Misoprostol is a drug used in horses to prevent ulcers from developing in the hindgut and stomach. It is commonly prescribed to horses that require regular use of non-steroidal anti-inflammatory drugs (NSAIDS), which can cause ulcers to form.

Misoprostol is also used to treat gastric ulcers in the stomach’s glandular region in horses that are not responding to conventional treatments, such as omeprazole or sucralfate.

This medication contains a synthetic (man-made) form of prostaglandin E1 (PGE1), a hormone naturally produced by horses and found in high amounts in the digestive tract. [1]

Prostaglandins protect the digestive tract from damage and support the healing of the intestinal barrier once ulcers have formed. If your horse is on long-term NSAID therapy for pain management, discuss misoprostol with your vet.

There are also other ways you can naturally reduce the risk of ulcers in your horse. These strategies should be used at the same time as administering Misoprostol.

 

Quiz: Assess Your Horse's Ulcer Risk

Misoprostol for Horses

Misoprostol (Cytotec®) is an FDA-approved drug used in humans to prevent or treat gastric ulcers caused by NSAIDs. [2]

In horses, it is used off-label to prevent NSAID-induced hindgut issues such as colitis or hindgut ulcers. In addition, it can be used to treat gastric ulcers in the stomach’s glandular region.

Misoprostol is synthetic prostaglandin E1 analogue that acts as a cytoprotectant, protecting cells from damage. [9] This drug can reduce inflammation in the gut and help ease some of the associated discomforts.

It has been shown to reduce the secretion of gastric acid in the stomach of horses. [13] Excessive acidity contributes to the formation of ulcers by eroding cells that line the intestinal tract.

Misoprostol has also been shown to improve intestinal barrier function in the gut of horses on NSAID medications. It helps to support the healing of the gastrointestinal mucosa following injury. [32]

Effects of NSAIDs

Pain-relieving NSAID medications – such as indomethacin, flunixin meglumine (banamine), and phenylbutazone (bute) – inhibit the enzyme cyclooxygenase-1 (COX-1). This enzyme is involved in pathways that activate inflammation following injury or infections.

In particular, the COX-1 enzymes make molecules called prostaglandins and thromboxane, which are involved in activating the immune system and causing a pain response.

Blocking COX-1 with NSAIDs is an effective way to relieve pain, inflammation and fever, which is why these drugs are commonly prescribed for horses with colic, arthritis or laminitis. Long-term use of NSAIDs may be required to provide comfort and improve the quality of life for these horses.

Prostaglandins and Gut Health

However, prostaglandins are also important for protecting cells of the digestive tract. The digestive tract is lined with a mucous barrier known as the mucosa. This blocks bacteria and toxins from being absorbed while allowing nutrients to pass into the blood.

Prostaglandins are involved in maintaining this defensive mucosal barrier and have several effects on the digestive tract, including: [3][4][5][6]

  • Increase blood flow in the mucosa by causing blood vessels to dilate
  • Raise mucosal bicarbonate secretion which helps to neutralize stomach acid
  • Decrease stomach acid production
  • Modulate immune responses

NSAIDs and Gut Injury

By blocking COX-1, NSAIDs suppress prostaglandin production, which compromises the mucosa’s ability to form a protective barrier between the environment inside the digestive tract and the cells lining it.

This allows stomach acidity and other irritants to cause inflammation, ulcers and bleeding throughout the gut.

In addition, NSAIDs will slow the recovery of pre-existing lesions by causing neutrophils to gather at the injury and exacerbate inflammation. [7][8]

COX-2-specific NSAIDs such as Equioxx and Previcox have been developed to lessen the digestive side effects of NSAID use. However, their long-term use may still induce injury in the small and large intestines. [31]

Ideally NSAIDs should be avoided in horses with pre-existing ulcers in the gut. However, these horses may develop conditions such as laminitis which require treatment with NSAIDs. Misoprostol may be applied concurrently with the NSAIDs to prevent ulcers from worsening. [7]

NSAID-Induced Colitis

Prolonged use or overuse of certain NSAIDs, particularly phenylbutazone, can cause non-specific colitis or right dorsal colitis (RDC) in the colon.

Colitis refers to inflammation in the colon that can lead to diarrhea and poor nutrient absorption. Horses on NSAIDs can develop this condition due to weakened protective qualities of the colon mucosa, which increases its permeability, allowing pathogens and toxins to induce inflammation.

Colitis is characterized by hindgut ulcers, inflammation, bleeding, ischemia (restricted blood flow), and cell death. In severe or prolonged cases, horses may require hospitalization for this condition.

NSAID use may also cause pre-existing chronic ulcerative colitis to flare up, resulting in more ulcers. [10][11]

Horses with colitis may present with the following clinical signs: [11]

A veterinarian will diagnose colitis through ultrasound, bloodwork, and a belly-tap to detect excessive swelling, while considering the horse’s symptoms and history of NSAID use.

Misoprostol for Colitis

Misoprostol can be administered to prevent colitis or accelerate recovery by improving the mucosal protection of the gut cells. It can also increase gut pH and promote blood vessel dilation in horses receiving NSAIDs.

These effects further promote healing by reducing damage from acid in the gut and improving the delivery of nutrients to the area. [12][13]

Equine Glandular Gastric Disease (EGGD)

Equine Gastric Ulcer Syndrome (EGUS) is a condition characterized by inflammation and lesions in the stomach. Gastric ulcers are common in horses, affecting up to 93% of performance horses. [14]

EGUS can be subdivided into two separate conditions: Equine Squamous Gastric Disease (ESGD) which affects the non-glandular region of the stomach, and Equine Glandular Gastric Disease (EGGD) which affects the glandular region of the stomach where stomach acid is produced. [15]

Common treatments for ESGD, including omeprazole and sucralfate, have limited efficacy for treating or preventing EGGD. Misoprostol can be used to treat EGGD and has the potential to also treat ESGD, although it has not been tested on ESGD.

Misoprostol is more effective than omeprazole and sucralfate for treating EGGD. [16] If your horse has ulcers, ask your veterinarian if misoprostol is appropriate for them.

Signs of Glandular Ulcers

If your horse shows any of the following signs of glandular ulcers, consider using misoprostol: [15] [16]

  • Poor performance
  • Lack of appetite
  • Behavioural changes, especially increased aggression or anxiety
  • Girthiness
  • Weight loss
  • Challenges maintaining weight
  • Dull coat
  • Recurrent colic
  • Teeth grinding (indicating abdominal pain)

Many of the symptoms of EGGD overlap with other health conditions, including colitis or NSAID-induced lesions in other parts of the gastrointestinal tract.

Risk of developing EGGD increases in horses undergoing an intense exercise regime, often related to the stress of trailering or being in an unfamiliar environment.

Horses fed high concentrate diets while receiving limited forage are particularly susceptible to EGGD.

Diagnosis of EGGD is made by a veterinarian after performing an endoscopy. The veterinarian will scope the horse’s stomach to look for lesions, may biopsy the lesions, and will grade the lesions based on their severity and location in the stomach. [15]

Reproductive Uses

Misoprostol has the potential to induce labour in mares or to facilitate the elimination of uterine contents.

In humans, misoprostol induces cervical dilation and uterine contractions. It has been used to induce labour or empty the uterus in case of early embryonic death. However, it is unclear whether misoprostol use in mares would have similar effects.

One case report found that misoprostol could dilate the mare’s cervix when applied as a cream directly to the cervix. The mare presented with endometritis and an inability to conceive despite being fertile.

As a result of misoprostol treatment, the mare’s cervix became dilated, allowing the mare to become pregnant. [17]

How to Use Misoprostol

Consult with your veterinarian for instructions and dosage guidelines for giving Misoprostol to your horse. Typical usage of Misoprostol in horses is 5 mcg/kg of bodyweight every 8-12 hours.

Plumb’s Veterinary Drug Handbook recommends administering Misoprostol three times per day with feed to avoid gastrointestinal side effects. [34]

Misoprostol is typically administered to horses in the form of an oral paste, chewable tablets, oil suspension, powder or topical gel. It may also be formulated in combination with other medications including:

  • Omeprazole
  • Metronidazole
  • Piroxicam
  • Phenytoin Sodium

Your veterinarian will help you determine which form of Misoprostol is best for your horse.

Women should handle Misoprostol carefully to avoid accidentally inhaling or ingesting this drug and experiencing uterine contractions. Wear gloves when preparing the drug for administration. [33]

It should not be handled by pregnant or breastfeeding women to avoid the risk of harm to the unborn or nursing baby. [33]

Risks of Misoprostol Administration in Horses

Limited clinical trials are available on the effects of Misoprostol in horses, and further research is needed to investigate possible side effects.

Anecdotally, is considered to be well tolerated. Some horses experience mild colic or diarrhea after taking Misoprostol. [33] In other animals, vomiting and excessive gas have been reported. [34]

There may be a risk of other adverse reactions including:

  1. Misoprostol causes cervical dilation and uterine contractions in humans and has been used to induce abortion during early-stage pregnancy. These effects were not seen in mid-gestation horses administered misoprostol for 5 days. However, the long-term effects are unknown. Misoprostol should be administered with caution or avoided in pregnant mares. [1] [18]
  2. Women who have received misoprostol during pregnancy often give birth to babies with birth defects including limb, joint and brain abnormalities. These abnormalities are believed to be attributed to the uterine contractions that disrupt fetal blood vessels. While congenital birth defects are a potential side-effect of misoprostol in horses, there is no published evidence as of yet. [21][22]
  3. High doses of misoprostol may decrease gut motility resulting in digestive upsets and discomfort. [19]
  4. Long-term administration of misoprostol in high doses can cause hyperostosis, or bone overgrowth, in mice. However, researchers have not been able to reproduce these effects in dogs or other rodents, so it is considered unlikely that this would occur in horses. [20]

Consult with your veterinarian before administering misoprostol to make sure it is the best treatment option for your horse. Your veterinarian will inform you of the appropriate dosage to use and how to minimize the risk of side effects.

Contraindications

Misoprostol should not be used in pregnant animals due to the risk of miscarriage. This medication should not be given to lactating mares as it passes into the milk and could cause severe diarrhea in the foal. [34]

Misoprostol is contraindicated for animals with a history of seizures or blood vessel problems. It could cause an unsafe drop in blood pressure or seizures. [34]

If your horse is on other medications, consult with your veterinarian to make sure Misoprostol is safe to use in combination with those medications.

How to Prevent NSAID-Induced Ulcers

While misoprostol and other drugs effectively treat NSAID-induced gastrointestinal injury, there are dietary modifications and management practices that horse owners can adopt to support recovery and prevent ulcer recurrence.

Forages such as hay, pasture, or haylage are rich in fibre, supporting a healthy mucosal barrier. [23] Forage should make up the bulk of your horse’s diet and be offered free-choice whenever possible.

Choose a hay that matches your horse’s energy needs in order to maximize ad libitum intake without impacting their body condition or performance.

Antioxidants, particularly vitamin E, vitamin A, selenium and flavonoids, also strengthen the mucosal barrier and promote mucus secretion to further protect the mucosa. [24][25]

Other dietary supplements are also beneficial for supporting the mucosal barrier and normal tissue repair processes. These include ingredients such as:

  • Glutamine: To provide the main source of energy for cells of the digestive tract [26]
  • Lecithin: To form a phospholipid barrier to protect the stomach lining from gastric acid [27][28]
  • Dietary nucleotides: To support healing through maturation of new cells in the digestive tract [29]
  • Mannan-oligosaccharides: To increase mucin production and modulate the gut’s immune response [30]

Mad Barn’s Visceral+ contains these ingredients along with prebiotics, probiotics and yeast to support gut health from the stomach to the hindgut.

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For additional feeding and management practices that can reduce the risk of ulcers, read our guide on how to feed the ulcer-prone horse.

Summary

Horses that are on NSAIDs should be monitored for signs of digestive issues.

Consult with your veterinarian if you are interested in using misoprostol to prevent issues that arise from NSAID use. Misoprostol can also be used for glandular ulcers, particularly if other treatments have failed.

Your equine nutritionist can help formulate a diet to reduce the risk of ulcers and support digestive health. Submit your horse’s information online for a free diet evaluation.

Is Your Horse's Diet Missing Anything?

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References

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  2. Searle, G. D. et al. Cytotec (misoprostol). FDA US Food and Drug Administration.
  3. Blikslager, A. et al. Equine intestinal mucosal pathobiology. Annu Rev Anim Biosci. 2018.
  4. Whittle, B. J. R. Role of prostaglandins in the defense of the gastric mucosa. Brain Res Bull. 1980.
  5. Wallace, J. L. Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself?. Physiol Rev. 2008.
  6. Martin, E. M. et al. Misoprostol Inhibits equine neutrophil adhesion, migration, and respiratory burst in an in vitro model of inflammation . Front Vet Sci. 2017.
  7. Marshall, J. F. et al. The effect of nonsteroidal anti-inflammatory drugs on the equine intestine . Equine Vet J Suppl. 2011.
  8. Rainsford, K. D. et al. Gastrointestinal mucosal injury following repeated daily oral administration of conventional formulations of indomethacin and other non-steroidal anti-inflammatory drugs to pigs: a model for human gastrointestinal disease. J Pharm Pharmacol. 2003.
  9. Dajani, E. Z. et al. Gastrointestinal cytoprotective effects of misoprostol. Clinical efficacy overview . Dig Dis Sci Suppl. 1985.
  10. Faucheron, J. L. et al. Non-steroidal anti-inflammatory drug-induced colitis. Int J Colorectal Dis. 1996.
  11. Galvin, N. et al. Right dorsal colitis in the horse: minireview and reports on three cases in Ireland. Ir Vet J. 2004.
  12. Torsher, K. J. et al. Misoprostol therapy following trinitrobenzene sulfonic acid-induced colitis accelerates healing. Prostaglandins Leukot Essent Fatty Acids. 1992.
  13. Sangiah, S. et al. Effects of misoprostol and omeprazole on basal gastric pH and free acid content in horses. Res Vet Sci. 1989.
  14. Tamzali, Y. et al. Prevalence of gastric ulcer syndrome in high-level endurance horses. Equine Vet J. 2011.
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  16. Varley, G. et al. Misoprostol is superior to combined omeprazole-sucralfate for the treatment of equine gastric glandular disease. Equine Vet J. 2019.
  17. Nie, G. J. et al. Use of prostaglandin E1 to induce cervical relaxation in a maiden mare with post breeding endometritis. Equine Vet Educ. 2010.
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  22. Vargas, F. R. et al/ Prenatal exposure to misoprostol and vascular disruption defects: a case-control study. Am J Med Genet. 2000.
  23. Aldoori, W. H. et al. Prospective study of diet and the risk of duodenal ulcer in men. Am J Epidemiol. 1997.
  24. Mahmood, T. et al. Prevention of duodenal ulcer formation in the rat by dietary vitamin A supplementation. JPEN J Parenter Enteral Nutr. 1986.
  25. Yoshikawa, T. et al. Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats. Gut. 1993.
  26. Arteriovenous differences for glutamine in the equine gastrointestinal tract . Am Vet J Res. 1992.
  27. Ferrucci, F. et al. Treatment of gastric ulceration in 10 standardbred racehorses with a pectin-lecithin complex . Vet Rec. 2003.
  28. Venner, M. et al. Treatment of gastric lesions in horses with pectin-lecithin complex. Equine Vet J. 2010.
  29. Carver, J.D. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr Suppl. 1999.
  30. Tiwari, U.P. et al. The role of oligosaccharides and polysaccharides of xylan and mannan in gut health of monogastric animals. J Nutr Sci. 2020.
  31. Whitfield-Cargile, C.M. et al. Differential effects of selective and non-selective cyclooxygenase inhibitors on fecal microbiota in adult horses. PLoS One. 2018.
  32. Tomlinson, JE. et al. Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum. Equine Vet J. 2005.
  33. Misoprostol – Client Information Leaflet. British Equine Veterinary Association.
  34. Plumb, Donald C. Misoprotol. Plumb’s Veterinary Drug Handbook. Wiley-Blackwell. 2018.