Anti Psychotic drug

                

Antipsychotic drugs: These are the drugs which are used for treatment of psychotic disorders.

Psychosis:

o   Serious distortion of behavior and thought.

o   Insight is absent (capacity to recognize reality)

o   Show perceptions like delusions (false belief) and hallucinations (may be sensory, auditory etc)

Schizophrenia: (Split Personality Disorder): It occurs due to over activity of dopamine in the mesolimbic system. Other neurotransmitter are also involved like serotonin, glutamate and nor epinephrine.

Sign and symptoms of Schizophrenia:

Positive symptoms		Negative symptoms
—  Hallucinations —  Delusions —  Disorganized thought —  Restlessness —  Insomnia —  Anxiety —  Fighting —  Aggression		—  Apathy (loss of interest) —  Loss of insight and volition (cognitive process by which a person decide to do a function) —  Affective flattening —  Poverty of speech —  Social withdrawal —  Lack of motivation —  Blunted effect (reduction in emotional response) —  Anhedonia (lack of pleasure in normal pleasure some events)
Dopamine Pathways:                                   1.Nigrostriatal – Substantia nigra to Caudate/Putamen –  It  Regulates Motor Function 2.Mesolimbic –Ventral tegmental area to Nucleus Accumbens and Amygdala – It Regulates Emotions 3.Mesocortical –Ventral tegmental area to Limbic Cortex –It Regulates Attention/Cognition 4.Tuberohypophysial (tuberoinfundibular pathway) – Arcuate Nucleus of hypothalamus to the median eminence and pituitary gland – Regulates Prolactin Release Of the above four pathways of Dopamine: mesolimbic pathway associated with schizophrenia (overactivity of dopamine)- So when schizophrenia is treated with antipsychotic drug; inhibition of dopaminergic overactivity of mesolimbic pathway is beneficial, inhibition of other pathway is harmful (side effects generate).
Classification of Atipsychotic drugs
Typical Agents		Atypical Agents
1.       Phenothiazines a.       Chlorpromazine b.      Triflupromazine c.       Fluphenazine d.      Trifluoperazine e.      Thioridazine 2.       Butyrophenones a.       Haloperidol b.      Penfluridol c.       Trifluperidol 3.       Thioxanthenes Flupenthixol Thiothixene 4.       Others Pimozide Loxapine		1.       Clozapine 2.       Aripiprazole 3.       Ziprasidone 4.       Risperidone 5.       Olanzapine 6.       Quetiapine 7.       Amisulpride 8.       Zotepine 9.       Asenapine 10.   Sertindole 11.   Lurasidone 12.   Paliperidone 13.   Iloperidone
Mechanism of action:
Typical Antipsychotic: These show there action by blocking D2 receptor (highly) in the mesolimbic system of brain.	Atypical Antipsychotic: These show there action by blocking D2 receptor weakly and 5-HT2 receptor significantly.
Positron Emission Tomography: Level of occupation of dopamine and other receptors in human brain can be estimated with positron emission tomography. Conclusion: —  Occupation of more than 75% of D2 receptors in basal ganglia is associated with risk of acute extrapyramidal dysfunction. —  Typical drugs occupy 70%-75% of D2 receptor in basal ganglia. So commonly associated with extrapyramidal side effects —  Clozapine occupy 40-50% of D2 receptor and 70-90% 5-HT2 receptors of cortical. So less associated with extrapyramidal side effects.
Typical Antipsychotics drugs are also divided into two categories:                                                                         Low potency v/s High potency Low potency (Chlorpromazine,Prochlorperazine,Thioridazine) High potency (Fluphenazine,Haloperidol,Thiothixene, Pimozide) Highly sedative (Chlorpromazine) Less sedative Less extrapyramidal side effects (Thioridazine-least extrapyramidal effects) more extrapyramidal side effects (Haloperidol-maximum extrapyramidal effects More anticholinergic action Low anticholinergic action More adrenergic blocking property Less adrenergic blocking property All are antemetic agent except Thioridazine All are antemetic agent These drugs increase prolactin release- cause galactorrhoea, amenorrhea These drugs increase prolactin release- cause galactorrhoea, amenorrhea Cardiac arrhythmia caused by thioridazine Cardiac arrhythmia caused by Pimozide  Cause weight gain, hyperlipidemia Cause weight gain (no weight gain with Haloperidol), hyperlipidemia
Atypical Antipsychotics drugs action: Ø  Cause less extrapyramidal side effects (Clozapine, Aripiprazole, Quetiapine cause no extrapyramidal effect) Ø  Cause weight gain, hyperlipidemia (except Ziprasidone, Aripiprazole) Ø  Clozapine and  olanzapine develop seizure in non epileptics Ø  Clozapine cause hypersalivation other cause dry mouth Ø  No Prolactin level rise up except Risperidone (Risperidone also show more extrapyramidal side effects other show less) Ø  Clozapine show more sedation than other Atypical Antipsychotics Ø  Extrapyramidal side effects- (develop due to D2 receptor blockade in limbic system),Acute muscular dystonia (develop within hours),Parkinsonism (develop between 1st-4th week of therapy),Akathisia Ø  Tardive dyskinesia,Rabbit like syndrome,Malignant neuroleptic syndrome
Thioridazine- inhibit ejaculation, cause retinal damage, cause caridiac arrhythmia, antiemetic action, least extrpyramidal side effects in typical category Clozapine suppress both positive and negative symptoms Clozapine -Hypersalication/Sialorrhoea Olanzapine –cause more cardiac arrhythmia than others Quetiapine-cause cataract Aripiprazole- partial agonist at D2 and 5-HT1 receptor but antagonist at 5-HT2 receptor Ziprasidone- partial agonist at 5-HT1 receptor Weight gain- with all except Haloperidol, Ziperasidone,Aripiprazole