Prochlorperazine Adverse Reactions
- agranulocytosis
- akathisia
- aplastic anemia
- blurred vision
- cholestasis
- constipation
- contact dermatitis
- corneal opacification
- diaphoresis
- dizziness
- drowsiness
- dystonic reaction
- ejaculation dysfunction
- eosinophilia
- galactorrhea
- headache
- hyperprolactinemia
- hypertension
- hyperthermia
- hypotension
- hypothermia
- ileus
- impotence (erectile dysfunction)
- insomnia
- jaundice
- leukocytosis
- leukopenia
- libido decrease
- mastalgia
- menstrual irregularity
- mydriasis
- neuroleptic malignant syndrome
- orthostatic hypotension
- pancytopenia
- photosensitivity
- priapism
- pseudoparkinsonism
- retinopathy
- seizures
- sinus tachycardia
- skin hyperpigmentation
- tardive dyskinesia
- thrombocytopenia
- urinary retention
- visual impairment
- weight gain
- withdrawal
- xerostomia
Prochlorperazine Adverse Reactions
The adverse effects of phenothiazines can affect all organ systems and may be attributed either to the drug’s effects on the central and autonomic nervous system, or to hypersensitivity reactions to the drug.
Extrapyramidal symptoms (EPS) occur frequently during treatment with phenothiazines and appear to be the result of D2-receptor blockade. These symptoms occur with greater severity and frequency during high-dose therapy. Extrapyramidal symptoms are categorized as dystonic reaction, akathisia (subjective and objective motor restlessness), and pseudoparkinsonism. Parkinsonian-like symptoms are more common in the elderly, whereas children most often develop dystonic reactions, which can be worsened by acute infections or severe dehydration. Dystonic reactions are seen during the first week of treatment. Akathisia and parkinsonian-like symptoms usually develop several days to weeks into therapy. Dystonia and pseudoparkinsonism usually are easily treated with concomitant benztropine, diphenhydramine, lorazepam, or amantadine. Akathisia may respond to dosage reduction or concomitant administration of a benzodiazepine (usually lorazepam) or propranolol. In rare patients, an alternate antipsychotic may be necessary. The elderly may be especially sensitive to development of neuromuscular adverse effects such as pseudoparkinsonism.
Neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS is characterized by hyperthermia, severe extrapyramidal dysfunction, alterations in consciousness, altered mental status, and autonomic instability (sinus tachycardia, low blood pressure or hypertension, diaphoresis). Increased serum creatine phosphokinase (CPK), acute renal failure, and leukocytosis also have occurred. NMS does not appear to be dose-related. Severe cases have resulted in death 3 - 30 days after the onset of the syndrome. Several predisposing factors may contribute to the development of NMS including heat stress, physical exhaustion, dehydration, and organic brain disease. NMS occurs more frequently in young men. The phenothiazine should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered. Hypothermia and hyperthermia have been reported with phenothiazines independent of the neuroleptic malignant syndrome and may be caused by the effect of the phenothiazine on the hypothalamic control of temperature regulation. Hyperpyrexia and heat stroke unrelated to NMS also have occurred.
Tardive dyskinesia (TD) is characterized by involuntary movements of the perioral region (tongue, mouth, jaw, eyelids, or face) or choreoathetoid movements in the extremities. It can develop during long-term therapy or following discontinuation of phenothiazine therapy, and it is observed more frequently in elderly women. The incidence of TD may be higher in patients with bipolar disorder than with schizophrenia. Some cases can be irreversible. While contradictory evidence exists, it has been suggested that the likelihood of developing TD increases with prolonged treatment and cumulative doses. Although this complication often occurs following prolonged treatment or with administration of high dosages, it also has been reported to occur after short periods of time and with low dosages. Routine monitoring (at 3- to 6-month intervals) of movement disorders is considered the standard practice when using phenothiazines. If signs or symptoms of TD develop, the neuroleptic should be reevaluated and possibly discontinued.
Phenothiazines can cause a variety of CNS effects. Drowsiness occurs occasionally during initial treatment with some phenothiazines. Tolerance usually develops with continued therapy. Dizziness may occur as a result of orthostatic hypotension. Clinicians should closely monitor the elderly for hypotension, especially if parenteral prochlorperazine is used. Other CNS effects reported less frequently include restlessness, insomnia, depression, headache, and cerebral edema. Seizures can occur and are of special significance in patients with preexisting seizure disorders or EEG abnormalities.
Anticholinergic effects of phenothiazines include blurred vision, xerostomia, mydriasis, nausea, adynamic ileus, urinary retention, impotence (erectile dysfunction), and constipation. These effects can be enhanced by the concomitant administration of anticholinergic antiparkinsonian drugs, antidepressants, or other anticholinergic agents. The elderly may be especially sensitive to the development of anticholinergic side effects due to prochlorperazine.
Leukopenia including agranulocytosis is the most common hematologic disturbance that has been reported during phenothiazine administration. Agranulocytosis has occurred rarely and has been associated with combination treatment with other agents. Post-marketing safety experience suggests that the incidence of agranulocytosis may be higher in geriatric patients compared to younger individuals who received prochlorperazine. Other hematologic abnormalities that have been associated with phenothiazine therapy include leukocytosis (usually in association with the neuroleptic malignant syndrome), eosinophilia, thrombocytopenia, pancytopenia, aplastic anemia, and anemia.
Prolonged therapy with phenothiazines can lead to skin hyperpigmentation. Hyperpigmentation generally is restricted to areas of the body exposed to sunlight. Photosensitivity can result, and patients should be warned either to keep out of the sun or to use effective sunscreens (SPF 15+) on exposed areas of the body. Withdrawal of the drug can reverse the effects. Contact dermatitis is also possible in predisposed individuals if they come in contact with liquid dosage forms of phenothiazines.
Phenothiazines can cause ocular changes. Pigmentary retinopathy can occur with or without pigmentary changes in the skin during therapy with phenothiazines. Symptoms of blurred vision, difficulty with nighttime vision, or defective color vision should be investigated promptly. Wearing protective dark glasses can reduce the possibility of this reaction. Phenothiazines have been associated with deposition of fine particles in the lens and cornea, which can lead to corneal opacification and visual impairment.
Liver impairment in the form of cholestasis has been reported rarely with administration of phenothiazines. Jaundice is also possible and may even occur in neonates of mothers who received phenothiazines during pregnancy. Cholestatic jaundice from phenothiazines is generally considered a hypersensitivity reaction.
Adverse cardiovascular reactions that have occurred during antipsychotic therapy include hypotension, hypertension, ventricular tachycardia, ECG changes such as QT prolongation, and other cardiac arrhythmias such as torsade de pointes. Cardiac arrhythmias such as torsade de pointes secondary to antipsychotic therapy have mainly been associated with thioridazine and haloperidol.
Dopamine blockade can lead to hyperprolactinemia. As a result, neuroleptics can cause galactorrhea. Other endocrine changes that can occur during therapy with neuroleptics include amenorrhea or other menstrual irregularity, breast enlargement or mastalgia, libido decrease, impotence, ejaculation dysfunction (no ejaculation), and priapism. Weight gain may also occur during therapy with phenothiazines.
Phenothiazines do not cause physical or psychological dependence. However, sudden withdrawal of prochlorperazine can produce nausea/vomiting, dizziness and trembling. These effects are only temporary, and can be reduced by a gradual reduction in dosage, or continuation of concomitant antiparkinsonian agents.
[ Last revised: 10/27/2005 7:28:00 PM ]
References
. Raehl CL, Patel AK, LeRoy M. Drug-induced torsade de pointes. Clin Pharm 1985;4:675 - 90.
. Kriwisky M, Perry GY, Tarchitsky D, et al. Haloperidol-induced torsades de pointes. Chest 1990;98:482 - 3.
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