Психотроптық дәрілер: Хлорпромазин және оның қолданылуы

Antipsychotic medication

Common side effects include movement problems, sleepiness, dry mouth, low blood pressure upon standing, and increased weight. It is on the World Health Organization's List of Essential Medicines. Its introduction has been labeled as one of the great advances in the history of psychiatry. It is available as a generic medication. A 2014 systematic review carried out by Cochrane included 55 trials that compared the effectiveness of chlorpromazine versus placebo for the treatment of schizophrenia. Compared to the placebo group, patients under chlorpromazine experienced less relapse during 6 months to 2 years follow up. No difference was found between the two groups beyond two years of follow up. Patients under chlorpromazine showed a global improvement in symptoms and functioning. The systematic review also highlighted the fact that the side effects of the drug were 'severe and debilitating', including sedation, considerable weight gain, a lowering of blood pressure, and an increased risk of acute movement disorders. They also noted that the quality of evidence of the 55 included trials was very low and that 315 trials could not be included in the systematic review due to their poor quality. They called for further research on the subject, as chlorpromazine is a cheap benchmark drug and one of the most used treatments for schizophrenia worldwide. Chlorpromazine has also been used in porphyria and as part of tetanus treatment. It still is recommended for short term management of severe anxiety and psychotic aggression. Resistant and severe hiccups, severe nausea/emesis, and preanesthetic conditioning are other uses. Symptoms of delirium in hospitalized AIDS patients have been effectively treated with low doses of chlorpromazine.

Chlorpromazine is an antagonist to H1 receptors (provoking antiallergic effects), H2 receptors (reduction of forming of gastric juice), M1 and M2 receptors (dry mouth, reduction in forming of gastric juice) and some 5 HT receptors (different anti allergic/gastrointestinal actions). Because it acts on so many receptors, chlorpromazine is often referred to as a "dirty drug".

+ Pharmacokinetic parameters of chlorpromazine Bioavailability tmax CSS Protein bound Vd t1/2 Details of metabolism Excretion Notes 10–80% 1–4 hours (Oral); 6–24 hours (IM) 100–300 ng/mL 90–99% 10–35 L/kg (mean: 22 L/kg) 30±7 hours CYP2D6, CYP1A2—mediated into over 10 major metabolites. Urine (43–65% after 24 hours) Its high degree of lipophilicity (fat solubility) allows it to be detected in the urine for up to 18 months.

In 1933, the French pharmaceutical company Laboratoires Rhône Poulenc began to search for new anti histamines. In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs. A year later, the French surgeon Pierre Huguenard used promethazine together with pethidine as part of a cocktail to induce relaxation and indifference in surgical patients. Another surgeon, Henri Laborit, believed the compound stabilized the central nervous system by causing "artificial hibernation", and described this state as "sedation without narcosis". He suggested to Rhône Poulenc that they develop a compound with better stabilizing properties. In December 1950, the chemist Paul Charpentier produced a series of compounds that included RP4560 or chlorpromazine. They also found that doses higher than those used by Laborit were required, giving patients 75–100 mg daily. By 1954, chlorpromazine was being used in the United States to treat schizophrenia, mania, psychomotor excitement, and other psychotic disorders. Rhône Poulenc licensed chlorpromazine to Smith Kline & French (today's GlaxoSmithKline) in 1953. In 1955 it was approved in the United States for the treatment of emesis (vomiting). The effect of this drug in emptying psychiatric hospitals has been compared to that of penicillin and infectious diseases. But the popularity of the drug fell from the late 1960s as newer drugs came on the scene. From chlorpromazine a number of other similar antipsychotics were developed. It also led to the discovery of antidepressants. Chlorpromazine largely replaced electroconvulsive therapy, hydrotherapy, psychosurgery, and insulin shock therapy. Chlorpromazine, in widespread use for 50 years, remains a "benchmark" drug in the treatment of schizophrenia, an effective drug although not a perfect one.

Chlorpromazine has tentative benefit in animals infected with Naegleria fowleri, and shows antifungal and antibacterial activity in vitro.

The veterinary use of chlorpromazine has generally been superseded by use of acepromazine. Chlorpromazine may be used as an antiemetic in dogs and cats, or, less often, as sedative before anesthesia. In horses, it often causes ataxia and lethargy, and is therefore seldom used.