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Flashcards in Peptic Ulcers, GERD Pharm Deck (51):
1

Categorize gastric acid, HCO3, pepsin and mucus as aggressive vs. defensive factors in the pathophysiology of acid-peptic diseases.

Aggressive factors: gastric acid, pepsin

Defensive factors: mucus, bicarbonate, LES (for GERD)

2

Name two acid-peptic diseases and describe the gastric injury common to them.

GERD
Peptic ulcer disease (PUD)

In all these conditions, caustic effects of aggressive factors overwhelm the defensive factors of the GI mucosa, resulting in mucosal erosions or formation of ulcerations

3

(Pathophysiology of GERD)

What are the two main patterns of LES dysfunction?

(1) Hypotensive LES (weak sphincter where there's not a lot of tension to keep it chronically contracted)

(2) pathologic transient LES relaxations = more frequent openings

4

(Pathophysiology of PUD)

What are two major types of ulcers?

What factors promote formation of ulcers?

Gastric and duodenal*

NSAIDs
H. Pylori
Inc. secretion of gastric acid
Dec. secretion of bicarbonate

*produce more acid particularly @night

5

What are symptoms associated with GERD?

Typical:

heartburn

regurgitation

dysphasia

Atypical: chest pain, hoarseness, chronic cough, sore throat, wheezing

6

What are symptoms associated with peptic ulcers?

Burning pain

Epigastric discomfort and fullness

Belching

7

What pharmacotherapy is available for treatment of acid-peptic diseases?

(1) agents that reduce intragastric acidity:
Antacids
H2- histamine antagonists
PPIs

(2) Agents that promote mucosal defense:
Cytoprotective agents =
Sucralfate
Bismuth compounds
Prostaglandin analogs

8

Describe the neural, paracrine and endocrine factors that regulate gastric acid secretion

Paracrine signaling:
Histamine from ECL cell will stimulate H2 receptor on gastric parietal cell to increase cAMP, resulting in secretion of acid.

Endocrine signaling:
Gastrin from blood vessels will stimulate CCK2 receptors on ECL and G cells => release of histamine and increased intracellular calcium, respectively.

Neural:
Neurotransmitter ACh stimulates M receptors on ECL and G cells to stimulate histamine and increased calcium, respectively

9

What is the MOA of antacids?

Neutralize gastric acid secreted from G cells (protons released from proton pump)

10

What is the clinical use of antacids?

Treatment of intermittent heartburn and dyspepsia

11

What are the instructions for use of antacids?

1 hour after meals

Frequent dosing: q1-2 hrs or to manage acute ulceration

12

What are examples of antacids? What side effects are expected from carbonate-containing formulations?

NaHCO3
CaCO3
Mg(OH)3
Al(OH)3

carbonate-containing release CO2 = gastric dissension and belching!

13

What are side effects of sodium bicarbonate antacids?

Fluid absorption - caution in patients with renal insufficiency, heart failure, high BP

Gastric dissension + belching

14

What are side effects associated with calcium carbonate antacids?

Milk-alkali syndrome: hypercalcemia, renal insufficiency from excessive doses with calcium-containing dairy

Increased gastric acid secretion (since Ca stimulates gastrin)

Gastric distension and belching

15

What are side effects associated with magnesium hydroxide?

Osmotic diarrhea

Hypermagnesemia (in patients with kidney disease)

Can chelate drugs in intestine, leading to dec. drug absorption

16

What are side effects associated with aluminum hydroxide?

Constipation

Can chelate to drugs in intestine, leading to dec. drug absorption

Absorbed and excited by kidneys - NOT for LONG TERM use in patients with renal insufficiency

17

Which salts are usually administered together in antacids?

Mg(OH)3
Al(OH)3

18

What are examples of H2RAs?

"tidines"

Cimetidine
Famotidine
Ranitidine
Nizatidine

19

What is the MOA of H2RAs?

Complete with histamine for H2 receptors on the basolateral membrane of parietal cells to inhibit basal acid secretion

20

What is the clinical use of H2RAs?

Gastric + duodenal ulcers

GERD

Zollinger-Ellison syndrome (tumor that autonomically secretes gastrin, leading to increased gastric acid secretion)

21

How are H2RAs excreted?

Kidneys

Dose reduction in patients with kidney disease

22

What are adverse effects of H2RAs?

CNS: headache, drowsiness, fatigue, muscular pain

GI: diarrhea, constipation

Dermatologic: rashes

Tolerance can develop to H+ suppressing effect because eventually enough histamine can be secreted and accumulate to compete with the H2RAs

23

What are side effects associated with Cimetidine?

Gynecomastia or impotence in men

Galactorrhea (spontaneous flow of milk) in women

24

What are DDIs with H2RAs?

Compete with creatinine and certain drugs for renal tubular secretion

May alter absorption of drugs with gastric pH dependent bioavailability

Cimetidine:
Interferes with hepatic pathways - CYP3A4 inhibitor (prolonged halflife of drugs metabolized through these pathways)

25

What are instructions for use of H2RAs?

Take at bedtime

Reduce nocturnal acid secretion

26

What are examples of PPIs?

"Prazoles"

Omeprazole, esomeprazole
Lansoprazole
Rabeprazole
Pantoprazole

27

What is the MOA of PPIs?

IRREVERSIBLE inhibitors of gastric H/K ATPase (proton pump) in active parietal cells in stomach

Inhibits both fasting and meal-stimulated secretion

28

Describe the anatomic route by which PPIs are delivered to the site of action, including the role of acid-resistant coating and acid-mediated activation.

PPIs are prodrugs. They travel through stomach until they are finally un coated by duodenal sphincter and into blood vessel. Activated in the acidic environment of parietal cell, where they bind to the ATPase irreversibly.

29

What is the therapeutic use for PPIs?

Gastric and duodenal ulcers

GERD

Zollinger-Ellison syndrome (tumors that autonomically secrete gastrin)

30

Briefly explain the difference between esomeprazole and omeprazole regarding its metabolism?

Omeprazole is metabolized by CYP2C19 (racemic mixture)

Esomeprazole is metabolized by CYP2C19 AND CYP3A4 (just the S isomer)

31

What are adverse effects of PPIs?

(Low toxicity)

N/D, abdominal pain, constipation, flatulence

Modest increase in risk of osteoporosis (since acid helps absorb food-bound minerals like calcium)

Subnormal B12 levels (since acid important for its release from food)

Respiratory + enteric infections (acid = defense barrier!)

Increased serum gastrin => can stimulate hyperplasia of ECL cells and can cause rebound acid hypersecretion w/ discontinuation

32

What are DDIs associated with PPIs?

Reduced absorption of drugs that require acidic environment, iron

Omeprazole inhibits CYP2C19 = dec. CL of phenytoin, warfarin, diazepam; inhibits conversion of clopidogrel to active form

33

What are instructions for use for PPIs?

Require systemic absorption before reaching gastric mucosa - so DON"T BREAK enteric coating

Give drug 1 hour BEFORE meal!

34

What is the MOA of Sucralfate?

Undergoes extensive cross linking in acidic environment (prodrug)

Forms viscous paste that binds selectively to ulcers or erosions

Protection of ulcerated area for up to 6 hours

35

What is the clinical use of sucralfate?

Peptic ulcers (rarely used though!)

36

What are adverse effects of sucralfate?

Not absorbed => no systemic AEs

BUT.. aluminum = constipation

37

What are DDIs associated with Sucralfate?

Antacids = avoid within 30 min.

PPIs

H2RAs

38

What are instructions for use of sucralfate?

Take on empty stomach 1 hour before meals

39

What is the MOA of BSS?

Creates protective layer against acid and pepsin for protection of ulcer site

Stimulates PG, mucus and bicarbonate secretion

Direct antibacterial effects

40

What is the clinical use of bismuth compounds?

Nonspecific treatment of dyspepsia and acute diarrhea

Traveler's diarrhea

41

What are adverse effects associated with BSS?

Black stools + tongue

Reye's syndrome from absorption of ASA

42

What is an example of a prostaglandin analog?

Misoprostol

43

What is the MOA of misoprostol?

Double protective effect:

1) stimulates EP3 receptors on parietal cells and surface of mucus cells to decrease cAMP, resulting in decreased secretion of acid

2) stimulation of mucin and carbonate

44

What is the clinical use of Misoprostol?

Prevention of NSAID-induced ulcers

Must be given QID

45

What are adverse effects associated with misoprostol?

Diarrhea, abdominal cramping

****Contraindicated in pregnancy!!!!!

46

List the 3 stages of GERD

Stage I: sporadic uncomplicated heartburn, often with known precipitating factor. Often not CC. No additional symptoms.
LESS than 2-3 episodes per week

Stage II: frequent symptoms
>>2-3 episodes/week

Stage III: chronic, unrelenting symptoms; immediate relapse off therapy; esophageal complications

47

Know the medical management for each stage of GERD.

Stage I:
Lifestyle modification
Antacids and/or H2RA PRN

Stage II:
PPIs more effective than H2RAs

Stage III:
PPI qD or BID

48

How do you treat PUD caused by H. pylori?

Heal ulcer + get rid of organism:

Amoxicillin
Clarithomycin
Omeprazole (PPI)

49

How do you treat NSAID-associated ulcer?

NSAID is discontinued: H2RA or PPI

NSAID required: PPI daily or BID; H2RA + misoprostol

50

What is the treatment of a stress-related ulcer?

IV:

H2RA or PPI

51

What is the treatment for PUD caused by Zollinger-Ellison syndrome?

PPI bid