Domperidone, Discovery, Action, Uses, Dosage, side effects, precautions ,and popular brands

Introduction

Domperidone is a medication that belongs to the dopamine antagonist group. It is used to treat various stomach-related issues, including nausea and vomiting, as well as stomach pain and discomfort caused by decreased movement of the stomach and upper gastrointestinal (GI) tract.

It works by blocking dopamine receptors in the gut, which increases the movement or contractions of the muscles in the stomach and intestines, facilitating the quicker and easier movement of food through the digestive tract. It also acts on the brain’s chemoreceptor trigger zone, which is able to control nausea and vomiting. This dual action makes domperidone effective in providing relief from gastrointestinal discomfort and improving overall digestive function.

Discovery of Domperidone

Domperidone was discovered and developed by the Belgian pharmaceutical company Janssen Pharmaceutica. The research and development of domperidone took place in the 1970s under the leadership of Dr. Paul Janssen, a prominent pharmacologist and founder of Janssen Pharmaceutica.

Dr. Janssen and his team were exploring new dopamine antagonists that could effectively treat nausea and vomiting with fewer side effects than existing medications. They aimed to find a compound that did not cross the blood-brain barrier significantly, thus reducing central nervous system side effects such as sedation and extrapyramidal symptoms, which were common with other dopamine antagonists, such as metoclopramide.

Key Milestones in Development

• 1974: Domperidone was first synthesized by researchers at Janssen Pharmaceutica.
• Late 1970s: Preclinical studies and clinical trials began to evaluate the efficacy and safety of domperidone in treating gastrointestinal disorders and nausea.
• 1980s: Domperidone was introduced into the market for the treatment of nausea, vomiting, and motility disorders. It became popular due to its lower side effect profile when compared to other antiemetics available at the time.

Mechanism of Action

Domperidone is a dopamine D2 receptor antagonist with both antiemetic and prokinetic properties. It exerts its effects through several key mechanisms in the gastrointestinal tract and the central nervous system’s chemoreceptor trigger zone (CTZ).

1. Blocking Dopamine Receptors in the Gut

• Enhanced Gastrointestinal Motility: Dopamine inhibits the contractions of the smooth muscle in the gastrointestinal tract, which can slow down the movement of food.
• It blocks dopamine D2 receptors located in the gut wall, reducing the inhibitory effect of dopamine.
• By antagonizing these receptors, It promotes gastric motility and increases the rate at which the stomach empties its contents into the intestines. This relieves symptoms such as bloating, fullness, and discomfort.

2. Effects on the Chemoreceptor Trigger Zone (CTZ)

• Antiemetic Action: The CTZ is an area in the brainstem that detects toxins in the blood and initiates the vomiting reflex. Dopamine D2 receptors in the CTZ play a significant role in mediating nausea and vomiting.
• Domperidone blocks dopamine D2 receptors in the CTZ, preventing dopamine from binding to these receptors.
• This action reduces the sensation of nausea and prevents the vomiting reflex.
• This makes domperidone effective in treating nausea and vomiting from various causes, including medication side effects, gastroenteritis, and chemotherapy.

3. Peripheral Action with Minimal Central Nervous System Effects

• Limited Central Penetration: One of the distinguishing features of domperidone is its poor ability to cross the blood-brain barrier. This selective peripheral action minimizes central nervous system side effects.
• While it effectively blocks dopamine receptors in the gut and CTZ, its limited penetration into the brain reduces the risk of side effects such as sedation drowsiness, and extrapyramidal symptoms (movement disorders) that are commonly associated with other dopamine antagonists like metoclopramide.

4:Enhanced Gastrointestinal Motility:

• By blocking dopamine D2 receptors in the gut, domperidone promotes the contractions of stomach and intestinal muscles, speeding up the passage of food through the digestive tract and relieving symptoms of delayed gastric emptying.
• Antiemetic Effects: It blocks dopamine D2 receptors in the chemoreceptor trigger zone, preventing nausea and suppressing the vomiting reflex, thus relieving nausea and vomiting symptoms.
• Peripheral Focus: Its limited ability to cross the blood-brain barrier ensures that domperidone acts mainly on peripheral dopamine receptors, reducing the likelihood of central nervous system side effects.

Domperidone uses

Domperidone is used in a variety of medical applications, primarily for its antiemetic (anti-sickness) and prokinetic properties. Here are the main medical uses of domperidone:

1. Treatment of Nausea and Vomiting

Domperidone is commonly prescribed to alleviate symptoms of nausea and vomiting caused by various factors, including gastrointestinal disorders, medication side effects, infections, motion sickness, and chemotherapy.

2. Management of Gastroparesis

Domperidone works by increasing gastrointestinal motility, allowing food to pass more easily through the digestive tract. Gastroparesis is a condition that causes delayed gastric emptying, resulting in symptoms like bloating, early satiety, nausea, and vomiting.

3. Relief of Gastrointestinal Discomfort

It is used to relieve stomach pain and discomfort caused by reduced movement in the stomach and upper gastrointestinal tract. It facilitates the faster movement of food through the digestive system, reducing symptoms like bloating and fullness.

4. Enhancement of Breast Milk Production

Domperidone has been found to raise prolactin levels, a hormone involved in milk production. As a result, it is sometimes prescribed off-label to breastfeeding women experiencing low milk supply, helping to boost milk production.

5. Adjunct Therapy in Gastroesophageal Reflux Disease (GERD)

In some cases of GERD (acid reflux), where delayed gastric emptying contributes to symptoms, it used as an adjunct therapy alongside acid-suppressing medications to improve gastric motility and alleviate reflux symptoms.

6. Symptomatic Treatment of Dyspepsia

Dyspepsia, or indigestion, is characterized by symptoms such as abdominal pain, bloating, and discomfort. Domperidone can help relieve these symptoms by promoting gastrointestinal motility and reducing the feeling of fullness.

Dosage

The dosage of domperidone can vary depending on the individual’s age, medical condition, and response to treatment. It is essential to follow the prescribing healthcare provider’s instructions and the dosage regimen provided on the medication label. The following are general dosage guidelines for domperidone:

For Adults:

Nausea and Vomiting:

• The typical starting dosage is 10 mg taken orally three to four times a day.
• It is usually recommended to take domperidone 15 to 30 minutes before meals and at bedtime if necessary.
• The maximum daily dose should not exceed 30 mg.

Gastroparesis:

• The dosage is higher, with some individuals requiring up to 20 mg taken orally four times a day.
• The dosing frequency and duration of treatment may be adjusted based on the severity of symptoms and individual response.

For Children

• The dosage for children is based on body weight and should be determined by a healthcare provider.
• Pediatric dosing is typically lower than adult dosing and may range from 0.25 mg to 0.5 mg per kg of body weight, administered orally three to four times daily.

Elderly patients

• Lower dosages may be appropriate for elderly patients, as they may be more susceptible to side effects.
• Healthcare providers may adjust the dosage based on renal function and other individual factors.

Patients with Hepatic Impairment:

• Dosage adjustments is necessary in patients with liver disease because domperidone is primarily metabolised in the liver.
• Healthcare providers will consider the degree of hepatic impairment when determining the appropriate dosage.

Side effects

Domperidone, like any medication, may cause side effects in some individuals. While not everyone will experience side effects, it’s essential to be aware of potential adverse reactions. Here are some common and less common side effects associated with domperidone:

Common Side Effects:

• Dry Mouth: A sensation of dryness in the mouth may occur.
• Abdominal Cramps: Mild to moderate abdominal discomfort or cramps may be experienced.
• Diarrhea: Some individuals may experience loose stools or increased bowel movements.

Less Common Side Effects

• Headache: Mild to moderate headaches may occur.
• Fatigue: Some individuals may experience feelings of tiredness or lethargy.
• Dizziness: A sensation of lightheadedness or dizziness may occur, especially when standing up quickly.
• Breast Pain or Tenderness:  Breast pain or tenderness is possible in some cases, especially in women.

Rare but Serious Side Effects

• Cardiac Arrhythmias: Domperidone may rarely cause irregular heart rhythms, including QT prolongation and potentially life-threatening arrhythmias.
• Extrapyramidal Symptoms: These are movement disorders characterized by involuntary muscle movements, tremors, rigidity, and restlessness, their side effects are less common than those of other dopamine antagonists, but they can still occur.

Allergic Reactions

• In rare cases, individuals may experience allergic reactions to domperidone, characterized by symptoms such as rash, itching, swelling of the face, lips, or tongue, and difficulty breathing.
• If symptoms of an allergic reaction appear, consult a physician.

Precautions and warnings

When taking domperidone, it is critical to be aware of certain precautions and warnings to ensure safe and effective treatment. The following are important precautions and warnings for domperidone:

Precautions

• Cardiac Risks: Domperidone may rarely cause serious cardiac arrhythmias, especially in individuals with underlying heart conditions or those taking medications that prolong the QT interval.
  Use caution when using it if you have a history of cardiac arrhythmias, heart disease, or electrolyte disturbances.
• Dosage and Duration: Follow the prescribed dosage regimen provided by your healthcare provider. Do not exceed the recommended dose or duration of treatment, as higher doses or prolonged use may increase the risk of adverse effects.
• Medical Conditions: Inform your healthcare provider about any pre-existing medical conditions, including liver disease, kidney disease, gastrointestinal disorders, or neurological disorders, as these may affect the safety and efficacy of domperidone.
• Drug Interactions: Inform your healthcare provider about all the medications you are taking, including prescription, over-the-counter, and herbal supplements. Domperidone may interact with certain medications, including those that prolong the QT interval or affect liver function.
• Pregnancy and Breastfeeding: If you are pregnant, planning to become pregnant, or breastfeeding, discuss the risks and benefits of domperidone with your healthcare provider.
  Domperidone may pass into breast milk, potentially affecting the nursing infant. Use caution or avoid breastfeeding while taking domperidone, as directed by your healthcare provider.

Warnings

• Cardiac Effects: Domperidone should be used with caution in individuals with underlying cardiac conditions or those at risk of cardiac arrhythmias.
  Monitor for signs of irregular heartbeats, fainting, or severe dizziness while taking domperidone, and seek medical attention if these symptoms occur.
• Extrapyramidal Symptoms: Although less common than with other dopamine antagonists, domperidone may rarely cause extrapyramidal symptoms such as tremors, muscle stiffness, or involuntary movements.
  If you notice any unusual movement disorders while taking it, contact your doctor right away.
• Allergic Reactions: If you have a known allergy to domperidone or any of its ingredients, do not use this medication.
  Seek immediate medical attention if you experience signs of an allergic reaction, such as rash, itching, swelling, or difficulty breathing.
• Liver Function: Domperidone is primarily metabolized in the liver. Individuals with impaired liver function should proceed with caution and monitor liver function tests as directed by their healthcare provider.

Domperidone Brands in Pakistan

There are several brands of Domperidone available in Pakistan, including:

1. Vomilux (Atco Laboratories Limited)
2. Motilium (Aspin Pharma)
3. Stomacol (Rasco Pharma)
4. Pelton-C (Global Pharmaceuticals)
5. Domel (Evergreen Pharmaceuticals Pvt Limited)
6. Pelton-V (Global Pharmaceuticals)
7. Gastroke (Evergreen Pharmaceuticals Pvt Limited)
8. Olidon (Olive Laboratories)
9. Omperin (Bio Labs Pvt Ltd)
10. Pelton (Global Pharmaceuticals)
11. Perid (Medisure Laboratories Pakistan Pvt Ltd)
12. Peridone (Sami Pharmaceuticals Pvt Ltd)
13. Perilium (Adamjee Pharmaceuticals Pvt Ltd)
14. Perill (Polyfine Chempharma Pvt Ltd)
15. Prokin (Neo Medix)
16. Rapidone (Zinta Pharmaceuticals Industries)
17. Residon (Rasco Pharma)
18. Sevidon (Bloom Pharmaceuticals Pvt Ltd)
19. Stardone (Star Laboratories Pvt Ltd)
20. Stomez (Werrick Pharmaceuticals)
21. Vomax (Rock Pharmaceuticals)
22. Vomilu (Atco Laboratories Limited)
23. Motilium-V (Aspin Pharma).