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Chlorpromazine: Trade Name: Thorazine
Chlorpromazine was originally developed to ease anxiety associated with patients before surgery. Henry Laborit, a heart surgeon, was experimenting with phenothiazines to inhibit the autonomic nervous system in his surgery patients. He was looking for something to solve the problem of shock to the human body caused by surgery. Also he wanted to relieve muscle tension in patients, which would make it easier to operate on them. What Laborit needed was a drug that would act on the central nervous system.
Paul Charpentier, a chemist with Specia Laboratories, developed chlorpromazine by splicing a chlorine atom onto a phenothiazine nucleus of a promazine nucleus at the request of Laborit. He then gave samples of the chlorpromazine he created to Laborit to test on his patients before surgery. The intended effect was to make patients euphoric and oblivious to their surrounding environment while the surgery was being performed. Laborit found that it soothed patient s fears but produced no loss in consciousness. It made the patient sleepy and gave them a disinterest in everything going on around them.
Laborit tallied all the effects of the drug on his patients and thought that it might be useful in the psychiatric setting to sooth manic episodes. He eventually persuaded Pierre Deniker, a psychiatrist, to order some chlorpromazine to try on his most agitated and uncontrollable patients. The results were stunning, patients who had stood in one spot without moving for weeks or who had to be restrained because of violent behavior, could now make contact with others and be left without supervision.
Chlorpromazine finally reached the US in 1954 and went on the market in 1955 to change the role of treatment for mental illness forever. The American drug company Smith-Kline purchased the rights to Chlorpromazine and gave it the trade name of Thorazine. Smith-Kline convinced psychiatrists and government institutions that Thorazine was the answer to overcrowding in institutions. The results of use in the institutions was nothing less than miraculous.
Thorazine changed the face of psychiatry by introducing an alternative to talk therapy. At first psychiatrists were hesitant to use the drug. During the fifties some expose`s were done to expose the horrid conditions of mental institutions, mainly looking at the issue of overcrowding. Psychiatrists were in a unique position; they were under fire and had to do something to ease the situation of overcrowding. The only solution was outpatient therapy; the question was how to release patients who were psychotic into the public without adverse side effects. The answer was Thorazine. It allowed psychiatrists to release patients to their own accord with the promise that the drug would ease their psychotic episodes and make them safe to be in public.
Thorazine was considered the new wonder drug of psychiatry. It offered a less aversive treatment then the traditional lobotomies and electroshock treatment for schizophrenia. It reduced the costs in mental institutions as well as relieving the terrible overcrowding. Patients and psychiatrists found a new freedom with the drug by basing therapies on an outpatient basis which was much more convenient than the mental institutions. However, it wasn t long until the drug was misused and overused.
Thorazine was used as an antihistamine at first, and then the word slowly spread about its anti-psychotic nature. Before long it was discovered to relieve all of the positive symptoms of schizophrenia in most of the patients who took the drug. After extended use it started causing Parkinson s disease-like symptoms in patients. Dopamine was already known to relieve some of the symptoms of Parkinson s disease, so it seemed the drugs caused an opposite effect in the brain. Later on when it became possible to radioactively label chemicals, it was found that the two drugs bind to the same receptors in the brain.
Thorazine is administered in four different ways depending on the desired effect: intramuscular, intravenous, oral, or rectal. It is rapidly absorbed by the GI tract and from parenteral sites of injection. Intramuscular injections are used for the quick control of manic episodes. Direct IV injections are used only to control nausea and anxiety during surgery. Oral and rectal doses are used to manage psychotic disorders, behavioral problems, and control of nausea and vomiting. The IM administration is three or four times as potent as the oral and rectal administration. Thorazine is rapidly absorbed but the injections are much quicker.
Depending on administration the half-life of Thorazine is between 3 and 24 hours. When Thorazine is used in long-term therapy the half-life may be as long as two months, however due to the complexity an exact half-life cannot be determined.
Thorazine requires a high dose in order to be therapeutic. The actual effects are not seen until there is extended regular dosing for weeks or even months. Generally an average daily oral dose of 25 to 75 mg for mild cases or 75 to 150mg for more severe cases is given. In some cases the dosage is gradually increased over time to obtain the desired effect on the patient. Once the optimum dosage is obtained, it is maintained as long as necessary for the control of symptoms during the critical phase of the illness. Eventually it will be gradually redused so that the patient can be maintained on the lowest effective dosage.
Thorazine was the first anti-psychotic drug released and is now used as a reference drug in comparison with all other anti-psychotic drugs in use today. Thorazine is the least potent of all other anti-psychotics, which have much longer half-lives (more than 24 hours).
Thorazine has a long list of side effects. The most commonly reported are sedation, dry eyes, blurred vision, hypotension, constipation, dry mouth, and photosensitivity. Some of the acute effects are dystonias, extrapyramidal side effects (akinesia and akathisia), and neuroleptic malignant syndrome. Nonneurological side effects include sedation, anticholinergic effects, postural hypotension, and weight gain. Tardive dyskinesia is also a side effect but only after prolonged usage. Some patients experience sexual dysfunction and gynecomastia (breast swelling). Some of the severe side effects are severe sedation, severe anti-cholinergenic, and severe postural hypotension.
The severity of side effects is dose related, becoming less severe as the dosage is reduced, but some extrapyramidal effects have been seen at low doses. Most of the time the patient tolerates the side effects since they dull in comparison to the nightmare effects of psychosis.
Dystonic reactions are characterized as involuntary muscle spasms, and sustained abnormal positions of body limbs, face and tongue. Dystonic reactions occur early in treatment while feelings of motor restlessness and Parkinson s signs are greater after several weeks. The affected patients neck and jaw may be twisted to one side, making any movement difficult. Sweating and fever may accompany Dystonic reactions. Patients have a hard time swallowing, chewing, and talking. These reactions usually occur within the first 24 to 48 hours of initial treatment and usually stop 24 to 48 hours after the discontinuation of the drug.
Akathasia is a feeling of motor restlessness that has symptoms of agitation, jitteriness, and the overall urge to move. Patients constantly move to relieve the sensation. It usually occurs within 2 to 3 days after initial treatment, but has been known to occur after several weeks of treatment. A reduction in the dosage can alleviate the symptoms; sometimes anti-Parkinson s disease medications are used.
After high doses of Thorazine over extended periods some patients experience drooling, shuffling gait, monotonous speech, and bad posture. Hand trembles and rolling of fingers begins to get worse. These side effects are the most commonly portrayed in mental institutions in the entertainment business.
Tardive dyskinsia can be a fatal side effect. At this point this side effect has no cure and can be permanent. It can occur after long-term treatments or even after discontinuation of use. The risk of developing tardive dyskinsia is higher in patients who receive large doses, elderly patients, and females.
Thorazine can also affect the cardiovascular system. It can direct negative inotropic and quinidine-like actions to the heart. Sudden death has rarely occurred. However, the symptoms usually subside in the first 30 to 120 minutes and the patient can build up a tolerance after continued treatment.
Neuroleptic Malignant Syndrome is another life threatening side effect. The patient has varying levels of consciousness, altered mental status, and autonomic instability. Patients become very rigid and may experience a rapid heartbeat, heavy sweating, and mental states ranging from confusion to coma. This syndrome can also release a chemical that can cause the kidneys to shut down.
Thorazine is the key drug in fighting the horrible effects of psychosis. This medicine isn t the cure but it does lower the symptoms significantly, and can in some cases shorten the course of the disease. The side effects are quite serious despite the therapeutic effects of the drug. However, patients who take Thorazine find that the side effects are easier to endure than the mind-altering state that it cures, in effect most patients don t mind taking the risks involved to feel normal again.
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