Pharmacology of Psychotic drugs,Pharmacological actions ,Adverse effects,Uses,Drug interactions,Pharmacokinetics.

4. CLASSIFICATION
1.Phenothiazenes:
Chlorpromazine, Triflupromazne,
Thioridazine, Trifluperazine, Fluphenazine.
2.Butyrophenones:
Haloperoidal,Trifluperidol,Penfluridol.
3.Thioxanthenes:
Fluphenthioxol.
4.Other Heterocyclics:
Pimozide, Loxapine.
5.Atypical Anti-psychotics:
Clozapine, Reserpidone, Olanzapine,Quetiapine,
Ziprasidone, Aripiprazole.

5. Mechanism Of Action
Most drugs bind to DA receptors in brain & periphery. DA receptors are a
class of G-PCR.
Of the 5types of DA receptors,D1& D5 are coupled to GS protein &
D2,D3,D4 are coupled to GI protein.
GS protein GI protein.
++ --
Adenyl cyclase Adenyl cyclase
CAMP Levels CAMP Levels
++ Protein kinase -- Protein kinase
Contractions/Excitation Relaxation/Inhibition

7. Typical Antipsychotics act by blocking D2 receptors in mesolimbic system of
brain.
Atypical antipsychotics act by blocking D4 receptors as it has higher affinity
for & also blocks D2 receptors. This partially shows minimal ability to
cause extra-pyramidal effects..
Dopaminergic blockade in the basal ganglia appears to cause Extra-pyramidal
symptoms due to the effect on Nigro-striatal pathways, while that in CTZ it
is responsible for it’s Anti-emetic action.

8. Atypical agents also exerts action through –n of
5-HT Receptors (5-HT2A) IP3/DAG levels  Excitation

9. Pharmacological actions
In normal’s: It’s referred as “Neuroleptic syndrome”-Psychomotor slowing, Emotional
quitening, Tendency to go off to sleep, Reduction in intiative, Minimized spontaneous
movements.
In Psychotics: Reduces behaviour, agitation, Aggresiveness, Controls psychotic
symptomatology.
Anxiety-relieved,
Disturbed thought & behaviour -Normalized.
Delusions, Hallucinations ,Hyperactivity –Suppressed.
Disturbed sleep pattern-Normalized.
Antiemetic.
Blocks Alpha-adrenergic blocking activity, graded
as:
CPZ = Triflupromazine >Thioridizine > Clozapine >
Fluphenazine >Haloperoidal >Trifluperazine
>Pimozide

10. Hypotension, Partial tolerance,
@ High doses-QT prolonged & T suppressed on ECG.
Reduces certain types of Spasticity.
Extrapyramidal effects:
Dystonias, Parkinson lyk symptoms, Akathesia, Tardive dyskinesia (On
Chronic treatment).
As D2 Receptors are blocked on Tubero-hypophyseal pathway&
Stimulates Prolactin secretion Breast swelling , Pain & Lactation
occurs Galoctorrhoea,Gynaecomastia..
Amennorrhoea & Infertility occurs occasionally.
ADH release  Urine volume.
Blurred vision, Xerostomia , IOP, Constipation, Urinary retention.

11. Oral Administration-Absorption in blood stream.
Plasma half life-15-30hrs.
Highly bound to plasma & tissue proteins.
Metabolism-CYP2D6 in liver.

12. Drowsiness, Lethargy, Mental confusion, Tolerance,
Increased appetite, Weight gain,
Postural hypotension, Palpitations, Cardiac arrhythmias.
Blurred vision, Retinal degeneration, Xerostomia , Skin
rashes, Urticaria,Constipation, Urinary hesitancy,
Hypersalivation, Jaundice,
Amenorrhoea, Gynaecomastia, Glactorrhoea, Infertility,
Akathesia, Acute muscular dystonia, Parkinsonism,

13. Neuroleptics potentiate CNS depressants
Neuroleptics
Abolishes
Anti-Hypertensive actions
of Guanethedine ,
Clonidine ,
Methyldopa.
Enzyme Inducers  Reduce blood levels of Neuroleptics.

14. USES