1) Anticholinergic effects are common. Extrapyramidal effects such as dystonia, dyskinesia, akathisia, torticollis, akinesia, chorea, tremor, and rigidity are fairly common. Oculogyric crisis and opisthotonus are rare. Other abnormalities seen with phenothiazine use include priapism, sexual dysfunction, elevated prolactin levels, hypoglycemia, and hyperglycemia. More serious but relatively rare effects that may be seen in therapeutic overdose include hepatic disease, aplastic anemia, and neuroleptic malignant syndrome. Phenothiazines may also cause QT prolongation, which may lead to dysrhythmias even at therapeutic doses.

1) MILD TO MODERATE TOXICITY: Anticholinergic effects are common and may include sedation, tachycardia, dry mucus membranes, mydriasis, urinary retention, and constipation.
2) SEVERE TOXICITY: Effects can include severe CNS depression or coma, respiratory depression, pulmonary edema, failure of airway reflexes, agitation, and seizures. Other severe effects can include temperature dysregulation with hypothermia or hyperthermia (more common), and hypertension or hypotension (more concerning). Overdose patients have suffered cardiac arrest and sudden death. Dysrhythmias such as ventricular tachycardia may occur, and may progress to torsades de pointes or ventricular fibrillation. Neuroleptic malignant syndrome is a rare but life-threatening occurrence that may happen in both therapeutic use and overdose. Other serious effects that can be seen in both therapeutic and overdose exposure include hepatic disease such as cholestatic jaundice or a mixed cholestatic and hepatocellular jaundice and hematologic abnormalities including anemia and agranulocytosis.

1) In mild to moderate toxicity, supportive care is the mainstay of treatment. Treat extrapyramidal effects with anticholinergics (diphenhydramine 25 to 50 mg IV or orally, or benztropine 1 to 2 mg IV or orally) or benzodiazepines (diazepam 5 mg IV or orally or lorazepam 2 mg IV). Treat agitation with benzodiazepines. If urinary retention is severe, insert a Foley catheter.

1) Patients with severe CNS depression require endotracheal intubation. Treat hypotension initially with IV 0.9% saline, add vasopressors (norepinephrine preferred) if hypotension persists. Control seizures with benzodiazepines, add propofol or barbiturates, if seizures persist. Treat QRS widening with sodium bicarbonate (1 to 2 mEq/kg IV bolus, repeat as necessary, monitor arterial blood gases, maintain pH 7.45 to 7.55). Unstable ventricular dysrhythmias require cardioversion. Treat torsades de pointes with magnesium, overdrive pacing. For neuroleptic malignant syndrome, initial treatment involves the use of intravenous benzodiazepines. Other potential treatments include external cooling, intravenous dantrolene, and oral bromocriptine. Neuromuscular paralysis and endotracheal intubation may be necessary in severe cases. Treat rhabdomyolysis with early aggressive fluid replacement. Consider the use of physostigmine for anticholinergic manifestations, but the vast majority of patients will improve with simple supportive care alone.
2) PARENTERAL EXPOSURE: Parenteral overdose should be managed similarly to oral overdose, except that GI decontamination will not be helpful.
3) DERMAL EXPOSURE: Simple decontaminations with soap and water should be sufficient treatment.

1) PREHOSPITAL: Emesis is not recommended because of the potential for a dystonic reaction or CNS depression and subsequent aspiration. Prehospital activated charcoal may be considered, but only if the patient is awake and cooperative and the ingestion relatively recent (within the past hour). These treatments could lead to more complications such as aspiration or other problems. No significant toxicity would be expected from dermal or ocular exposures, but simple washing or eye irrigation would be reasonable.
2) HOSPITAL: Consider activated charcoal for ingestions that are relatively recent (within the past hour) and if the patient is awake and alert. There is no evidence for the use of multiple doses of activated charcoal. Gastric lavage may be considered for massive overdoses that are relatively recent (within the past hour) but generally is not indicated as severe toxicity is rare.

1) Airway management may be necessary in patients with significant CNS or respiratory depression, or NMS. However, early intubation is usually not mandated for phenothiazine toxicity.

1) There is no specific antidote for phenothiazine toxicity.

1) These drugs generally have large volumes of distribution and/or significant protein binding. Hemodialysis and hemoperfusion are not likely to be helpful after overdose.

1) HOME CRITERIA: Children who inadvertently ingest a therapeutic dose, and an adult who inadvertently ingests an extra dose can be managed at home if asymptomatic.
2) OBSERVATION CRITERIA: Any patients who are symptomatic or with an intentional overdose should be sent to a healthcare facility for observation. Patients may be sent home or cleared for psychiatric evaluation if they are clearly improving or asymptomatic for a period of observation of 4 to 6 hours.
3) ADMISSION CRITERIA: Patients with worsening symptoms or who continue to remain symptomatic even after a period of observation of several hours should be admitted to the hospital. Depending on the severity of their symptoms (such as CNS depression requiring intubation or neuroleptic malignant syndrome), patients may require an intensive care unit admission. Patients should not be discharged from the hospital until they show clear clinical improvement or are asymptomatic.
4) CONSULT CRITERIA: Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear. Patients who are critically ill and requiring intensive care unit admission should have the involvement of a critical care specialist.

1) Pitfalls in managing these patients include not providing sufficiently aggressive supportive care. Consider the possibility of multi-drug overdose. Extrapyramidal effects are likely to recur, patients who develop these should be discharged with several days worth of diphenhydramine or benztropine. Effects after overdose of decanoate formulations will be long lasting.

1) CHLORPROMAZINE: Moderate bioavailability, hepatic metabolism with renal excretion of metabolites. Volume of distribution is 8 to 160 L/kg, protein binding 90% to 99%. Half-life is 6 hours.
2) FLUPHENAZINE: Poor bioavailability, hepatic metabolism, and half-life is 33 hours.
3) MESORIDAZINE: Protein binding 75% to 91%, urinary and fecal elimination, and minor hepatic metabolism.
4) PERPHENAZINE: Poor bioavailability, extensive hepatic metabolism, half-life is 8.4 to 12.3 hours and volume of distribution is 10 to 34 L/kg.
5) PROCHLORPERAZINE: Poor bioavailability, hepatic metabolism, half-life is 6.8 to 9 hours, and volume of distribution is 12.9 to 17.7 L/kg.
6) TRIFLUOPERAZINE: Readily absorbed, hepatic metabolism with renal elimination of metabolites, half-life is 24 hours and protein binding is 90% to 99%.
7) TRIFLUPROMAZINE: Hepatic metabolism with renal excretion of metabolites, and highly protein bound.

1) Patients at extremes of age or hepatic dysfunction may be more sensitive to adverse effects from these medications.

1) These overdoses may be confused with other overdoses that may cause anticholinergic manifestations (eg, antihistamines, certain mushrooms, etc) or other etiologies that may cause altered or depressed mental status.

1) HYPERTHERMIA
2) HYPOTHERMIA

1) HYPERTHERMIA

1) HYPOTENSION

1) MYDRIASIS is common with ingestion of chlorproMAZINE.
2) CORNEAL TOXICITY may occur.

1) LOSS OF GAG REFLEX has been reported.

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) DYSRHYTHMIA

1) WITH POISONING/EXPOSURE

1) CHLORPROMAZINE

1) WITH THERAPEUTIC USE

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE
2) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) Although phenothiazines have been implicated in several cases of congenital malformations (Freeman, 1972; Rafla, 1987), a definite cause-effect relationship has not been established; the incidence of malformations does not appear to be greater than that seen in the general population. Most studies have found phenothiazines to be safe for both mother and fetus if used in low doses during pregnancy (Ayd, 1976; Kris, 1965; Milkovich & Vandenberg, 1976).

1) AMITRIPTYLINE/PERPHENAZINE: CASE REPORT: A mother ingested a combination of amitriptyline and perphenazine in a suicide gesture at 8 days gestation. The infant was born with multiple congenital defects such as microcephaly, "cotton-like" hair with pronounced shedding, cleft palate, micrognathia, ambiguous genitalia, and dermal ridges (Wertelecki et al, 1980).
2) FLUPHENAZINE: CASE REPORT: A mother was treated with doxylamine during the first trimester and fluphenazine enanthate injections throughout pregnancy. She gave birth to an infant with multiple anomalies such as cleft lip and palate, imperforate anus, ocular hypertelorism with telecanthus, hypospadias of penoscrotal type, episodic rapid nystagmoid movements, rectourethral fistula, and poor ossification of frontal bone (Donaldson & Bury, 1982).
3) TRIFLUOPERAZINE: According to manufacturer reports, of 480 women who received trifluoperazine during pregnancy, 87% received trifluoperazine to control nausea and vomiting. The rate of congenital malformation in this group was compared to that of a control group composed of 8472 patients treated by the same obstetricians. Five malformed infants were delivered in the treated group (1.1%), compared with 113 in the control group (1.5%). The rates of abortion and stillbirth were also similar in the 2 groups. There have also been other reports of congenital anomalies such as hydrocephalus, phocomelia of all 4 limbs, a reduction defect of the arm, and transposition of the great vessels of the heart (Corner, 1962; Hall, 1963; Vince, 1969; Moriarty, 1963).
4) PROCHLORPERAZINE: CASE REPORTS: Two cases of congenital abnormalities were reported with prochlorperazine. The first child was born with a below-elbow amputation of one arm with a small atrophic hand attached to the stump. In the second case a mother gave birth to twins; one twin was born with a below-knee amputation of one leg with a rudimentary foot attached to the stump, while the other twin was without defect. In each instance the infant's mothers received prochlorperazine (dose and duration not reported) during the first 12 weeks of pregnancy (Rafla, 1987a).
5) PROCHLORPERAZINE: CASE REPORT: An infant with various birth defects was born to a mother exposed to multiple medications, including prochlorperazine. These birth defects included cleft palate, micrognathia, Wormian bones, congenital heart disease, dislocated hips, absent tibiae, bowed fibulae, preaxial polydactyly of the feet, and abnormal dermal patterns (Ho et al, 1975).
6) PROCHLORPERAZINE: CASE REPORT: A woman was treated for 14 days during the first trimester of pregnancy with prochlorperazine in doses of 5 mg 3 times daily. The drug was discontinued when pregnancy was diagnosed, which was approximately 2 months after her last menstrual period. It was also noted that the patient received concomitant amitriptyline therapy. Subsequently she gave birth to an infant with malformed left arm which upon x-ray examination revealed hypoplasia of the radius and ulnar bones with a vestigial wrist and hand. However, a definite cause and effect relationship was not established in this case (Freeman, 1972a).

1) Maternal use of antipsychotic drugs during the third trimester of pregnancy has been associated with an increased risk of neonatal extrapyramidal and/or withdrawal symptoms (eg, agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) following delivery. Severity of these adverse effects have ranged from cases that are self-limiting to cases that required prolonged periods of hospitalization and ICU care (Prod Info prochlorperazine edisylate IV, IM injection, 2010; Prod Info perphenazine oral tablets, 2010; Prod Info fluphenazine HCl IM injection, 2010; Prod Info chlorpromazine HCl oral tablets, 2010; Prod Info trifluoperazine HCl oral tablets, 2010).
2) CHLORPROMAZINE: CASE REPORTS: Ingestion of 8000 mg of chlorproMAZINE during the last 10 days of pregnancy resulted in the delivery of a lethargic, hypnotic infant (Hammond & Toseland, 1970; Briggs et al, 1998). Administration of chlorproMAZINE (400 to 600 mg/day) to one mother during pregnancy resulted in extrapyramidal dysfunction in a newborn infant (Levy & Wisniewski, 1974).
3) CHLORPROMAZINE, THIORIDAZINE, AND TRIFLUOPERAZINE: CASE REPORT: Extrapyramidal symptoms, including hypertonia, tremor, and abnormal hand posturing, which resolved between 10 and 22 months of age, was reported in an infant maternally exposed to thioridazine, trifluoperazine, and chlorproMAZINE. A second child delivered by the same mother of the above child while treated with a lower dose of chlorproMAZINE developed similar, but milder symptoms (Hill et al, 1966).
4) FLUPHENAZINE: CASE REPORT: Rhinorrhea, upper respiratory distress, emesis, and extrapyramidal movements occurred in an infant exposed in utero to fluphenazine. The symptoms developed 8 hours after the infant was born, and gradually improved over 3 days (Nath et al, 1996).
5) FLUPHENAZINE DECANOATE: CASE REPORT: ChlorproMAZINE up to 1200 mg/day and fluphenazine decanoate up to 100 mg/day were administered to a schizophrenic woman throughout her pregnancy. She also received electroshock therapy and smoked 60 to 80 cigarettes per day. At 39 weeks gestation she gave birth to a normal, healthy infant. Three weeks after birth (6 weeks after the last fluphenazine decanoate injection) the infant developed excessive irritability, choreiform and dystonic movements, and hypertonicity. These were somewhat controlled with diphenhydramine. At approximately 9 months, after gradual withdrawal of the diphenhydramine, no abnormal neurologic signs were apparent. The onset of his symptoms were consistent with a withdrawal syndrome developing after the long-acting effects of fluphenazine decanoate. This case suggests that high doses of phenothiazines should not be given during pregnancy (O'Connor et al, 1981).

1) CHLORPROMAZINE and PROMAZINE cross the placental barrier (Briggs et al, 1998).

1) CHLORPROMAZINE
2) PHENOTHIAZINES
3) PROMAZINE
4) PROMETHAZINE

1) TRIFLUOPERAZINE

1) FLUPHENAZINE: There is insufficient clinical experience with the use of fluphenazine in nursing women to confirm its safety for the infant. Its passage into human breast milk is expected, although neither the drug nor its metabolites have been measured in human milk (Iqbal et al, 2001). Phenothiazines do not accumulate in concentrations high enough to produce clinical adverse effects in breast-fed infants (White & White, 1984; Anon: The American Academy of Pediatrics Committee on Drugs, 1983). There are no documented cases of adverse events in nursing infants exposed through maternal use.

1) GENERAL: Phenothiazines and their metabolites are excreted into breast milk. With therapeutic use, they do not accumulate in concentrations high enough to produce clinical adverse effects in the infant (Ayd, 1973; Knowles, 1965; White & White, 1984a; Anon, 1983); data for overdose are lacking.
2) CHLORPROMAZINE: Breast milk concentrations of chlorproMAZINE following a single dose of 1200 mg were measured in a lactating, psychotic woman (Blacker, 1962). Milk samples were taken 60, 120, and 180 minutes after the dose. The serum concentration of chlorproMAZINE in the mother was 0.75 mcg/mL at 90 minutes; milk levels were barely detectable. The serum chlorproMAZINE concentration was 0.29 mcg/mL at 120 minutes. The authors estimated that the infant would have received only 10 mcg of chlorproMAZINE if 124 mL of milk were ingested. The mother received chlorproMAZINE 1200 mg daily throughout breastfeeding with no abnormality in growth, activity, or development of the infant noted. Another case did report an infant displaying drowsiness and lethargy due to maternal ingestion of chlorproMAZINE (Llewellyn & Stowe, 1998; Chisholm & Kuller, 1997). Placidity, a soporific effect, drowsiness, and lethargy have been reported in breastfeeding infants exposed to chlorproMAZINE via breast milk (Wiles et al, 1978; Ayd, 1973a). Metabolites do not accumulate in concentrations high enough to produce clinical adverse effects in the infant (White & White, 1984).
3) ETHOPROPAZINE is excreted into breast milk, however the amount is too small to affect the nursing infant (JEF Reynolds , 1991).
4) TRIFLUOPERAZINE: One report, based on fewer than 20 subjects, compared trifluoperazine to haloperidol and chlorproMAZINE and suggested that trifluoperazine appeared to be transferred into human breast milk in smaller quantities than the 2 other drugs. Therefore, trifluoperazine may be less likely than those agents to affect infant performance on developmental tests (Yoshida et al, 1998). The American Academy of Pediatrics considers trifluoperazine compatible with breastfeeding (Briggs et al, 1998).

1) PERPHENAZINE: Using data from one lactating mother treated with perphenazine, a milk-to-plasma ratio was estimated at 1.0, corresponding to a dose of 0.1% of the maternal dose available to the nursing infant. No indication of adverse effects was noted in the breast-fed infant, and after 3.5 months of exposure to perphenazine in breast milk, the infant's growth and development were considered normal (Olesen et al, 1990).

1) Monitor acid-base status.

1) Monitor fluid and electrolyte balance, hepatic enzyme concentrations (serum ALK Phos, AST, and ALT), and renal function. Patients with clinical signs of neuroleptic malignant syndrome should be monitored for rising serum CPK concentrations and leukocyte count.

1) Monitor the WBC count in patients with clinical signs of neuroleptic malignant syndrome.

1) CROSS-REACTIVITY: Phenothiazines and phenothiazine metabolites have demonstrated a cross-reactivity with the Syva Emit(R) toxicological Serum Tricyclic Antidepressant Assay (Schroeder et al, 1986).
2) Benitez et al (1986) also demonstrated that phenothiazines gave a false positive result for the Emit Tri-Tox system which is used to test for tricyclics (Benitez et al, 1986).

1) Monitor urine output.

1) Phenothiazines have been reported to impart a pink to red, purple, orange, or rust color to the urine (Wallach, 1978; Baran & Rowles, 1973). This change in urine color is variable among patients.

1) ECG

a) The absence of radiographic findings should not preclude the use of emesis, lavage, or charcoal in the management of ingestion.

a) These are the most useful tests in acute emergency situations. These colorimetric assays utilize combinations of 5 parts of 5% ferric chloride, 45 parts of 20% perchloric acid, and 150 parts of 50% nitric acid solutions as the main reagent.
b) The method involves adding 1 mL of reagent to 10 mL of urine in a test tube: shake gently and check the color produced against a standardized card to differentiate among the various phenothiazine agents.

A) Patients with worsening symptoms or who continue to remain symptomatic even after a period of observation of several hours should be admitted to the hospital. Depending on the severity of their symptoms (such as CNS depression requiring intubation or neuroleptic malignant syndrome), patients may require an intensive care unit admission. Patients should not be discharged from the hospital until they show clear clinical improvement or are asymptomatic.

A) Children who inadvertently ingest a therapeutic dose, and an adult who inadvertently ingests an extra dose can be managed at home if asymptomatic.

A) Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear. Patients who are critically ill and requiring intensive care unit admission should have the involvement of a critical care specialist.

A) Any patients who are symptomatic or with an intentional overdose should be sent to a healthcare facility for observation. Patients may be sent home or cleared for psychiatric evaluation if they are clearly improving or asymptomatic for a period of observation of 4 to 6 hours.

A) Patients with worsening symptoms or who continue to remain symptomatic even after a period of observation of several hours should be admitted to the hospital. Depending on the severity of their symptoms (such as CNS depression requiring intubation or neuroleptic malignant syndrome), patients may require an intensive care unit admission. Patients should not be discharged from the hospital until they show clear clinical improvement or are asymptomatic.

A) Children who inadvertently ingest a therapeutic dose, and an adult who inadvertently ingests an extra dose can be managed at home if asymptomatic.

A) Consult a medical toxicologist or poison center for patients with severe toxicity or in whom the diagnosis is unclear. Patients who are critically ill and requiring intensive care unit admission should have the involvement of a critical care specialist.

A) Any patients who are symptomatic or with an intentional overdose should be sent to a healthcare facility for observation. Patients may be sent home or cleared for psychiatric evaluation if they are clearly improving or asymptomatic for a period of observation of 4 to 6 hours.

1) Emesis is not recommended because of the possibility of a dystonic reaction or CNS depression and subsequent aspiration.

1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) INDICATIONS: Consider gastric lavage with a large-bore orogastric tube (ADULT: 36 to 40 French or 30 English gauge tube {external diameter 12 to 13.3 mm}; CHILD: 24 to 28 French {diameter 7.8 to 9.3 mm}) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes).
2) PRECAUTIONS:
3) LAVAGE FLUID:
4) COMPLICATIONS:
5) CONTRAINDICATIONS:

1) In mild to moderate toxicity, supportive care is the mainstay of treatment. Treat extrapyramidal effects with anticholinergics (diphenhydramine 25 to 50 mg IV or orally, or benztropine 1 to 2 mg IV or orally) or benzodiazepines (diazepam 5 mg IV or orally or lorazepam 2 mg IV). Treat agitation with benzodiazepines.
2) Patients with severe CNS depression require endotracheal intubation. Treat hypotension initially with IV 0.9% saline, add vasopressors (norepinephrine preferred) if hypotension persists. Control seizures with benzodiazepines, add propofol or barbiturates, if seizures persist.

1) Monitor vital signs and mental status.
2) Obtain an ECG and institute continuous cardiac monitoring.
3) Monitor serum electrolytes, renal function, hepatic enzymes and urine output.
4) Specific drug levels are not readily available and clinical correlation to drug levels is often poor.

1) SUMMARY
2) DIAZEPAM
3) NO INTRAVENOUS ACCESS
4) LORAZEPAM
5) PHENOBARBITAL
6) OTHER AGENTS

1) CHOICE OF VASOPRESSORS: Fluid challenge is sufficient for correction of hypotension in most patients. Some reviews recommend avoidance of mixed alpha/beta agonists (epinephrine, dopamine) due to theoretical production of unopposed beta vasodilation, resulting in worsened hypotension (Benowitz et al, 1979). Primary alpha agonists such as norepinephrine or phenylephrine may be more effective. No primary research or case reports in either humans or animals could be found to substantiate this theory.
2) SUMMARY
3) DOPAMINE
4) NOREPINEPHRINE

1) PROLONGED QT: Phenothiazine overdose, may produce prolongation of the QT interval, decreased T wave amplitude, and prominent U waves (Buckley et al, 1995).
2) VENTRICULAR TACHYCARDIA/FIBRILLATION: The major dysrhythmias likely to occur. Unstable rhythms require cardioversion. Lidocaine may also be effective for ventricular dysrhythmias. Sodium bicarbonate may also be effective in treating dysrhythmias and QRS widening (Parsons & Buckley, 1997).
3) ATRIOVENTRICULAR BLOCK: If a high grade atrioventricular block is evident, implant a catheter pacemaker in the right ventricle.

1) Sodium bicarbonate may be effective in treating ventricular dysrhythmias and QRS widening based on experience with other sodium channel blocking drugs (Parsons & Buckley, 1997). Initial dose is 1 to 2 mEq/Kg, repeat as needed to maintain arterial pH 7.45 to 7.55. Monitor ECG and arterial blood gases frequently.

1) LIDOCAINE/INDICATIONS
2) LIDOCAINE/DOSE
3) LIDOCAINE/MAJOR ADVERSE REACTIONS
4) LIDOCAINE/MONITORING PARAMETERS

1) SUMMARY
2) MAGNESIUM SULFATE
3) OVERDRIVE PACING
4) POTASSIUM REPLETION
5) ISOPROTERENOL
6) OTHER DRUGS
7) AVOID

1) ADULT
2) CHILDREN
3) When the dystonia resolves, patient should be put on maintenance doses of Benadryl(R) or Cogentin(R) for two days.

1) Please refer to the NEUROLEPTIC MALIGNANT SYNDROME document for more information.

1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
6) MANNITOL/INDICATIONS
7) RHABDOMYOLYSIS/MYOGLOBINURIA
8) ADVERSE EFFECTS
9) PRECAUTION
10) MONITORING PARAMETERS

a) Blood flow was 160 mL/min and dialysate flow was 600 mL/min. Only 160 mg was eliminated from the plasma compartment during this procedure.
b) The plasma chlorprothixene concentration decreased over 10 mcg/mL to less than 0.1 mcg/mL during the procedure.
c) The calculated elimination half-life was 30 minutes. The patient appeared to improve clinically during the procedure.
d) Prior to hemoperfusion/hemodialysis this patient was lavaged with 10 L of saline and administered charcoal and cathartic "for interruption of enterohepatic circulation". Clinical improvement may have been largely the result of this therapeutic intervention.

a) Following admission, the patient suffered a grand mal seizure. She died 7 hours later from cardiac arrest. Her ECG prior to death showed agonal rhythm; her serum mesoridazine concentration was 0.4 mg/100mL.
b) The second patient ingested approximately 2500 mg of mesoridazine and was found dead within 24 hours of ingestion. Her plasma mesoridazine concentration was 0.3 mg/100 mL. Death was presumed to be due to cardiotoxicity.

a) Despite decontamination efforts, the child lost consciousness within approximately 30 minutes of ingestion, and was unresponsive to stimuli with a blood pressure of 84/62 mm Hg on admission to a hospital another 30 minutes later.
b) Arterial blood gases, electrolytes, and physical exam were normal; the only signs besides altered state of consciousness were weak peripheral pulses and sinus tachycardia.
c) With fluid bolus and supportive care, the child regained consciousness and was alert and comfortable 6 hours postingestion. He was released after 24 hours of observation.

1) ORAL
2) INJECTION

1) The recommended initial dose is 2.5 to 10 mg/day ORALLY or IM in divided doses every 6 to 8 hours (Prod Info fluphenazine HCl IM injection, 2010); oral doses up to 40 mg/day may be required. The recommended maintenance dose is 1 to 5 mg/day ORALLY in single or divided doses (Prod Info FLUPHENAZINE HCl oral film coated tablet, 2010).

1) The recommended initial dose is 12.5 to 25 mg IM OR SUBQ. The recommended maintenance dose is usually 50 mg IM OR SUBQ every 1 to 4 weeks, as needed and tolerated. Doses above 50 mg should be cautiously increased in 12.5-mg increments. MAXIMUM DOSE: 100 mg (Prod Info fluphenazine decanoate injection, 2005).

1) ORAL
2) INJECTION

1) ORAL
2) INJECTION

1) RECTAL SUPPOSITORY: 25 mg rectally twice daily (Prod Info COMPRO(R) rectal suppository, 2010).

1) The typical dosage for prochlorperazine edisylate can range from 5 to 20 mg a day IM or IV, depending on indication. Intravenous single dose should not exceed 10 mg, rate of administration should not exceed 5 mg/min. The MAXIMUM parenteral dose should not exceed 40 mg a day. Patients with schizophrenia have received dosages of 10 to 20 mg IM every 2 to 4 hours; however, more than 3 to 4 doses to control symptoms is rarely necessary (Prod Info prochlorperazine edisylate intramuscular intravenous injection, 2011).

1) ORAL

1) ORAL: The starting dose can range from 1 to 5 mg twice daily. Optimum response is generally achieved with 15 mg or 20 mg daily, although 40 mg a day or more may be required (Prod Info trifluoperazine HCl oral tablets, 2010).

1) LESS THAN 6 MONTHS OF AGE
2) 6 MONTHS TO 12 YEARS OF AGE

1) Safety and efficacy have not been established in pediatric patients (Prod Info SERENTIL(R) oral tablets, injection, oral solution, 2001).

1) LESS THAN 12 YEARS OF AGE: Use is not recommended (Prod Info perphenazine oral tablets, 2010; Prod Info TRILAFON(R) injection, oral tablets, 2002).
2) OVER 12 YEARS OF AGE: May receive the lowest limit of adult dosage (Prod Info TRILAFON(R) injection, oral tablets, 2002).

1) RECTAL

1) INJECTION

1) ORAL TABLET

1) 6 YEARS OF AGE AND OLDER: ORAL: The usual starting dose is 1 mg once or twice daily. Severe symptoms in older children may require doses above 15 mg daily (Prod Info trifluoperazine HCl oral tablets, 2010).

a) 350 mg was lethal in a 4-year-old child (Wallman, 1957). Four deaths were reported in children following 20 to 74 mg/kg (Davis et al, 1968). Adults have survived ingestions of 9.75 g.
b) The acute fatal dose for chlorproMAZINE reportedly ranges from 15 to 150 mg/kg (Parsons & Buckley, 1997).

a) In a review of the literature, inadvertent exposure of 1 to 2 tablets from exposure to medium- (eg, perphenazine) or high-potency (eg, fluphenazine, trifluoperazine) agents which are available at lower strengths, resulted in no serious toxic effects in toddlers. In rare cases, serious toxicity has been observed following 1 to 2 tablets of low-potency agents available at higher strengths, which were exclusively associated with chlorproMAZINE exposure.

a) Berns & Wright (1993) reported a case of a 2.5-year-old boy who survived, experiencing only loss of consciousness, after ingesting 75 to 100 mg of acepromazine which had been prescribed for the family dog. The boy received prompt medical care.
b) Clutton (1985) reported a case of an adult who survived, experiencing only sedation and sinus tachycardia, after ingesting 1.25 g acepromazine (Clutton, 1985).

a) Coma and respiratory arrest developed in a 1-year-old toddler ingesting 200 mg of chlorproMAZINE (Cann & Verhulst, 1960). Adults have survived 9.75 g. Two adults became comatose after 0.8 and 17 g (Cann & Verhulst, 1960).

a) Ingestion of 3.1 g of mesoridazine resulted in ventricular tachycardia, severe hypotension, and cardiac arrest in a 20-year-old woman (Marrs-Simon et al, 1987). With medical treatment, an adult survived an ingestion of 6 g (Niemann et al, 1981).

a) In one instance, workers exposed to 15 to 48 mg/m(3) of phenothiazine dust developed skin irritation as well as discolored hair and fingernails (due to a dyeing effect of this compound). Tolerance to the skin irritation generally developed after 1 to 4 weeks of exposure.
b) In other instances, photosensitization with direct sunlight has been noted. No systemic toxicity has been reported at exposure concentrations associated with hair and fingernail discoloration.

1) CHLORPROMAZINE - Wide inter-patient variation between plasma concentrations and clinical response occurs with chlorproMAZINE (McIntyre & Gershon, 1985; Curry et al, 1970; Sakalis et al, 1972; Sakurai et al, 1980; May et al, 1981). The greatest clinical improvement is seen with chlorproMAZINE plasma concentrations of 100 to 300 ng/mL.

1) GENERAL
2) SPECIFIC SUBSTANCE

1) 5 g/kg (RTECS, 2006)

a) Dose in chlorproMAZINE equivalents and expected physiological effects.

a) In addition, acetophenazine increases the secretion of prolactin and has a marked suppressive effect on the chemoreceptor trigger zone. Acetophenazine also produces peripheral blockade of cholinergic neurons (Gilman et al, 1990).

a) Tablets - 5 milligrams, light orange, in bottles of 100; 10 milligrams, orange, in bottles of 100 and 500; 25 milligrams, yellow, in bottles of 100 and 500 (Prod Info Promace(R), acepromazine maleate, 1988).
b) Another oral formulation comes in 10 and 25 milligram formulations which are imprinted with the strength and are packaged in bottles of 100 and 500 tablets (Prod Info Acepromazine(R), 1988).

a) It is available in No. 500 and No. 1000 bottles to dose 500 and 1000 pounds body weight, respectively (Prod Info Dyrex(R), phenothiazine, piperazine and trichlorfon, 1988).

a) URINE AND MILK may be discolored for several days after exposure to phenothiazine. The discoloration is not necessarily indicative of toxicosis (Beasley et al, 1989).

1) Administration of 2 milligrams/kilogram resulted in a fall in hemoglobin concentration and red cell numbers.
2) Administration of 2 to 4 milligrams/kilogram resulted in tachycardia, hypertension, and depression (Humphreys, 1988).

1) Accidental intracarotid injection of acepromazine can result in disorientation, seizures, and death (Prod Info Promace(R), acepromazine maleate, 1988).

1) Occasionally, a horse treated therapeutically with Dyrex(R) will react with a decreased packed cell volume and hemoglobin concentration, and hematuria or hemoglobinuria within 72 hours of treatment (Prod Info Dyrex(R), phenothiazine, piperazine and trichlorfon, 1988).

1) Treatment included fluid therapy and pentobarbital (4.8 mg/kg) with phenobarbital (520 mg) in repeated doses.
2) These treatments were given as needed, and duration between doses decreased from once every 30 minutes to twice daily over 5 days. The horse was normal on the sixth day and was released.

1) CHLORPROMAZINE/GENERAL - General signs associated with overdosage include acute hypotension, respiratory depression, jaundice, eosinophilia and granulocytosis, and circulatory collapse (Humphreys, 1988).
2) DARBAZINE/GENERAL - Overdosage causes signs referable to both components of Darbazine, including dilated pupils, constipation, nervous depression, rigidity, weakness, tremor, hypotension, torticollis and ataxia (Prod Info Darbazine(R), prochlorperazine and isoproramide, 1988).

1) INDUCTION OF EMESIS is not recommended unless the animal is physiologically capable of it (horse and cattle are not) and ingestion has definitely occurred within the last 20 minutes.

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

1) Sample vomitus, blood, urine, and feces for analysis.

1) GENERAL TREATMENT

1) HYPOTENSION/SHOCK - Establish a large-bore intravenous line and administer fluid therapy. NOREPINEPHRINE is the drug of choice to combat hypotension. Do NOT use epinephrine.
2) SEIZURES -

1) ACEPROMAZINE -
2) PROMAZINE - Granules: Dosage in HORSES: 1.63 to 3.26 grams per 45 kilograms (100 pounds) body weight. One level capful from the container per 300 pounds body weight is a widely used field dosage (Prod Info Promazine(R), 1988).
3) DARBAZINE - Dosage of capsule no. 1 (DOGS): 1 capsule twice daily for dogs of 4 to 15 pounds body weight; 1 to 2 capsules twice daily for 16 to 30 pounds.
4) PHENOTHIAZINE -

1) PHENOTHIAZINE -

A) SPECIFIC TOXIN

A) GENERAL TREATMENT

A) GENERAL TREATMENT

A) GENERAL

A) DIFFERENTIAL DIAGNOSIS

A) GASTRIC DECONTAMINATION

A) SMALL ANIMALS
B) LARGE ANIMALS

A) GENERAL

A) GENERAL

A) GENERAL

A) DOGS/CATS

A) GENERAL TREATMENT

1) CHLORPROMAZINE - Absorption from the gut is both rapid and complete (Humphreys, 1988).
2) PROMAZINE - With oral dosage of granules, the drug takes effect in 45 minutes. Maximal effect occurs in 1 to 2 hours and duration is approximately 4 to 6 hours (Prod Info Promazine(R), 1988).

1) Phenothiazines are oxidized in the liver and excreted in the urine.

1) URINE AND MILK may be discolored for several days after exposure to phenothiazine. The discoloration is not necessarily indicative of toxicosis (Beasley et al, 1989).