Specialty Spotlight: The Rational Use of PPIs – How Much is Too Much?

September 25th, 2024 | Posted in General, Medical Articles

The Rational Use of PPIs – How Much is Too Much?
Samantha Duxbury DVM, DACVIM (SAIM)

Physiology:
Gastric acid secretion is a normal physiologic process for which the stomach has inherent, natural protective mechanisms to prevent erosion and ulceration¹. Gastric acid has several important roles and aids in protein digestion as well as the absorption of cobalamin, iron² and calcium³. Furthermore, it also suppresses bacterial overgrowth in the stomach which in turn contributes to maintenance of the intestinal microbiome⁴.

Mechanism of Action:
Proton pump inhibitors (PPIs) bind the H-K-ATPase on the secretory surface of the parietal cell which results in inhibition of hydrogen ion release into the stomach. PPIs typically take 2-4 days to reach maximal efficacy^5,6.

Prescribing patterns:
PPIs have been repeatedly demonstrated to be over-prescribed in human medicine despite clear prescribing guidelines and recent studies suggest similar prescribing patterns in veterinary medicine^7,8. This may contribute to adverse events, unintended medication interactions and play a role in caregiver burden and client compliance associated with medication administration.

Indications for use⁹:

1. Reflux or erosive esophagitis
2. Gastroduodenal ulceration and erosion with or without upper GI bleeding
3. Gastric or duodenal perforation
4. Prophylaxis for diseases mediated by gastric hyperacidity (mast cell disease, gastrinoma)
5. NSAID toxicosis

Unknown Indication for use⁹:

1. IHPSS
   • One retrospective study evaluating endovascular treatment of IHPSS suggested a decrease in deaths associated with GI bleeding following implementation of life-long acid suppression¹⁰.
2. CKD IRIS Stage IV
   • New studies suggest dogs with CKD may not develop hypergastrinemia and gastric hyperacidity as previously suspected¹¹
3. Thrombocytopenia-induced GI bleeding
   • Gastric pH > 6.8 may aid in clot stabilization, but commonly prescribed PPIs (pantoprazole, omeprazole) do not adequately achieve this target pH⁹. Esomeprazole may be promising for future study¹².

No indication for use⁹:

1. Treatment of nausea
2. Gastritis
3. Pancreatitis
4. Hepatic disease (with the possible exception of IHPSS)
5. CKD IRIS stage 1-3
6. Ulcer prophylaxis when prescribing NSAIDs or steroids

Outpatient prescribing of Acid Suppressants:
Omeprazole is generally considered superior to famotidine, which demonstrates a diminished acid suppression with continued administration and fails to meet pH goals for ulcer healing by day 13¹³. Although omeprazole has been previously recommended to be administered once daily, several studies have demonstrated that twice daily administration is necessary to achieve pH goals outlined for people to promote gastric ulcer healing. Doses as low as 0.5 mg/kg PO are likely effective as long as they are administered every 12 hours^14,15.

-Samantha Duxbury, DVM, DACVIM (Internal Medicine)

References

1. Abdel-Salam OM, Czimmer J, Debreceni A, et al. Gastric mucosal integrity: gastric mucosal blood flow and microcirculation. An overview. J Physiol Paris. 2001; 95(1–6): 105-127.
2. Betesh AL, Santa Ana CA, Cole JA, Fordtran JS. Is achlorhydria a cause of iron deficiency anemia? Am J Clin Nutr. 2015; 102: 9-19.
3. Haffner-Luntzer M, Heilmann A, Heidler V, et al. Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton. J Orthop Res. 2016; 34: 1914-1921.
4. Friis-Hansen L. Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse. Scand J Clin Lab Invest. 2006; 66: 607-621.

1. Äbelö A, Holstein B, Eriksson UG, Gabrielsson J, Karlsson MO. Gastric acid secretion in the dog: a mechanism-based pharmacodynamic model for histamine stimulation and irreversible inhibition by omeprazole. J Pharmacokinet Phar. 2002;29(4):365-382.
2. Larsson H, Carlsson E, Junggren U, et al. Inhibition of gastric acid secretion by omeprazole in the dog and rat. Gastroenterology. 1983;85(4):900-907.

7. Duxbury S, Sorah E, Tolbert MK. Evaluation of proton pump inhibitor administration in hospitalized dogs in a tertiary referral hospital. J Vet Intern Med. 2022;36(5):1622-1627. doi:10.1111/jvim.16491
8. Ullal TV, Marks SL, Evenhuis JV, Figueroa ME, Pomerantz LK, Forsythe LR. Evaluation of gastroprotectant administration in hospitalized cats in a tertiary referral hospital. J Feline Med Surg. 2023;25(10):1098612X231201769. doi:10.1177/1098612X231201769
9. Marks SL, Kook PH, Papich MG, Tolbert MK, Willard MD. ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats. J Vet Intern Med. 2018;32(6):1823-1840. doi:10.1111/jvim.15337
10. Weisse C, Berent AC, Todd K, Solomon JA, Cope C. Endovascular evaluation and treatment of intrahepatic portosystemic shunts in dogs: 100 cases (2001-2011). J Am Vet Med Assoc. 2014 Jan 1;244(1):78-94. doi: 10.2460/javma.244.1.78. PMID: 24344856.
11. Grady K, Ernst E, Secoura PL, et al. Gastric pH and serum gastrin concentration in age-matched healthy dogs and dogs with chronic kidney disease. J Vet Intern Med. 2023;37(6):2119-2124. doi:10.1111/jvim.16907
12. Kuhl A, Odunayo A, Price J, et al. Comparative analysis of the effect of IV administered acid suppressants on gastric pH in dogs [published correction appears in J Vet Intern Med. 2020 May;34(3):1359. doi: 10.1111/jvim.15790]. J Vet Intern Med. 2020;34(2):678-683. doi:10.1111/jvim.15718
13. Tolbert MK, Graham A, Odunayo A, et al. Repeated Famotidine Administration Results in a Diminished Effect on Intragastric pH in Dogs. J Vet Intern Med. 2017;31(1):117-123. doi:10.1111/jvim.14615
14. Bersenas A, Mathews K, Allen D, et al. Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs. Am J Vet Res. 2005; 66(3): 425-431.
15. Gaier A, Price J, Grubb L, Fitzgerald S, Tolbert MK. A prospective, randomized, masked, placebo-controlled crossover study for the effect of 10 mg omeprazole capsules on gastric pH in healthy dogs. J Vet Intern Med. 2021; 35(2): 887-891.