Pharm GI drugs 1

Question 1

what stimulates acid production?

Answer 1

1. gastrin (form antrum)
2. acetylcholine (vagal inputs, CNS)
3. histamine (stimulated by acetylcholine and gastrin from mast cells)
4. parietal cell H/K ATPase - final common pathway

Question 2

where is stomach acid made and what stimulates its release?

Answer 2

parietal cell - stimulated by histamine, gastrin, and acetylcholine

Question 3

how does acetylcholine stimulate the proton pump?

Answer 3

through Ca activating a protein kinase

Question 4

how does gastrin stimulate the proton pump?

Answer 4

through Ca activating a protein kinase

Question 5

how does histamine stimulate the proton pump?

Answer 5

through g couple protein causing increased cAMP which activates teh protein kinase

Question 6

what has an inhibitory affect on acid release?

Answer 6

prostaglandin E2

Question 7

what is the approach to treating ulcers?

Answer 7

1. relief of symptoms (esp pain)
2. promotion of healing
3. prevention of complications such as perforation, hemorrhage, scar formation
4. prevention of recurrence

Question 8

what are the three mechanisms for pharmacologic interventions for treatment of ulcers?

Answer 8

1. neutralize acid
2. decrease acid production
3. increase mucosal resistance

Question 9

what pharmacologic agents are used to neutralize acid?

Answer 9

antacids

Question 10

what pharmacologic agents are used to decrease acid production?

Answer 10

1. anticholinergics (antimuscarinic)
2. antihistamines
3. proton pump inhibitors

Question 11

what pharmacologic agents are used to increase mucosal resistance?

Answer 11

1. prostaglandins
2. sucralfate
3. bismuth

Question 12

what does acid neutralizing efficiency depend on?

Answer 12

1. neutralizing power of the antacid
2. the degree or rate of acid secretion
3. the rate of stomach emptying

Question 13

what are the characteristics of an ideal antacid?

Answer 13

1. elevate pH to at least 5
2. best taken about 1 hr after each meal (acidity at peak)
3. liquid formulations act more promptly and are more effective than tablet

Question 14

what are the antacids?

Answer 14

1. calcium carbonate
2. sodium bicarbonate
3. magnesium hydroxide and magnesium carbonate
4. aluminum hydroxide

Question 15

calcium carbonate therapeutics and side effects

Answer 15

therapeutics: ulcer and GERD
SE: milk-alkali syndrome, nephrocalcinosis, “rebound” acidity, digitalis antagonism

Question 16

sodium bicarbonate therapeutics and side effects

Answer 16

therapeutics: ulcer and GERD
SE: systemic alkalosis (rarely used now)
also enhanced effects of amphetamine, quinidine, and cinchophen

Question 17

magnesium hydroxide and magnesium carbonate therapeutics and side effects

Answer 17

therapeutics: ulcer and GERD
SE: diarrhea!, hypokalemia, hypermagnesemia, iron deficiency
*magnesium toxicity in renal disease

Question 18

aluminum hydroxide therapeutics and side effects

Answer 18

therapeutics: ulcer and GERD
SE: phosphate depletion and sequelae (weakness, anemia, tetany, apnea), constipation!
*used in patients with renal failure (also helps eliminate phosphate!)

Question 19

what are other common ingredients used in antacid preparations?

Answer 19

1. defoaming agent (antiflatulent effects)

2. sodium (can cause some salt and water retention - careful in cardiac failure, edema, ascites, HTN)

Question 20

what do antacids cause enhanced absorption of?

Answer 20

dicumarol and L-dopa

Question 21

what do antacids caused reduced absorption of?

Answer 21

phenothiazines, INH, nalidixic acid, nitrofurantoin, penicillin G, sulfonamides, calcium

Question 22

what is a difficulty when prescribing antacids?

Answer 22

patient compliance (stop when pain stops and then ulcer relapses)

Question 23

side effects of anticholinergic agents

Answer 23

dryness of mouth, blurred vision, atony of the bladder, constipation, drowsiness, mental confusionatropine

Question 24

what are the anticholinergics used to decrease acid production?

Answer 24

atropine sulfate, propantheline, metantheline bromide

Question 25

when are anticholinergics administered?

Answer 25

30 min before meals and at bedtime

Question 26

what are contraindications for anticholinergics?

Answer 26

pyloric obstruction, patients with hiatus hernia, peptic esophagitis

Question 27

what are the drugs that competitively inhibit the histamine H2 receptor?

Answer 27

-tidines | cimetidine, ranitidine, famotidine, nizatidine

Question 28

why are the H2 receptors blockers good drugs to use for decreasing acid production?

Answer 28

- decrease basal and food stimulated acid secretion - don't have to be administered in relationship to meals - one large dose just as effective as frequent smaller doses - can be used prophylacticly - long-term maintenance, reducing relapse - more convenient = better compliance

Question 29

what is a disadvantage to using H2 blockers?

Answer 29

rebound hyperacidity (more acid output after stopping treatment) - need to taper dose

Question 30

side effects of H2 blockers?

Answer 30

severe adverse effects uncommon. headache, lethargy, confusion, depression, hallucinations

Question 31

what are the proton pump inhibitors?

Answer 31

-prazoles | omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, dexlansoprazole

Question 32

when are proton pump inhibitors (-prazoles) taken?

Answer 32

~30 min before you eat - parietal cell has to be turned on in order to be turned off

Question 33

which proton pump inhibitor can be given IV and has no P450 inhibition?

Answer 33

pantoprazole

Question 34

what is the proton pump inhibitor mechanism?

Answer 34

non competitively inhibits more than 90% 24 acid secretion but requires acid environment to activate (can't take with antacids)

Question 35

proton pump inhibitor clinical uses?

Answer 35

ulcer treatment, GERD

Question 36

which -prazoles are effective at treating H pylori? what are they prescribed with?

Answer 36

omeprazole and lansoprazole | -triple therapy: add tetracycline, metronidazole, and clarithromycin

Question 37

adverse side effects of -prazoles

Answer 37

headache, gynecomastia, inhibition of cytochrome P450 (delayed metabolism of diazepam, warfarin, dilantin), gastric hyperplasia long term (don't use long term)

Question 38

which proton pump inhibitors have the most P450 interference?

Answer 38

omeprazole and lansoprazole

Question 39

what is the prostaglandin E analog? what is its mechanism

Answer 39

misoprostol - decreases acid production, increase mucous and bicarbonate secretion

Question 40

when is misoprostol used?

Answer 40

ulcer treatment when prostaglandin production is decreased (RA patients taking lots of NSAIDs)

Question 41

what mechanisms maintain mucosal integrity?

Answer 41

epithelial cells secreting mucus and bicarbonate | mucosal blood flow

Question 42

what is a characteristic of duodenal ulcer patients?

Answer 42

acid stimulated bicarbonate production is reduced

Question 43

what are factors impairing mucosal resistance to acid?

Answer 43

smoking, genetics, stress, NSAIDs, H pylori leading impaired mucosal defense = ulcer

Question 44

what are mechanisms to increase mucosal resistance?

Answer 44

1. coat ulcer crater (bismuth salts and sucralfate) 2. increase mucous and bicarb secretion (prostaglandin E2 analogs) 3. eradicate H Pylori

Question 45

bismuth mechanism

Answer 45

mechanical protector: coats teh ulcer crater, increasing mucosal resistance

Question 46

sucralfate mechanism

Answer 46

mechanical protector: an aluminum hydroxide complex of sucrose, binds to ulcerated tissue, activated in acid environment

Question 47

side effects of mechanical protectors (bismuth salts and sucralfate)

Answer 47

no serious adverse effects - occasional constipation, aluminum toxicity, possible renal failure

Question 48

what is used to treat h pylori?

Answer 48

triple therapy: PPI or ranitidine bismuth citrate plus 2 of : amoxicillin, clarithromycin, or metronidazole