Prochlorperazine

373.94

373.94

200-379-4

YHP6YLT61T

DTXSID7023514

C774

Viscous liquid

N - Nervous system

29159020

35

4.6

Solid

1.2±0.1 g/cm3

228 °C

260-275 °C @ Press: 2 Torr

271.2±30.1 °C

1.621

14.96mg/L(24 ºC)

Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

1.18X10-9 mm Hg at 25 deg C (est)

LD50 oral in rat: 1800mg/kg

8.1None

Henry's Law constant = 1.07X10-13 atm-cu m/mol at 25 °C (est)

8.1|pKa = 8.1

183.7 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Minute crystals; Solubility in water: less than 0.1% at 20 °C; slightly soluble in methanol, ethanol; practically insoluble in ether, benzene, chloroform; MP: 228 °C /Prochlorperazine dimaleate/|White to very light yellow crystalline powder; 1 g is soluble in about 2 mL water, in about 1500 mL alcohol; insoluble in ether, chloroform; odorless; solutions are acidic to litmus /Edisylate/|White or pale yellow crystalline powder; almost completely odorless; saturated solution is acidic to litmus; practically insoluble in water and ethanol; slightly soluble in warm chloroform /Dimaleate/|Hydroxyl radical reaction rate constant = 3.52X10-10 cu m/molec-sec at 25 °C (est)

II

8

UN 3261 8/PG 2

3

S26-S36/37/39-S45-S38-S28A-S36-S16

SENSITIVE TO LIGHT.

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Prochlorperazine edisylate injection is physically and/or chemically incompatible with some drugs, but the compatibility depends on several factors (eg, concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine edisylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine edisylate/|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine maleate/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Prochlorperazine dimaleate is included on this list. /Prochlorperazine dimaleate/|For more FDA Requirements (Complete) data for Prochlorperazine (9 total), please visit the HSDB record page.

Engineering controls such as exhaust ventilation are recommended.|Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|Use safety glasses or goggles and protect exposed skin.

May cause irritation /to the eyes, skin, and mucous membranes/. Avoid inhalation. Remove to fresh air. Avoid contact. Flush /eyes/ with copious quantities of water for at least 15 minutes. Avoid /skin/ contact. Flush with copious quantities of soap and water.

**LD50 and Overdose** 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. 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. **Nonclinical Toxicology** 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. **Use in specific populations** 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.

Liver test abnormalities are uncommon during prochlorperazine therapy, perhaps because it is rarely given long term or in high doses chronically. Aminotransferase elevations can occur during therapy, but they are usually mild, asymptomatic and transient and reversible even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to prochlorperazine which resemble the cholestatic liver injury associated with chlorpromazine. The onset of jaundice is usually within 1 to 4 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Immunoallergic features (fever and eosinophilia) occur in some cases, but they are usually mild and self-limited; autoantibodies are rare. Liver biopsy typically shows a cholestatic hepatitis. Importantly, prochlorperazine jaundice can be prolonged and has been associated with rare cases of vanishing bile duct syndrome (Case 1) that can be fatal or ultimately require liver transplantation.

Chlorpromazine and some other antipsychotic drugs ... may block antihypertensive effects of guanethidine. /Phenothiazines/|Chlorpromazine is used concurrently with meperidine to enhance its analgesic effect. ... Prochlorperazine...reported to interact with meperidine.|Benztropine is useless in treating tardive dyskinesia caused by chlorpromazine & possibility exists that it contributes to this adverse effect. ... Other phenothiazines associated with tardive dyskinesia including ... prochlorperazine. Similarly acting phenothiazines would be expected to have capability of producing dyskinesia.|QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/|For more Interactions (Complete) data for Prochlorperazine (30 total), please visit the HSDB record page.

LD50 Rat oral 1800 mg/kg|LD50 Mouse oral 400 mg/kg|LD50 Mouse ip 120 mg/kg|LD50 Mouse sc 400 mg/kg

/AQUATIC SPECIES/ Environmental fates and effects of pharmaceuticals in the aquatic environment have been the focus of recent research in environmental ecotoxicology. Worldwide studies of common over-the-counter pharmaceuticals have reported detectable levels in the aquatic environment, but there are few studies examining impacts on marine habitats. These drugs can affect the functions of various vertebrates and invertebrates. The stability of two pharmaceuticals, cyclizine (CYC) and prochlorperazine (PCZ), in seawater was examined under light and dark conditions, as well as the toxicity of these compounds to larvae of the barnacle Balanus amphitrite, which is a cosmopolitan marine organism found in most of the world's oceans. CYC was very stable under all the tested conditions. On the other hand, PCZ degraded in light but not in the dark, and was more stable in seawater than fresh water. For the barnacle larvae, the LC50 of prochlorperazine was 0.93 microg/mL and the LC50 for CYC was approximately 0.04 microg/mL.

Geriatric patients appear to be particularly sensitive to adverse nervous system (eg, tardive dyskinesia, parkinsonian signs and symptoms, akathisia, sedation), anticholinergic, and cardiovascular (eg, orthostatic hypotension) effects of antipsychotic agents. Because the risk of falling and associated hip fracture in geriatric patients may be increased with use of antipsychotic agents, phenothiazine therapy should be initiated at reduced dosages and such patients observed closely. /Phenothiazine General Statement/

There is limited data on protein binding of prochlorperazine.

Phenothiazines ... may appear in milk of nursing mothers... /Phenothiazines, human, oral, im/

NIOSH (NOES Survey 1981-1983) has statistically estimated that 7,332 workers (6,543 of these were female) were potentially exposed to prochlorperazine in the US(1).

Indicated for the symptomatic treatment of severe nausea and vomiting. 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. 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.|FDA Label

Prochlorperazine is a phenothiazine used primarily as an antiemetic agent. In rare instances, prochlorperazine can cause clinically apparent acute and chronic cholestatic liver injury.

Gastrointestinal Agents; Antipsychotic Agents

Antiemetics; Antipsychotic Agents, Phenothiazine; Dopamine Antagonists|/Prochlorperazine is indicated/ for control of severe nausea and vomiting. /Included in US product label/|/Prochlorperazine is indicated/ for the treatment of schizophrenia. /Included in US product label/|Prochlorperazine is effective for the short-term treatment of generalized non-psychotic anxiety. However, prochlorperazine is not the first drug to be used in therapy for most patients with non-psychotic anxiety, because certain risks associated with its use are not shared by common alternative treatments (eg, benzodiazepines). /Included in US product label/|For more Therapeutic Uses (Complete) data for Prochlorperazine (7 total), please visit the HSDB record page.

/BOXED WARNING/ Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Prochlorperazine maleate is not approved for the treatment of patients with dementia-related psychosis.|VET: Epinephrine may further lower, rather than elevate, blood pressures in animals on this phenothiazine derivatives.|Do not use in patients with known hypersensitivity to phenothiazines.|Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.).|For more Drug Warnings (Complete) data for Prochlorperazine (53 total), please visit the HSDB record page.

Toxic dose: 100 ug/dL /From table/|3. 3= MODERATELY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 0.5-5 G/KG, BETWEEN 1 OZ & 1 PINT (OR LB) FOR 70 KG PERSON (150 LB).

Phenothiazines produce varying degrees of sedation without hypnosis or anesthesia in normal and psychotic patients; however, the drugs potentiate the CNS depressant actions of sedatives, hypnotics, and anesthetics. Tolerance to the sedative effects develops over a period of days or weeks during long-term therapy. /Phenothiazine General Statement/|Tolerance usually develops to the sedative effects of neuroleptics over a period of days or weeks.

Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons. 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. Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors. The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well. 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. 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.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. (See all compounds classified as Antipsychotic Agents.)|Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)|Drugs used to prevent NAUSEA or VOMITING. (See all compounds classified as Antiemetics.)

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. 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.|Prochlorperazine is reported to be mainly excreted via the feces and bile. Low quantities of unchanged prochlorperazine and its metabolite were detectable in the urine.|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. Prochlorperazine is reported to be distributed to most body tissues with high concentrations being distributed into liver and spleen. There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.|The mean plasma clearance (CL) of prochlorperazine following intravenous administration in healthy volunteers was approximately 0.98L/h x kg. The mean renal clearance was about 23.6 mL/h.|Phenothiazines are generally well absorbed from the GI tract and from parenteral sites; however, absorption may be erratic, particularly following oral administration. Considerable interindividual variations in peak plasma concentrations have been reported. The variability may result from genetic differences in the rate of metabolism, biodegradation of the drug in the GI lumen, and/or metabolism of the drug during absorption (in the GI mucosa) and first pass through the liver.|Phenothiazines are highly bound to plasma proteins.|Phenothiazines and their metabolites are distributed into most body tissues and fluids, with high concentrations being distributed into the brain, lungs, liver, kidneys, and spleen. /Phenothiazine General Statement/|Phenothiazines readily cross the placenta. It is not known if the drugs are distributed into milk; however, the size of the molecules and their ability to readily cross the blood-brain barrier suggest that the drugs would be distributed into milk.|For more Absorption, Distribution and Excretion (Complete) data for Prochlorperazine (12 total), please visit the HSDB record page.

Prochlorperazine undergoes hepatic metabolism involving oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid. The oxidation reaction is mediated by CYP2D6. N-desmethyl prochlorperazine was detected in the plasma, as well as prochlorperazine sulfoxide, prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, following oral and buccal administration. Prochlorperazine may enter the enterohepatic circulation.|Most metabolites of phenothiazines are pharmacologically inactive; however, certain metabolites (eg, 7-hydroxychlorpromazine, mesoridazine) show moderate pharmacologic activity and may contribute to the action of the drugs. There is limited evidence to indicate that some phenothiazines (eg, chlorpromazine) may induce their own metabolism. /Phenothiazine General Statement/|Metabolized primarily in liver /by/ oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid; metabolic alterations in side chain may also occur.|After chronic administration of piperazine-substituted phenothiazine drugs ... to rats, tissues contained drug metabolites, in which piperazine ring fission by multiple oxidative n-dealkylation had occurred to give substituted ethylenediamine. Thus, n-[gamma-(2-chlorphenothiazinyl-10)-propyl]ethylenediamine ... from prochlorperazine ...|Yields 2-chloro-10-(3-(4-methylpiperazin-1-yl)propyl)phenothiazine-n-oxide and 2-chloro-10-(3-(4-methylpiperazin-1-yl)propyl)phenothiazine sulfoxide in rats|For more Metabolism/Metabolites (Complete) data for Prochlorperazine (7 total), please visit the HSDB record page.

Following intravenous and single oral dose administration, the terminal elimination half live were 9 and 8 hours, respectively.

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 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). Prochlorperazine exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D2 dopamine receptors in the CTZ..|The principal pharmacologic effects of prochlorperazine are similar to those of chlorpromazine. Prochlorperazine has weak anticholinergic effects, moderate sedative effects, and strong extrapyramidal effects. Prochlorperazine has strong antiemetic activity.|The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/|In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking, and adrenergic activity. The antipsychotic activity of phenothiazines may be related to any or all of these effects, but it has been suggested that the drugs' effects on dopamine are probably most important. It has also been suggested that effects of phenothiazines on other amines (eg, gamma-aminobutyric acid [GABA]) or peptides (eg, substance P, endorphins) may contribute to their antipsychotic effect. Further study is needed to determine the role of central neuronal receptor antagonism and of effects on biochemical mediators in the antipsychotic action of the phenothiazines and other antipsychotic agents. /Phenothiazine General Statement/|Although the exact mechanism(s) of action has not been conclusively determined, phenothiazines have an antiemetic effect. The antiemetic activity may be mediated via a direct effect of the drugs on the medullary chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors in the CTZ. Phenothiazines inhibit the central and peripheral effects of apomorphine and ergot alkaloids. Phenothiazines generally do not inhibit emesis caused by the action of drugs at the nodose ganglion or by local action on the GI tract. /Phenothiazine General Statement/|For more Mechanism of Action (Complete) data for Prochlorperazine (15 total), please visit the HSDB record page.

Cardiovascular monitoring should begin immediately and should include continuous ECG monitoring to detect possible arrhythmias. Treatment may include correction of electrolyte abnormalities and acid-base balance, lidocaine, phenytoin, isoproterenol, ventricular pacing, and defibrillation. Antiarrhythmic agents that can prolong the QT interval (eg, class IA [disopyramide, procainamide, quinidine] or III agents) should be avoided in treating overdosage-associated arrhythmias in which prolongation of QTc is a manifestation. Appropriate therapy (IV fluids and a vasopressor) should be instituted if hypotension occurs; epinephrine, bretylium, or dopamine should not be used. For the management of refractory hypotension, vasopressors such as phenylephrine, levarterenol, or metaraminol may be used. Appropriate therapy should be instituted if excessive sedation occurs; CNS stimulants that may cause seizures should be avoided. If seizures occur, treatment should not include barbiturates because these drugs may potentiate phenothiazine-induced respiratory depression. Hypothermia is common and sometimes difficult to control. In some patients with acute toxicity, exchange transfusions may be useful, but hemodialysis, forced diuresis, hemoperfusion, or manipulation of urine pH is of little value in enhancing elimination of phenothiazines. /Phenothiazine General Statement/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus.|/SIGNS AND SYMPTOMS/ Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.|/SIGNS AND SYMPTOMS/ In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia or CNS stimulation with convulsions followed by respiratory depression may occur; patients with early or mild intoxication may experience drowsiness, restlessness, disorientation, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included shock (eg, ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, bilateral bundle branch block, atrioventricular block, ventricular tachycardia, ventricular fibrillation, torsades de pointes, myocardial depression, agitation, dry skin, nasal congestion, urinary retention, oliguria, uremia, blurred vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, constipation, ileus, dry mouth, vomiting, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, and pulmonary edema, possibly with sudden apnea. /Phenothiazine general Statement/|/SIGNS AND SYMPTOMS/ Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Prochlorperazine maleate is not approved for the treatment of patients with dementia-related psychosis|For more Human Toxicity Excerpts (Complete) data for Prochlorperazine (18 total), please visit the HSDB record page.

Compazine

Prochlorperazine preparations: (AHFS, 2010)|Prochlorperazine Edisylate preparations: (AHFS, 2010)|Prochlorperazine Maleate preparations: (AHFS, 2010)

Compazine /is the/ trademark for a brand of prochlorperazine, as the maleate or the edisylate|Prochlorperazine has questionable utility as an antipsychotic agent... it is rarely employed in psychiatry

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals