Changes

====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.<ref name="EGUC">The Equine Gastric Ulcer Council (1999) Tutorial Article: Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS).  ''Equine Vet Educ'', 11(5):262-272.</ref> 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.<ref name="EGUC">The Equine Gastric Ulcer Council (1999) Tutorial Article: Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS).  ''Equine Vet Educ'', 11(5):262-272.</ref> Currently recommended doses proposed to be effective in the majority of horses(Sanchez) are:

*'''Cimetidine''' 20-30mg/kg PO every 8 hours or 6.6mg/kg IV every 6 hours

*'''Cimetidine''' 20-30mg/kg PO every 8 hours or 6.6mg/kg IV every 6 hours

*'''Ranitidine''' 6.6mg/kg PO every 8 hours or 1.5-2mg/kg IV every 6 hours

*'''Ranitidine''' 6.6mg/kg PO every 8 hours or 1.5-2mg/kg IV every 6 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,<ref name="EGUC">The Equine Gastric Ulcer Council (1999) Tutorial Article: Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS).  ''Equine Vet Educ'', 11(5):262-272.</ref> 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<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> 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.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> 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<ref name="EGUC">The Equine Gastric Ulcer Council (1999) Tutorial Article: Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS).  ''Equine Vet Educ'', 11(5):262-272.</ref> and the product may be ineffective in the alkaline conditions created by acid suppression agents.(123-125 in Sanchez)

====Prostaglandin analogues====

====Prostaglandin analogues====

====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.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> Such compounds include bethanechol, metaclopramide, erythromycin and cisapride which have been shown to hasten gastric empyting in adult horses.<ref name="EGUC">The Equine Gastric Ulcer Council (1999) Tutorial Article: Recommendations for the diagnosis and treatment of equine gastric ulcer syndrome (EGUS).  ''Equine Vet Educ'', 11(5):262-272.</ref> 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.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref>

====Treatment problems====

====Treatment problems====

==Prognosis==

==Prognosis==

Improvement in most clinical signs should be noted within 1-3 weeks of commencing treatment.  Colic or diarrhoea should resolve within 48 hours.(Sanchez)  Complications related to gastric ulcers are most frequent and severe in foals and include perforation, delayed gastric emptying, gastroesophageal reflux and oesophagitis, and megaoesophagus secondary to chronic gastroesophageal reflux. Sudden gastric perforation without prior signs occurs sporadically in foals.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>Ulcers in the proximal duodenum or at the pylorus can cause fibrosis and stricture. The latter complication is seen in both foals and adult horses.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>  In mature animals, the most common complication is the recurrence of EGUS after treatment has ceased.  This is typically because the inciting managemental causes have not been altered.

Improvement in most clinical signs should be noted within 1-3 weeks of commencing treatment.  Colic or diarrhoea should resolve within 48 hours.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> Complications related to gastric ulcers are most frequent and severe in foals and include perforation, delayed gastric emptying, gastroesophageal reflux and oesophagitis, and megaoesophagus secondary to chronic gastroesophageal reflux. Sudden gastric perforation without prior signs occurs sporadically in foals.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>Ulcers in the proximal duodenum or at the pylorus can cause fibrosis and stricture. The latter complication is seen in both foals and adult horses.<ref name="Merck">Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial</ref>  In mature animals, the most common complication is the recurrence of EGUS after treatment has ceased.  This is typically because the inciting managemental causes have not been altered.

==Prevention==

==Prevention==

*Prevented ulcers in horses maintained under ulcerogenic conditions (White et al. 2003; McClure et al. 2005a,b,c;White et al. 2007).

*Prevented ulcers in horses maintained under ulcerogenic conditions (White et al. 2003; McClure et al. 2005a,b,c;White et al. 2007).

*Treating ulcers in asymptomatic performance horses may lead to improved performance.(Orsini)

*Treating ulcers in asymptomatic performance horses may lead to improved performance.(Orsini)

*Prophylaxis in foals controversial as gastric acidity may be protective against bacterial translocation (Sanchez).

*Prophylaxis in foals controversial as gastric acidity may be protective against bacterial translocation.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref>

*May benefit foals receiving substantial doses of NSAIDs for orthopaedic pain (Sanchez)

*May benefit foals receiving substantial doses of NSAIDs for orthopaedic pain.<ref name="Sanchez">Sanchez, L.C (2010) 'Diseases Of The Stomach' in  Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref>

==References==

==References==