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Microsoft word - tolbert.gastroprotectants.docxGASTROPROTECTANTS: STRATEGIES FOR USING THEM
WINN FELINE FOUNDATION
Katie Tolbert, DVM, PhD, DACVIM
Gastrointestinal (GI) mucosal protectants including acid suppressants, antacids, misoprostol, and coating agents
(sucralfate, barium) are commonly used for the prevention and treatment of gastritis and ulcerative disease in dogs
and cats. However, results of veterinary studies investigating these drugs are heterogeneous with some studies
failing to demonstrate a benefit. Inappropriate dosing and misuse of these medications for diseases in which they
have not proven to be beneficial are likely to blame. Recently published dosing recommendations and suggested
indications for use of GI mucosal protectants are likely to improve the outcome of dogs and cats with and at risk for
erosive and ulcerative disease. Evidence and indications for the use of acid suppressants can be found as a separate
Sucralfate is a polyaluminum sucrose sulfate that is activated in the acidic environment of the stomach. Its primary
mechanism of action is to coat injured and denuded gastroesophageal mucosal epithelium. Other proposed
mechanisms of action include prostaglandin stimulation and inhibition of substances that could be injurious to the
subepithelium including pepsin and bile acids. Very few studies have evaluated the efficacy of sucralfate for
treatment of mucosal injury. In one of the only available studies, sucralfate was not effective in treatment of GI
bleeding in dogs undergoing spinal surgery and receiving high dose steroids.1 However, sucralfate is relatively
benign with few side effects aside from constipation and potential drug interactions, thus many clinicians including
myself administer the medication to dogs and cats with or at-risk for gastric bleeding. More studies are needed to
determine if this practice is beneficial for dogs and cats. Sucralfate is available in both tablet and suspension form.
Drug interaction studies suggest that sucralfate is not as effective when administered as a tablet.2 Therefore, prior to
administration, the tablets should be crushed and mixed with water to create an oral slurry. The aluminum
component of the sucralfate suspension can interfere with the absorption of other drugs including tetracyclines and
fluoroquinolones. Thus, sucralfate administration should be delayed by at least 2 hours prior to administration of
these drugs.2 Since activation of sucralfate is dependent on an acidic pH, drugs that increase gastric pH (e.g.,
antacids, acid suppressants) should be delayed for at least 1 hr following sucralfate administration.
Barium is speculated to have mucoprotective and pro-coagulant effects. It has been reported to have hemostatic
effects for a variety of causes of gastrointestinal bleeding in humans.3 To my knowledge, it has not been studied in
companion animals but is used frequently in clinical practice. I do not use it in my practice but know many
veterinarians who like to use it in combination with acid suppressants for patients who have severe gastric bleeding
and can tolerate oral medications. Endoscopy should be delayed at least 24 hours following administration of barium
as barium can hinder visualization of the gastrointestinal mucosa and can obstruct the endoscope instrument channel
if aspirated. Barium should not be used if gastrointestinal perforation is suspected.4
Antacids (e.g., calcium carbonate, aluminum hydroxide, magnesium hydroxide) are often incorrectly referred to as
acid suppressants. Unlike acid suppressants, which target the production of gastric acid by the parietal cell, antacids
are acid-neutralizing drugs and have no effect on the parietal cell proton pump. Therefore, antacids have to be
administered more frequently to avoid rebound gastric acid secretion. For this reason, effective administration of
antacids can be problematic in vomiting or anorectic patients. Other proposed mechanisms of action of antacids
include decreased pepsin activation as a result of increased gastric pH, stimulation of bicarbonate secretion, and
formation of complexes with refluxed bile salts. Other common adverse effects of antacids include undesired drug
interactions (as mentioned for sucralfate), constipation (aluminum preparations), and diarrhea (magnesium
preparations). Similar to the coating agents, antacids are a vastly understudied class of drugs in veterinary medicine.
Because of their requirement for frequent administration and the perceived superiority of acid suppressants, I rarely
use antacids for gastric bleeding.
Gastric parietal cells are responsible for the production and secretion of gastric acid. Parietal cells are stimulated by
neural and hormonal inputs. Acid suppressant drugs act to block acid production either at the receptors for these
inputs or directly at the parietal cell proton pumps. Acid suppressants are more effective and have a longer duration
of action and have therefore supplanted antacids as the treatment of choice for documented or suspected acid-related
injury and/or gastric hyperacidity in dogs and cats. Two classes of acid suppressants, histamine-2 receptor
antagonists (H2RAs) and proton pump inhibitors (PPIs), are used in veterinary medicine. H2RAs are competitive
inhibitors for the interaction of histamine with its receptor but differ in potency (famotidine > ranitidine >
cimetidine hydrochloride). Peak concentration of H2RAs occurs within hours after oral dosing. In contrast, PPIs
(e.g., omeprazole, pantoprazole, esomeprazole) form covalent bonds with active proton pumps and are thus
inactivators. New proton pumps are subsequently recruited and require further inactivation; thus delaying the peak
effect (approximately 1–4 days) with PPIs. Pharmacokinetic and pharmacodynamic differences exist between PPI
drugs that might affect clinical response depending on the individual patient and disease. However, most clinicians
use drugs within the PPI class interchangeably.
Misoprostal is a drug that mimics endogenous prostaglandin E1 (PGE1). Its mechanisms of action parallel that of
the endogenous eicosanoid including stimulation of mucus and bicarbonate secretion, increased mucosal blood flow
and epithelial repair. Misoprostal may prevent or reduce gastric hemorrhage secondary to NSAID administration but
is not effective for prevention of steroid-induced GI bleeding even when administered thrice-daily at high doses (4–
6 mcg/kg PO).5 Misoprostal should be reserved for animals with or at high-risk (e.g., older animal, dogs receiving
drugs with predominately COX1 selectivity) for NSAID toxicity. Adverse effects include diarrhea, inappetence, and
abdominal pain. Misoprostal can stimulate uterine contractions and thus should not be used in pregnant animals.
Twice-daily administration may be sufficient as a preventative for at risk animals but I recommend thrice-daily
administration for animals with documented toxicity.6,7
Zinc-ʟ-carnosine formulated with vitamin E (GastriCalm®) is a neutraceutical marketed for treatment of gastric
mucosal injury. Zinc-carnosine has been demonstrated to reduce and/or prevent gastrointestinal lesions in rats;
however, two placebo-controlled studies failed to demonstrate a benefit to the use of GastriCalm in dogs with drug-
induced gastritis.8,9 Thus, I do not currently recommend GastriCalm for the treatment of gastric mucosal injury in
dogs and cats.
Herbal medications including sea buckthorn oil10 and yunnan baiyao have been marketed for their hemostatic
properties. I have used yunnan baiyao for hospice care in dogs and cats with terminal nasal and gastric cancers with
some success. However, most herbal medications do not undergo rigorous safety testing and therefore caution is
advised with their use.
1. Hanson SM, Bostwick DR, Twedt DC, et al. Clinical evaluation of cimetidine, sucralfate, and misoprostol for
prevention of gastrointestinal tract bleeding in dogs undergoing spinal surgery. American journal of veterinary
2. KuKanich K, KuKanich B. The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs.
Journal of veterinary pharmacology and therapeutics 2015;38:169–173.
3. Nagata N, Niikura R, Shimbo T, et al. High-dose barium impaction therapy for the recurrence of colonic
diverticular bleeding: a randomized controlled trial. Annals of surgery 2015;261:269–275.
4. Gfeller RW, Sandors AD. Naproxen-associated duodenal ulcer complicated by perforation and bacteria- and
barium sulfate-induced peritonitis in a dog. Journal of the American Veterinary Medical Association 1991;198:644–
5. Rohrer CR, Hill RC, Fischer A, et al. Efficacy of misoprostol in prevention of gastric hemorrhage in dogs treated
with high doses of methylprednisolone sodium succinate. American journal of veterinary research 1999;60:982–985.
6. Ward DM, Leib MS, Johnston SA, et al. The effect of dosing interval on the efficacy of misoprostol in the
prevention of aspirin-induced gastric injury. Journal of veterinary internal medicine / American College of
Veterinary Internal Medicine 2003;17:282–290.
7. Murtaugh RJ, Matz ME, Labato MA, et al. Use of synthetic prostaglandin E1 (misoprostol) for prevention of
aspirin-induced gastroduodenal ulceration in arthritic dogs. Journal of the American Veterinary Medical Association
8. Baan M, Sherding RG, Johnson SE. Effects of zinc-L-carnosine and vitamin E on aspirin-induced gastroduodenal injury in dogs. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine 2011;25:39–46. 9. Wilson LS, Rosenkrantz WS, Roycroft LM. Zinc-carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis. Veterinary dermatology 2011;22:53–60. 10. Dogra R, Tyagi SP, Kumar A. Efficacy of Seabuckthorn (Hippophae rhamnoides) Oil vis-a-vis Other Standard Drugs for Management of Gastric Ulceration and Erosions in Dogs. Veterinary medicine international 2013;2013:176848.
International Journal of Medicinal Mushrooms, 15(5): 435–448 (2013) Cytotoxicity of Blended Versus Single Medicinal Mushroom Extracts on Human Cancer Cell Lines: Contribution of Polyphenol and Polysaccharide ContentKsenija Durgo,1 Mladen Koncar,1 Drazenka Komes,1 Ana Belscak-Cvitanovic,1 Jasna Franekic,1 Ivan Jakopovich,2* Neven Jakopovich,2 & Boris Jakopovich2