Antiemetic Drugs -Neuroleptics

Name of the Neuroleptics antiemetic Drugs

• Chlorpromazine
• Prochlorperazine
• Haloperidol.

1.Chlorpromazine

Mechanism of Action

Depresses brain areas that control activity and aggression, including the cerebral cortex, hypothalamus, and limbic system, by an unknown mechanism. Prevents nausea and vomiting by inhibiting or blocking dopamine receptors in the medullary chemoreceptor trigger zone and peripherally by blocking the vagus nerve in the GI tract. May relieve anxiety by indirect reduction in arousal and increased filtering of internal stimuli to the reticular activating system in the brain stem.

Pharmacokinetics

• Metabolism
• Metabolized by hepatic P450 enzyme CYP2D6
• Metabolites: 10-12 different compounds
• Elimination
• Half-life: 30 hr
• Excretion: Urine

Administration

• Know that I.V. infusion is recommended only for severe hiccups.
• When giving by I.V. infusion for intractable hiccups, dilute in 500 to 1,000 ml of normal saline solution and infuse slowly.
• For direct I.V. injection, dilute to 1 mg/ml using normal saline solution. Administer at a rate of at least 1 mg/ minute for adults or 2 mg/minute for children.
• When giving I.M., use Z-track injection method to minimize tissue irritation.
• Don’t inject subcutaneously.
• Know that in preoperative use, drug increases risk of neuromuscular excitation and hypotension when followed by barbiturate anesthestics

Contraindications

• Hypersensitivity to drug, other phenothiazines, sulfites (injection), benzyl alcohol (sustained-release capsules)
• Angle-closure glaucoma
• Bone marrow depression 
• Severe hepatic or cardiovascular disease

Precautions :

• Cardiac disease, diabetes mellitus, respiratory disease, prostatic hypertrophy, CNS tumors, epilepsy, intestinal obstruction
• Elderly patients
• Pregnant or breastfeeding patients  children

Adverse reactions

• CNS: sedation, drowsiness, extrapyramidal reactions, tardive dyskinesia, pseudoparkinsonism, neuroleptic malignant syndrome, seizures
• CV: tachycardia, hypotension (especially with I.M. or I.V. use)
• EENT: blurred vision, dry eyes, lens opacities, nasal congestion
• GI: constipation, ileus, anorexia, dry mouth
• GU: urinary retention, menstrual irregularities, galactorrhea, gynecomastia, inhibited ejaculation, priapism
• Hematologic: eosinophilia, agranulocytosis, leukopenia, hemolytic anemia, aplastic anemia, thrombocytopenia
• Hepatic: jaundice, hepatitis
• Skin: rash, photosensitivity, pigmentation changes, sterile abscess
• Other: allergic reactions, hyperthermia, pain at injection site

Patient monitoring

• Monitor blood pressure closely during I.V. infusion.
• Stay alert for signs and symptoms of neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, altered mental status, irregular pulse or blood pressure, tachycardia, diaphoresis, and arrhythmias). Stop drug immediately if these occur.
• Assess for extrapyramidal symptoms.

Patient teaching

• Tell patient to take capsules or tablets with a full glass of water, with or without food.
• Instruct patient not to crush sustained-release capsules.
• Tell patient to mix oral concentrate in juice, soda, applesauce, or pudding.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

Nursing Considerations

• Don’t open or crush E.R. capsules.
• Chlorpromazine shouldn’t be used to treat dementia-related psychosis in the elderly because of an increased risk of death.
• Use chlorpromazine cautiously in patients (especially children) with chronic respiratory disorders (such as severe asthma or emphysema) or acute respiratory tract infections because drug has CNS depressant effect. Also use cautiously in patients with cardiovascular, hepatic, or renal disease because of increased risk of developing hypotension, heart failure, and arrhythmias.
• Because of chlorpromazine’s anticholinergic effects, use it cautiously in patients with glaucoma. Also use it cautiously in those who are exposed to extreme heat or organophosphate insecticides and those receiving atropine or related drugs.  Protect concentrate from light. Refrigeration isn’t required.
• Dilute concentrate in at least 60 ml of diluent just before administering it. Use tomato or fruit juice, milk, simple syrup, orange syrup, a carbonated beverage, coffee, tea, water, or semisolid food, such as pudding and soup. • Protect parenteral solution from light. Solution should be clear and colorless to pale yellow. Discard markedly discolored solution.
• Don’t inject drug by subcutaneous route because it can cause severe tissue necrosis.
• Wear gloves when working with liquid or injectable form because parenteral solution may cause contact dermatitis.
• For I.V. injection, dilute chlorpromazine with sodium chloride to a concentration of 1 mg/ml.
• Give I.M. injection slowly and deep into upper outer quadrant of buttocks, such as in the gluteus maximus. To minimize hypotensive effects, keep patient lying flat and monitor blood pressure for 30 minutes after injection.  Monitor patient for increased sensitivity to drug’s CNS effects if patient has a history of hepatic encephalopathy from cirrhosis

2.Prochlorperazine

Mechanism of Action:

Alleviates psychotic symptoms by blocking dopamine receptors, depressing release of selected hormones, and producing alphaadrenergic blocking effect in the brain. Prochlorperazine also alleviates nausea and vomiting by centrally blocking dopamine receptors in the medullary chemoreceptor trigger zone and by peripherally blocking the vagus nerve in the GI tract. Anticholinergic effects and alphaadrenergic blockade reduce anxiety by decreasing arousal and filtering internal stimuli to the brain stem reticular activating system.

Pharmacokinetics

• Metabolism: Metabolized by liver
• Metabolites: N-desmethyl prochlorperazine (active)
• Half-life: 6.8-9 hr (PO); 6-10 hr (IV)
• Dialyzable: No
• Excretion: Feces (primarily)

Administration

• For I.V. infusion, dilute 20 mg in 1 L of compatible I.V. solution, such as normal saline solution.  Don’t mix in same syringe with other drugs.
• Know that injection solution may cause contact dermatitis. Don’t get it on hands or clothing. 2Give I.V. by slow infusion only. Don’t give as bolus.
• Know that I.M. injection is not preferred because it can cause local irritation. However, if I.M. route is prescribed, inject deep into upper outer quadrant of gluteal area.
• Don’t give by subcutaneous route.
• After desired response, switch to P.O. form as prescribed.
• When infusing I.V., watch for hypotension. Keep patient supine for 30 minutes after infusion.

Contraindications

• Hypersensitivity to drug or other phenothiazines
• Coma
• Concurrent use of large amounts of CNS depressants
• Pediatric surgery
• Children younger than age 2 or weighing less than 9 kg (20 lb)

Precautions :

• Cardiovascular or hepatic disease, glaucoma, seizures
• Anticipated exposure to extreme heat
• Children with acute illness.

Adverse reactions

• CNS: sedation, extrapyramidal reactions, tardive dyskinesia, neuroleptic malignant syndrome
• CV: orthostatic hypotension, ECG changes, tachycardia
• EENT: blurred vision, lens opacities, pigmentary retinopathy, dry eyes
• GI: constipation, ileus, dry mouth, anorexia
• GU: pink or reddish-brown urine, urinary retention, galactorrhea
• Hematologic: agranulocytosis, leukopenia
• Hepatic: cholestatic jaundice, hepatitis
• Metabolic: hyperthermia
• Skin: photosensitivity, pigmentation changes, rash
• Other: allergic reactions

Patient monitoring

• Monitor neurologic status, especially for signs and symptoms of neuroleptic malignant syndrome (high fever, sweating, unstable blood pressure, stupor, muscle rigidity, and autonomic dysfunction).
• In long-term therapy, assess for other adverse CNS effects, including extrapyramidal symptoms and tardive dyskinesia.
• Monitor patient closely if he’s receiving drug for nausea and vomiting associated with chemotherapy, because it may mask symptoms of chemotherapy toxicity.
• Evaluate CBC and liver function tests.

Patient teaching

• Instruct patient to dilute oral solution with tomato or fruit juice, milk, coffee, soda, tea, water, or soup.
• Teach patient to recognize and immediately report signs and symptoms of an allergic reaction or neuroleptic malignant syndrome.
• Inform patient about drug’s other CNS effects. Tell him to contact prescriber if these occur.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, alertness, and motor skills.
• Tell patient drug may turn urine pink or reddish brown.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

Nursing Considerations

• Prochlorperazine shouldn’t be used to treat dementia-related psychosis in the elderly because of increased mortality risk.
• Avoid contact between skin and solution forms of prochlorperazine because contact dermatitis could result.
• Inject I.M. form slowly, deep into upper outer quadrant of buttocks. Keep patient supine for 30 minutes after injection to minimize hypotensive effects.
• Rotate I.M. injection sites to prevent irritation and sterile abscesses.
•  Be aware that I.V. form may be given undiluted as injection or diluted in isotonic solution as infusion (mesylate form requires dilution in at least 1 L). Both forms should be given at no more than 5 mg/minute.
• Protect prochlorperazine from light.
• Parenteral solution may develop slight yellowing that won’t affect potency. Don’t use if discoloration is pronounced or precipitate is present. Expect antipsychotic effects to occur in 2 to 3 weeks, although range is days to months.

3.Haloperidol

Mechanism of Action

May block postsynaptic dopamine receptors in the limbic system and increase brain turnover of dopamine

Pharmacokinetics

• Bioavailability :60-70%
• Metabolized by hepatic P450 enzyme CYP3A4
• Metabolites: Hydroxyhaloperidol
• Biological half-life : 18 hr; 3 weeks (decanoate)
• Excretion : Urine (30%), feces (15%)

Administration

IV/IM Administration

Haloperidol lactate and haloperidol decanoate are both administered IM; haloperidol lactate has also been administered IV (off-label); haloperidol decanoate should not be administered IV

Contraindications

• Hypersensitivity to drug, tartrazine, sesame oil, or benzyl alcohol (with some products)
• Severe CNS depression or comatose states
• Parkinson’s disease

Precautions :

• Torsades de pointes, QT interval prolongation
• Patients with allergies
• Hepatic disease, bone marrow depression, cardiac disease, respiratory insufficiency, CNS tumors history of seizures, patients receiving anticonvulsants, EEG abnormalities
• Concurrent anticoagulant use
• Elderly patients
• Pregnant or breastfeeding patients
• Children (parenteral form not recommended)

Adverse reactions

• CNS: confusion, drowsiness, restlessness, extrapyramidal reactions, sedation, lethargy, insomnia, vertigo, tardive dyskinesia,seizures, neuroleptic malignant syndrome
• CV: hypotension, hypertension, tachycardia, ECG changes, torsades de pointes (with I.V. use)
• EENT: blurred vision, dry eyes
• GI: constipation, ileus, dry mouth, anorexia
• GU: urinary retention, menstrual irregularities, gynecomastia, priapism
• Hematologic: anemia, leukocytosis, leukopenia
• Hepatic: jaundice, drug-induced hepatitis
• Metabolic: galactorrhea
• Respiratory: dyspnea,respiratory depression, bronchospasm, laryngospasm
• Skin: diaphoresis, photosensitivity, rash
• Other: hyperpyrexia, hypersensitivity reactions

Patient monitoring

• Monitor CNS status closely, especially for seizures and neuroleptic malignant syndrome (shown by extrapyramidal symptoms, hyperthermia, and autonomic disturbances). 2Monitor cardiovascular status, particularly for ECG changes, blood pressure changes, torsades de pointes, and atypical rapid ventricular tachycardia, which may progress to ventricular fibrillation (with I.V. use).
• Assess respiratory status.
• Monitor liver function test results and CBC with white cell differential.
• With prolonged use, assess for tardive dyskinesia (which may occur months or even years after starting drug).

Patient teaching

• Tell patient to dilute oral concentrate with water, cola, or juice immediately before taking. 2Instruct patient to immediately report signs or symptoms of serious adverse reactions, such as unusual weakness, yellowing of skin or eyes, difficulty breathing, or symptoms of neuroleptic malignant syndrome (such as fever, muscle pain or rigidity, rapid or irregular pulse, increased sweating, change in urination pattern, or decreased mental acuity).
• Advise patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

Nursing Considerations

• Haloperidol shouldn’t be used to treat dementia-related psychosis in the elderly because of an increased mortality risk.
• Use haloperidol cautiously in patients with a history of prolonged QT interval, patients with uncorrected electrolyte disturbances, and patients receiving Class IA or III antiarrhythmics because of an increased risk of prolonged QT interval. Monitor elderly patients closely because they may have an increased risk of prolonged QT interval.
• Dilute oral solution with a beverage, such as cola or orange, apple, or tomato juice.
• Give haloperidol decanoate (long-acting form prepared in sesame oil to produce slow, sustained release) by deep I.M. injection into gluteal muscle using Z-track technique and 21G needle. Don’t give more than 3 ml per site. Expect to reach stable plasma level after third or fourth dose.
• If injection solution has a slight yellow discoloration, be aware that this change doesn’t affect potency.
• Watch for tardive dyskinesia (potentially irreversible involuntary movements) in patients receiving long-term therapy, especially elderly women who take large doses.
• Monitor CBC, especially if patient has a low WBC count or history of druginduced leukopenia or neutropenia, often during the first few months of therapy. If WBC count drops, especially if neutrophil count drops below 1,000/mm3, expect haloperidol to be discontinued. If neutropenia is significant, also monitor patient for fever or other symptoms of infection and provide appropriate treatment, as prescribed.
• If extrapyramidal reactions occur during the first few days of treatment, reduce dosage, as prescribed. If symptoms persist, drug may be discontinued. Dystonia also may occur during first few days of treatment, especially in patients receiving higher doses and in males and younger agegroups. Notify prescriber.
• Avoid stopping haloperidol abruptly unless severe adverse reactions occur.
• Monitor for signs of neuroleptic malignant syndrome, a rare but possibly fatal disorder linked to antipsychotic drugs. Signs include altered mental status, arrhythmias, fever, and muscle rigidity

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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