Chlorpromazine

 
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More about Chlorpromazine

What is/are Chlorpromazine Tablets?

CHLORPROMAZINE has many different uses. It is used to treat certain mental and behavioral disorders. This medicine is also used to control nausea and vomiting, nervousness before surgery, and hiccups that will not go away. It is also used to treat episodes of porphyria and in combination with other medicines to treat tetanus. This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care providers before I take this medicine?

They need to know if you have any of these conditions:

blood disorders or disease dementia frequently drink alcoholic beverages liver disease Parkinson's disease Reye's syndrome uncontrollable movement disorder an unusual or allergic reaction to chlorpromazine, sulfa drugs, other medicines, foods, dyes, or preservatives pregnant or trying to get pregnant breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking this medicine suddenly. This can cause nausea, vomiting, and dizziness. Ask your doctor or health care professional for advice if you are to stop taking this medicine.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. While this medicine may be prescribed for children as young as 6 months for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

Note: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following:

amoxapine arsenic trioxide certain antibiotics like gatifloxacin, grepafloxacin, sparfloxacin chloroquine cisapride clozapine droperidol ephedrine levomethadyl maprotiline medicines for mental depression medicines to control irregular heart rhythms phenylpropanolamine pimozide pindolol propranolol ranolazine risperidone trimethobenzamide ziprasidone

This medicine may also interact with the following:

barbiturate medicines for inducing sleep or treating seizures, like phenobarbital diuretics local and general anesthetics phenytoin prescription pain medicines warfarin

This list may not describe all possible interactions. Give your health care providers a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What side effects may I notice from this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue breast enlargement in men or women breast milk in women who are not breast-feeding breathing problems changes in vision chest pain confusion, drooling, restlessness dark urine fast, irregular heartbeat feeling faint or lightheaded, falls fever, chills, sore throat seizures stomach area pain uncontrollable movements of the eyes, mouth, head, arms, legs unusual bleeding, bruising unusually weak ot tired yellowing of skin or eyes

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

change in sex drive or performance headache trouble passing urine trouble sleeping

This list may not describe all possible side effects.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress.

You may get drowsy, dizzy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol can increase possible dizziness or drowsiness. Avoid alcoholic drinks.

This medicine can reduce the response of your body to heat or cold. Try not to get overheated. Avoid temperature extremes, such as saunas, hot tubs, or very hot or cold baths or showers. Dress warmly in cold weather.

This medicine can make you more sensitive to the sun. Keep out of the sun. If you cannot avoid being in the sun, wear protective clothing and use sunscreen. Do not use sun lamps or tanning beds/booths.

Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water may help. Contact your doctor if the problem does not go away or is severe.

Where should I keep this medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

Medical uses

Chlorpromazine is classified as a low-potency typical antipsychotic and in the past was used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of bipolar disorder as well as amphetamine-induced psychoses. Low-potency antipsychotics have more anticholinergic side effects such as dry mouth, sedation and constipation, and lower rates of extrapyramidal side effects, while high-potency antipsychotics (such as haloperidol) have the reverse profile.

The use of chlorpromazine and other typical antipsychotics has been largely replaced by newer generation of atypical antipsychotics which are generally better tolerated. Recent global review of data supports its effectiveness as an antipsychotic.

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 aggressive episodes. Resistant and severe hiccups, severe nausea/emesis and preanesthetic conditioning are other uses. Symptoms of delirium in medically hospitalized AIDS patients have been effectively treated with low doses of chlorpromazine.

Adverse effects

The main side effects of chlorpromazine are due to its anticholinergic properties; these effects overshadow and counteract, to some extent, the extrapyramidal side effects typical of many early generation antipsychotics. These include sedation, slurred speech, dry mouth, constipation, urinary retention and possible lowering of seizure threshold. Appetite may be increased with resultant weight gain, and Glucose tolerance may be impaired. It lowers blood pressure with accompanying dizziness. Memory loss and amnesia have also been reported. Chlorpromazine, which has sedating effects, will increase sleep time when given at high doses or when first administered, although tolerance usually develops. Antipsychotics do not alter sleep cycles or REM sleep.

Dermatological reactions are frequently observed. In fact three types of skin disorders are observed: hypersensitivity reaction, contact dermatitis, and photosensitivity. During long-term therapy of schizophrenic patients chlorpromazine can induce abnormal pigmentation of the skin. This can be manifested as gray-blue pigmentation in regions exposed to sunlight.

There are adverse effects on the reproductive system. Phenothiazines are known to cause hyperprolactinaemia leading to amenorrhea, cessation of normal cyclic ovarian function, loss of libido, occasional hirsutism, false positive pregnancy tests, and long-term risk of osteoporosis in women. The effects of hyperprolactinemia in men are gynaecomastia, lactation, impotence, loss of libido, and hypospermatogenesis. These antipsychotics have significant effects on gonadal hormones including significantly lower levels of estradiol and progesterone in women whereas men display significantly lower levels of testosterone and DHEA when undergoing antipsychotic drug treatment compared to controls. According to one study of the effects on the reproductive system in rats treated with chlorpromazine there were significant decreases in the weight of the testis, epididymis, seminal vesicles, and prostate gland. These effects were accompanied by a decline in sperm motility, sperm counts, viability, and serum levels of testosterone in chlorpromazine rats compared to control rats. It has been reported that a change in either the absolute or relative weight of an organ after a chemical is administered is an indication of the toxic effect of the chemical. Therefore, the observed change in the relative weight of the testis and other accessory reproductive organs in rats treated with chlorpromazine indicates that the drug might be toxic to these organs at least during the period of treatments. Furthermore, the weights of the kidney, heart, liver, and adrenal glands of these treated rats were not affected both during administration of the drug and recovery periods, suggesting that the drug is not toxic to these organs.

Antipsychotic drugs may cause priapism, a pathologically prolonged and painful penile erection, which is usually unassociated with sexual desire or intercourse. Although this effect is rare it is a potentially serious complication that can lead to permanent impotence and other serious complications.

Even therapeutically low doses may trigger seizures in susceptible patients, such as those with an abnormally low genetically determined seizure threshold, presumably by lowering the seizure threshold. The incidence of the first unprovoked seizure in the general population is from 0.07 to 0.09%, but in patients treated with commonly used antipsychotic drugs it reportedly ranges from 0.1 to 1.5%. In overdose, the risk reaches 4 to 30%. This wide variability among studies may be due to methodological differences. The risk is greatly influenced by the individual's inherited seizure threshold, and particularly by a history of epilepsy, brain damage or other conditions. The triggering of seizures by antipsychotic drugs is generally agreed to be a dose-dependent adverse effect.

Tardive dyskinesia and akathisia are less commonly seen with chlorpromazine than they are with high potency typical antipsychotics such as haloperidol or trifluoperazine, and some evidence suggests that, with conservative dosing, the incidence of such effects for chlorpromazine may be comparable to that of newer agents such as risperidone or olanzapine.

A particularly severe side effect is neuroleptic malignant syndrome, which can be fatal. Other reported side effects are rare, though severe; these include a reduction in the number of white blood cells—referred to as leukopenia—or, in extreme cases, even agranulocytosis, which may occur in 0.01% of patients and lead to death via uncontrollable infections and/or sepsis. Chlorpromazine is also known to accumulate in the eye—in the posterior corneal stroma, lens, and uveal tract. Because it is a phototoxic compound, the potential exists for it to cause cellular damage after light exposure. Research confirms a significant risk of blindness from continued use of chlorpromazine, as well as other optological defects such as color blindness and benign pigmentation of the cornea.

Cardiotoxic effects of phenothiazines in overdose are similar to that of the tricyclic antidepressants. Cardiac arrhythmia and apparent sudden death have been associated with therapeutic doses of chlorpromazine, however they are rare cases. The sudden cardiovascular collapse is attributable to ventricular dysrhythmia. Supraventricular tachycardia may also develop. Patients on chlorpromazine therapy exhibit abnormalities on the electrocardiographic T and U waves. These major cardiac arrhythmias that are lethal are a potential hazard even in patients without heart disease who are receiving therapeutic doses of antipsychotic drugs. In order to quantify the risk of cardiac complications to patients receiving therapeutic doses of phenothiazines a prospective clinical trial is suggested.

Interactions

Chlorpromazine intensifies the central depressive action of drugs with such activity (such as tranquilizers, barbiturates, Benzodiazepines, narcotics, antihistamines, OTC antiemetics). It also intensifies the actions and undesired side effects of antihypertensive and anticholinergic drugs. The combination of chlorpromazine with other antipsychotics may result in increased central depression, hypotension and extrapyramidal side effects, but may enhance the clinical results of therapy. The anti-worm drug (antihelminthic) piperazine may intensify extrapyramidal side effects. In general, all antipsychotics may lead to seizures in combination with tramadol (Ultram). Chlorpromazine may increase the insulin needs of diabetic patients. Chlorpromazine enhances the CNS depressant effects of alcohol.

Chlorpromazine is able to inhibit dextromethorphan 0-demethylation, a selective marker for CYP2D6, in a concentration dependent manner. It inhibits the catalytic activity of cytochrome P450 isoforms. CYP2D6 enzyme is not only important in the metabolism of chlorpromazine and associated antipsychotics but is also important in the metabolism of tricyclic antidepressants and selective serotonin reuptake inhibitors that are commonly prescribed to patients with psychiatric disorders. This may result in significant drug interactions which may put these people at a heightened risk for side effects that may be masked by the positive effects or side effects of antipsychotic drugs themselves. Therefore, drugs that inhibit the enzymes that metabolize chlorpromazine would be expected to cause increases in the concentration of other antipsychotic drugs that are co-administered. These increases in concentration may in turn lead to the development of antipsychotic-induced side effects, developing pharmacokinetic interactions with other antipsychotics and antidepressant drugs that are coadministered. Differential expression of various CYP isoforms in specific brain locations leads to the conclusion that antipsychotic drugs could be metabolized to different products in different regions of the brain. The varying levels of expression of the CYP isoforms between individuals and for each particular antipsychotic as well as the possibility of differential metabolism in the brain provides one possible reason why there is such a wide range of adverse effects and therapeutic effects of chlorpromazine and the other antipsychotic drugs in the population of patients currently using.

As chlorpromazine can enhance the central nervous system depression produced by other CNS depressant drugs, its administration with alcohol results in increased sedative effects and impaired co-ordination. An interaction between phenothiazine and caffeinated beverages has been reported. Addition of coffee or tea to phenothiazine or butyrophenone antipsychotics forms a precipitant in vitro. This finding was of initial concern as many psychiatric patients might drink coffee or tea immediately after receiving oral medication. However in humans caffeine use was only slightly related to antipsychotic levels. These negative findings between in vitro studies and human epidemiological studies can be attributable to the stomach acidity which reverses any precipitation. It still remains unclear whether the caffeine-antipsychotic precipitation phenomenon has any clinical significance. The neurophysiology of this relationship is derived from the fact that cytochrome P450 CYP1A2 isoenzyme is responsible for metabolism of caffeine as well as chlorpromazine, thus they may compete for the isoenzyme. Support of this possible competition of the isoenzyme comes from the observation that high doses of caffeine can cause tremors and restless legs both of which could be mistaken for or could aggravate neuroleptic induced extrapyramidal effects.

Chlorpromazine has been shown to inhibit the human ether-a-go-go related gene (hERG) potassium channels. This is a serious side effect of the drug and could lead to death. When this occurs long QT syndrome (aLQTS) is acquired by the prolongation of the cardiac action potential due to a block in the cardiac ion channels and delayed repolarization of the heart. Patients with aLQTS are exposed to a higher chance of torsade de pointes arrhythmias and sudden cardiac arrest.

Chlorpromazine is notorious for depositing ocular tissues when taken in high dosages for long periods of time. In one specific case a 59 year old schizophrenic man on chlorpromazine therapy with cumulative dosage of 2500 g resulted in multiple white deposits in the endothelium of both corneas. Confocal microscopy revealed significant pleomorphism and polymegethism of endothelial cells. The anterior lens capsules opacities were star- shaped and concentrated in the centre. In this patient chlorpromazine deposited mainly in the corneal endothelium, central anterior lens capsule and epithelial cells. This is common with many patients that receive high dosages of chlorpromazine.

Tolerance and withdrawal

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotic treatment to avoid acute withdrawal syndrome or rapid relapse. While withdrawal symptoms can occur, there is no evidence that tolerance develops to the drug's antipsychotic effects. A patient can be maintained for years on a therapeutically effective dose without any decrease in effectiveness being reported. Tolerance appears to develop to the sedating effects of chlorpromazine when it is first administered. Tolerance also appears to develop to the extrapyramidal, parkinsonian and other neuroleptic effects, although this is debatable.

A failure to notice withdrawal symptoms may be due to the relatively long half life of the drug resulting in the extremely slow excretion from the body. However, there are reports of muscular discomfort, exaggeration of psychotic symptoms and movement disorders, and difficulty sleeping when the antipsychotic drug is suddenly withdrawn, but after years of normal doses these effects are not normally seen.

This article uses material from the Wikipedia article Chlorpromazine, which is released under the Creative Commons Attribution-Share-Alike License 3.0.

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