
HEALTH GUIDE / Prescription Drugs / Prokinetics

Prokinetics

Prokinetic Drugs, Prokinetic Medications

About

About prokinetics

Prokinetics are medications that stimulate contractions of the stomach muscles. Although these drugs may be used to treat dyspepsia, they are primarily used to prevent episodes of gastroesophageal reflux disease (GERD), in which acid from the stomach moves up into the esophagus, causing heartburn and damaging the tissue.

In healthy individuals, the lower esophageal sphincter (LES) – which is located at the junction of the stomach and the esophagus – keeps digestive acids in the stomach. However, this valve is weakened in some patients, which prevents it from closing tightly and allows acid to be refluxed back up into the esophagus. This can damage the tissue of the esophagus and cause the burning sensation in the chest known as heartburn.

Prokinetics reduce this abdominal discomfort by tightening the LES. This helps prevent acid from refluxing from the stomach into the esophagus. These medications also help the stomach to empty faster, which further reduces the reflux of stomach acid.

For example, the prokinetic metoclopramide lowers the pressure threshold in the stomach that triggers the process of peristalsis (coordinated, rhythmic muscle contractions that help move food through the digestive tract). This drug also boosts both the strength and frequency of muscle contractions and relaxes the pyloric sphincter, which helps food in the stomach empty more quickly into the small intestine.

In addition to helping prevent or reduce reflux, metoclopramide is sometimes used to treat abdominal pain and gastroparesis (disorder in which the stomach takes too long to empty its contents) caused by diabetes. Metoclopramide acts on the brain to reduce nausea and vomiting and helps boost appetite.

Although prokinetics can be effective in treating certain disorders, they only provide short-term symptom relief for patients. In addition, they commonly cause side effects that somewhat limit their usefulness. For example, metoclopramide is associated with depression and severe muscle twitching. The medication bethanecol may cause dizziness or lightheadedness. The prokinetic cisapride has been linked to fatal heart arrhythmias (abnormalities in heartbeat rhythm) and is now only available to patients who meet certain criteria established by the drug’s manufacturer. A physician must enroll a patient in a special program before the medicine is provided.

Researchers continue to look at ways to improve prokinetics so they cause fewer side effects.

Prokinetics are available in tablet, oral solution and injection form. Certain prokinetics such as cisapride and domperidone are not available by prescription in the United States. Types of prokinetics include:

Generic Name	Brand Name(s)
cisapride	Propulsid
metoclopramide	Maxolon Octamide Reclomide Reglan
bethanecol	Duvoid Urabeth Uracholine
tegaserod	Zelnorm
domperidone	Domstal Dometa

Conditions

Conditions of concern

Patients should inform their physician of any history of allergic reactions to prokinetics or other substances such as foods, preservatives or dyes.

Cisapride should not be used by patients with heart, lung or kidney disease. It also should not be used by those who have abdominal or stomach bleeding, intestinal obstruction, or low potassium levels in the blood. Serious cardiac arrythmias (heart rhythm abnormalities) have been noted in individuals taking cisapride with some medications such as antibiotics, antifungals and anti-HIV medications.

Metoclopramide should not be taken by patients who have abdominal or stomach bleeding, intestinal obstruction, asthma, cirrhosis of the liver, congestive heart failure, high blood pressure, depression, Parkinson’s disease, epilepsy, kidney disease or pheochromocytoma (a type of tumor).

Bethanecol should not be used by patients with intestinal obstruction, peptic ulcers, heart disease, Parkinson’s disease or a history of seizures.

Side effects

Potential side effects of prokinetics

Prokinetics have been linked to several significant side effects, some of which are potentially fatal. For example, cisapride has been associated with fatal heart arrhythmias (abnormalities in heartbeat rhythm). For this reason, this drug is not prescribed in the United States.

The prokinetic metoclopramide is associated with agitation, depression and severe muscle twitching (tardive dyskinesia). Both men and women may experience painful swelling of the breasts when taking this drug.

Other side effects associated with prokinetics include:

Jitteriness
Insomnia
Sedation
Anxiety
Diarrhea
Dizziness

Interactions

Drug or other interactions

Patients should consult their physicians before using alcohol and/or taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications in conjunction with prokinetics.

Cisapride may interact poorly with many medicines. Some of these drugs include:

Antispasmodics (medicines used to treat abdominal or stomach spasms or cramps)
Certain antibiotics (e.g., erythromycin, clarithromycin)
Antidepressants (medicines used to treat depression)
Antidyskinetics (medicines used to treat Parkinson's disease or other conditions affecting muscle control)
Antihistamines (drugs used to treat or reverse allergic reactions)
Antipsychotics (medicines for mental illness, such as schizophrenia)
Diuretics (water pills)
Antifungals (drugs used to treat fungus and yeast infections)
Antiemetics

Grapefruit and grapefruit juice may increase the effects of cisapride and should not be consumed while taking the medication.

Metoclopramide may interact poorly with the following drugs:

Antispasmodics
Antihypertensives (drugs used to treat high blood pressure)
Antipsychotics
Central nervous system depressants
MAO inhibitors (a class of antidepressants)
Cyclosporine (immunosuppressant that increases tear production)
Digoxin (antiarrhythmic heart drug)

Patients who are taking metoclopramide should not drink alcohol, as it may increase feelings of depression.

Bethanecol may interact poorly with the following medications:

Antispasmodics
Antihypertensives
Antiarrhythmics

How to use

Pregnancy use issues

Women who are pregnant, thinking of becoming pregnant or breastfeeding should discuss the potential risks and benefits of taking prokinetics with a physician. Cisapride has caused birth defects in animal studies and is known to pass into breast milk. Metocopramide has not been shown to cause birth defects in animal studies, but it does pass into breast milk.

Child use issues

Children may be more sensitive than adults to the potential side effects associated with cisapride. In addition, children who take metocopramide may experience muscle spasms of the jaw, neck and back, and may experience jerking movements of the head and face. Blood problems can develop in infants who take high doses of metoclopramide.

Elderly use issues

Older adults may be more sensitive than younger adults to the potential side effects associated with cisapride. Older adults who take metoclopramide for a long period of time may experience symptoms such as shuffling walk and trembling or shaking hands. Older patients with impaired kidney function may need to adjust their dosage level.

Symptoms of prokinetic overdose

Patients exhibiting disorientation, dystonia (repetitive muscle contractions that may cause twisting or jerking movements) or seizures should contact their physician immediately.

Questions for your doctor

Patients may wish to ask their doctor the following questions about prokinetics:

I’ve heard that prokinetics are potentially dangerous – why are you suggesting that I use them?
Which type of prokinetic is best for me?
How will prokinetics work to treat my condition?
I understand that cisapride is a good option for treating my condition – how can I qualify to take this drug?
What risks are associated with the use of prokinetics?
Will prokinetics interfere with any of the other medications I am currently taking?
Will I have to make any dietary adjustments while taking prokinetics?
How long will it take for me to notice improvement in my condition?
Which side effects should I report immediately to you?
What other medication options do I have if I am unable to take prokinetics?

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