P cab

potassium competitive acid blocker in contrast to Proton pump inhibitors

1. Potassium-Competitive Acid Blockers Dr. sumit kumar mahato

2. Potassium-competitive acid blockers (P-cabs) are a group of drugs developed in the early 1980s. First drug developed was SCH28080, an antisecretory drug inhibited H+K+ATPase via a competitive interaction with K+ site of the enzyme. Drug was stopped due to its toxic effects on the liver AZD0865( Linaprazan ), a reversible inhibitor of H+K+ATPase with rapid onset of action. In phase II and III trials, showed similar efficacy to esomeprazole for treating esophagitis and for symptomatic relief of nonerosive reflux disease (NERD) Further trials could not be conducted on this drug, as it was not superior to esomeprazole, and there was an adverse drug reaction: hepatotoxicity with reversible elevation of hepatic transaminases

3. Tegoprazan was approved for the treatment of erosive esophagitis (EE) and NERD in South Korea in July 2018.

4. Pharmacokinetics

5. THERAPEUTIC BENEFITS OF P-CABs GERD is a common condition leading to various gastrointestinal symptoms and complications Goals of the treatment: Symptomatic relief, Heal and maintain remission of Erosive Esoghagitis , Prevent complications and Improve quality of life. PPIs and H 2 receptor antagonists are the current treatment of choice of this condition, by causing gastric acid suppression

6. 21 (87.5 %) out of 24 patients, esophageal mucosal breaks were successfully treated by 20 mg VPZ. The median frequency scale for the symptoms of gastroesophageal reflux disease ( FSSG) score was significantly lower on days 1–7, 14, and 28 after the initiation of VPZ .

7. Based on these trials , 10 mg of vonoprazan was approved for maintenance therapy to prevent recurrence of erosive reflux disease in Japan. In case of failure with this dose , 20 mg of vonoprazan can be used for maintenance

8. Peptic ulcer disease Vonoprazan has been approved in Japan for the treatment of gastric and duodenal ulcers. Two randomized controlled trials were conducted to evaluate the drugs vonoprazan and lansoprazole for the treatment of gastric ulcer (GU) and duodenal ulcer (DU). For GU, approximately 93.5% of patients treated with vonoprazan and 93.8% of patients treated with lansoprazole achieved a cure with a difference of 0.3% in cure rate. In case of DU, 95.5% of patients on vonoprazan and 98.3% on lansoprazole achieved a cure, a difference of 2.8%, vonoprazan was not inferior to lansoprazole. Treatment-emergent adverse events with vonoprazan were slightly lower in GU than DU

9. H. pylori eradication On 27 February 2017, WHO listed H. pylori among the 16 antibiotic-resistant bacteria that pose the greatest threat to human health H. pylori infection can be eradicated by elevating intragastric pH using an acid suppressant in combination with at least 2 antibiotics . H. pylori enters the growth phase from a stationary phase at intragastric pH above 5, where it becomes susceptible to antibiotics. A multicenter study was done to assess the safety and efficacy of vonoprazan -based triple treatment . The triple therapy included treatment with vonoprazan and two antibiotics (amoxicillin and clarithromycin or metronidazole).

10. 1st line included vonoprazan 20 mg, amoxicillin 750 mg and clarithromycin 200 or 400 mg, twice a day for one week 2nd line consisted of vonoprazan 20 mg, amoxicillin 750 mg, and metronidazole 250 mg, twice a day for one week. Concluding that vonoprazan -based triple therapy was safe and effective for H. pylori eradication The eradication among 799 patients in the study was 94.4% in the per-protocol analysis for the first-line therapy and 97.1% for the second-line therapy.

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12. Secondary prevention of low dose aspirin or NSAID induced gastric mucosal damage

13. Conclusion Vonoprazan overcomes many of the weakness of traditional PPI therapy vonoprazan is superior to conventional PPIs for suppressing acid secretion, especially at night i.e nocturnal acid breakthrough N o difference in efficacy depending on CYP2C19 genotype status

14. Thank you

15. The relative potency of other antisecretory drugs has clinically been based on their ability to maintain intragastric pH above a desired value. For example, a pH of ≥3 for ulcer healing, a pH of ≥4 for reflux esophagitis, and a pH of ≥6 for cure of H pylori infections and prevention of rebleeding after endoscopic hemostasis. Relative PPI potency is mostly based on pH4time, defined as the time the intragastric pH remains ≥4 over 24 hours after ≥5 days of therapy. Relative PPI potency, defined in omeprazole equivalents (OE), has been determined for Western populations based on pH4time for once a day and twice a day administrations.

16. Antimicrobials that are used clinically against H. pylori are: amoxicillin, clarithromycin, tetracycline and metronidazole/ tinidazole . The US-FDA approved regimen is: Lansoprazole 30 mg + Amoxicillin 1000 mg + clarithromycin 500 mg, all given twice daily for 2 weeks National Formulary of India (NFI, 2010) suggests a model of 1 week consisting of: Omeprazole 40 mg OD + Metronidazole 400 mg TDS + Amoxicillin 500 mg TDS Quadruple therapy: CBS 120 mg QID + tetracycline 500 mg QID + metronidazole 400 mg TDS + omeprazole 20 mg BD