Chemistry of PPIs

Question 1

Pyridylthioacetamide

Answer 1

S-C-N groups overcome C=S toxicity
H 77/67 anti-secretory activity
Pyridine base

Question 2

Timoprazole

Answer 2

Prevents uptake of iodine by thyroid

Question 3

Picoprazole

Answer 3

Free from side effects
Changes adjusting hydrophilicity and hydrophobicity

Question 4

Log P

Answer 4

Unionised, environment has no effect on drug molecule

Question 5

Log D

Answer 5

Distribution coefficient, ionised and unionised states
pH dependant
Less than log P
Prefers aqueous environment over organic (oil)

Question 5

Log D

Answer 5

Distribution coefficient, ionised and unionised states
pH dependant
Less than log P
Prefers aqueous environment over organic (oil)

Question 6

Omeprazole chemistry

Answer 6

Increasing pKa of pyridine ring by placing electron donating groups on it

Permanently charged quaternary ammonium salt

pH decreases to 1 and becomes ionised
Becomes active sulphonamide, salt

Sulphonamide reacts with thiols in food and gastric acid

Question 7

Omeprazole MOA

Answer 7

Stomach - ionised
Intestine - unionised

Conversion to sulphonamide due to steep proton gradient caused by proton pump

Diffuse through fatty secretary canals of parietal cells

Question 8

Omeprazole drug deisgn

Answer 8

Gelatin coated capsule

80mg abolishes acid in 4 hrs

40mg affects acid 72 hrs after given, takes 3-5 for effects to disappear

20mg 2-4 week (duodenal ulcer), 8 weeks (gastric ulcer)

R-enantiomer 15% gastric inhibition
S-enantiomer 90% inhibition (esomprazole)