pharm of schizophrenia and antypsychotics

what are the 3 drug families of 1st gen typical neuroleptics

1. phenothiazines

2. thioxanthenes

3. butyrophenones

phenothiazines and action

1. chlorpromazine: non-specific binding to A2 adrenoceptors, H1 receptors, mAch receptors and weak affinity for D2

2. trifluoperazine: weak binding to D1 and 2

3. fluphenazine: weak binding to D1 and 2

4. thioridazine: binds to mAch

they all bind and inhibit the receptors

thioxanthenes

flupentixole

butyrophenones

haloperidol: strongest binding affinity for D2

how do typical neuroleptics works and what are their side effects

they work by binding and inhibiting D2 receptors to decrease +ve symtpoms but have no effect on -ve symptoms

• effects is correlated to their binding affinity for D2 receptors

side effects:

1. causes parkinson’s like extrapyramidal symptoms: resting tremor, rigidity and akinesia

2. hyperprolactinaemia

3. orthostatic hypotension

4. chlorpromazine causes aplastic anaemia

5. neuroleptic malignant syndrome syndrome

6. sedation

   1. mAch blocking causes dry mouth, constipation and urinary retention

what are the 2 classes of atypical 2nd gen neuroleptics

1. dibenzazepine derivatives: olanzapine, quetiapine, clozapine

2. benzisoxazole derivative: risperidone, paliperidone, ziprasidone

how do 2nd gen work

weak binding affinity for D2 but also inhibits 5HT action to address -ve and +ve symptoms

side effect:

• less extrapyramidal symptoms due to low D2 affinity

• weight gain

• T2DM and hypercholesterolinaemia

• hyperprolactinaemia

• orthostatic hypotension

• prolonged QT interval

  • agranulocytosis and leukopenia

3rd gen neuroleptic and mechanism

aripiprazole

1. 5HT1A agonist

2. 5HT2A antagonist

3. D2 receptor partial agonist

   1. low [] weak agonist

   2. high[] doesn’t elicit as large of a response as normal agonist → competitive antagonist