Clinical Pharmacology Series: NSAIDs, PPIs, H2As, and Antacids

Question 1

systemic and topic pathophysiology of NSAID

Answer 1

1. systemic: prostaglanded mediated

PGs regulate the secretion of bicarbonate and
mucous, inhibit gastric acid secretion, and are
important in maintaining epithelial cell restitution
and mucosal blood flow

 In PG-mediated NSAID-induced GI injury, inhibition
of cyclo-oxygenase ( COX) leads to decreased
mucosal PGs

2. topical: nonprostaglandin mediated

 Most NSAIDs are weak organic acids  Non-ionized and lipid-soluble in gastric milieu  Diffuse across mucosal cell membranes into cytoplasm
(neutral pH), become ionized and lipid-insoluble  Become trapped
and accumulate
within cells, leading
to cellular injury

Question 2

2 COX enzyme isoforms

Answer 2

cytoprotective PG synthesis - COX 1- maintains mucosal integrity. Constant inhibition of COX1 causes ulcers and bleeding

COX2: inflammatory PG synthesis: inhibition of COX2 reduces inflammation, pain and fever.

Question 3

in addition to COX 1 and COX 2 inhibition, how else can NSAIDS cause bleeding?

Answer 3

causes epithelial cell damage, rsulting in impaired platelet aggregation and subsequent injury and bleeding/ TOPICAL THEORY

Question 4

Risk factors for GI complications in NSAID users

Answer 4

1. prior history of complicated ulcers ***
2. Concomitant use of anticoagulants ***
3. Multiple NSAID use, including low-dose aspirin
4. Prior hisotyr of uncomplicated ulcer
5. high HNSAID dose
6. Age >60 years
7. severe illness
8. H. Pylori
9. Concomitant use of corticosteroids

Question 5

prevention strategies of GI risk due to NSAIDS

Answer 5

Question 6

function of antacids

Answer 6

1. neutralize gastric acid
2. inhibit the formation of pepsin (can reduce digestion/absorption)

Question 7

Adverse affects of Al, Mg, Sodium bicarbonate, CO2, and Ca containing antacids

Answer 7

Al containing acids: constipation and osteoporosis

Mg containing antacids: Diarrhea

Sodium bicarb antacids: sodium overload, alkalosis,

Co2 antacids: distention, belching

Ca containinng: Kidney stones

Question 8

drug interactions of antacids

Answer 8

by raising gastric pH and forming insoluble complexes, antacids frequently alter the absorption of other oral drugs

Question 9

PPIs and H2As are labeled as____

Answer 9

anti-secretory agents. these agents reduce gastric acid secretion.

Question 11

____s can suppress secretion of gastric acid in all phases but mainly nocturnal acid secretion. It is used in GERN and treatment of GU/DUs

Answer 11

H2As

Question 12

drug interactions of H2As

Answer 12

H2As inhibit CYP-P450, which inhibits the
metabolism of many drugs
 eg. warfarin, theophylline, phenytoin, quinidine, antacids
 Antacids reduce the absorption of H2As

similar drug interactions as PPIs

Question 13

mechanism of PPI

Answer 13

irreversibly
binds to and inactivates H+/K+
ATPase (“proton pump”),
inhibiting gastric acid secretion
by the parietal cell

Acid secretion resumes only
after synthesis of new enzymes

Question 14

H2Ra or PPI?

Answer 14

PPI works way better than H2As. but give H2A if you need over the counter stuff, or if you have occasional. heartburn, or you’re allergic to all PPIs

Question 15

when should the PPI be given?

Answer 15

13-30 min before the meal.

Question 16

How long to prescribe PPIs for HP eradication? Duodenal ulcer? Gastric Ulcer? GERD? ZES?

Answer 16

HP: 7-14 days

DU: 4 weeks

GU: 8 weeks

GERD: indefinite period of time or use on demand

ZES: Indefinite period of time

Question 17

PPI dosage for active peptic ulcer bleed

Answer 17

1. 80 mg bolus
2. followed by infusion of 8mg/hr over 72 hours
3. 40mg BID if orall intake is resumed