Anti-Ulcer Pharm

Question 1

What are the main classes of anti-ulcer agents?

Answer 1

• H₂ receptor antagonists
• PPIs
• surface acting agents (sucralfate)
• PGE₁ analogs (misoprostol)
• bismuth compounds
• antacids

Question 2

What is a good example of why it is important to ask about OTC medications that is exemplified by anti-ulcer medications?

Answer 2

some OTC medications have CYP450 inhibition

• cimetidine
• omeprazole

*both are prototypical examples of CYP inhibitors used in questions

Question 3

What anti-ulcer classes are used in an acute settings to decrease acid?

What is their relative order of effective onset of action/symptom relief?

Answer 3

antacids > H₂ antagonists > PPIs

rapid/instant > 0.5-2 hours > 1-2 days

Question 4

What anti-ulcer medications are used primarily in prophylactic settings?

Answer 4

-PGE₁ analogs (misoprostol)

*prophylactic for NSAID related ulcers

Question 5

What anti-ulcer class does not affect amount of acid produced/present?

Answer 5

-surface acting agents (sucralfate)

Question 6

What is the common suffix of H₂ receptor antagonists?

What are the main drugs in the class?

Answer 6

“-tidine”

• cimetidine
• famaotidine
• nizatidine
• ranitidine _(zantac)

Question 7

Where do H₂ receptor antagonists act and what is their mechanism of action?

How does this relate to its effectiveness in reducing acid production?

Answer 7

indirect inhibition of acid production

• reverisbly inhibits H₂ receptor on basolateral membrane of parietal cells
• decreases cAMP -> decreased acid production

Because there are multiple pathways of stimulating acid production and this is only indirectly blocks acid production via one pathway, other pathways can still stimulate acid production (20-50% reduction in acid)

Question 8

What are the general adverse effects of H₂ receptor antagonists?

Answer 8

relatively uncommon and mild -> most are OTC for this reason

Adverse effects:

-GI s/x _{(diarrhea/constipation)}

-CNS s/x _{(HA/dizziness)}

Question 9

What adverse effects are associated with cimetidine specifically?

Answer 9

Rare (assoc. w/ long-term use and high does)

• weak anti-androgen effect (most prominent in cimetidine) -> gynecomastia in men/galactorrhea in women
• even more rare, impotency in men

Question 10

What drug interactions occur with H₂ receptor antagonists?

Answer 10

• cimetidine is a CYP450 inhibitor -> many interactions
• ranitidine also but 10%
• no interacitons in others

Question 11

What are contraindications for H₂ receptor antagonist use?

Answer 11

-pregnancy (relative contraindication) - if necessary, use ranitidine

Question 12

What is the common suffix of PPIs?

What are the main drugs in the class?

Answer 12

“-prazole”

• omeprazole**
• esomeprazole
• lansoprazole/dexlansoprazole
• pantoprazole
• rabeprazole

Question 13

Where do PPIs act and what is their mechanism of action?

How does this relate to its effectiveness in reducing acid production?

Answer 13

direct inhibition of acid production:

• irreverisbly inhibit H⁺/K⁺ ATPase on apical surface of parietal cells
• covalently binds sulfhydryl group preventing function

Directly inhibits acid secretion 50-90+% reduction in acid depending on dose/frequency

Question 14

What are the adverse effects of PPIs?

Answer 14

relatively uncommon and mild -> some are OTC for this reason

Adverse effects:

• risk of CDAD (C. difficile-associated diarrhea)
• GI s/x _{(diarrhea/constipation)}
• CNS s/x _{(HA/dizziness)}
• decreased Mg²⁺/Mg²⁺

Question 15

What drug interactions occur with PPI use?

Answer 15

-omeprazole is a CYP450 inhibitor -> many interactions

Question 16

What are contraindications for PPIs use?

Answer 16

development of profuse, watery diarrhea -> likely developed CDAD

-pregnancy (relative contraindication) - if necessary, use lansoprazole

Question 17

What is the main surface acting agent used for ulcer treatment?

Answer 17

-sucralfate _(carafate)

octasulfate of sucrose with aluminum hydroxide added

Question 18

What is the mechanism of action of sucralfate?

Answer 18

Acts as a bandaid:

-cross-links in stomach acid creating a viscous substance that covers ulcers and protects from further acid damage

-no effect on pH -> does not fix underlying problem, just provides symptomatic relief

Question 19

What are the adverse effects of sucralfate?

Answer 19

-constipation (from aluminum)

Question 20

What drug interactions occur with sucralfate use?

Answer 20

-viscous polymer formed can trap other medications taken with it -> take 2 hours after other medicatoins

Question 21

How does sucralfate complicate medication schedules?

Answer 21

• must be given at least 2 hours after other medicaitons due to its ability to trap them (all oral meds, not just anti-ulcer)
• sucralfate is administered QID while most other anti-ulcer medications are less frequently leading to complicated scheduling (especially since must be taken 2 hours after)

Question 22

What are contraindications for sucralfate use?

Answer 22

-severe renal failure (aluminum exacerbates)

Question 23

What is the main PGE₂ analog used for ulcer-prevention?

Answer 23

misoprostol

Question 24

What is the mechanism of action for misoprostol and what is it used for because of this?

Answer 24

analog to PGE₂ which stimulates bicarbonate and mucous release (cytoprotective) and inhibits acid production

-PGE₂ production is blocked by aspirin/NSAIDs so misoprostol is for prophylaxis of NSAID-induced gastritis

Question 25

What are the **adverse effects** of **misprostol**?

Answer 25

relatively **uncommon and mild** **Adverse effects:** **-GI s/x** _{(diarrhea/constipation)} **-CNS s/x** _{(HA/dizziness)}

Question 26

What are **contraindications** for **misoprostol** use?

Answer 26

- desired **pregnancy** (teminates pregnancy; this is also an off-label use) - **IBD**

Question 27

What is the main bismuth compound?

Answer 27

-**bismuth sub**_salicylate_****

Question 28

What is the action of bismuth subsalicylate?

Answer 28

- **anti-microbial actions** (*H. pylori*) - anti-diarrheal

Question 29

What are the adverse effects of bismuth subsalicylate?

Answer 29

Dose related adverse effects: - **constipation** (due to anti-diarrheal effect) - **black/dark,** **_regularly formed_** stools from formation of _bismuth sulfide_, a black pigment (as _opposed to dark/tarry in GI bleed_)

Question 30

What are **contraindications** for **bismuth subsalicylate** use?

Answer 30

_mostly related to salicylate_ component Relative: - **taking antiplatelet/anticoagulants** - severe **renal failure** Absolute: - **GI bleeding** - **salicylate hypersensitivity**

Question 31

After what time frame should H₂ receptor antagonists and PPIs show full symptomatic relief? What should be considered if symptoms persist?

Answer 31

symptoms should resolve without medications after **4-8 weeks** as the **ulcer should be fully healed** by that time -if **symptoms persist**, ***H. pylori* should be investigated** as these ulcers will not heal w/o antibiotics

Question 32

How does anti-ulcer treatment affect *H. pylori* testing?

Answer 32

**bismuth and PPIs inhibit ​*H. pylori*** but don't eliminate it and can give **false negatives** on **gastric urease or urea breath tests** -should be **off these meds for _4 weeks_ prior to test**

Question 33

What is the first line treatment for *H. pylori*? (schedule/duration)

Answer 33

triple-drug regimen of two abx and a PPI: - **clarithromycin** - **amoxicillin** -or- **metronidazole** - **PPI** taken **BID for 14 days**

Question 34

What drug is sometimes added to H. pylori treatment making it a quadruple therapy? What are the benefits/complicaitons of this?

Answer 34

-**bismuth subsalicylate** Benefits: -**more effective**, often used _after failure of triple therapy_ w/ _consideration of replacing abx_ Complications: - **abx and bismuth given QID** while **PPI given BID**, complicating scheduleing - bismuth increases **risk of constipation**

Question 35

What changes should be made if a patient doesn't respond to standard triple therapy for *H. pylori* containing **metronidazole​**?

Answer 35

**Replace metronidazole** and consider **quadruple therapy**: - **metronidazole -\> tetracycline** -or- amoxicillin - keep clarithromycin - addition of **bismuth subsalicylate** -\> abx and bismuth given QID w/ PPI gien BID

Question 36

What changes should be made in treating **clarithromycin resistant** H. pylori?

Answer 36

**Replace clarithromycin** and **consider quadruple therapy**: - **clarithromycin -\> tetracycline** -or- metronidazole/amoxicillin (whichever isn't already in regimen) - keep other abx - addition of **bismuth subsalicylate** -\> abx and bismuth given QID w/ PPI gien BID

Question 37

What changes should be made in treating H. pylori in a pt with a penicillin allergy?

Answer 37

Triple therapy (**w/o amoxicillin** as option): - **clarithromycin** - **metronidazole** (instead of metronidazole or amoxicillin) - **PPI**

Question 38

How should PUD be treated in a pregnant woman (no *H. pylori*)

Answer 38

**H₂ receptor antagonists and PPIs relatively contraindicated** - first consider **antacids or sucralfate** - if insufficient -\> **ranitidine** (H₂ antagonist) - if still insufficient -\> **lansoprazole** (PPI) **Misoprostol absolutely contraindicated** -\> termination of pregnancy

Question 39

What considerations should be taken with NSAIDs and PUD?

Answer 39

If _not required_: -**d/c NSAID** and consider **acetaminophen** If _required_: - **consider COX-2 NSAID** instead of COX-1 - additionally **consider adding PPI or misoprostol** (PGE₂ analog) to either COX-1/2 NSAID