Upper GI Drugs

Question 1

Peptic Ulcer Disease (PUD) is ____ erosions d/t corroding factors overwhelming protective factors

Answer 1

Peptic Ulcer Disease (PUD) is mucosal erosions d/t corroding factors overwhelming protective factors

Question 2

Gastric ulcers from NSAID use and epigastric pain is _____ by eating

whereas

Duodenal ulcers from H. pylori infection, epigastric pain ____ by eating

Answer 2

Gastric ulcers from NSAID use and epigastric pain is worsened by eating

whereas

Duodenal ulcers from H. pylori infection, epigastric pain relieved by eating

Question 3

Describe the image

Answer 3

2 physiological states of gastric acid production: Basal & Meal stimulated

Question 4

Antacids are weak ____ obtained without prescription → causes ____ of low gastric pH → protects esophageal mucosa from ____

Answer 4

Antacids are weak bases obtained without prescription → causes neutralization of low gastric pH → protects esophageal mucosa from reflux corrosion

Antacid + HCl → salt + H2O

Time of onset: 5 minutes
Duration of action: 30 mins – 1 hour

Question 5

Antacids can affect other drugs by ____ gastric and urinary pH or by _____ gastric emptying.

All can cause ____.

Answer 5

Antacids can affect other drugs by increasing gastric and urinary pH or by delaying gastric emptying.

All can cause hypokalemia.

Question 6

(Antacids)

Aluminum Hydroxide causes ____

Magnesium Hydroxide causes ____

therefore, combined to produce _____

Answer 6

(Antacids)

Aluminum Hydroxide causes constipation
“Aluminimum amount of feces”

Magnesium Hydroxide causes osmotic diarrhea
“Must _g_o 2 the washroom (Mg2+)”

Al and Mg combined to produce no change in bowel movements

Question 7

Calcium Carbonate is an ____, CO2 causes _____, can lead to metabolic _____, aka ____ syndrome.

Answer 7

Calcium Carbonate is an antacid, CO2 causes belching, can lead to metabolic alkalosis, aka milk alkali syndrome.

Question 8

describe antacid drug interactions

Answer 8

• Binding/chelation of many drugs
• Increased gastric pH alters dissolution of weakly charged drugs
• Decreased absorption of co-administered:
  
  • Tetracyclines, Fluoroquinolones, Itraconazole, Iron

Question 9

H2 receptor antagonists suppress ___-induced gastric acid secretion, and reduce signal transduction for ____ and ____-induced gastric acid production

Answer 9

H2 receptor antagonists suppress histamine-induced gastric acid secretion, and reduce signal transduction for ACh and Gastrin-induced gastric acid production

Question 10

H2 receptor antagonists are selective _____ inhibitors at the ____ cell H2 Gs protein coupled receptor

Time of onset: 2.5 hours
Duration of action: 4- 10 hours
_____ develops in 2- 6 weeks

Answer 10

H2 receptor antagonists are selective competitive inhibitors at the parietal cell H2 Gs protein coupled receptor

Time of onset: 2.5 hours
Duration of action: 4- 10 hours
Tachyphylaxis develops in 2- 6 weeks

Question 11

list the H2 Receptor Antagonists

Answer 11

• Cimetidine – prototype with many adverse effects
• Ranitidine, Famotidine, Nizatidine – 2nd generation with no anti-androgenic or CNS adverse effects

Question 12

describe the effect of H2RAs on Gastric Acid Secretion

Answer 12

H2RAs strongly suppress basal gastric acid secretion

Question 13

list the H2 receptor antagonist indications

Answer 13

• GERD
• PUD
• Nonulcer dyspepsia
• Prophylaxis against stress-related gastritis

Question 14

what is the only H2 receptor antagonist with adverse effects

Answer 14

CIMETIDINE

Question 15

AEs of Cimitidine

Answer 15

• acts as nonsteroidal anti-androgen and prolactin stimulant → gynecomastia, galactorrhea, and male impotence
• Crosses BBB → confusion, dizziness and headaches
• Increases gastric pH → B12 deficiency and myelosuppression (long term use)
• Potent CYP450 inhibitor increasing serum [] of:
  
  • Warfarin, Diazepam, Phenytoin

Question 16

______ are the most potent inhibitors of gastric acid secretion → inhibit 90–98% of 24-hour acid secretion

Answer 16

Proton pump inhibitors are the most potent inhibitors of gastric acid secretion → inhibit 90–98% of 24-hour acid secretion

Question 17

PPIs ____ bind and inhibit the ____ ATPase pump of gastric ____ cells

suppressing the final ____ pathway of gastric acid secretion

Answer 17

PPIs irreversibily bind and inhibit the H+-K+ ATPase pump of gastric parietal cells

suppressing the final common pathway of gastric acid secretion

Question 18

describe the image

Answer 18

PPIs strongly suppress basal & meal stimulated gastric acid production

Question 19

list PPIs

Answer 19

• Omeprazole
• Esomeprazole
• Lansoprazole
• Rabeprazole
• Pantoprazole

Question 20

list the indications for PPIs

Answer 20

• Patients who fail twice-daily H2RA therapy
• Severe symptoms of GERD that impair quality of life
• PUD
  
  • H. pylori eradication
  • NSAID associated ulcers
  • Prevention of peptic ulcer rebleeding
• Gastrinoma
• Nonulcer dyspepsia
• Prophylaxis against stress-related gastritis

Question 21

PPI adverse effects

Answer 21

• Vitamin B12 deficiency – d/t reduced pepsin function
• Increased risk of CAP and C. difficile colitis
• Hypomagnesemia
• Osteopenia – possibly via reduced Ca2+ absorption or osteoclast inhibition
  
  • FDA-mandated warning of possible increased risk of fractures
• Diarrhea, abdominal pain and headache reported in less than 5% of patients

Question 22

____ and ____ inhibit CYP450 decreasing metabolism of which drugs?

Answer 22

Omeprazole and Cimitidine inhibit CYP450 decreasing metabolism of Warfarin, Diazepam, Phenytoin

Question 23

Clopidogrel (prodrug) requires activation by hepatic P450 _____ isoenzyme

drugs that affect this isoenzyme are (3) - what is their effect on clopidogrel?

Answer 23

Clopidogrel (prodrug) requires activation by hepatic P450 CYP2C19 isoenzyme

(LEO) Lansoprazole, Esomeprazole, Omeprazole inhibit CYP2C19 reducing Clopidogrel activation

Question 24

____ or ____ are preferred in persons taking clopidogrel

Answer 24

pantoprazole or rabeprazole are preferred in persons taking clopidogrel

Question 25

H. Pylori is gram \_\_\_\_, contains ____ and H +/-? causes inflammatory response, with increased risk of:

Answer 25

H. Pylori is gram **negative**, contains **urease** and **H+** causes inflammatory response, with increased risk of: * Peptic ulcer disease (esp. duodenal) * Gastritis * Gastric MALToma * Gastric adenocarcinoma

Question 26

H. Pylori eradication triple therapy combines two ____ with a \_\_\_\_, resulting in \<15% recurrence

Answer 26

H. Pylori eradication triple therapy combines two **antibiotics** with a **PPI**, resulting in \<15% recurrence

Question 27

describe how PPIs promote eradication of H. pylori

Answer 27

1. Direct antimicrobial properties 2. Increased gastric pH → lowers minimal inhibitory concentrations of antibiotics needed to clear the organism

Question 28

Triple therapy for ____ days - which drugs?

Answer 28

Triple therapy for **10-14** days - which drugs? ## Footnote **Clarithromycin + Amoxicillin + PPI** **Clarithromycin + Metronidazole + PPI**

Question 29

Quadruple therapy for ___ days - which drugs?

Answer 29

Quadruple therapy for **14** days ## Footnote **Bismuth Subsalicylate + Tetracycline + Metronidazole + PPI**

Question 30

list the mucosal protective agents

Answer 30

* Misoprostol * Sucralfate * Bismuth Subsalicylate

Question 31

Misoprostol is a ____ analog

Answer 31

Misoprostol is a **PGE₁** analog

Question 32

\_\_\_\_ binds to EP₃ receptor on ___ cells stimulating \_\_\_ pathway → decreasing gastric acid secretion

Answer 32

**Misoprostol** binds to EP₃ receptor on **parietal** cells stimulating **G_i** pathway (decreasing cAMP) → decreasing gastric acid secretion

Question 33

Misoprostol also stimulates ___ and ___ secretion, and enhances mucosal \_\_\_\_

Answer 33

Misoprostol also stimulates **mucus** and **bicarbonate** secretion, and enhances mucosal **blood flow**

Question 34

\_\_\_\_ is used for **preventing NSAID-induced ulcers** in high-risk patients

Answer 34

**Misoprostol** is used for **prevention** of **NSAID-induced** **ulcers** (NSAIDS block PGE₁ production)

Question 35

Misoprostol AEs and contraindications

Answer 35

* Diarrhea, abdominal pain, cramps (30%) * Contraindicated in **pregnancy** d/t **abortifacient** effects

Question 36

Sucralfate MOA

Answer 36

* Sucralfate: sucrose salt + sulfated aluminum hydroxide * Forms viscous paste that **binds selectively to ulcers** * -ve sucrose sulfate binds +ve proteins forming a physical barrier → restricting further caustic damage * Stimulates mucosal **PG** and **bicarbonate** secretion

Question 37

Sucralfate clinical use

Answer 37

initial management of **GERD** in **pregnancy**

Question 38

Bismuth subsalicylate (BSS) suppresses \_\_\_\_ Does it have a neutralizing action on gastric acid?

Answer 38

Bismuth subsalicylate (BSS) suppresses **H. pylori** ## Footnote **NO neutralizing action on gastric acid**

Question 39

Bismuth Subsalicylate clinical use

Answer 39

* **Quadruple** antibiotic therapy of **H. pylori-positive ulcers** * Pepto-Bismol is widely used for **dyspepsia and acute diarrhea**

Question 40

Bismuth toxicity and contraindications

Answer 40

* Rare * Metabolite bismuth sulfide causes **harmless blackening of the stool →** may be confused with gastrointestinal bleeding * BSS can cause **salicylate toxicity** in combination with other salicylate products * Contraindicated in **renal failure**

Question 41

Prokinetic agents enhance coordinated GI \_\_\_ Ideally should act ___ of ACh

Answer 41

Prokinetic agents enhance coordinated GI **motility** Ideally should act **upstream** of ACh (at receptor sites on the enteric neuron itself or higher)

Question 42

Why are muscarinic (M1) receptor agonists **not currently preferred** for treating GI motility disorders?

Answer 42

Activated M1-receptors enhance contractions in an **uncoordinated** fashion, producing **little/no net propulsive activity** ## Footnote *Bethanechol (cholinomimetic agent) and Neostigmine (ACh esterase inhibitor) are not preferred for treating GI motility disorders*

Question 43

Erythromycin (macrolide) has ____ effects at the ___ receptor Rapid down-regulation of this receptor leads to \_\_\_\_\_\_→ use is limited to short courses

Answer 43

Erythromycin (macrolide) has **agonistic** effects at the **motilin** receptor Rapid down-regulation of this receptor leads to **early tolerance** → use is limited to short courses

Question 44

Erythromycin is a CYP450 \_\_\_\_

Answer 44

Erythromycin is a CYP450 **inhibitor**

Question 45

best established indication for Erythromycin is

Answer 45

Diabetic gastroparesis

Question 46

Describe Cisapride

Answer 46

* 5-HT₄ agonist * increase cAMP, stimulates enteric neurons * 5-HT₃ antagonist * smooth muscle stimulant * was used for GERD and Gastroparesis * no longer available in U.S. → can induce **serious/fatal cardiac ventricular arrhythmias**

Question 47

*Metoclopramide:* \_\_\_\_ **agonist** vagal and central ___ **antagonist** \_\_\_ receptor **antagonist**

Answer 47

*Metoclopramide:* **5-HT₄** receptor **agonist** vagal and central **5-HT₃** receptor **antagonist** **D2** receptor **antagonist**

Question 48

\_\_\_\_ increases LES tone and stimulates antral & small intestinal contractions

Answer 48

**Metoclopramide** increases LES tone and stimulates antral & small intestinal contractions

Question 49

Metoclopramide clinical indications

Answer 49

* **Antiemetic** (d/t central 5-HT₃ block) * symptom relief in GERD (doesn't heal) * Diabetic gastroparesis * acid suppression therapy is more efficacious/preferred

Question 50

Metoclopramide AEs

Answer 50

* **Extrapyramidal effects** * **​**d/t DA antagonism * mc in children/young adults at higher doses * **Galactorrhea** * blocks dopamine which normally inhibits prolactin release * **QT prolongation → torsades** * **Depression**