Pharmacology of GORD/Peptic Ulcer Disease

Question 1

what drug class is naproxen?

Answer 1

NSAID

Question 2

naproxen is commonly used to treat?

Answer 2

swelling and pain due to menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever

Question 3

mechanism of action of naproxen to reduce pain

Answer 3

inhibits COX enzymes (non-selective, both 1 +2) at peripheral nociceptive nerve endings

Question 4

mechanism of action of naproxen to reduce inflammation

Answer 4

indirectly through its pain reduction mechanism, COX produce prostaglandins which mediate inflammation, naproxen inhibits COX

Question 5

how can naproxen cause intermittent upper abdominal pain (adverse effect)?

Answer 5

inhibits COX 1 enzyme on gastric mucosal cells > inhibits prostaglandin production > inhibits prostaglandin mediated protection of gastric mucosa

Question 6

describe prostaglandin mediated protection of gastric mucosa

Answer 6

increase bicarbonate release
increase mucus production
increase blood flow

Question 7

topical drugs can cause?

Answer 7

systemic side effects

Question 8

why shouldn’t naproxen and diclofenac be prescribed together?

Answer 8

increases risk of side effects in the GI tract e.g. inflammation, bleeding, ulceration, + rarely, perforation

Question 9

what is the best course of action for patient with peptic ulcer disease, no active bleeding and H. pylori negative?

Answer 9

for patients on NSAID, stop NSAID where possible, offer full-dose proton pump inhibitor therapy for 4-8 wks

Question 10

give an example of PPI therapy

Answer 10

omeprazole:20 mg orally once daily

Question 11

what drug class in omeprazole?

Answer 11

proton pump inhibitor

Question 12

what drug class in diclofenac?

Answer 12

NSAID

Question 13

mechanism of action of proton pump inhibitors

Answer 13

inhibits H+/K+-ATPase on parietal cells > reduced acid production

Question 14

compare treatment recommendations vs in practice for PPI prescriptions

Answer 14

data suggests most are treated at twice the standard dose for at least 3 months

Question 15

if a patient has osteoporosis why is a histamine receptor antagonist chosen instead of a PPI?

Answer 15

PPI increase risk of fracture

Question 16

recall a proposed mechanism for how PPIs can increase risk of fracture

Answer 16

mechanism of action unclear, although absorption of calcium salts is pH dependent, so the change in pH induced by PPIs might be responsible for reduction in absorption + decrease in calcium available for bone

Question 17

mechanism of action of histamine (H2) receptor antagonists in the treatment of peptic ulcer disease

Answer 17

targets H2 receptor on cell surface of the parietal cell > decrease acid production via cAMP dependent activation activation of H+/K+ ATPase