Drug terminology.<br />Typical(First generation) antipsychotic.<br />Major tranquilizer- a misnomer.<br />Neuroleptics-prominent neurological side effects (EPS).<br />Fig: Chlorpromazine<br />
Psychosis & Schizophrenia.<br />John Nash.(1928) SydBarret (1946-2006) <br />Nobel Prize Winner in 1994 Rock star.<br />in mathematics.<br />
Psychosis & Schizophrenia.<br />Psychosis : “Cluster of disorders characterized by hallucination and / or loss of contact with reality.”<br />Psychosis disorders : i) Schizophrenia.ii) Schizoaffective disorder.iii) Delusional disorder.<br />Schizophrenia : “Neurological disease that affects a person’s perception,thinking,language,emotionand social behavior.”<br />
Psychosis & Schizophrenia.<br />Symptoms may be classified as :<br />Positive – “attention getter” symptoms i.e. hallucinations, delusions, bizarre behavior, disorganized speech<br />Negative– “crippling” symptoms i.e. apathy, lack of motivation, anhedonia<br />Cognitive - i.e. difficulty with attention, memory, and problem solving<br />Disorganized– i.e. disorganized speech, inappropriate affect<br />
Structure Activity Relationship.<br />Chemical structure of chlorpromazine.(C17H19ClN2S)<br />
Structure Activity Relationship.<br /> The phenothiazinestructure from the basic nucleus of chlorpromazine. <br /> Substitution at position (2) imparts antipsychotic activity <br />Substitution on the nitrogen at position(10) alters potency and adverse effects; the principal substitutions are: aliphatic, piperidine and piperazine.<br />
Pharmacokinetics.<br />Absorption: Readily absorbed from the GI tract.Bioavailability varies <br />due to first-pass metabolism by liver. <br />Volume distribution: 20 L/Kg<br />Protein binding : >90% to plasma proteins,primarilyalbumin.<br />
Pharmacokinetics.<br />Metabolism : Extensively metabolized in the liver and kidney. It is extensively metabolized by cytochrome P450 isozymes CYP2D6(mainly).Hydroxylation at position 3 and 7 of the phenothaizine nucleus. In urine,20% of chlorpromazine and its metabolized are excreted unconjugated in the urine as unchanged drug. The remaining 80% consists of conjugated metabolites.Themejor metabolites are the monoglucuronide of N-dedimethylchlorpromazine and 7-hyroxychlorpromazine.Approximately,37% of the administered dose of chlorpromazine is excreted in urine.<br />
Pharmacokinetics.<br />Route of elimination : Kidney, 37% in urine.<br />Half life :Approximately 30hours.<br />Route of administration: 1.Oral.2.parental.3.Rectal.<br />
Mechanism of Action.<br />Dopamine receptor blockade in mesolimbic-mesocorticaldopaminergic system. The primary therapeutic action of phenothiazines and haloperidol appears to involve blockade of the D2-receptor, which inhibits adenylylcyclase.<br />Cont….<br />
Limitations in treatment with chlorpromazine.<br />No decrease in negative symptoms .<br /> Patients often unable to function in society .<br />Require medication – disease is not cured .<br /> Drop in number of institutionalized patients .<br />No substitute support system provided .<br />
Acknowledgement.<br /> Dr. AnupRahman Sir.<br />Prof.Dr. EhsanulBarri Sir.<br /> Dr. Joan Heller Brown, PhD<br />Special Thanks.<br />Dip<br />Rabby.<br />Tushar.<br />Ramim<br />And all of my friends for giving me the courage to make that path to step ahead.<br /> Ref: -www.drugbank.ca - www.en.wikipedia.org - www.iucr.org<br />
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