Stemetil Md Uses
Boyan Atanaschev
Prochlorperazine, also known as compazine, is a piperazine phenothiazine and first-generation antipsychotic drug that is used for the treatment of severe nausea and vomiting, as well as short-term management of psychotic disorders such as generalized non-psychotic anxiety and schizophrenia.Label It mainly works by depressing the chemoreceptor trigger zone and blocking D2 dopamine receptors in the brain. It was shown to also block histaminergic, cholinergic and noradrenergic receptors.9 Prochlorperazine was first developed in the 1950s 11 and was first approved by the FDA in 1956. Although newer antiemetic agents such as 5-HT3 antagonists are more heavily promoted, prochlorperazine is still widely used in nausea and vomiting.10
Indicated for the management of manifestations of psychotic disorders, such as schizophrenia and generalized non-psychotic anxiety. The use of prochlorperazine for the management of generalized non-psychotic anxiety is typically not a first-line therapy and should be limited to doses of less than 20 mg per day or for shorter than 12 weeks.Label,8
Off-label uses include use in emergency settings for adult and pediatric migraines. The American Headache Society recommends the use of prochlorperazine as the first-line medication in this setting. In pediatric migraines, a non-steroidal anti-inflammatory agent is often used in combination with dopamine antagonist.9
Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons.10 It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting.3 Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors.1,9 The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well.10 Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics.12 Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.9
The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its anti-dopaminergic effects. Prochlorperazine blocks the D2 dopamine receptors in the brain, which are somatodendritic autoreceptors. Inhibition of D2 receptor signaling results in the blockade of postsynaptic dopamine receptors in the mesolimbic system 11 and an increased dopamine turnover. Nausea and vomiting are proposed to arise from peripheral or central stimulation of serotonin type 3 (5-HT3) and dopamine type 2 receptors, the predominant receptors expressed at the chemoreceptor trigger zone (CTZ).6,11 Prochlorperazine exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D2 dopamine receptors in the CTZ.3.
Following oral administration, prochlorperazine is reported to be well absorbed from the gastrointestinal tract. The onset of pharmacological action is about 30 to 40 minutes following oral administration and 10 to 20 minutes following intramuscular administration. The duration of action for all routes is about 3 to 4 hours.12 Following oral administration in healthy volunteers, the mean oral bioavailability was about 12.5%. In these patients, the time to reach the peak plasma concentrations was about 5 hours. Repeated oral dosing resulted in an accumulation of prochlorperazine and its metabolite. Following multiple twice daily dosing, the steady state of prochlorperazine was reached by 7 days.1
In a preliminary pharmacokinetic study involving healthy volunteers, the mean apparent volume of distribution following intravenous administration of 6.25 mg and 12.5 mg prochlorperazine were approximately 1401 L and 1548 L, respectively.4 Prochlorperazine is reported to be distributed to most body tissues with high concentrations being distributed into liver and spleen.12 There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.Label
Prochlorperazine undergoes hepatic metabolism involving oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid.13 The oxidation reaction is mediated by CYP2D6.3 N-desmethyl prochlorperazine was detected in the plasma1, as well as prochlorperazine sulfoxide, prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, following oral and buccal administration.5 Prochlorperazine may enter the enterohepatic circulation.12
Oral LD50 in rats is 750 mg/kg. Intraperitoneal and subcutaneous LD50 in mice are 191 mg/kg and 320 mg/kg, respectively.MSDS In placebo-controlled trials, there were increased incidences of mortality in elderly patients with dementia-related psychosis receiving antipsychotic medications. The risk of death in drug-treated patients was about 1.6 to 1.7 times that of placebo-treated patients. Deaths were largely resulting from cardiovascular, such as heart failure and sudden death, or infectious, such as pneumonia, conditions.Label Due to its antagonist action on dopamine receptors, prochlorperazine is associated with a risk for developing extrapyramidal symptoms such as tardive dyskinesia, which is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements. This risk is also conferred on other antipsychotic agents that block dopamine receptors. It is proposed that increased duration of the drug treatment is likely thus increased total cumulative dose of antipsychotic drugs administered to the patient leads to increased risk for developing the syndrome and the likelihood that it will become irreversible. As with other antipsychotic agents, prochlorperazine is associated with a risk for causing neuroleptic malignant syndrome (NMS), which is a potentially fatal symptom complex, which is manifested as hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability.
There is no known antidote for prochlorperazine thus overdose treatment should be supportive and symptomatic. Overdose of prochlorperazine may produce dystonic reactions that involve extrapyramidal mechanism. To reduce these symptoms, antiparkinsonism drugs, barbiturates, or diphenhydramine may be used. Symptoms of central nervous system depression, such as somnolence or coma, may also be observed. Amphetamine, destroamphetamine, or caffeine and sodium benzoate may be used to induce stimulatory effects. In contrast, agitation and restlessness may also be seen in case of overdose. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever, and autonomic reactions such as hypotension, dry mouth and ileus. Hypotension can be responded with the standard measures for managing circulatory shock.Label
In a rat developmental or reproductive toxicity study, abnormalities in both the reproductive measures and neurobehavioral testing were observed following administration of 25 mg/kg of prochlorperazine.13
As the use of antipsychotic agents during the third trimester of pregnancy is associated with a risk for extrapyramidal and/or withdrawal symptoms following delivery, the use of prochlorperazine in pregnant patients is generally not recommended and it should be limited after careful consideration of the potential benefit of drug therapy justifying the potential risk to the fetus. Caution should be exercised when prochlorperazine is administered to a nursing mother. While lower doses of prochlorperazine is reported to be safe for elderly patients, caution is still advised, especially those with higher susceptibility to hypotension and neuromuscular reactions.Label
This medication is used to treat severe nausea and vomiting from certain causes (for example, after surgery or cancer treatment). Prochlorperazine belongs to a class of drugs known as phenothiazines.This medication is not recommended for use in children younger than 2 years or in children going through surgery.
The dosage is based on your age, medical condition, and response to treatment. In children, the dosage may also be based on weight. Do not increase your dose or take this medication more often than directed.
Tell your doctor if your condition lasts or gets worse. Side Effects Drowsiness, dizziness, lightheadedness, blurred vision, constipation, or dry mouth may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.
Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).
A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. Warnings There may be a slightly increased risk of serious, possibly fatal side effects (such as heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication with the doctor. Precautions Before taking prochlorperazine, tell your doctor or pharmacist if you are allergic to it; or to other phenothiazines (such as chlorpromazine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
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