Flashcards in Pharm GI drugs 1 Deck (48):
1
what stimulates acid production?
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
2
where is stomach acid made and what stimulates its release?
parietal cell - stimulated by histamine, gastrin, and acetylcholine
3
how does acetylcholine stimulate the proton pump?
through Ca activating a protein kinase
4
how does gastrin stimulate the proton pump?
through Ca activating a protein kinase
5
how does histamine stimulate the proton pump?
through g couple protein causing increased cAMP which activates teh protein kinase
6
what has an inhibitory affect on acid release?
prostaglandin E2
7
what is the approach to treating ulcers?
1. relief of symptoms (esp pain)
2. promotion of healing
3. prevention of complications such as perforation, hemorrhage, scar formation
4. prevention of recurrence
8
what are the three mechanisms for pharmacologic interventions for treatment of ulcers?
1. neutralize acid
2. decrease acid production
3. increase mucosal resistance
9
what pharmacologic agents are used to neutralize acid?
antacids
10
what pharmacologic agents are used to decrease acid production?
1. anticholinergics (antimuscarinic)
2. antihistamines
3. proton pump inhibitors
11
what pharmacologic agents are used to increase mucosal resistance?
1. prostaglandins
2. sucralfate
3. bismuth
12
what does acid neutralizing efficiency depend on?
1. neutralizing power of the antacid
2. the degree or rate of acid secretion
3. the rate of stomach emptying
13
what are the characteristics of an ideal antacid?
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
14
what are the antacids?
1. calcium carbonate
2. sodium bicarbonate
3. magnesium hydroxide and magnesium carbonate
4. aluminum hydroxide
15
calcium carbonate therapeutics and side effects
therapeutics: ulcer and GERD
SE: milk-alkali syndrome, nephrocalcinosis, "rebound" acidity, digitalis antagonism
16
sodium bicarbonate therapeutics and side effects
therapeutics: ulcer and GERD
SE: systemic alkalosis (rarely used now)
also enhanced effects of amphetamine, quinidine, and cinchophen
17
magnesium hydroxide and magnesium carbonate therapeutics and side effects
therapeutics: ulcer and GERD
SE: diarrhea!, hypokalemia, hypermagnesemia, iron deficiency
*magnesium toxicity in renal disease
18
aluminum hydroxide therapeutics and side effects
therapeutics: ulcer and GERD
SE: phosphate depletion and sequelae (weakness, anemia, tetany, apnea), constipation!
*used in patients with renal failure (also helps eliminate phosphate!)
19
what are other common ingredients used in antacid preparations?
1. defoaming agent (antiflatulent effects)
2. sodium (can cause some salt and water retention - careful in cardiac failure, edema, ascites, HTN)
20
what do antacids cause enhanced absorption of?
dicumarol and L-dopa
21
what do antacids caused reduced absorption of?
phenothiazines, INH, nalidixic acid, nitrofurantoin, penicillin G, sulfonamides, calcium
22
what is a difficulty when prescribing antacids?
patient compliance (stop when pain stops and then ulcer relapses)
23
side effects of anticholinergic agents
dryness of mouth, blurred vision, atony of the bladder, constipation, drowsiness, mental confusionatropine
24
what are the anticholinergics used to decrease acid production?
atropine sulfate, propantheline, metantheline bromide
25
when are anticholinergics administered?
30 min before meals and at bedtime
26
what are contraindications for anticholinergics?
pyloric obstruction, patients with hiatus hernia, peptic esophagitis
27
what are the drugs that competitively inhibit the histamine H2 receptor?
-tidines
cimetidine, ranitidine, famotidine, nizatidine
28
why are the H2 receptors blockers good drugs to use for decreasing acid production?
-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
29
what is a disadvantage to using H2 blockers?
rebound hyperacidity (more acid output after stopping treatment) - need to taper dose
30
side effects of H2 blockers?
severe adverse effects uncommon. headache, lethargy, confusion, depression, hallucinations
31
what are the proton pump inhibitors?
-prazoles
omeprazole, lansoprazole, rabeprazole, esomeprazole, pantoprazole, dexlansoprazole
32
when are proton pump inhibitors (-prazoles) taken?
~30 min before you eat - parietal cell has to be turned on in order to be turned off
33
which proton pump inhibitor can be given IV and has no P450 inhibition?
pantoprazole
34
what is the proton pump inhibitor mechanism?
non competitively inhibits more than 90% 24 acid secretion but requires acid environment to activate (can't take with antacids)
35
proton pump inhibitor clinical uses?
ulcer treatment, GERD
36
which -prazoles are effective at treating H pylori? what are they prescribed with?
omeprazole and lansoprazole
-triple therapy: add tetracycline, metronidazole, and clarithromycin
37
adverse side effects of -prazoles
headache, gynecomastia, inhibition of cytochrome P450 (delayed metabolism of diazepam, warfarin, dilantin), gastric hyperplasia long term (don't use long term)
38
which proton pump inhibitors have the most P450 interference?
omeprazole and lansoprazole
39
what is the prostaglandin E analog? what is its mechanism
misoprostol - decreases acid production, increase mucous and bicarbonate secretion
40
when is misoprostol used?
ulcer treatment when prostaglandin production is decreased (RA patients taking lots of NSAIDs)
41
what mechanisms maintain mucosal integrity?
epithelial cells secreting mucus and bicarbonate
mucosal blood flow
42
what is a characteristic of duodenal ulcer patients?
acid stimulated bicarbonate production is reduced
43
what are factors impairing mucosal resistance to acid?
smoking, genetics, stress, NSAIDs, H pylori leading impaired mucosal defense = ulcer
44
what are mechanisms to increase mucosal resistance?
1. coat ulcer crater (bismuth salts and sucralfate)
2. increase mucous and bicarb secretion (prostaglandin E2 analogs)
3. eradicate H Pylori
45
bismuth mechanism
mechanical protector: coats teh ulcer crater, increasing mucosal resistance
46
sucralfate mechanism
mechanical protector: an aluminum hydroxide complex of sucrose, binds to ulcerated tissue, activated in acid environment
47
side effects of mechanical protectors (bismuth salts and sucralfate)
no serious adverse effects - occasional constipation, aluminum toxicity, possible renal failure
48