19 pgs ts ánh ứng dụng đặc điểm dl ppi english

USE OF PPI IN CLINICAL PRACTICE Asso Prof PhD TRẦN NGỌC ÁNH Hanoi Medical University Hospital PPIs: nature & common characteristics • Omeprazole and Lansoprazole is the equilibrium mixture of R and S isomers • Esomeprazole is the S isomer of Omeprazole • Dexlansoprazole is the R isomer of Lansoprazole Mechanism of PPIs • Exogenous substances, a class of compounds called benzimidazoles substituted Similar structure, different functional group • Sulfenamide form of PPIs reaction with or some of cysteine/ proton pump   disulfide covalent bond  irreversible inhibition of proton pump activity  inhibition of HCl secretion Principles of pharmacology: Pathophysiologic basis of drug therapy 4th 2017 Lippincott Williams & Wilkins (Golan) Lippincott's Illustrated Reviews-Pharmacology 6th 2015 PPIs: Pharmacokinetic characteristics Active ingredient Bioavailabili ty Basic & Clinical Pharmacology 13th 2015 McGraw-Hill UpToDate 21.6 (offline) 2015 (h) (h) PPIs: metabolism enzyme Main UpToDate 21.6 (offline) 2015 Sub Mechanism of PPIs • Active form concentrated 100.000 – mil fold in blood • PPIs: strong (>90%) in acid the •  Binding with proton pump by suppression resting covalent bond  permanently and inhibition activation • Potentially acid inhibition: pH >4    Need 18 hours to synthesize a new proton pump during >16h / day • pH> 4: Reduced H + 1000 fold / stomach, the activity of pepsin • PPIs highest ulcer healing Gomollon F Calvet X Drugs 2005; 25-22 Prolonged duration of action by: • There is no more indication of anti H2 Mechanism of PPIs • Before breakfast: reducing acid secretion better than the evening Not affect to acid suppression in night-time • Before lunch: Affect to acid suppression in night-time • If using times/day: before breakfast or lunch • IF NOT RESPONDING: separate dosage?? Increase dosage?? Theo Gomollo F Drugs 2005 • PPI times/day  maximal acid suppression, approx 66% after days of treatment • Using intermittent and "on demand" therapy  acid suppression and clinical response are unreliable • The first dose PPI: only some proton pump are inactivated  need to using continuous medication for 3-4 days to achieve optimal acid suppression 10 ... needed enzyme CYP2C19 /liver to mebolite into active form  prevent platelet aggregation • Due to CYP2C19 metabolism is also related to PPI  hypothesis: the competition by PPIs may reduce the... 21.6 (offline) 2015 (h) (h) PPIs: metabolism enzyme Main UpToDate 21.6 (offline) 2015 Sub Mechanism of PPIs • Active form concentrated 100.000 – mil fold in blood • PPIs: strong (>90%) in acid... dysfunction patients 11 Safety • Guideline on the management of GERD in 2008 (AGA)  Not enough evidence to recommend for or against the below indications in patients taking PPIs:  Bone density