Treatment of acid-peptic disease

Question 1

what are the two main acid-related diseases? pathophysiology of them?

Answer 1

peptic ulcer disease and GERD. from an imbalance of defensive (health epithel, mucus, bicarb, prostaglandins) and agressive factors (HCl, pepsin, NSAIDs, H pylori)

Question 2

types of cells in gastric glands and what do they do?

Answer 2

parietal cells secrete HCl (2.5L a day for a pH <1) and intrinsic factor. chief cells secrete pepsinogen (that get converted into pepsin). mucus cells secrete a layer of bicarb rich, viscous mucus so pH is ~7 at the cell membrane level.

Question 3

schwarz’s dictum?

Answer 3

no acid, no ulcer

Question 4

H pylori (characteristics)

Answer 4

gram negative bacilli - spiral shaped

Question 5

major causal factor for gastric/duodenal ulcers?

Answer 5

use of NSAIDs including low dose ASA

Question 6

3 categories of drugs for acid-peptic disease

Answer 6

antacids. antisecretory drugs. cytoprotective agents

Question 7

what are antacids? they do not? duration of action? also inhibit? bind? cytoprotection?

Answer 7

basic compounds that neutralize HCl; don’t reduce volume of acid secreted; short lived because they raise pH which stimulate more acid and pepsin secretion. inhibit pepsin because increasing pH. can bind bile acids. cytoprotection by increasing bicarb/pge in mucus

Question 8

antacids: chemistry? how much do they change pH?

Answer 8

inorganic salts of Al, Mg, Ca, Na. rarely raise pH above 4.

Question 9

adverse effects of al? ca? mg? na?

Answer 9

Al = constipation. Ca = const, renal stones, hypercalcemia. Mg = diarrhea. Na = fluid retention and flatulence

Question 10

3 antacid combos

Answer 10

Al + Mg to balance side effects. simethicone for antifoaming agent = less bloating/flatulence. alginate = forms a raft that protects lower eso. mucosa

Question 11

drug interactions with antacids - how?

Answer 11

change gastric pH = interfere with absorption. urine pH - elimination. can also decrease drug absorption by adsorption or chelation - ex: tetracycline, iron salts, thyroxin

Question 12

antisecretory drugs act by? (3 ways)

Answer 12

blockade of receptors (H2 blockers, M1 antagonists). inhibit H/K ATPase (PPIs). inhibit intracellular cAMP/Ca metabolism (PGE analogues)

Question 13

Ex of H2 blockers? how they work?

Answer 13

cimetidine, ranitidine, famotidine, nizatidine. competitively & reversibly inhibit binding of histamine
to H2 receptors on parietal cells in a dose-dependent
manner.
Promote healing of ulcers.

Question 14

problem with H2 blockers? adverse effects?

Answer 14

exhibit tolerance = lose efficacy after 1 week. after stopping, can also get temp, rebound hypersecretion of acid. adverse effects: diarrhea, headache, skin rash, confusion, cimitedine with anti-androgenic activity, and inhibit CYP450

Question 15

final common pathway for acid secretion? what drug does what? ex of these drugs?

Answer 15

H/K ATPase aka proton pump on lumen side of parietal cells: can be blocked by PPI which are more effective than H2 blockers. Omeprazole
• Esomeprazole
• Pantoprazole
• Lansoprazole
•Dexlansoprazole
• Ribeprazole

Question 16

PPI: composition? activation? duration of action? when does acid secretion start again?

Answer 16

acid labile weak bases, pro drugs so activated (protonated and trapped) by acid in canaliculi or parietal cells. half life <2h, but duration much longer (can use 1-2 a day and effective). secretion resumes after new PPs are formed in membrane.

Question 17

best time to take PPIs and why

Answer 17

most effective 30-60 mins before meal - when fasting, only 5% PP are active on canalicular membrane, if you take it before eating that’s when most of the PPs will be activated

Question 18

PPI adverse effects

Answer 18

headache, diarrhea, nausea, abdo discomfort. no correlation with cancer. rebound secretion when stopping suddenly. C diff, pneumonia, osteoporotic fractures, low Mg, nephritis.

Question 19

to heal ulcers, what do you have to do

Answer 19

maintain intragastric pH >4 for 16h per day

Question 20

8 uses of PPIs

Answer 20

duodenal/gastric ulcer healing. maintenance therapy to prevent ulcers. eradicate H pylori. prevent NSAID/anti-platelet bleeding. treat GERD/erosive esophagitis. treat acute upper GI bleed. prevent aspiration syndrome. zollinger ellison syndrome.

Question 21

3 cytoprotective agents? what are they?

Answer 21

misoprostol = prostaglandin analgogue with longer half life. sucralfate = complex of sucrose + AlOH that polymerizes into sticky protective gel on top of epithl. cells when pH <4. colloidal bismuth = coats base of peptic ulcers to protect against HCl/pepsin.

Question 22

cytoprotective agents: what is normally synthesized by gastric mucosa? roles?

Answer 22

prostaglandins + prostacyclines - inhibit HCl secretion, increase mucus and bicarb secretion, increase gastric mucosal blood flow, and promote epithl. healing/turnover

Question 23

adverse effects of misoprostol

Answer 23

diarrhea. abdo cramps. increase uterine contractions = abortifacient. teratogenic

Question 24

adverse effects of NSAIDs and mechanism? (2) + PPIs?

Answer 24

local irritation. loss of cytoprotective prostaglandins due to COX 1 inhibition = G/D ulcers, intestinal injuries. PPIs seem to exacerbate mucosal lesions.

Question 25

risk factors for NSAID-associated G/D ulcers/bleeding? (8)

Answer 25

advanced age. previous ulcers. previous GI bleed. more than 1 NSAID or high dose. glucocorticoid/SSRI use. oral anticoags or antiplatelets. other serious systemic disorder. H pylori.

Question 26

3 ways to prevent NSAID-induced G/D ulcers?

Answer 26

PPI recommended. also: misoprostol. double dose H2 blocker.