GI & Peptic 2

Question 1

PPI

• Bioavailability of all agents is decreased by what?
• How is this fixed?****

Answer 1

• Bioavailability of all agents is decreased by what?
• How is this fixed?****
• Food***
• Administer approximately 30 - 60 mins BEFORE a meal (usually breakfast)***

(Know this)

Question 2

PK of PPIs

• Acid inhibition lasts up to __ hours.
• How many hours are required for synthesis of new H+/K+-ATPase pump molecules
• Undergo which rapid 1st pass systemic effect?
• Which type of clearance neglible?

Answer 2

Acid inhibition lasts up to 24 hours.

hours required for synthesis of new H+/K+-ATPase pump molecules: 18 hours

1st pass hepatic

Question 3

PK of PPIs

• Dose reduction in pts w/ what condition?

Answer 3

​

• Severe liver impairment

Question 4

Which nerve stimulates postganglionic neurons of the enteric nervous system to release acetylcholine (ACh), which binds to M3 receptors on parietal cells and ECL cell?

Answer 4

Vagus

Question 5

3 SE of PPIs

Answer 5

• Diarrhea**
• HA
• Abdominal pain

Question 6

PPI adverse effects

• Acid is important in releasing what from food?
• Acid also promotes absorption of what 3 food bound minerals?***
  
  • What should you monitor?
  • What could you supplement with?

Answer 6

• Releasing B12 from food
• 3 food-bound minerals: iron, Ca, Mg*** (know this)
• Monitor: bone density
• Ca supplements

Question 7

Adverse effects of which agent?

• Community-acquired respiratory infections and nosocomial pneumonia
• 2- to 3-fold increased risk for hospital- and community-acquired Clostridium difficile infection
• Salmonella, Shigella, E coli, Campylobacter

Answer 7

PPI

Question 8

PPI Drug Interactions

• Decreased gastric acidity may alter absorption of what 4 drugs? Which drug especially?**

Answer 8

• Ketoconazole
• Itraconazole
• Digoxin***
• Atazanavir

“A KID”

Question 9

PPI Drug Interactions

Omeprazole may inhibit the metabolism of what 3 drugs?

Answer 9

• Warfarin***
• Diazepam
• Phenytoin

“Omeprazole went to War w/ P. diddy”

Question 10

PPI Drug Interactions

• Which 2 PPIs have no significant drug interactions?

Answer 10

• Rabeprazole
• Pantoprazole

“A rabbi wearing pants is getting no action…”

Question 11

PPI Drug Interactions

• Metabolized by P450 cytochromes
• What is the “prodrug” which requires activation by the hepatic P450 CYP2C19?
• PPIs could reduce activation of what drug?

Answer 11

• Clopidogrel
• Clopidogrel

Question 12

PPI Drug Interactions

• Which 2 PPIs are preferred bc/ of minimal CYP2C10 inhibition?

Answer 12

Rabeprazole & Pantoprazole

“Rabbi wearing Pants”

Question 13

Mucosal Protective Agents

• Gastroduodenal mucosa evolved defense mechanisms to protect itself against the noxious effects of what 2 substance?

Answer 13

• acid & pepsin

Question 14

What substance appears to be important in stimulating mucus and bicarbonate secretion and mucosal blood flow?

Answer 14

Mucosal prostaglandins

Question 15

What are the 3 Mucosal Protective Agents?

Answer 15

• Sucralfate
• Prostaglandin analogs
• Bismuth

Question 16

Which Mucosal Protective Agent?

• Salt of sucrose complexed to sulfated aluminum hydroxide
• forms a viscous, tenacious paste that binds selectively to ulcers or erosions for up to 6 hours

Answer 16

Sucralfate

Question 17

Which Mucosal Protective Agent?

• Negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosion
• Forms a physical barrier that restricts caustic damage
• Stimulates mucosal prostaglandin and bicarbonate secretion

Answer 17

Sucralfate

Question 18

Which Mucosal Protective Agent?

• Used to prevent stress-related bleeding

Answer 18

Sucralfate

Question 19

Adverse effects of which Mucosal Protective Agent?

• Small amount of aluminum is absorbed
• Do not be used for prolonged periods in patients with renal insufficiency

Answer 19

Sucralfate

Question 20

Prostaglandin Analogs

• What are the 2 primary prostaglandins?

Answer 20

E & F

Question 21

What is the name of a prostaglandin analog? (Methyl Analog of PGE1)

Answer 21

Misoprostol

Question 22

Misoprostol (prostaglandin analog)

• Metabolized to what?
• Serum half life is how long?
• Excreted how?

Answer 22

• Metabolized to a metabolically active free acid
• Half life: less than 30 mins
• Excreted in the urine

Question 23

T/F

• Dose reduction of Misoprostol is NOT needed in pts w/ renal insufficiency

Answer 23

True

Question 24

Prostaglandin Analogs: Misoprostol

Pharmacodynamics

• Has what 2 properties?
• Binds to prostaglandin receptor on parietal cells, reducing histamine stimulated _____ production and causing modest acid inhibition
• Prostaglandins stimulate what 3 things?

Answer 24

Prostaglandin Analogs: Misoprostol

Has what 2 properties?

Acid inhibitory & Mucosal protective properties

Binds to prostaglandin receptor on parietal cells, reducing histamine stimulated cAMP production and causing modest acid inhibition

• Prostaglandins stimulate what 3 things?*
  1. Intestinal electrolyte & fluid secretion
  2. Intestinal motility
  3. Uterine contractions

Question 25

**Which medication?** Reduces the incidence of NSAID-induced ulcers

Answer 25

**Misoprostal** | (Prostaglandin Analog)

Question 26

**Adverse reactions of which medication?** **uterine contractions** **do not use in pregnancy/childbearing women** unless they have a neg. serum pregnancy test and on effective contraceptive measures

Answer 26

**Misoprostol** | (Prostaglandin Analog)

Question 27

What are the 2 bismuth compounds?

Answer 27

* bismuth **subsalicylate** * bismuth **subcitrate potassium**

Question 28

**Which bismuth compound?** * combination prescription product that also contains metronidazole and tetracycline for the treatment of H pylori.

Answer 28

bismuth subcitrate potassium

Question 29

**Bismuth** * Over 99% of bismuth appears where? * What substance is (like ASA), readily absorbed and excreted in the urine

Answer 29

* in the stool * Salicylate

Question 30

**Bismuth Compounds** * May stimulate what 3 things? * Which bismuth reduces stool frequency and liquidity in acute infectious diarrhea?

Answer 30

* **secretion of:** prostaglandin, mucus, bicarbonate * Bismuth subsalicylate

Question 31

Bismuth has direct ____ effects against ______ and binds enterotoxins, accounting for its benefits in preventing and treating \_\_\_\_\_\_\_.

Answer 31

Bismuth has direct **_antimicrobial**_ against _**H. pylori**_ and binds enterotoxins, accounting for its benefits in preventing and treating _**traveler's diarrhea._**

Question 32

Which bismuth is for **prevention of traveler's diarrhea**?

Answer 32

Bismuth subsalicylate

Question 33

* Which bismuth therapy is **first line** due to **"superior compliance?"** * Which is 2nd line?

Answer 33

**1st: "Triple Therapy"** * Proton Pump Inhibitor * Clarithromycin * Amoxicillin or Metronidazole (twice daily) **2nd: Bismuth based quadruples**

Question 34

**ADEs of Bismuth Compounds** * What are 2 harmless effects? * Avoided in pts w/ _____ insufficiency * Bismuth toxicity results in what? * Bismuth toxicity is NOT reported in which 2 forms of bismuth? * High dosages of bismuth subsalicylate can lead to what?

Answer 34

* 2 harmless: **blackening of stool & darkening of tongue** * Avoided in pt w/ **_renal_** insufficiency * Bismuth toxicity -\> **encephalopathy (ataxia, HAs, confusion, seizures)** * 2 forms bismuth toxicities NOT reported in: **bismuth subsalicylate & bismuth citrate** * salicylate toxicity

Question 35

ADEs of what drug? * Nausea, Vomiting, Diarrhea * Flatulence * **hypomagnesemia, hypocalcemia**

Answer 35

PPI

Question 36

**Which drug requires monitoring of:** * Pregnancy test * Serum phosphate * Should avoid in pregnancy

Answer 36

Misoprostol

Question 37

H. pylori can lead to what 2 cancers?

Answer 37

* Mucosa-associated lymphoid tissue **(MALT) lymphoma** * **Gastric cancer**

Question 38

What are the 4 **"established indications"** to treat an **H. pylori infection?**

Answer 38

* Gastric or duodenal **ulcer** * **MALT lymphoma** * **After endoscopic resection of gastric cancer** * Uninvestigated **dyspepsia**

Question 39

What is the **triple therapy** to eradicate H. pylori?

Answer 39

* #1: PPI * #2: Clarithroymycin * #3: Amoxicillin or Metronidazole (all twice daily)

Question 40

What is the **quadruple therapy** to tx H. pylori?

Answer 40

* bismuth * metronidazole * tetracycline * PPI

Question 41

Eradication of H. pylori after abx tx may be confirmed how?

Answer 41

* **urea** breath test * **Stool antigen** test * upper **endoscopy** (+ result = persistent infection)