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==Treatment==
==Treatment==
===Histamine 2 receptor antagonists===
This concept follows from the still widely held belief, ‘no acid, no ulcer’ (Fig 19). The current treatment of choice is to suppress acid production from the parietal cells. These cells release acid when any one of 3 distinct receptors (histamine, acetylcholine, gastrin) is stimulated. Currently, the most popular treatment involves an histamine receptor antagonist (H2 blocker). The proton-pump inhibitors constitute a new treatment approach that blocks acid production within the cell. This modality is receptor-independent and therefore more effective.(EGUC)
This concept follows from the still widely held belief, ‘no acid, no ulcer’ (Fig 19). The current treatment of choice is to suppress acid production from the parietal cells. These cells release acid when any one of 3 distinct receptors (histamine, acetylcholine, gastrin) is stimulated. Currently, the most popular treatment involves an histamine receptor antagonist (H2 blocker). The proton-pump inhibitors constitute a new treatment approach that blocks acid production within the cell. This modality is receptor-independent and therefore more effective.(EGUC)
Histamine receptor (H2) antagonists
Histamine receptor (H2) antagonists
The problem with treatment of gastric ulcers in horses is that individuals have different dose requirements for effective treatment. This probably relates to varying bioavailability of the drug in individual horses. The bioavailability of H2 antagonists is generally lower in horses than in man. The wide variability among horses in acid suppression achieved with H2 antagonists may be a result of other unknown factors as well; this variability is most pronounced at low doses. The medication selected, dosage and duration of treatment depend on the location and severity of lesions, clinical signs, and owner considerations.,
The problem with treatment of gastric ulcers in horses is that individuals have different dose requirements for effective treatment. This probably relates to varying bioavailability of the drug in individual horses. The bioavailability of H2 antagonists is generally lower in horses than in man. The wide variability among horses in acid suppression achieved with H2 antagonists may be a result of other unknown factors as well; this variability is most pronounced at low doses. The medication selected, dosage and duration of treatment depend on the location and severity of lesions, clinical signs, and owner considerations.,
The recommended dose of oral ranitidine is 6.6 mg/kg bwt 3 times daily. The equivalent dose of cimetidine is 40-60 mg/kg/day; and of famotidine 10 mg/kg/day. Treatment is effective and alleviates clinical signs in those that are affected. Lower dosages may be effective in some horses, but the percentage of individuals that fail to respond increases as the dosage decreases.(Orsini)
The recommended dose of oral ranitidine is 6.6 mg/kg bwt 3 times daily. The equivalent dose of cimetidine is 40-60 mg/kg/day; and of famotidine 10 mg/kg/day. Treatment is effective and alleviates clinical signs in those that are affected. Lower dosages may be effective in some horses, but the percentage of individuals that fail to respond increases as the dosage decreases.(Orsini)
Proton-pump inhibitors
===Proton-pump inhibitors===
This class of compounds is the newest addition to the antisecretory group. Unlike Ha-receptor antagonists, proton-pump inhibitors block the enzyme (pump) responsible for a hydrogen-potassium exchange. Blocking this enzyme exchange retards the final step in parietal cell acid production. Omeprazole, one of 2 compounds in this class currently licensed in the United States for use in man, is now licensed for use in horses. It has demonstrated an excellent efficacy and safety profile. In double-blind, placebo-controlled field trials, omeprazole paste, administered at 4 mgkg bwt was effective in eliminating or substantially reducing the severity of gastric ulcers. At this dose rate, pH >6 persisted for 24 h after the last treatment. In human medicine, omeprazole has been approved for long term and prophylactic use in patients with erosive oesophagitis. This is meaningful, because ulcers in the squamous portion of the equine stomach are most prevalent (>go%) and resemble the human form of erosive oesophagitis.(EGUC)
This class of compounds is the newest addition to the antisecretory group. Unlike Ha-receptor antagonists, proton-pump inhibitors block the enzyme (pump) responsible for a hydrogen-potassium exchange. Blocking this enzyme exchange retards the final step in parietal cell acid production. Omeprazole, one of 2 compounds in this class currently licensed in the United States for use in man, is now licensed for use in horses. It has demonstrated an excellent efficacy and safety profile. In double-blind, placebo-controlled field trials, omeprazole paste, administered at 4 mgkg bwt was effective in eliminating or substantially reducing the severity of gastric ulcers. At this dose rate, pH >6 persisted for 24 h after the last treatment. In human medicine, omeprazole has been approved for long term and prophylactic use in patients with erosive oesophagitis. This is meaningful, because ulcers in the squamous portion of the equine stomach are most prevalent (>go%) and resemble the human form of erosive oesophagitis.(EGUC)
Treatment of uncomplicated equine peptic ulcer disease
Treatment of uncomplicated equine peptic ulcer disease
Antacids
===Antacids===
Treatment with antacids is usually ineffective or impractical because antacids must be administered frequently - every 2 4 h - to be effective, and the volume given - 170-230 g - may necessitate nasogastric tubing.(Orsini)
Treatment with antacids is usually ineffective or impractical because antacids must be administered frequently - every 2 4 h - to be effective, and the volume given - 170-230 g - may necessitate nasogastric tubing.(Orsini)
Antacids, such as magnesium aluminum hydroxide have been used but must be administered frequently (up to 6 to 12 time/day). The therapeutic or prophylactic efficacy has not been critically tested in horses. Furthermore, the number of treatments required would probably be impractical to administer and potentially stressful.(EGUC)
Antacids, such as magnesium aluminum hydroxide have been used but must be administered frequently (up to 6 to 12 time/day). The therapeutic or prophylactic efficacy has not been critically tested in horses. Furthermore, the number of treatments required would probably be impractical to administer and potentially stressful.(EGUC)
Mucosal protectants
===Mucosal protectants===
Sucralphate, a complex salt of sucrose and aluminium hydroxide, has been used successfully to treat gastric and duodenal ulcers in man. Its main protective action is through adherence to the ulcerated surface. The
Sucralphate, a complex salt of sucrose and aluminium hydroxide, has been used successfully to treat gastric and duodenal ulcers in man. Its main protective action is through adherence to the ulcerated surface. The
aluminum and magnesium hydroxide buffering agents may have a prostaglandin-stimulating action as a heavy metal effect. The mucosal protective functions stimulated by prostaglandin E are discussed below.
aluminum and magnesium hydroxide buffering agents may have a prostaglandin-stimulating action as a heavy metal effect. The mucosal protective functions stimulated by prostaglandin E are discussed below.
Sucralphate inhibits pepsin, enhances the protective mucusbicarbonate layer, increases local protective prostaglandins and increases binding and enhancement of local epidermal growth factor, all of which allow ulcers to heal. However, sucralphate is only indicated for gastric glandular or duodenal ulcers, not for gastric squamous ulcers. Sucralphate has no effect on the healing of gastric squamous epithelial ulcers in horses, but is effective in treating gastric glandular ulcers. Therefore, sucralphate should not be used alone in the treatment of gastric ulcers in foals or mature horses without an endoscopic examination confirming glandular ulcers (Murray 1994). (Orsini)
Sucralphate inhibits pepsin, enhances the protective mucusbicarbonate layer, increases local protective prostaglandins and increases binding and enhancement of local epidermal growth factor, all of which allow ulcers to heal. However, sucralphate is only indicated for gastric glandular or duodenal ulcers, not for gastric squamous ulcers. Sucralphate has no effect on the healing of gastric squamous epithelial ulcers in horses, but is effective in treating gastric glandular ulcers. Therefore, sucralphate should not be used alone in the treatment of gastric ulcers in foals or mature horses without an endoscopic examination confirming glandular ulcers (Murray 1994). (Orsini)
Prostaglandin analogues
===Prostaglandin analogues===
When used in man, prostaglandin El analogues are thought to act by inhibiting gastric acid secretion and enhancing mucosal protection. They have been shown to increase bicarbonate and mucus secretion in man and dogs. Published experimental data demonstrate that PGE analogues protect the gastric mucosa from NSAIDinduced ulceration. Side effects (diarrhoea, abdominal distention bloating) reported in man may also apply to the horse. Anecdotal reports vary with regard to safety.(EGUC)
When used in man, prostaglandin El analogues are thought to act by inhibiting gastric acid secretion and enhancing mucosal protection. They have been shown to increase bicarbonate and mucus secretion in man and dogs. Published experimental data demonstrate that PGE analogues protect the gastric mucosa from NSAIDinduced ulceration. Side effects (diarrhoea, abdominal distention bloating) reported in man may also apply to the horse. Anecdotal reports vary with regard to safety.(EGUC)
Gastric prokinetics
===Gastric prokinetics===
Compounds with recognised gastric prokinetic potential, such as bethanechol, metoclopramide, erythromycin, and cisapride, may be useful adjuncts to antacid therapy in the horse in cases in which there is no serious physical obstruction to gastric outflow. With the exception of metoclopramide, each of these agents has been shown to increase gastric emptying rate in controlled experiments in mature horses. Currently, however, only bethanechol has been used as an adjunct treatment of equine gastric ulcer disease and while it appears to have been helpful in some cases, no controlled therapeutic trials have been reported(EGUC)
Compounds with recognised gastric prokinetic potential, such as bethanechol, metoclopramide, erythromycin, and cisapride, may be useful adjuncts to antacid therapy in the horse in cases in which there is no serious physical obstruction to gastric outflow. With the exception of metoclopramide, each of these agents has been shown to increase gastric emptying rate in controlled experiments in mature horses. Currently, however, only bethanechol has been used as an adjunct treatment of equine gastric ulcer disease and while it appears to have been helpful in some cases, no controlled therapeutic trials have been reported(EGUC)
Other compounds
===Other compounds===
Because omeprazole is a substituted benzimidazole, there has been interest in the potential value of the
Because omeprazole is a substituted benzimidazole, there has been interest in the potential value of the
benzimidazole anthelmintic, fenbendazole, for treatment of gastric ulcer disease in the horse. At present there is insufficient scientific evidence to support the use of other benzimidazole compounds.(EGUC)
benzimidazole anthelmintic, fenbendazole, for treatment of gastric ulcer disease in the horse. At present there is insufficient scientific evidence to support the use of other benzimidazole compounds.(EGUC)
Antibiotics
===Antibiotics===
While there is little doubt that H2 blockers and proton pump inhibitors suppress acid production and induce healing in humans, there is an alarming rate of recurrence (50% over 6 months and 95% over 2 years).
While there is little doubt that H2 blockers and proton pump inhibitors suppress acid production and induce healing in humans, there is an alarming rate of recurrence (50% over 6 months and 95% over 2 years).
Recent reports indicating that Helicobacter pylori plays a pivotal role in the disease process led to antibiotic therapies and to the use of antibiotics in combination with acid-suppression therapies.
Recent reports indicating that Helicobacter pylori plays a pivotal role in the disease process led to antibiotic therapies and to the use of antibiotics in combination with acid-suppression therapies.