Class H2 Receptor Antagonist

Ranitidine

3/11/10 Part I Notes

Class – H2 receptor antagonist

Mechanism of Action

- competitive blockade of H2 receptors -> decrease in secretion - also decreases action of gastrin & Ach

Pharmaceutics

- injection: 25mg/mL - tablets: 150, 300mg - syrup: 15mg/mL

- IV: 50mg QID - PO: 150mg bd

Indications

(1) peptic ulder disease (2) GORD (3) Zollinger-Ellison syndrome (4) preventionf of stress ulceration in ICU (5) prior to GA in aspiration risk

Adverse Effects

- LFTs derangement - rash - anaphylactoid reaction - confusion - thrombocytopenia - leukopenia

Absorption – bioavailability = 50% Distribution – 15% protein bound, Vd = 1.5 L/kg Metabolism – hepatic Elimination – t ½ = 2 hrs

Evidence

Jeremy Fernando (2011) Cook, D et al (1998) “A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation” Canadian Critical Care Trials Group, NEJM, 338:791-7

- MRCT - placebo vs ranitidine vs sucralfate -> GIH: placebo ( ), ranitidine (1.7%), sucralfate (3.8%) – P < 0.05 -> pneumonia incidence: ranitidine (19.2%), sucralfate (16.2%) – P > 0.05 -> no change in LOS or mortality

Mariki, P. E. et al (2010) “Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis” Critical Care Medicine: Volume 38 - Issue 11 - pp 2222-2228

Background

- stress ulceration uncommon (1%) - prophylaxis may be unwarranted if feeding can be established early - prophylaxis may increase risk of hospital-acquired pneumonia and Clostrodium difficile infection

- meta-analysis of RCT’s - histamine-2 receptor blockers vs placebo - 17 studies (1836 patients)

- primary end point: clinically significant GIH - secondary end points: incidence of HAP and hospital mortality. - sub group analysis performed by grouping studies by enteral nutrition or no enteral nutrition

-> significant decrease in risk of gastrointestinal bleeding (OR 0.47, p < 0.02) -> BUT only noted in a subgroup of patients who did not receive enteral nutrition (OR 1.26, CI 0.43-3.7) -> if patients fed, prophylaxis did not alter the risk of GI bleeding -> no increase in risk of HAP overall -> BUT, those who were fed had an increased risk of HAP (p 0.02, or 2.81) -> stress ulcer prophylaxis did not change mortality -> the subgroup who received stress ulcer prophylaxis AND enteral feeding had a elevated HAP rate (? both increasing gastric pH and thus allowing gastric multiplication of bacteria and subsequent aspiration)

Internal Validity

- clinically significant GIH was defined by each individual study - if there wasn’t a definition of clinically significant bleeding then endoscopic bleeding was used. - used H2 antagonists: cimetidine, ranitidine, famotidine - varying doses - some studies ran infusions - only 3 studies looked at enteral nutrition

External Applicability

- we use omeprazole

Jeremy Fernando (2011) - those who were fed may have been sicker than those that weren’t which may explain increase in HAP and death (confounding)

MY APPROACH

- feed early unless contraindicated - don’t use prophylaxis if feeding established - if unable to establish enteral feed, risk assess for GIH: if high risk -> use prophylaxis - if develops stress ulcers treat - vigilance for the development of hospital acquired pneumonia - may need to take ulcer prophylaxis of FASTHUG sticker!

Jeremy Fernando (2011)