Changes

==Treatment==

==Treatment==

===Histamine 2 receptor antagonists===

====Histamine 2 receptor antagonists====

Parietal cells secrete HCl upon stimulation of histamine, acetylcholine or gastrin receptors.(EGUC)  Competitive H2 receptor antagonists have successfully elevated gastric pH and treated gastric ulcers in mature horses and foals.(44,85,97 in Sachez)  There appears to be a great variability among horses in their dose requirements for H2 antagonists which may be explained by individual bioavilability for these compounds.(EGUC)  Currently recommended doses proposed to be effective in the majority of horses(Sanchez) are:

Parietal cells secrete HCl upon stimulation of histamine, acetylcholine or gastrin receptors.(EGUC)  Competitive H2 receptor antagonists have successfully elevated gastric pH and treated gastric ulcers in mature horses and foals.(44,85,97 in Sachez)  There appears to be a great variability among horses in their dose requirements for H2 antagonists which may be explained by individual bioavilability for these compounds.(EGUC)  Currently recommended doses proposed to be effective in the majority of horses(Sanchez) are:

*'''Famotidine''' 10-15mg/kg PO every 24 hours

*'''Famotidine''' 10-15mg/kg PO every 24 hours

===Proton-pump inhibitors (PPIs)===

====Proton-pump inhibitors (PPIs)====

PPIs irreversibly bind to the H+K+-ATPase proton pump of the parietal cell and block the secretion of hydrogen ions.  These agents are more effective than H2 antagonsists as their action is receptor-independent,(EGUC) blocking the final pathway of acid secretion and they have a prolonged effect allowing for once-daily dosing.((Brown and Rees 1994). Papich 1993, Sanchez)  '''Omeprazole (Gastroguard™)''', a subsituted benzimidazole, is currently the only PPI licensed for use in horses.  At a dose rate of 4mg/kg per day omeprazole has proven effective in reducing the severity of gastric ulcers in Thoroughbred horses in active race training (Vatistas 1999) and no adverse effects have been observed.  The paste formulation is easy to administer and generally well accepted by horses.  Omeprazole has demonstrated efficacy in the resolution ofboth naturally-occurring and NSAID-induced gastric ulcers in horses.(103.104 in Sanchez)  A single dose has also produced an increase in gastric pH in clinically ill neonatal foals<ref>Javsicas, L.H, Sanchez, L.C (2008) The effect of omeprazole paste on intragastric pH in clinically ill neonatal foals.  ''Equine Vet J'', 40(1):41-4.</ref> and has contributed to ulcer healing in neonates.(103 in Sanchez)  A potential concern is that altering gastric pH may encourage bacterial overgrowth.  Thus further work is needed to evaluate the long-term safety of omeprazole in horses and particularly, foals.(Vatistas 1999)

PPIs irreversibly bind to the H+K+-ATPase proton pump of the parietal cell and block the secretion of hydrogen ions.  These agents are more effective than H2 antagonsists as their action is receptor-independent,(EGUC) blocking the final pathway of acid secretion and they have a prolonged effect allowing for once-daily dosing.((Brown and Rees 1994). Papich 1993, Sanchez)  '''Omeprazole (Gastroguard™)''', a subsituted benzimidazole, is currently the only PPI licensed for use in horses.  At a dose rate of 4mg/kg per day omeprazole has proven effective in reducing the severity of gastric ulcers in Thoroughbred horses in active race training (Vatistas 1999) and no adverse effects have been observed.  The paste formulation is easy to administer and generally well accepted by horses.  Omeprazole has demonstrated efficacy in the resolution ofboth naturally-occurring and NSAID-induced gastric ulcers in horses.(103.104 in Sanchez)  A single dose has also produced an increase in gastric pH in clinically ill neonatal foals<ref>Javsicas, L.H, Sanchez, L.C (2008) The effect of omeprazole paste on intragastric pH in clinically ill neonatal foals.  ''Equine Vet J'', 40(1):41-4.</ref> and has contributed to ulcer healing in neonates.(103 in Sanchez)  A potential concern is that altering gastric pH may encourage bacterial overgrowth.  Thus further work is needed to evaluate the long-term safety of omeprazole in horses and particularly, foals.(Vatistas 1999)

===Antacids===

====Antacids====

The use of antacids to treat EGUS in the horse has not been critically evaluated(Sanchez) and some believe they are contraindicated due to potential rebound effects.  Furthermore, the requirement for frequent dosing of large volumes of these products (owing to their poor efficacy) makes them an unattractive, stressful and impractical alternative to omeprazole. (Orsini)

The use of antacids to treat EGUS in the horse has not been critically evaluated(Sanchez) and some believe they are contraindicated due to potential rebound effects.  Furthermore, the requirement for frequent dosing of large volumes of these products (owing to their poor efficacy) makes them an unattractive, stressful and impractical alternative to omeprazole. (Orsini)

===Mucosal protectants===

====Mucosal protectants====

Sucralfate is a complex salt of sucrose and aluminium hydroxide.  It is thought to promote ulcer healing via several mechanisms: adherence to ulcerated mucosa, stimulation of mucus secretion, pepsin inibition, increasing prostgalandin E synthesis and enhancing the local production of epidermal growth factor.(Sanchez)  It has been used effectively to treat and prevent stress-induced ulcers in man and has been recommended at 10-20mg/kg three times daily for the treatment of glandular ulcers in horses.(murray 1994 in Orsini)  However, the effect of sucralfate on equine squamous gastric ulcers remains inconclusive(EGUC) and the product may be ineffective in the alkaline conditions created by acid suppression agents.(123-125 in Sanchez)

Sucralfate is a complex salt of sucrose and aluminium hydroxide.  It is thought to promote ulcer healing via several mechanisms: adherence to ulcerated mucosa, stimulation of mucus secretion, pepsin inibition, increasing prostgalandin E synthesis and enhancing the local production of epidermal growth factor.(Sanchez)  It has been used effectively to treat and prevent stress-induced ulcers in man and has been recommended at 10-20mg/kg three times daily for the treatment of glandular ulcers in horses.(murray 1994 in Orsini)  However, the effect of sucralfate on equine squamous gastric ulcers remains inconclusive(EGUC) and the product may be ineffective in the alkaline conditions created by acid suppression agents.(123-125 in Sanchez)

===Prostaglandin analogues===

====Prostaglandin analogues====

   

   

Synthetic prostaglandin E1 analogues are believed to inihibit gastric acid secretion and enhance mucosal cytoprotection(127 in Sanchez).  Misoprostol has been an effective agent in the treatment of human gastric and duodenal ulcers and at 5µg/kg has been shown to increase gastric pH in horses (128 in Sanchez).  Although contraindicated in pregnant mares, Misoprostol may be beneficial for mucosal recovery in the face of flunixin treatment.(129 in Sanchez)

Synthetic prostaglandin E1 analogues are believed to inihibit gastric acid secretion and enhance mucosal cytoprotection(127 in Sanchez).  Misoprostol has been an effective agent in the treatment of human gastric and duodenal ulcers and at 5µg/kg has been shown to increase gastric pH in horses (128 in Sanchez).  Although contraindicated in pregnant mares, Misoprostol may be beneficial for mucosal recovery in the face of flunixin treatment.(129 in Sanchez)

===Gastric prokinetics===

====Gastric prokinetics====

In cases of gastrooesophageal reflux, duodenal disease and delayed gastric emptying without a serious physical obstruction to gastric outflow, gastric prokinetics might be considered.(Sanchez)  Such compounds include bethanechol, metaclopramide, erythromycin and cisapride which have been shown to hasten gastric empyting in adult horses.(EGUC)  To date only the parasympathomimetic agent bethanechol has been used as an adjunct for EGUS and cholinergic side effects are possible.  Cisapride has been withdrawn from the US and UK markets over concern about its potential to cause adverse cardiac effects in man.(Sanchez)

In cases of gastrooesophageal reflux, duodenal disease and delayed gastric emptying without a serious physical obstruction to gastric outflow, gastric prokinetics might be considered.(Sanchez)  Such compounds include bethanechol, metaclopramide, erythromycin and cisapride which have been shown to hasten gastric empyting in adult horses.(EGUC)  To date only the parasympathomimetic agent bethanechol has been used as an adjunct for EGUS and cholinergic side effects are possible.  Cisapride has been withdrawn from the US and UK markets over concern about its potential to cause adverse cardiac effects in man.(Sanchez)

===Treatment problems===

====Treatment problems====

The prevalence of gastric ulcers in horses remains high regardless of the common use of antiulcer treatments.  This has been attributed to the expense of recommended products encouraging subtherapeutic and curtailed dosing schedules(Orsini et al 2003 in Nadeau 2009).  Omeprazole and ranitidine must be administered for at least 28 days for adequate ulcer healing.(Nadeau 2009) In the USA, compounded omeprazole from bulk powders are used as a cheaper substitute for the FDA approved products. However, these formulations lack efficacy and are not regulated (Nieto et al. 2002; Merritt et al. 2003; Orsini et al. 2003).(Nadeau 2009)  A considerable challenge lies in the management of abdominal pain associated with EGUS, since the commonly used NSAIDs for pain control may worsen and even induce further ulcerative lesions.<ref>Videla, R, Andrews, F.M (2009) New perspectives in equine gastric ulcer syndrome.''Vet Clin North Am Equine Pract'', 25(2):283-301.</ref>  Another challenge is the horse in which oral medication is prohibited.  However, Andrews and colleagues (2006) have demonstrated the efficacy of an omeprazole powder, adminstered IV in sterile water, which signifcantly increases the pH of equine gastric contents and may be useful in problem horses.<ref>Andrews, F.M, Frank, N, Sommardahl, C.S, Buchanan, B.R, Elliott, S.B, Allen, V.A (2006) Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses.  ''J Vet Intern Med'', 20(5):1202-6.</ref>  An ongoing point of debate is the use of antiulcer medication in competition horses.  In 2000, the Bureau of the The Fèdèration Equestre Internationale (FEI) permitted the use of cimetidine, ranitidine and omeprazole to prevent and treat gastric ulcers.  This decision was based on evidence that the compounds were not performance enhancing and that EGUS was such a widespread concern. However, these drugs are still listed under prohibited substances in the 2009 Appendices of the American Endurance Ride Conference (AERC) Rules and Regulations.  The argument is that a horse requiring such treatment is not suffciently well to compete and should be withdrawn form competition if it needs preventative medication.  A related concern is that the AERC permits the use of hyperosmolar oral electrolyte pastes which may cause gastric ulcers.(Holbrook et al. 2005)  Without the protection afforded by antiulcer agents, these horses may be at considerable risk for EGUS.(Nadeau 2009)

The prevalence of gastric ulcers in horses remains high regardless of the common use of antiulcer treatments.  This has been attributed to the expense of recommended products encouraging subtherapeutic and curtailed dosing schedules(Orsini et al 2003 in Nadeau 2009).  Omeprazole and ranitidine must be administered for at least 28 days for adequate ulcer healing.(Nadeau 2009) In the USA, compounded omeprazole from bulk powders are used as a cheaper substitute for the FDA approved products. However, these formulations lack efficacy and are not regulated (Nieto et al. 2002; Merritt et al. 2003; Orsini et al. 2003).(Nadeau 2009)  A considerable challenge lies in the management of abdominal pain associated with EGUS, since the commonly used NSAIDs for pain control may worsen and even induce further ulcerative lesions.<ref>Videla, R, Andrews, F.M (2009) New perspectives in equine gastric ulcer syndrome.''Vet Clin North Am Equine Pract'', 25(2):283-301.</ref>  Another challenge is the horse in which oral medication is prohibited.  However, Andrews and colleagues (2006) have demonstrated the efficacy of an omeprazole powder, adminstered IV in sterile water, which signifcantly increases the pH of equine gastric contents and may be useful in problem horses.<ref>Andrews, F.M, Frank, N, Sommardahl, C.S, Buchanan, B.R, Elliott, S.B, Allen, V.A (2006) Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses.  ''J Vet Intern Med'', 20(5):1202-6.</ref>  An ongoing point of debate is the use of antiulcer medication in competition horses.  In 2000, the Bureau of the The Fèdèration Equestre Internationale (FEI) permitted the use of cimetidine, ranitidine and omeprazole to prevent and treat gastric ulcers.  This decision was based on evidence that the compounds were not performance enhancing and that EGUS was such a widespread concern. However, these drugs are still listed under prohibited substances in the 2009 Appendices of the American Endurance Ride Conference (AERC) Rules and Regulations.  The argument is that a horse requiring such treatment is not suffciently well to compete and should be withdrawn form competition if it needs preventative medication.  A related concern is that the AERC permits the use of hyperosmolar oral electrolyte pastes which may cause gastric ulcers.(Holbrook et al. 2005)  Without the protection afforded by antiulcer agents, these horses may be at considerable risk for EGUS.(Nadeau 2009)