Antiemetic Drugs -Prokinetics

Name of the Prokinetics Drugs

• Metoclopramide
• Domperidone
• Cisapride
• Mosapride
• Itopride

1.Metoclopramide

Mechanism of Action

Antagonizes the inhibitory effect of dopamine on GI smooth muscle. This causes gastric contraction, which promotes gas tric emptying and peristalsis, thus reducing gastroesophageal reflux. Metoclopramide also blocks dopaminergic receptors in the chemoreceptor trigger zone, preventing nausea and vomiting.

Pharmacokinetics

• Bioavailability : IM, 74-96%; PO, 65-95%
• Metabolism :liver
• Metabolites: Metoclopramide glucuronides, metoclopramide sulfates, aminoacetic acid (inactive)
• Biological half-life :  (IV/IM): 5-6hr (adults); 4 hr (children)
• Excretion :Primarily urine (85%)

Administration

• Mix oral solution with water, juice, carbonated beverage, or semisolid food (such as applesauce or pudding) just before administration.
• Remove orally disintegrating tablets with dry hands immediately before administering. After removing, place tablet on patient’s tongue, where it will dissolve in approximately 1 minute. Tell patient to swallow saliva.
• Give I.M. or direct I.V. without further dilution.
• Administer low doses (10 mg or less) by direct I.V. injection slowly over 2 minutes. (Rapid injection may cause intense anxiety and restlessness followed by drowsiness.)
• For I.V. infusion, dilute with 50 ml of 5% dextrose in 0.9% sodium chloride solution, 5% dextrose in 0.45% sodium chloride solution, or lactated Ringer’s solution. Infuse over at least 15 minutes

Contraindications

• Hypersensitivity to drug
• Pheochromocytoma
• Parkinson’s disease
• Suspected GI obstruction, perforation, or hemorrhage
• History of seizure disorders

Precautions :

• Diabetes mellitus, renal dysfunction
• History of depression
• Elderly patients
• Pregnant or breastfeeding patients
• Children.

Adverse reactions

• CNS: drowsiness, restlessness, anxiety, depression, irritability, fatigue, lassitude, insomnia, tardive dyskinesia, parkinsonian-like reactions, extrapyramidal reactions, akathisia, dystonia
• CV: hypertension, hypotension, arrhythmias, neuroleptic malignant syndrome
• GI: nausea, constipation, diarrhea, dry mouth
• GU: gynecomastia

Patient monitoring

• Monitor blood pressure during I.V. administration.
• Stay alert for depression and other adverse CNS effects. 2Watch for extrapyramidal reactions, which usually occur within first 24 to 48 hours of therapy. To reverse these symptoms, give diphenhydramine 50 mg I.M. or benztropine 1 to 2 mg I.M., as prescribed.
• Check for development of parkinsonian-like symptoms, which may occur within first 6 months of therapy and usually subside within 2 to 3 months after withdrawal. 2With long-term use, assess patient for tardive dyskinesia and discontinue drug if signs or symptoms of tardive dyskinesia develop. Avoid treatment for longer than 12 weeks in all but rare cases in which therapeutic benefit outweighs risk of developing tardive dyskinesia. 2Monitor patient closely for signs and symptoms of neuroleptic malignant syndrome (hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability [irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias]); immediately discontinue drug if these symptoms occur.
• In diabetic patient, stay alert for gastric stasis. Insulin dosage may need to be adjusted.

Patient teaching

• Tell patient to take 30 minutes before meals.

• Tell patient taking orally disintegrating tablets to remove tablet with dry hands immediately before use. Instruct patient to place tablet on tongue, where it will dissolve in approximately 1 minute, and then swallow saliva.
• Instruct patient to report involuntary movements of face, eyes, or limbs; muscle rigidity; altered consciousness; irregular pulse or blood pressure; rapid or irregular heartbeats; or excessive sweating.
• Caution patient to avoid driving and other hazardous activities until drug’s effects are known.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

Nursing Considerations

• Use metoclopramide cautiously in patients with hypertension because it may increase catecholamine levels
• Monitor patient with NADH-cytochrome b5 reductase deficiency because metoclopramide increases risk of methemoglobinemia and sulfhemoglobinemia, and patient can’t receive methylene blue.
• Assess patient for signs of intestinal obstruction, such as abnormal bowel sounds, diarrhea, nausea, and vomiting, before administering metoclopramide. Notify prescriber if you detect them.
• For I.V. use, you need not dilute doses of 10 mg or less. Give drug over 1 to 2 minutes. For doses larger than 10 mg, dilute in 50 ml normal saline solution, half-normal (0.45) saline solution, D5W, or lactated Ringer’s solution and infuse over at least 15 minutes.
• Avoid rapid I.V. delivery because it may cause anxiety, restlessness, and drowsiness.
• Monitor patient, especially one with heart failure or cirrhosis, for possible fluid retention or volume overload due to transient increase in plasma aldosterone level.
• Monitor patient closely for neuroleptic malignant syndrome, a rare but potentially fatal disorder characterized by hyperthermia, muscle rigidity, altered level of consciousness, irregular pulse or blood pressure, tachycardia, diaphoresis, and arrhythmias.
• Store drug in a light-resistant container; discard if discolored or contains particulate.

2.Domperidone

Mechanism of action:

Domperidone blocks peripheral dopamine receptors resulting in gastric peristalsis and lowering of the esophageal sphincter pressure. This causes increased gastric emptying and decreased small bowel transit time Its antiemetic properties are the result of blocking dopamine receptors at the chemoreceptor trigger zone as well as at the gastric level

Dosage:

Domperidone 10 mg po TID. maximum recommended total dose is 30 mg/day

Adverse Effects:

Galactorrhea, gynecomastia, hot rarely causes asthenia, extrapyramidal effects, lethargy, dizziness, irritability, nervousness or thirst Dry mouth, loose stool, headache, Rashes, Cardiac arrhythmias

Administration

• Domperidone is best taken about 15 to 30 minutes before meals, with a glass of water.
• If you take domperidone after a meal, it will still work, but it may take longer to have an effect.
• It is not harmful if you miss a dose of domperidone. If you miss a dose, take it when you remember. But, if it is nearly time for your next dose, just take the next dose at the right time.  Do not take double the dose.

Precautions

• Take Domperidone before meals as directed by your doctor.
• Avoid alcohol while using Domperidone.
• Do not exceed seven days of Domperidone use without consulting your doctor.
• Avoid use in children under 12 years old or weighing less than 35 kg.
• Use caution in elderly patients over 65 years old; dosage adjustments may be needed.
• Use in pregnant women only if benefits outweigh risks; consult a doctor first.
• Avoid use in breastfeeding mothers due to potential adverse effects on the infant

Pharmacokinetics

• Bioavailability: oral: 13-17%
• Metabolism: hepatic and intestinal
• Biological half-life: 7.5 hours
• Excretion: urine, faeces

Contraindications:

Known existing prolonged QT interveal ,electrolyte disturbances, cardiac disease, moderate/severe liver impairment

Dosing information

Adults and adolescents 12 years of age and older and with a body weight of 35 kg or more:

• Tablet. The usual dose is one 10mg tablet taken up to three times per day, if possible before meals. It is usually recommended not to take more than three tablets (30 mg) per day, but in some cases your doctor may recommend taking up to 4 tablets (40 mg) per day.
• Oral suspension. The usual dose is 10 ml taken up to three times per day, if possible before meals. Do not take more than 30 ml per day.
• Suppositories. The usual dose is one 30 mg suppository two times a day. Do not use more than two suppositories per day

Who should not take domperidone?

Do not take domperidone tablets if:

• You are allergic to domperidone or any of the other ingredients in it. Signs of an allergic reaction include:
• Rash
• Swallowing or breathing problems
• Swelling of your lips, face, throat or tongue
• You have a tumor of the pituitary gland (prolactinoma)
• You have a blockage or tear in your intestines
• You have black, tarry bowel motions (stools) or notice blood in your bowel motions. This could be a sign of bleeding in the stomach or intestines.
• You have a moderate or severe liver disease
• Your ECG (electrocardiogram) shows a heart problem called “prolonged QT corrected interval”
• You have or had a problem where your heart cannot pump the blood round your body as well as it should (condition called heart failure)
• You have a problem that gives you a low level of potassium or magnesium, or a high level of potassium in your blood
• You are taking certain medicines 

3.Cisapride

Mechanism of Action:

Promotes gastric emptying, increases lower esophageal sphincter tone and esophageal peristalsis

Increases gastric motility and cardiac rate possibly by releasing acetylcholine at the myenteric plexus; may act at the serotonin-4 receptor

Pharmacokinetics

• Onset of action: 0.5-1 hr
• Bioavailability: 35-40%
• Half-life: 6-12 hr
• Protein binding: 97.5-98%
• Metabolism: Liver
• Excretion: Urine and feces

Administration

• Take this medicine by mouth with a glass of water. Follow the directions on the label. Take this medicine on an empty stomach, at least 15 minutes before eating and at bedtime. Do not take your medicine more often than directed.
• Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
• Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

Contraindications

Hypersensitivity, Serious cardiac arrhythmias , History of renal failure, ventricular arrhythmias, ischemic heart disease, CHF, clinically significant bradycardia, uncorrected electrolyte disorders (eg, hypomagnesemia, hypokalemia), and respiratory failure

Side effects

• Blurred vision or other changes in vision
• Convulsions (seizures)
• Dizziness
• Fainting or feeling faint
• Fast or racing heartbeat
• Pounding or irregular heartbeat
• Swelling of face, hands, lower legs, and/or feet
• Unusual weight gain

Cautions

• Decrease dose by 50% with liver impairment
• Potential benefits should be weighed against risks prior to initiating therapy in patients that may develop prolongation of cardiac conduction intervals, especially QTc
• Serious cardiac arrhythmias, tachycardia, ventricular fibrillation, torsade de pointes, and QT prolongation reported in patients taking CYP3A4 inhibitors
• Not for use in patients that might experience rapid reduction of plasma potassium as those resulting from potassium wasting diuretics and/or insulin in acute settings

4.Mosapride

Mechanism of Action: 

This drug is a selective 5-HT₄ receptor agonist. It is considered that this drug stimulates 5-HT₄ receptors in the gastrointestinal nerve plexus, which increases the release of acetylcholine, resulting in enhancement of gastrointestinal motility and gastric emptying.

Side effects:

• Diarrhea,
• Abdominal pain,
• Dizziness,
• Constipation,
• Headache,
• Sleeplessness,
• Nausea and vomiting.

Pharmacokinetics

• Half-life: 1.6-2.4 hours
• Protein binding: 99.0%
• Metabolism: Liver
• Excretion: Urine and feces

Contraindications:

Hypersensitivity.

Precautions

Caution should be exercised in patients with history of liver or kidney impairment, elderly, children, during pregnancy and breastfeeding. Continuous admin of this drug is not recommended if no improvement in GI symptoms is observed after treating for 2 weeks with this medication

5. Itopride

Mechanism of action

Itopride increases acetylcholine   concentrations by inhibiting dopamine D2 receptors and acetylcholinesterase. Higher acetylcholine increases GI peristalsis increases the lower esophageal sphincter pressure, stimulates gastric motility, accelerates gastric emptying, and improves gastro-duodenal coordination.  

Dosage & administration:

The recommended dose of Itopride hydrochloride for adult patients is 150 mg daily [one tablet (50 mg) takenorally three times a day before meals).

The dose may be reduced according to the patient’s age & symptoms.

Indications:

• Functional dyspepsia.
• Non-ulcer dyspepsia (chronic gastritis) i.e.: sensation of bloating, early satiety, upper abdominal pain or discomfort, anorexia, heartburn, nausea & vomiting.

Side effects

• Major & minor side effects for Itopride
• Diarrhea
• Abdominal pain
• Headache
• Nausea
• Decrease in white blood cells and platele ts
• Gynecomastia
• Allergic skin reaction
• Increased liver enzyme levels
• Jaundice

Contraindications of Itopride

• If you are allergic to itopride or similar medicines.
• If you have a blockage, perforation (tear) or bleeding in the intestine or stomach.

Gastrointestinal Haemorrhage

This medicine is not recommended for use in patients having internal bleeding of the stomach and intestine. This may be attributed to various reasons including a ruptured bowel (Gastrointestinal Perforation).

Mechanical Bowel Obstruction

This medicine is not recommended for use in patients having a blockage in the intestine.

Parkinson’s Disease

This medicine is not recommended for use in patients having dopamine related disorders like Parkinson’s disease.

Pharmacokinetics

• Bioavailability: 60%
• Half-life: 6 hr
• Protein binding: 96 %
• Metabolism: gastrointestinal tract
• Excretion: Urine

Administration:

• The recommended dose of Itopride hydrochloride for adult patients is 150 mg daily [one tablet (50 mg) taken orally three times a day before meals).
• The dose may be reduced according to the patient’s age & symptoms.

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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