endocrine control. Dopamine agonists decrease prolactin release. The antagonists effect may stimulate it.
Dopamine Hypothesis
Amphetamine, Levodopa, Bromocriptine and Apomorphine, increased D2 binding in the brain, D2 antagonists control disorder. Evidence of genetic variation in D4 receptors was discovered with some antipsychotics having high affinity for D4. LSD produces hallucinations and behavioural disturbance. Some antipsychotics act on 5HT receptors as antagonists. 5HT has a modulatory effect on dopaminergic neurons.
Modes of action of antipsychotics
Inhibition of D2 with some action of D4
5HT2 receptor blockade (increase negative symptoms)
Histamine blockade H1 ( drowsiness)
Alpha adrenoceptor blockade. (Postural hypotension)
Classes of Antipsychotics
Phenothiazines eg chlorpromazine and pimozide.
Butyrophenone eg Haloperidol
Thioxanthene derivatives eg Thiothixene
Atypical agents eg Aripiprazole, Clozapine, Risperidone, Quetiapine, Amisulpride, Olanzepine.
Autonomic nervous system effects
Loss of accommodation, mouth and difficulty urinating due to muscarinic cholinoreceptor blockade.
Orthostatic hypotension, impotence, failure to ejaculate due to alpha adrenoceptor blockade.
Central nervous system effects
Parkinson’s like symptoms, akathisia and dystonia due to dopamine receptor blockade.
Tardive dyskinesia due to super sensitivity if dopamine receptors.
Toxic confusional state due to muscarinic blockade.
Endocrine system effects
Amenorrhea, galactorrhea, infertility, hyperprolactinemia due to dopamine receptor blockade.
Weight gain due to H1 and 5HT2 blockade.
