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==Treatment==
==Treatment==
Proton pump inhibitors: only omeprazole (Gastroguard) is licensed for horses. Given PO once daily (4mg/kg) for 3-4 wks, most effective drug at controlling HCl secretion (decreases basal and stimulated release). Expensive and not absorbed in foas with diarrhoea
Despite the wide spread use of antiulcer medications the prevalence of EGUS remains high. This is probably due to the cost of antiulcer agents, which results in shorter than prescribed treatment courses, the administration of sub-therapeutic doses, or substitution of compounded medications or feed supplements that are ineffective (Orsini et al. 2003).(Nadeau 2009)
Omeprazole and ranitidine are approved in many countries for treatment and prevention of EGUS (Andrews et al. 1999; Doucet et al. 2003; Lester et al. 2007), but these drugs are often expensive and require at least 28 days of treatment for complete healing. Omeprazole (4 mg/kg bwt, per os, q. 24 h, 28 days) has been shown to be more effective than ranitidine (6.6 mg/kg bwt, per os, q. 8 h, 28 days) in treatment of EGUS in horses..
Recently, an omeprazole powder (0.5 mg/kg bwt, i.v.) was given to horses daily for 5 days (Andrews et al. 2006). In that study, gastric juice pH significantly increased 1 h after the first injection and remained increased 24 h after the 4th injection and after the 5th daily injection. Due to the variability of gastric juice pH in the horses, the authors recommended the administration of a loading dose of 1 mg/kg bwt, i.v., then a maintenance dose (0.5 mg/kg bwt, i.v.) daily for treatment of gastric ulcers in horses that are not able to be given the oral paste formulation.
In the USA, compounded omeprazole from bulk powders are used as a substitute for the FDA approved formulation. However, these compounds are not regulated and many lack efficacy intreatment of gastric ulcers (Nieto et al. 2002; Merritt et al. 2003; Orsini et al. 2003). These compounds are used because of the expense of approved products.(Nadeau 2009)
Vet Clin North Am Equine Pract. 2009 Aug;25(2):283-301.
New perspectives in equine gastric ulcer syndrome.
Videla R, Andrews FM.
Management of horses with abdominal pain caused by gastric ulcers is especially difficult, because non-steroidal anti-inflammatory agents, typically used to control abdominal pain, may exacerbate this condition.
Acid suppression
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
The 4 most popular Hz antagonists licensed in the United States for man are cimetidine, ranitidine, famotidine and nizatidine. Cimetidine has been shown to affect hepatic disposition of some drugs.
Most of these compounds have been tested in the horse; cimetidine and ranitidine have been studied most extensively (Table 2). Ranitidine at a dose of 6.6 mgkg bwt q. 8 h has been demonstrated to maintain a pH level >4 when horses are allowed free access to hay.(EGUC)
Horses with documented gastric ulcers respond well to treatment with histamine type-2 receptor (Hz) antagonists such as ranitidine (Furr and Murray 1989; Murray and Grodinsky 1992).
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)
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)
Treatment of uncomplicated equine peptic ulcer disease
Omeprazole has the advantages that:
It is licensed for use in horses
Its efficacy has been demonstrated in controlled clinical trials
Its ease of administration and once-daily dosing promotes compliance with a recommended treatment
strategy.(EGUC)
A newer and more effective treatment approach is inhibition of the proton pump, also Proton pump inhibitors bind irreversibly to the enzyme hydrogen-potassium adenosine triphosphate (H+, K+, ATPase) needed for secretion of hydrogen ions from parietal cells into the gastric lumen. The proton pump is the final pathway in gastric acid secretion. Maximum control of acid production is achieved regardless of the stimulus to the parietal cell. One important advantage of proton pump inhibitors is their ability to inhibit acid production for 24 h with once-a-day dosing (Papich 1993). The recommended dose of oral omeprazole is 4.0 mgkg bwt every 24 h.(Orsini)
J Vet Intern Med. 2006 Sep-Oct;20(5):1202-6.
Effects of intravenously administrated omeprazole on gastric juice pH and gastric ulcer scores in adult horses.
Andrews FM, Frank N, Sommardahl CS, Buchanan BR, Elliott SB, Allen VA.
The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste. Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment.
Omeprazole, a substituted benzimidazole Omeprazole inhibits H+K+ATPase, the enzyme responsible for the final production of acid by parietal cells. In man, it has recently been shown that healing of erosive oesophagitis with antisecretory drugs is directly correlated to both the duration of acid suppression over a 24 h period and the elevation of intraoesophageal pH above 4 for at least 96% of the 24 h period (Tibbling 1993). In horses, orally administered omeprazole has been shown to increase stomach pH above 4 and to significantly inhibit gastric secretion for at least 27 h after treatment (Bough et al. 1995) In addition, omeprazole has a longer duration of action than the H2 receptor antagonists and, consequently, only requires once daily dosing (Brown and Rees 1994). No side-effects were observed in any of the horses in our study. Similarly, in 2 studies in which omeprazole was administered orally to horses over a 5 day period no adverse effects were noted (Ryberg et al. 1989; Bough et al. 1995). At the present dosage, omeprazole appears safe for use in horses, although further studies are required. As with human individuals suffering GERD (Gunasekaran and Hassall 1993), once omeprazole treatment was stopped in the horses, ulceration returned within 2 weeks. Presumably the same factors responsible for the development of ulcers in horses were still present at the end of the trial. In man, long-term treatment of GERD has been achieved by placing patents on a maintenance dose of omeprazole (Gunasekaran and Hassall 1993). Although no side-effects were observed in human patients receiving long-term omeprazole therapy (Goldberg
1992; Gunasekaran and Hassall 1993), one potential problem may be that increasing gastric pH may allow bacterial overgrowth in the small intestine by preventing the entry of organisms normally inhibited by gastric acidity. Consequently, further studies are required to determine the long-term efficacy and safety of omeprazole in horses.
Acceptability of omeprazole as a paste was, in general, excellent. Omeprazole, administered once daily at the dosage in this study, was effective in reducing the severity of gastric ulcers in Thoroughbred horses in active race training. Further studies are required to determine the optimal dosage and long-term safety of omeprazole in horses. (Vatistas 1999)
Equine Vet J. 2008 Jan;40(1):41-4.
The effect of omeprazole paste on intragastric pH in clinically ill neonatal foals.
Javsicas LH, Sanchez LC.
Omeprazole paste effectively increases intragastric pH in clinically ill neonatal foals after one dose at 4 mg/kg bwt orally.
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)
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
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.
Results of some recent studies of sucralphate in horses indicate questionable efficacy in the treatment of squamous ulcers.(EGUC)
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
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
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
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)
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).
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.
When compared to acid suppression alone, these combination therapies demonstrate greater short-term efficacy and recurrence rates that were reduced by 80%. In addition to its superior acid-suppression properties, omeprazole has been shown to have a bacteriostatic effect on H. pylori.
Numerous strategies have been developed to combine antibiotics with antisecretory compounds to treat the human syndromes. Omeprazole and amoxicillin have been shown to be the most effective and produce few side effects.(EGUC)
Proton pump inhibitors: only omeprazole (Gastroguard) is licensed for horses. Given PO once daily (4mg/kg) for 3-4 wks, most effective drug at controlling HCl secretion (decreases basal and stimulated release). Expensive and not absorbed in foals with diarrhoea
Histamine H2 receptor antagonists:
Histamine H2 receptor antagonists:
*ranitidine 7mg/kg TID for 3-4wks
*ranitidine (Zantac, Zeneca, UK) 7mg/kg TID for 3-4wks
*cimetidine 25mg/kg QID for 3-4wks (cheaper but less effective so must be given more frequently)
*cimetidine 25mg/kg QID for 3-4wks (cheaper but less effective so must be given more frequently)
Gastric protectants: sucralfate 10-20mg/kg TID for 2-4wks
Gastric protectants: sucralfate 10-20mg/kg TID for 2-4wks
Antacids: magnesium and aluminium hydroxides (NOT recommended as have massive rebound effect)
Antacids: magnesium and aluminium hydroxides (NOT recommended as have massive rebound effect)
Foal tx (see medicine notes)
Controversy: competition and treatment regulations
The administration of medications to horses prior to and during competition has been a source of controversy in the equine world. The administration of antiulcer medications was once forbidden by regulatory authorities during competitions, as it was thought to be a performance enhancing drug. However, in 2000, because of the high prevalence of gastric ulcers in horses and recent information that antiulcer drugs were not performance enhancing (McKeever et al. 2006), the Bureau of the The Federation Equestre Internationale (FEI) with the advice of its Veterinary Committee and Medication Sub-Committee allowed 3 drugs to prevent and treat gastric ulceration: cimetidine, ranitidine and omeprazole. This decision is subject to annual review. However, not all organisations allow the use of antiulcer medications during competition. Although the prevalence of gastric ulcers was found to be 67% in horses competing in endurance rides (Nieto et al. 2004), the Board of the American Endurance Ride Conference (AERC) requested “a variance for the discipline of Endurance Riding to the recently passed FEI Rule allowing the anti-ulcer medication during competition” since they wanted endurance to remain a “no foreign substance category sport” (Higgins 2004). FEI rules supersede national rules for competition so this did create a problem. The view of the AERC is that any horse that needs gastric ulcer medication is too ill to compete and that if a horse needs the drug used as a preventative, it should be withdrawn from competition. These drugs are still listed under prohibited substances in the 2009 Appendices of the AERC Rules and Regulations. Many endurance horses are given concentrated electrolyte paste orally, which are not considered medications by the AERC.
However, a recent study showed that these concentrated pastes may cause gastric ulcers due to their hyperosmolality (Holbrook et al. 2005). Thus, allowing the administration of concentrated electrolyte pastes and not allowing the use of antiulcer medications may put horses competing in endurance rides at risk for EGUS.(Nadeau 2009)
==Prognosis==
==Prognosis==