DRUGS USED TO TREAT PEPTIC ULCER DISEASE AND GASTROESOPHAGEAL REFLUX DISEASE (2)

Proton Pump Inhibitors (PPIs)

What class of drugs inhibits the H+/K+-ATPase enzyme system (proton pump) and suppress the secretion of hydrogen ions into the gastric lumen?

Membrane- Bound Proton Pump

What is the final step in the secretion of gastric acid that PPIs inhibit?

Dexlansoprazole
Esomeprazole
Lansoprazole
Omeprazole
Pantoprazole
Rabeprazole

Examples of PPIs

- Omeprazole
- Esomeprazole
- Lansoprazole

Which PPIs are available OTC for short-term GERD treatment?

Acid-Resistant Enteric Coating

What formulation protects PPIs (a prodrug/ weak base) from premature degradation by gastric acid in the stomach?

Alkaline Duodenum

Where is the enteric coating of PPIs removed to allow drug absorption?

Parietal Cell

After absorption, where is the PPI prodrug transported for activation?
- There, it is converted to the active drug and forms a stable covalent bond with the H+/K+-ATPase enzyme.
- It takes about 18 hours for the enzyme to be resynthesized, and acid secretion is inhibited during this time.
- At standard doses, PPIs inhibit both basal and stimulated gastric acid secretion by more than 90%.

Sodium Bicarbonate

Proton Pump Inhibitors (PPIs)
What combination with omeprazole is available for faster absorption is also available over the counter and by prescription?

Proton Pump Inhibitors (PPIs)

What is the preferred drug class for treating stress ulcers, GERD, erosive esophagitis, active duodenal ulcer, and pathologic hypersecretory conditions?

Zollinger-Ellison Syndrome

Proton Pump Inhibitors (PPIs)
What condition in which a gastrin-producing tumor causes hypersecretion of HCl?

Increase to twice daily or add an H2 antagonist in the evening.

How can PPI therapy be modified if once-daily dosing is only partially effective for GERD?

It reduce proton pump activity, which PPIs need to be active.

Why should H2-receptor antagonists be taken well after a PPI?

NSAID-Induced Ulcers (ex. aspirin)

What type of ulcers do PPIs reduce the risk of bleeding from?

H. pylori infection

In combination with antimicrobial regimens, what infection do PPIs help eradicate?

30 to 60 minutes before breakfast or the largest meal of the day

What is the preferred timing for taking PPIs for maximum effect?

Dexlansoprazole

Which PPI can be taken without regard to food due to its dual delayed-release formulation?

- Esomeprazole
- Lansoprazole
- Pantoprazole

Which PPIs are also available in intravenous formulations?

Due to covalent bonding with the H+/K+- ATPase enzyme.

Why do PPIs have a long duration of action despite their short half-life?

- Omeprazole
- Esomeprazole

Proton Pump Inhibitors (PPIs)
- It may decrease the effectiveness of clopidogrel because they inhibit CYP2C19 and prevent the conversion of clopidogrel to its active metabolite.
- Although the effect on clinical outcomes is questionable, concomitant use of these PPIs with clopidogrel is not recommended because of a possible increased risk of cardiovascular events.

Increased risk of fractures

What bone-related risk may increase with PPI use longer than one year?

Vitamin B12 deficiency

What vitamin deficiency can result from prolonged PPI use due to suppressed acid because acid is required for its absorption in a complex with intrinsic factor?

Calcium Citrate

Proton Pump Inhibitors (PPIs)
Which calcium salt is recommended for patients on acid-suppressive therapy, since absorption of the citrate salt is not affected by gastric pH? (Elevated gastric pH may also impair the absorption of calcium carbonate.)

- Diarrhea
- Clostridium difficile colitis

What may occur with PPI use in community patients?

- Hypomagnesemia
- Increased Incidence of Pneumonia

Additional AE of PPIs

True

TRUE OR FALSE
Patients must be counseled to discontinue PPI therapy and contact their physician if they have diarrhea for several days.

Prostaglandin E

Produced by the gastric mucosa, inhibits the secretion of acid and stimulates secretion of mucus and bicarbonate (cytoprotective effect).

Deficiency of Prostaglandins

What is thought to contribute to the pathogenesis of peptic ulcers?

Misoprostol

What analog of prostaglandin E, is approved for the prevention of NSAID-induced gastric ulcers?

Prophylactic use of Misoprostol

Should be considered in patients who are taking NSAIDs and are at moderate to high risk of NSAID-induced ulcers, such as elderly patients and those with previous ulcers.

Stimulate uterine contractions and cause miscarriage

Why is misoprostol contraindicated in pregnancy?

- Dose-Related Diarrhea
- Nausea

What are the most common adverse effects of misoprostol?

Proton pump inhibitors (PPIs)

Which agents are preferred over misoprostol for preventing NSAID-induced ulcers?

Antacids

Are weak bases that react with gastric acid to form water and a salt to diminish gastric acidity.

Above pH 4.

ANTACIDS
At what pH is pepsin inactive, thus reducing its proteolytic activity?

- Chemical Composition
- Acid-neutralizing Capacity
- Sodium Content
- Palatability
- Price

What factors do antacid products vary in?

- Aluminum Hydroxide
- Magnesium Hydroxide

What are commonly used antacid salts?

Calcium carbonate [CaCO3 ]

ANTACIDS
Reacts with HCl to form CO2 and CaCl2 and is also a commonly used preparation.

Sodium bicarbonate

Which antacid is not recommended for long-term use due to systemic absorption?

Transient Metabolic Alkalosis

ANTACIDS
What is a side effect of systemic absorption of sodium bicarbonate?

Antacids

- For symptomatic relief of peptic ulcer disease and GERD, and they may also promote healing of duodenal ulcers.
- They should be administered after meals for maximum effectiveness.

- Aluminum Hydroxide
- Calcium Carbonate
- Magnesium Hydroxide
- Sodium Bicarbonate

Examples of Antacids

Calcium Carbonate Preparations

ANTACIDS
Are also used as calcium supplements for the treatment of osteoporosis.

Aluminum Hydroxide

AE OF ANTACIDS
Tends to cause constipation

Magnesium Hydroxide

AE OF ANTACIDS
Tends to produce diarrhea

To balance constipation and diarrhea effects, normalizing bowel function.

Why are aluminum and magnesium antacids often combined?

Renal Impairment

Absorption of the cations from antacids (Mg2+, Al3+, Ca2+) is usually not a problem in patients with normal renal function; however, accumulation and adverse effects may occur in patients with?

Mucosal Protective Agents

Also known as cytoprotective compounds, these agents have several actions that enhance mucosal protection mechanisms, thereby preventing mucosal injury, reducing inflammation, and healing existing ulcers.

- Bismuth subsalicylate
- Sucralfate

Examples of Mucosal Protective Agents

- Aluminum Hydroxide
- Sulfated Sucrose

MUCOSAL PROTECTIVE AGENTS
What is sucralfate composed of (binds to positively charged groups in proteins of both normal and necrotic mucosa)?

Sucralfate

MUCOSAL PROTECTIVE AGENTS
- By forming complex gels with epithelial cells which creates a physical barrier that protects the ulcer from pepsin and acid, allowing the ulcer to heal.
- Is effective for the treatment of duodenal ulcers and prevention of stress ulcers, its use is limited due to the need for multiple daily dosing and drug–drug interactions.

It needs acidic pH for activation.

MUCOSAL PROTECTIVE AGENTS
Why should sucralfate not be given with PPIs, H₂ antagonists, or antacids?

Sucralfate

MUCOSAL PROTECTIVE AGENTS
- It is well tolerated, but it can interfere with the absorption of other drugs by binding to them.
- This agent does not prevent NSAID-induced ulcers, and it does not heal gastric ulcers.

Bismuth Subsalicylate

MUCOSAL PROTECTIVE AGENTS
- This agent is used as a component of quadruple therapy to heal peptic ulcers.
- In addition to its antimicrobial actions, it inhibits the activity of pepsin, increases secretion of mucus, and interacts with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer.