PPI and H2 antagonists chemistry

Question 1

omeprazole mechanism of action

Answer 1

• omeprazole is diffused through the fatty secretory canals of parietal cells (pH 1)
• this causes omeprazole to be completely ionised and ion trapping occurs causing a build up of omeprazole
• omeprazole is then chemically converted to sulphenamide
• sulphenamide reacts with thiol groups in H+/K+ ATPase enzyme which forms a stable disulphate complex
• no more acid is produced until new enzyme is made

Question 2

omeprazole drug design

Answer 2

• formulated in hard gelatine capsules to prevent conversion of sulphenamide whilst in stomach
• R-enantiomer produced 15% gastric acid inhibition where as S-enantiomer gave 90& inhibition
• S-enantiomer was prepared as esomeprazole