Antacids Flashcards
Main pathomechanisms of GI ulceration and main DDx
Direct injury
Interference with prostagladins
Interference with mucus or bicarbonate
Reduced blood flow
Hypersecretion of gastric acid
Main DDX: neoplasia (46% of cats), MCT, gastrinoma, gastritis, Helicobacter, FB, hepatic disease,
Mechanism of NSAID induced
NSAIDs can cause direct mucosal damage and interfere with PG production → blood flow → mucus and bicarbonate production.
They also increase the risk of gastric perforation in both dogs and cats.
COX 2 selective NSAIDs are less ulcerogenic in humans but this has not been demonstrated in dogs/cats
PG Independent direct damage can occur from ion trapping of the drug within cells. Most NSAIDS are weak organic acids remaining non-ionised in gastric juice and lipid soluble. Diffusing across the gastric mucosal epithelial cell membranes in the cytoplasm they are re-ionised and thus trapped within cells leading to cellular injury through mitochondrial damage and free radical generation.
How does coadministration of PPI and NSAID increase ulcer risk
SIBO can increase risk of intestinal ulceration when used concurrently with NSAIDs - most notable near duodenal papilla due to enterohepatic cycling of NSAID
This is a non-PG related direct injury to mucosa and due to enterohepatic recycling of NSAID resulting in its concentration at the duo pap –> mucosal injury
Combined with dysbiosis and predominance of G- bact from dysbiosis
Recent studies supporting negative effects of NSAID and PPI coadministration
JVIM 2020 - coadministration of carprofen and omeprazole INCREASED faecal calprotectin and DI compared to baseline or carprofen alone.
No difference in plasma iohexol or LPS levels.
Increased intestinal inflammatory marker and dysbiosis with concurrent omeprazole
JVIM 2021 - prospective, random, PC, DB trial of adverse effects in dogs receiving piroxicam +/- omeprazole or famotidine
GI AEs ~80% in both acid suppression groups and were more severe than placebo group.
JVIM 2023 - omeprazole + probiotic did not change frequency of AES or alter faecal calprotectin/SCFA. Though higher DI reported.
Antacids (Al-OH, Ca-CO3, Mg-OH) MOA, ACVIM consensus
May ↓ pepsin, bind bile acids in stomach, stimulate local PGE2 synthesis.
- not strong enough buffer to increase gastric pH
Although antacids may produce partial short-term neutralization of gastric acid, insufficient evidence is available to recommend antacids for treatment of gastroduodenal ulceration and erosion (GUE) or GER disease in dogs and cats. These agents may be difficult to administer with the frequency needed to control gastric acid, and other longer acting and more effective acid-suppressing agents are available
H2R antags (ranitidine, famotidine) - MOA, ACVIM consensus
Block H2R –> reduced parietal cell H+ release
Tolerance develops
There is a lack of benefit for administration of H2RAs on a once-daily basis in dogs and cats to treat GUE and reflux esophagitis. Monotherapy with an H2RA given twice daily is inferior to PPI treatment given twice daily in dogs and cats. There is no evidence of benefit of administration of an H2RA with a PPI for ulcer healing, and this combination may diminish the effectiveness of the PPI
Subsequent study showed famotidine CRI inferior to q12 esomeprazole IV
PPI - MOA, ACVIM consensus
substituted benzimidazole drugs that target the final common pathway of acid production.
- acidic environment required for them to become protonated => forms disulphide bonds to H+/K+ATPase preventing new proton release.
Acid secretion only resumes when new proton pumps are generated
Max inhibitory effect 2-4 days
CytoP450 drug
May cause SIBO, affect other drug absorption,.
Taper after prolonged use to prevent rebound hyperacidity
Misoprostol - MOA, indications, ACVIM consensus
synthetic PGE1 analogue with relative specificity for parietal cell receptor and decreases histamine, pentagastrin and meal stimulated gastric acid secretion.
→ increased HCO3 secretion, decreased pepsin, preservation of tight junctions, increased mucosal blood flow
Misoprostol is effective for decreasing gastric lesions in dogs treated with high-dose aspirin, but it is unknown if misoprostol is effective for preventing GUE associated with administration of other NSAIDs in dogs and cats. There is no evidence that misoprostol decreases GUE from glucocorticoids in dogs and cats
Sucralfate MOA, indications/ACVIM guidelines
- Forms stable complexes with protein in damaged mucosa.
- In acid becomes viscous & interferes with action of pepsin (binding to or barrier to prevent diffusion)
→ stimulates PG release - Intraluminal pH buffering for oesophageal acid injury
JVIM 2018 - ex vivo study reported faster recovery of barrier function after injury with sucralfate application on gastric antral mucosa
Impairs absorption of multiple other drugs
There is moderate evidence that sucralfate may have analgesic effects in people post-tonsillectomy, but no studies have evaluated the analgesic properties of sucralfate in people or animals with esophagitis.
No evidence of benefit to combining with PPI or H2R antag
ACVIM recommendations of indications for antacids
Gastric ulcers - duh, PPis only one with evidence
GER - lack of evidence in dogs/cats but good empirical evidence in people of benefit (also that PPi > H2R antag). Especially if undergoing GA and high risk (but will not prevent reflux just reduce acidity)
Unsure - Gastritis, hepatic disease (ulcers reported in 10% in recent study, may be used as prophylactic??)
Nope - pancreatitis, Helicobacter, Thrombocytopaenia associated mucosal bleeding, CKD
What did studies of antacid prescribing habit sin hospitals find
- often not adequate indication based on consensus (one study reported improvement after publication)
- frequently inadequate dosing
- often no instructions provided for duration, timing with feeding or tapering if indicated
Similar in 2 dog and 1 cat study.
