Pharm: Acid Peptic Drugs

Question 1

T/F PUD can involve any of the upper GI organs

Answer 1

T

Question 2

Which cell layer is involved in PUD

Answer 2

PUD includes inflammatory mucosal disorders of the upper GI tract

Question 3

What kind of receptor is the histamine receptor in the fundus of the stomach?

Answer 3

H2

Question 4

What kind of receptor is the acetylcholine receptor in the fundus of the stomach?

Answer 4

M3

Question 5

What activates the H+/K+ ATPase in the parietal cell?

Answer 5

increase in cAMP and intracellular Ca2+

Question 6

Does the H+/K+ ATPase in the parietal cell use energy?

Answer 6

yes

Question 7

What other cells support the HCl secretory function of parietal cells?

Answer 7

neighboring enterochromaffin like cells have receptors for ACh and gastrin and secrete histamine when stimulated.

Question 8

Which excitatory input is not regulated by negative feedback at the level of the parietal cell in gastric acid secretion?

Answer 8

ACh

Question 9

Which cells secrete pepsin

Answer 9

gastric chief cells

Question 10

Above what pH is pepsin inactivated?

Answer 10

4

Question 11

Above what pH is pepsin IRREVERSIBLY inactivated?

Answer 11

6 –> means new enzyme has to be synthesized

Question 12

T/F pepsin will be inactivated by anything that increases the gastric pH

Answer 12

T

Question 13

T/F bile can be damaging to the GI lining in the absence of acid.

Answer 13

T

Question 14

What usually prevents reflux of bile into the stomach and esophagus?

Answer 14

pylorus and LES

Question 15

Bile gastritis is a consequence of surgery in what kind of patient?

Answer 15

in patients in whom the anatomy of the pylorus has been disrupted (pyloroplasty)

Question 16

What environmental factor enhances acid secretion and lowers LES pressure?

Answer 16

caffeine

Question 17

What environmental factor is directly toxic to upper GI organs?

Answer 17

alcohol

Question 18

What environmental factor may increase acid secretion but does not impair mucosal protective factors?

Answer 18

tobacco

Question 19

What areas of the GI tract secret bicarbonate?

Answer 19

stomach, duodenal surface epithelia, mucus neck cells, Brunner’s glands

Question 20

Which prostaglandins enhance cytoprotective mechanisms, increase bicarbonate secretion, increase mucous thickness, and increase mucosal blood flow in the GI tract?

Answer 20

PGE 1 and 2

Question 21

What structural element in the GI tract ensures mucosal integrity against back diffusion of H+?

Answer 21

tight junctions between gastric cells

Question 22

What is the target of PPIs?

Answer 22

H+/K+ ATPase

Question 23

What is the target of H2receptor antagonist?

Answer 23

Rs histamine receptor

Question 24

How are H2RA’s metabolized?

Answer 24

hepatic p450

Question 25

How are H2RA's excreted?

Answer 25

renally

Question 26

How are H2RA's dosed?

Answer 26

continuous dosing for a gastric pH of 4

Question 27

How do H2RA's work?

Answer 27

blocks H2 to limit H+ secretion --> elevated pH inactivates pepsin

Question 28

How quickly are H2RA's absorbed and onset?

Answer 28

rapid absorption and quick onset

Question 29

What are the primary drug interactions of H2RAs?

Answer 29

1. cimetidine binds to p450 and increases levels of warfarin, phenytoin, diazepam 2. ranitidine binds less avidly, famotidine and nizatidine do not bind the p450 systme

Question 30

How do PPI's work?

Answer 30

irreversibly block H+/K+ ATPase in the final common pathway and reduce acid secretion by parietal cells in lumen

Question 31

What kind of receptor function do H2RAs have?

Answer 31

competitive antagonist

Question 32

Of PPIs and H2RAs, which is more effective?

Answer 32

PPIs have more effect and longer lasting effect on acid secretion

Question 33

How are PPIs delivered?

Answer 33

prodrugs with acid resistant coating

Question 34

Where is the outer layer of PPIs dissolved?

Answer 34

small intestine --> alkaline environment

Question 35

T/F lipophilic prodrug of PPI is inactive at neutral/alkaline pH

Answer 35

true

Question 36

How is PPI prodrug absorbed?

Answer 36

blood stream

Question 37

What happens to PPIs at the level of the parietal cell?

Answer 37

cross membrane, protonated, concentrated, sulphonated, binds to atpase

Question 38

Plasma half life of PPIs like omebrazole?

Answer 38

1-2 hours but duration of action is 24-36 hours because of the capsule --> highly effective with single dose inhibiting ~65% of acid secretion

Question 39

PPI side effects

Answer 39

1. high level of gastrin production interferes with negative feedback loop and may cause gastric carcinoid tumors (in rats) 2. long term use reduces calcium absorption and reduced osteoclast acid production = hip fx risk 3. increased respiratory infections from changed bacteria in GI tract

Question 40

weak bases that neutralize HCl to form a salt and H2O are called ____

Answer 40

antacids

Question 41

Antacid adverse effects depend on ____

Answer 41

the specific ion--> but they all have chalky tastes and may affect the absorption of other drugs, specifically tetracyclines

Question 42

Adverse effects of antacids: Mg

Answer 42

diarrhea, muscle weakness --> Mg accumulation can cause renal failure

Question 43

Adverse effects of antacids: AL

Answer 43

constipation, binds phosphate (protects against renal failure) --> may contribute to osteomalacia

Question 44

Adverse effects of antacids: Ca (TUMS)

Answer 44

rebound acid secretion, nephrocalcinosis ("milk alkali syndrome")

Question 45

Tx of H pylori

Answer 45

triple/quadruple regimens: 1. clarithromycin, amoxiccilin ppi 2. clarithomycin, metranidazole, ppi 3. levofloxacin, metronidazole, ppi, bisumuth

Question 46

Misoprostol GI effects

Answer 46

primary prevention of GU in NSAID users, decrease hemorrhage risk if already using NSAID --> use limited by GI side effects of bloating and diarrhea + abortifacient effect

Question 47

Sucralfate MOA

Answer 47

binds to GI mucosa and stimulates mucous, bicarbonate and PGE2 production/secretion --> increases resistance to pepsin * not absorbed, no direct effect on acid production basically coats your tummy and makes you feel better

Question 48

Misoprostol GI effects

Answer 48

primary prevention of GU in NSAID users, decrease hemorrhage risk if already using NSAID --> use limited by GI side effects of bloating and diarrhea + abortifacient effect

Question 49

Sucralfate MOA

Answer 49

binds to GI mucosa and stimulates mucous, bicarbonate and PGE2 production/secretion --> increases resistance to pepsin * not absorbed, no direct effect on acid production basically coats your tummy and makes you feel better