Enprostil is a synthetic prostaglandin designed to resemble dinoprostone. Enprostil was found to be a highly potent inhibitor of gastric HCl secretion.[rx] It is an analog of prostaglandin E2 but unlike this prostaglandin, which binds to and activates all four cellular receptors viz., EP1, EP2, EP3, and EP4 receptors, enprostil is a more selective receptor agonist in that it binds to and activates primarily the EP3 receptor.[rx] Consequently, enprostil is expected to have a narrower range of actions that may avoid some of the unwanted side effects and toxicities of prostaglandin E2. A prospective multicenter randomized controlled trial conducted in Japan found combining enprostil with cimetidine was more effective than cimetidine alone in treating gastric ulcer.[rx]
A synthetic PGE2 analog that has an inhibitory effect on gastric acid secretion, a neuroprotective effect, and a postprandial lowering effect on gastrin. It has been shown to be efficient and safe in the treatment of gastroduodenal ulcers.
Enprostil is a synthetic prostaglandin E2 (PGE2) analog. Prostaglandins are naturally occurring substances in the body that have various physiological effects, including regulation of gastric acid secretion and protection of the gastric mucosa. As an analog of PGE2, enprostil is designed to mimic some of these actions.
Historically, enprostil was studied and sometimes used for the treatment of peptic ulcer disease. The drug can reduce gastric acid secretion and promote healing of the ulcerated areas of the stomach or duodenum.
However, other drugs like proton pump inhibitors (e.g., omeprazole, lansoprazole) and H2-receptor antagonists (e.g., ranitidine, famotidine) later became more commonly used for the treatment of peptic ulcers due to their efficacy and safety profile.
Mechanism Of Actions
Mechanism Simplified
The mechanism of Enprostil is fascinating, and here’s a simplified breakdown:
- Gastric Acid Secretion Control: One of the primary actions of Enprostil is to reduce gastric acid secretion. Excessive gastric acid can harm our stomach lining and lead to ulcers. By controlling this secretion, Enprostil helps in protecting the stomach.
- Enhanced Mucus Production: Our stomach has a protective layer of mucus that acts as a barrier against the acidic environment. Enprostil promotes mucus production, ensuring that this protective layer is thick and effective.
- Improving Blood Flow: Enprostil has the ability to increase blood flow in the stomach lining. This is crucial because a good blood supply ensures that the stomach lining can repair itself effectively, reducing the chances of ulcer formation.
Indications
Primary Indications of Enprostil:
- Gastric Ulcers: One of the main uses of Enprostil is for the treatment and prevention of gastric ulcers. Gastric ulcers are essentially sores in the stomach lining, often resulting from the imbalance between aggressive and protective factors in the stomach. By acting like our body’s own prostaglandins, Enprostil helps to fortify the protective lining of the stomach, reducing the risk of ulcers. This makes it particularly useful for individuals who are at higher risk of developing these ulcers, especially due to the long-term use of certain medications.
- Duodenal Ulcers: Just like the stomach, the duodenum (the first part of the small intestine) can also develop ulcers. Enprostil can be indicated to treat or prevent ulcers in this region. It acts by enhancing mucus production and bicarbonate secretion, both of which play a role in shielding the duodenum from the corrosive effects of stomach acid.
- As an NSAID Adjunct: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen or aspirin can, at times, irritate the stomach and increase the risk of ulcers. Enprostil, due to its protective qualities, is sometimes prescribed alongside NSAIDs to safeguard the stomach lining.
- Other Off-label Uses: Beyond the primary indications, doctors might prescribe Enprostil for other reasons based on their clinical judgment. However, always ensure you’re using the drug as recommended.
Contraindications
1. Allergy to Enprostil or its ingredients: If you’ve had allergic reactions to Enprostil or any of its components before, it’s crucial not to take this drug. Symptoms might include itching, hives, swelling, or difficulty breathing.
2. Pregnancy: Enprostil can induce contractions in pregnant women, possibly leading to miscarriage or premature labor. If you’re pregnant or plan to become pregnant, discuss other alternatives with your doctor.
3. Children: The safety and effectiveness of Enprostil in children have not been established. It’s best to avoid its use in this age group unless specifically advised by a pediatrician.
4. Concurrent use with certain other medications: Enprostil can interact with other drugs, leading to unwanted side effects or decreased efficacy. Inform your doctor of all the medicines you’re taking to ensure there’s no risk of harmful interactions.
5. Specific gastrointestinal conditions: In patients with certain intestinal or stomach conditions, using Enprostil might exacerbate the problem. It’s essential to notify your doctor if you’ve had a history of gastrointestinal issues.
Dosage
Dosage for Specific Conditions:
- Peptic Ulcers: For the treatment of peptic ulcers, Enprostil is generally prescribed in a dosage of 400 to 600 micrograms (mcg) per day, divided into two or three doses.
- Gastrointestinal Bleeding: In cases of gastrointestinal bleeding, the recommended Enprostil dosage is typically around 200 to 400 mcg per day, divided into two doses.
- Prevention of Stress Ulcers: To prevent stress ulcers in critically ill patients, Enprostil is often given in a dosage of 400 mcg per day, administered in two divided doses.
- Enhanced Mucosal Healing: For the purpose of promoting mucosal healing, a dosage of 600 mcg per day in divided doses may be prescribed.
Side Effects
Common Side Effects of Enprostil:
- Diarrhea: This is the most common side effect of Enprostil. If it persists or becomes bothersome, it’s essential to seek medical attention.
- Stomach cramps: Some people may experience stomach discomfort when taking Enprostil. This usually subsides after a few days.
- Nausea: Feeling queasy or wanting to vomit can occur but is typically mild.
- Gas: An increase in flatulence or gas may be experienced.
Less Common Side Effects:
- Headaches: While not as frequent, some users report experiencing headaches after consuming Enprostil.
- Dizziness: Feeling lightheaded or woozy can happen, especially when standing up quickly.
- Constipation: A reduced frequency in bowel movements might be observed.
- Vomiting: Though rare, some individuals may throw up after taking Enprostil.
Rare but Serious Side Effects: If you experience any of the following symptoms, it is crucial to contact a healthcare provider immediately.
- Allergic reactions: Symptoms can include itching, rash, swelling, severe dizziness, and difficulty breathing.
- Unusual/extreme tiredness.
- Persistent or severe abdominal pain.
- Blood in stool or dark-colored stools.
- Difficulty swallowing.
Drugs interactions
Potential drug interactions.
- Aspirin: When combined with Enprostil, the risk of stomach bleeding can increase.
- Ibuprofen: Increases stomach ulcer risk when taken with Enprostil.
- Warfarin: Enprostil may enhance the anti-blood-clotting effect of Warfarin.
- Digoxin: Enprostil can affect the absorption of Digoxin, altering its effectiveness.
- Naproxen: Similar to Ibuprofen, increases the risk of stomach ulcers.
- Ketoprofen: Can augment the potential for gastrointestinal bleeding.
- Clopidogrel: Enhanced anti-clotting effect when combined with Enprostil.
- Phenytoin: Enprostil may increase Phenytoin levels, possibly causing toxicity.
- Insulin: Potential to alter blood sugar control.
- Metformin: Possible change in blood sugar regulation when combined.
- Glipizide: Enprostil might affect blood sugar control with this drug.
- Levothyroxine: Enprostil may decrease its absorption, reducing efficacy.
- Atenolol: A potential for decreased blood pressure effects.
- Lisinopril: Enprostil may alter the blood pressure-lowering effects.
- Prednisone: Increased risk of gastrointestinal side effects.
- Methylprednisolone: Like Prednisone, increased stomach side effects.
- Tacrolimus: May amplify kidney side effects.
- Cyclosporine: Similar to Tacrolimus, enhanced kidney risks.
- Caffeine: Enprostil might increase caffeine levels, causing jitteriness.
- Theophylline: Elevated levels of Theophylline might be observed.
- Antacids: Might decrease Enprostil’s effectiveness.
- Omeprazole: Possible decrease in ulcer-healing effects.
- Furosemide: Enprostil may decrease its diuretic effect.
- Losartan: Potential alteration in blood pressure control.
- Amlodipine: Like other BP drugs, might affect pressure regulation.
- Celecoxib: Increased risk of stomach issues.
- Diazepam: Enprostil may increase Diazepam’s sedative effects.
- Cimetidine: Might elevate levels of Enprostil, increasing side effects.
- Ranitidine: Can decrease the ulcer-healing effect.
- Methotrexate: Enprostil might decrease its elimination, raising toxicity.
- Zolpidem: Potentially exaggerated sedative effect.
- Alcohol: Augments the risk of gastrointestinal bleeding.
- Hydrochlorothiazide: Altered diuretic and BP effects.
- Chlorpromazine: Enprostil may enhance its side effects.
- Propranolol: Potential changes in blood pressure control.
- Terfenadine: Enprostil might heighten its side effects.
- Sildenafil: Risk of decreased effectiveness.
- Tadalafil: Similar to Sildenafil, reduced effectiveness.
- Simvastatin: Altered cholesterol-lowering effect.
- Nifedipine: Changes in blood pressure effects.
- Esomeprazole: Potential decline in ulcer-healing properties.
- Allopurinol: Enprostil may heighten the risk of rash.
- Lansoprazole: Decrease in anti-ulcer effects.
- Glyburide: Potential change in blood sugar regulation.
- Pantoprazole: Reduced ulcer-healing effectiveness.
- Gemfibrozil: Enprostil might decrease its effect.
- Lovastatin: Altered cholesterol management effects.
- Raloxifene: Enprostil may diminish its osteoporosis benefits.
- Atorvastatin: Change in cholesterol-lowering potency.
- Pravastatin: Similar to other statins, reduced effectiveness.
Pregnancy and Lactations
Enprostil During Pregnancy
1. Safety Concerns: There are inherent concerns when taking any medication during pregnancy. The question is whether Enprostil could harm the unborn baby or affect the pregnancy outcome.
2. Available Research: Up to my last update in September 2021, research on Enprostil’s use during pregnancy is limited. Like many medications, determining its absolute safety during pregnancy is challenging due to ethical concerns related to testing drugs on pregnant individuals.
3. FDA Classification: Medications are classified by the FDA based on their demonstrated safety in pregnancy. It’s essential to check Enprostil’s current classification and discuss it with a healthcare professional.
4. Recommendations: While limited data is available, it is generally recommended to avoid non-essential medications during pregnancy. If Enprostil is deemed necessary, the potential benefits must outweigh the potential risks.
Enprostil During Lactation
1. Transfer to Breast Milk: Medications can sometimes pass into breast milk, which means a lactating individual could potentially pass it to their nursing infant. The extent to which Enprostil transfers to breast milk remains a critical question.
2. Potential Infant Effects: Even if Enprostil does pass into breast milk, the next question is how it might affect the infant. Factors to consider include the drug’s potency, the amount transferred, and the infant’s ability to process it.
3. Recommendations: As with pregnancy, the mantra during lactation is “caution.” If Enprostil is essential for the mother’s health, its use should be carefully discussed with a doctor, considering both the mother’s and infant’s well-being.
General Guidelines for Expecting and Nursing Mothers
- Consultation: Always consult with a healthcare professional before starting or stopping any medication during pregnancy or lactation.
- Stay Updated: Medical research is continuously evolving. Stay updated with the latest information about medications during pregnancy and lactation.
- Natural Doesn’t Mean Safe: Just because something is natural or over-the-counter doesn’t necessarily mean it’s safe during pregnancy or while breastfeeding.
- Risk vs. Benefit: Always weigh the potential risks of taking medication against the potential benefits. Sometimes, the health benefits for the mother might outweigh the potential risks to the baby.
