Usage
Gastroprokinetics are prescribed to treat conditions where gastric motility (movement of the stomach and intestines) is impaired. These conditions include gastroparesis (delayed gastric emptying), functional dyspepsia (indigestion with no clear cause), and pseudo-obstruction of the intestines. They are classified as motility stimulants. Gastroprokinetics work by increasing the frequency and strength of contractions in the gastrointestinal tract, thus promoting the movement of food through the digestive system.
Alternate Names
Motility Agents, Prokinetic Agents. Specific drug names vary (e.g., Metoclopramide, Erythromycin). Brand names also vary depending on the manufacturer.
How It Works
Pharmacodynamics: Gastroprokinetics enhance coordinated contractions of the gastrointestinal muscles, speeding up transit time. The mechanism varies based on the specific medication. Some, such as metoclopramide, act as dopamine D2 receptor antagonists in the chemoreceptor trigger zone and enhance acetylcholine release, which can stimulate upper GI tract motility. Others, like erythromycin (in low doses), act as a motilin receptor agonist, stimulating gastric contractions.
Pharmacokinetics: Absorption, metabolism, and elimination differ based on the specific drug. For example, metoclopramide is rapidly absorbed orally, metabolized in the liver, and excreted mainly via the kidneys. Erythromycin, when used as a prokinetic, is given intravenously or orally, metabolized in the liver by CYP3A4 enzymes, and mainly excreted in the bile.
Mode of Action: The cellular mechanisms of gastroprokinetics vary depending on the drug, involving interactions with receptors (e.g., motilin, 5-HT4), ion channels, or neurotransmitters. For example, metoclopramide acts as a dopamine antagonist and cholinergic agonist. Erythromycin, at low doses, activates motilin receptors, promoting gastric emptying.
Elimination: Elimination pathways depend on the drug used. Metoclopramide is primarily excreted through the kidneys. Erythromycin undergoes hepatic metabolism and is excreted in the bile.
Dosage
Dosage guidelines vary significantly depending on the specific gastroprokinetic agent. The following is a general overview and is NOT a substitute for consulting drug-specific information:
Standard Dosage
Adults:
Dosage depends on the chosen prokinetic and the condition treated. For example, metoclopramide might be given as 10 mg orally three to four times a day. Erythromycin, when used for its prokinetic effect, is often given intravenously at a dose of 3 mg/kg three times a day, or orally, in doses ranging from 50 mg to 500 mg, three to four times a day.
Children:
Pediatric dosing is complex and must be calculated based on the child’s weight or body surface area and requires careful consideration of the specific prokinetic agent and its potential side effects.
Special Cases:
- Elderly Patients: Dose adjustments are often necessary due to age-related decline in organ function. Lower doses may be required to avoid adverse effects.
- Patients with Renal Impairment: Reduced renal function can affect drug clearance, requiring dose reduction for some prokinetics.
- Patients with Hepatic Dysfunction: Impaired liver function affects drug metabolism, thus requiring dose adjustments.
- Patients with Comorbid Conditions: Pre-existing conditions like diabetes or heart disease may influence dose selection and drug choice.
Clinical Use Cases
The specific gastroprokinetic chosen and its dosage depend on the clinical situation:
- Intubation/Surgical Procedures: Specific agents may be used to promote gastric emptying before or after surgical procedures or intubation to decrease the risk of aspiration.
- Mechanical Ventilation/ICU Use: Prokinetics can be used to help manage gastrointestinal dysfunction, which is common in critically ill patients.
- Emergency Situations: Certain prokinetics can be used to manage specific acute issues like gastric stasis.
Dosage Adjustments
Dose adjustments are necessary for patients with renal/hepatic impairment, metabolic disorders, and other factors affecting drug metabolism.
Side Effects
Side effects vary depending on the specific prokinetic.
Common Side Effects:
Common side effects may include diarrhea, nausea, headache, and extrapyramidal symptoms (with metoclopramide). Erythromycin may cause gastrointestinal upset.
Rare but Serious Side Effects:
Serious but rare side effects may include tardive dyskinesia (a movement disorder) with metoclopramide, and QT interval prolongation or cardiac arrhythmias with erythromycin.
Long-Term Effects:
Long-term effects of some prokinetics may include tardive dyskinesia with metoclopramide.
Adverse Drug Reactions (ADR):
ADRs depend on the medication and may include severe allergic reactions, cardiac arrhythmias, neuroleptic malignant syndrome, or extrapyramidal reactions.
Contraindications
Contraindications are drug-specific but may include gastrointestinal obstruction, hemorrhage, perforation, epilepsy, Parkinson’s disease, and hypersensitivity to the drug.
Drug Interactions
Gastroprokinetics can interact with other medications, such as anticholinergics, opioid analgesics, and certain antidepressants. Erythromycin is a CYP3A4 inhibitor and can significantly interact with many drugs metabolized by this pathway.
Pregnancy and Breastfeeding
The safety of gastroprokinetics during pregnancy and breastfeeding varies. Metoclopramide is often considered compatible with breastfeeding. Erythromycin is generally considered safe during pregnancy but should be used with caution during breastfeeding.
Drug Profile Summary (Example using Metoclopramide)
- Mechanism of Action: Dopamine D2 receptor antagonist, cholinergic agonist.
- Side Effects: Nausea, diarrhea, extrapyramidal symptoms, tardive dyskinesia (rare).
- Contraindications: Gastrointestinal obstruction, hemorrhage, perforation, pheochromocytoma.
- Drug Interactions: Anticholinergics, opioids.
- Pregnancy & Breastfeeding: Generally considered safe but consult specialist guidelines.
- Dosage: 10mg orally 3-4 times daily.
- Monitoring Parameters: Observe for extrapyramidal symptoms, monitor bowel sounds.
Popular Combinations
Specific combinations depend on the clinical context. For example, metoclopramide can be used with analgesics for managing post-operative nausea and vomiting.
Precautions
Precautions include assessment of renal/hepatic function, screening for gastrointestinal obstruction, and monitoring for extrapyramidal symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Gastroprokinetics Plain?
A: Dosage is specific to each drug and the patient’s condition. It’s crucial to consult the prescribing information for each specific gastroprokinetic.
Q2: What are the common side effects of metoclopramide?
A: Common side effects include diarrhea, nausea, restlessness, fatigue, and extrapyramidal symptoms like tremors or dystonia.
Q3: Can erythromycin be used in patients with hepatic impairment?
A: Erythromycin is metabolized in the liver, so dose adjustment might be necessary in patients with hepatic impairment.
Q4: What is the mechanism of action of domperidone?
A: Domperidone is a peripheral dopamine D2 receptor antagonist that enhances gastric motility and emptying.
Q5: Are there any contraindications to the use of metoclopramide?
A: Yes. Contraindications include gastrointestinal obstruction, perforation, hemorrhage, pheochromocytoma, and Parkinson’s disease.
Q6: What are the potential drug interactions with erythromycin when used as a prokinetic?
A: Erythromycin can interact with numerous drugs metabolised by CYP3A4, potentially increasing their serum concentrations and leading to adverse effects.
Q7: Can gastroprokinetics be used in pregnant women?
A: The safety of gastroprokinetics in pregnancy varies. Consult specialist guidelines and weigh the risks and benefits before prescribing in pregnancy.
Q8: How should I monitor a patient taking metoclopramide?
A: Closely monitor bowel sounds and look for signs of extrapyramidal side effects.
Q9: Are there any dietary restrictions while taking gastroprokinetics?
A: Dietary restrictions are typically not necessary for most prokinetics, but individual patient needs may vary. Consult specific drug information.
