phenothiazines
phenothiazines
Mechanism of action of phenothiazines is not fully understood. Antipsychotic drugs block postsynaptic dopamine receptors in the brain, but this may not be necessary and sufficient for antipsychotic activity; depresses the RAS, including the parts of the brain involved with wakefulness and emesis; anticholinergic, antihistaminic (H1), and alphaadrenergic blocking activity also may contribute to some of its therapeutic (and adverse) actions.
Indications
Management of manifestations of psychotic disorders Control of severe nausea and vomiting, intractable hiccups Contraindications and cautions
Contraindicated with coma or severe CNS depression, bone marrow depression, blood dyscrasia, circulatory collapse, subcortical brain damage, Parkinson’s disease, liver damage, cerebral arteriosclerosis, coronary disease, severe hypotension or hypertension, prolonged QTc interval. Use cautiously with respiratory disorders (“silent pneumonia” may develop); glaucoma, prostatic hypertrophy; epilepsy or history of epilepsy; breast cancer; thyrotoxicosis; peptic ulcer, decreased renal function; myelography within previous 24 hr or scheduled within 48 hr; exposure to heat or phosphorous insecticides; pregnancy; lactation; children younger than 12 yr, especially those with chickenpox, CNS infections (children are especially susceptible to dystonias that may confound the diagnosis of Reye’s syndrome). Adverse effects
Autonomic:Dry mouth, salivation, nasal congestion, nausea, vomiting, anorexia, fever, pallor, flushed facies, sweating, constipation, paralytic ileus, urine retention, incontinence, polyuria, enuresis, priapism, ejaculation inhibition, male impotence CNS: Drowsiness,insomnia, vertigo, headache, weakness, tremor, ataxia, slurring, cerebral edema, seizures, exacerbation of psychotic symptoms, extrapyramidal syndromes—pseudoparkinsonism; dystonias; akathisia, tardive dyskinesias, potentially irreversible (no known treatment) neuroleptic malignant syndrome CV: Hypotension, orthostatic hypotension, hypertension, tachycardia, bradycardia, cardiac arrest, heart failure, cardiomegaly, refractory arrhythmias, pulmonary edema, prolonged QTc interval EENT: Glaucoma, photophobia, blurred vision, miosis, mydriasis, deposits in the cornea and lens (opacities), pigmentary retinopathy Endocrine: Lactation, breast engorgement in females, galactorrhea; syndrome of inappropriate ADH secretion; amenorrhea, menstrual irregularities; gynecomastia in males; changes in libido; hyperglycemia or hypoglycemia; glycosuria; hyponatremia; pituitary tumor with hyperprolactinemia; inhibition of ovulation, infertility, pseudopregnancy; reduced urinary levels of go- nadotropins, estrogens, progestins Hematologic: Eosinophilia, leukopenia, leukocytosis, anemia; aplastic anemia; hemolytic anemia; thrombocytopenic or nonthrombocytopenic purpura; pancytopenia Hypersensitivity: Jaundice, urticaria, angioneurotic edema, laryngeal edema, photosensitivity, eczema, asthma, anaphylactoid reactions, exfoliative dermatitis Respiratory: Bronchospasm, laryngospasm, dyspnea; suppression of cough reflex and potential for aspiration (sudden death related to asphyxiaor cardiac arrest has been reported) Other: Urine discolored pink to redbrown Interactions
Drug-drug Additive CNS depression with alcohol Additive anticholinergic effects and possibly decreased antipsychotic efficacy with anticholinergic drugs Increased likelihood of seizures with metrizamide (contrast agent used in myelography) Increased chance of severe neuromuscular excitation and hypotension if given to patients receiving barbiturate anesthetics (methohexital, phenobarbital, thiopental) Increased risk of cardiac arrhythmias and serious Adverse effects
if combined with drugs that prolong the QTc interval ?Drug-lab test False-positive pregnancy tests (less likely if serum test is used) Increase in protein-bound iodine, not attributable to an increase in thyroxine Nursing considerations
Assessment
History: Coma or severe CNS depression; bone marrow depression; blood dyscrasia; circulatory collapse; subcortical brain damage; Parkinson’s disease; liver damage; cerebral arteriosclerosis; coronary disease; severe hypotension or hypertension; respiratory disorders; glaucoma, prostatic hypertrophy; epilepsy or history of epilepsy; breast cancer; thyrotoxicosis; peptic ulcer, decreased renal function; myelography within previous 24 hr or myelography scheduled within 48 hr; exposure to heat or phosphorous insecticides; pregnancy; children younger than 12 yr, especially those with chickenpox, CNS infections Physical: Weight, T; reflexes, orientation, IOP; P, BP, orthostatic BP; R, adventitious sounds; bowel sounds and normal output, liver evaluation; urinary output, prostate size; CBC, urinalysis, thyroid, LFTs, renal function tests, ECG analysis Interventions
Obtain baseline ECG with QTc interval noted. Dilute oral concentrate only with water, saline, 7-Up, homogenized milk, carbonated orange drink, and pineapple, apricot, prune, orange, V-8, tomato, or grapefruit juices; use 60 mL of diluent for each 16 mg (5 mL) of concentrate. Do notmix with beverages that contain caffeine (coffee, cola), tannics (tea), or pectinates (apple juice); physical incompatibility may result. Give IM injections only to seated or recumbent patients, and observe for Adverse effects
for a brief period afterward. Monitor pulse and BP continuously during IV administration. Do not change long-term therapy dosage more often than weekly; it takes 4–7 days to achieve steady-state plasma levels of drug. Adverse effects
in italics are most common; those in bold are life-threatening. U Do not crush. Avoid skin contact with oral solution; contact dermatitis has occurred. Arrange for discontinuation of drug if serum creatinine, BUN become abnormal or if WBC count is depressed. Monitor bowel function, arrange therapy for severe constipation; adynamic ileus with fatal complications has occurred. Monitor elderly patients for dehydration and institute remedial measures promptly; sedation and decreased sensation of thirst related to CNS effects of drug can lead to severe dehydration. Consult physician regarding warning of patient or patient’s guardian about tardive dyskinesias. Consult physician about reducing dosage, using anticholinergic antiparkinsonians (controversial) if extrapyramidal effects occur. Provide safety measures (side rails, assist) if sedation, ataxia, vertigo, orthostatic hypotension, vision changes occur. Provide positioning to relieve discomfort of dystonias. Provide reassurance to deal with extrapyramidal effect, sexual dysfunction. Teaching points
Take these drugs exactly as prescribed. The full effect may require 6 weeks–6 months of therapy. Avoid skin contact with drug solutions. Avoid driving or engaging in activities requiring alertness if CNS, vision changes occur. Avoid prolonged exposure to sun or use a sunscreen or covering garments. Maintain fluid intake, and use precautions against heatstroke in hot weather. Report sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, impaired vision, dark urine (pink or reddish brown urine is to be expected), pale stools, yellowing of the skin or eyes. Representative drugs
chlorpromazine fluphenazine perphenazine prochlorperazine thioridazine