1. Chapter 28 Drugs for Digestive Disorders
Department of Pharmacology
Qin Yubing

2. Drugs for Peptic Ulcers
What is a peptic ulcer?
What are the complications of peptic ulcer?
What are the causes of peptic ulcers?
What is the treatment for peptic ulcers?
Peptic ulcer summary

3. Peptic ulcer
Erosion or excavation of mucosal wall of the esophagus, stomach, pylorus, duodenum
(most common). “Autodigestion”
Requires acid environment to develop
Mucosal defenses impaired; cannot protect from effects of acid/pepsin
Result from infection with H. pylori or Zollinger-Ellison syndrome
Risk factors:
Alcohol, smoking, and stress, medications

4. Three types of peptic ulcer
Gastric
Duodenal
Stress

5. Peptic ulcer

6. Gastric ulcer
Mucus and bicarb. generally protect mucosal barrier from acid
Most common in the lesser curvature of stomach near the pylorus
H. pylori plays a role
Break in gastric mucosal barrier allows HCl to damage epithelium via “back diffusion”
Bile reflux from duodenum may break integrity
Decreased blood flow

7. Duodenal ulcer Results from excessive acid
Associated with protein-rich meals, Ca++, and vagal stimulation)
Rapid emptying of food from stomach large acid load in duodenum
H. pylori infection plays key role in development
produces substances that damage the mucosa, and contributes to higher acid concentrations

8. Stress ulcer Occurs after acute medical crisis, surgery, or trauma
Proximal portion of stomach and duodenum are most common sites
Ischemia and elevated HCl contribute to evolution of erosions  ulcerations
May progress to hemorrhage

9. What is a peptic ulcer?
Peptic ulcer disease is common, affecting millions of China yearly. Moreover, peptic ulcers are a recurrent problem; even healed ulcers can recur unless treatment is directed at preventing their recurrence.

10. What is a peptic ulcer?
A peptic ulcer is a break in the inner lining of the esophagus, stomach, or duodenum. A peptic ulcer of the stomach is called a gastric ulcer; of the duodenum, a duodenal ulcer; and of the esophagus, an esophageal ulcer.

11. What is a peptic ulcer?
Peptic ulcers occur when the lining of these organs is corroded by the acidic digestive (peptic) juices which are secreted by the cells of the stomach.
A peptic ulcer differs from an erosion because it extends deeper into the lining of the esophagus, stomach, or duodenum and excites more of an inflammatory reaction from the tissues that are eroded.

12. What is a peptic ulcer?
The medical cost of treating peptic ulcer and its complications runs into billions of dollars annually. Recent medical advances have increased our understanding of ulcer formation. Improved and expanded treatment options now are available.

13. Diagnostic tests Esphagogastroduodenoscopy
Fiberoptic endoscope allows direct visualization of esophagus, stomach and duodenum

14. Diagnostic tests: Upper GI series
Patients ingests barium, a thick, white, milkshake-like liquid, then multiple X-rays. Can detect structural disorders
After the exam, provide plenty of liquids for 24 to 48 hours.
The barium may make the stool white for several days.
If constipation occurs, the doctor may recommend a mild laxative.

15. Complications of ulcers: Hemorrhage
Manifested by:
Orthostatic hypotension,  BP, HR, cool, clammy skin overt bleeding
Hematemesis (bloody vomit) – bright red or coffee ground (more likely with gastric ulcer)
Melena (bloody or tarry [black] stool) – more likely with duodenal ulcer
 Hgb,  Hct

16. What are the causes of peptic ulcers?
For many years, excess acid was believed to be the major cause of ulcer disease. Accordingly, the emphasis of treatment was on neutralizing and inhibiting the secretion of stomach acid.

17. What are the causes of peptic ulcers?
While acid is still considered necessary for the formation of ulcers, the two most important initiating causes of ulcers are infection of the stomach by a bacterium called "Helicobacter pyloricus" (H. pylori) and chronic use of anti-inflammatory medications,

18. What are the causes of peptic ulcers?
Commonly referred to as NSAIDs (nonsteroidal anti-inflammatory drugs), including aspirin. Cigarette smoking also is an important cause of ulcer formation as well as failure of ulcer treatment.

19. What are the causes of peptic ulcers?
Infection with H. pylori is very common, affecting more than a billion people worldwide. It is estimated that half of the United States population older than age 60 has been infected with H. pylori.

20. What are the causes of peptic ulcers?
It is estimated that half of the United States population older than age 60 has been infected with H. pylori.
Infection usually persists for many years, leading to ulcer disease in 10% to 15% of those infected.

21. What are the causes of peptic ulcers?
In the past, H. pylori was found in more than 80% of patients with gastric and duodenal ulcers.
With increasing appreciation, diagnosis and treatment of this infection, however, the prevalence of infection with H. pylori as well as the proportion of ulcers caused by the bacterium has decreased;

22. What are the causes of peptic ulcers?
it is estimated that currently only 20% of ulcers are associated with the bacterium. While the mechanism by which H. pylori causes ulcers is complex, elimination of the bacterium by antibiotics has clearly been shown to heal ulcers and prevent the recurrence of ulcers.

23. What are the causes of peptic ulcers?
NSAIDs are medications used for the treatment of arthritis and other painful inflammatory conditions in the body. Aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and etodolac (Lodine) are a few of the examples of this class of medications.

24. What are the causes of peptic ulcers?
Prostaglandins are substances which are important in helping the linings of the esophagus, stomach, and duodenum to resist damage by the acidic digestive juices of the stomach. NSAIDs cause ulcers by interfering with prostaglandins in the stomach.

25. What are the causes of peptic ulcers?
Cigarette smoking not only causes ulcers, but it also increases the risk of complications from the ulcers such as ulcer bleeding, stomach obstruction, and perforation. Cigarette smoking also is a leading cause of failure of treatment for ulcers.

26. What are the causes of peptic ulcers?
Contrary to popular belief, alcohol, coffee, colas, spicy foods, and caffeine have no proven role in ulcer formation. Similarly, there is no conclusive evidence to suggest that life stresses or personality types contribute to ulcer disease.

27. What is the treatment for peptic ulcers?
The goal of ulcer treatment is to relieve pain, heal the ulcer, and prevent complications. The first step in treatment involves the reduction of risk factors (NSAIDs and cigarettes). The next step is medications.
NSAIDs---non-steroidal anti-inflammatory drugs. All NSAIDs act by inhibiting cyclooxygenase（COX),which reduces prostaglandin synthesis.

28. Approaches for the treatment of peptic ulcers are:
1.Reduction of gastric acid secretion
（a) H2 antithistamines :Cimetidine, Ranitidine, famotidine, Roxatidine
(b)Proton pump inhibitors: Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole

29. Approaches for the treatment of peptic ulcers are:
(c)Anticholinergics :Pirenzepine, Propantheline ,Oxyphenonium
(d)Prostaglandin analogue: Misoprostol

30. Approaches for the treatment of peptic ulcers are:
2.Neutralization of gastric acid (Antacids)
(a)Systemic: Sodium bicarbonate, Sod. Citrate
(b)Nonsystemic: Magnesium hydroxide, Mag. Trisilicate, Aluminium hydroxidegel, Magaldrate, Calcium carbonate

31. Approaches for the treatment of peptic ulcers are:
3.Ulcer protectives: Sucralfate, Colloidal bismuth subcitrate(CBS)
4. Anti-H. Pylori drugs: Amoxicillin, Clarithromycin, Metronidazole, Tetracycline

32. Role of drugs in peptic ulcer disease
Duodenal ulcer is a chronic remitting and relapsing disease lasting several years. Goals of antiulcers therapy are:
(a)Relief of pain
(b)Ulcer healing
(c)Prevention of complications
(d)Prevention of relaps

33. What is the treatment for peptic ulcers?
Antacids
Antacids neutralize existing acid in the stomach. Antacids such as Maalox, Mylanta, and Amphojel are safe and effective treatments.

34. Antacids
However, the neutralizing action of these agents is short-lived, and frequent dosing is required. Magnesium containing antacids, such as Maalox and Mylanta, can cause diarrhea, while aluminum containing agents like Amphojel can cause constipation
Ulcers frequently return when antacids are discontinued.

35. H2 blockers
Studies have shown that a protein released in the stomach called histamine stimulates gastric acid secretion. Histamine antagonists (H2 blockers) are drugs designed to block the action of histamine on gastric cells and reduce the production of acid.

36. H2 blockers
Examples of H2 blockers are cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepcid).
While H2 blockers are effective in ulcer healing, they have a limited role in eradicating H. pylori without antibiotics.

37. H2 blockers
Therefore, ulcers frequently return when H2 blockers are stopped.
Generally, H2 blockers are well tolerated and have few side effects even with long term use
In rare instances, patients report headache, confusion, lethargy, or hallucinations. Chronic use of cimetidine may rarely cause impotence or breast swelling.

38. H2 blockers
Both cimetidine and ranitidine can interfere with the body's ability to handle alcohol. Patients on these drugs who drink alcohol may have elevated blood alcohol levels.
These drugs may also interfere with the liver's handling of other medications like phenytoin (Dilantin), warfarin (Coumadin), and theophylline. Frequent monitoring and adjustments of the dosages of these medications may be needed.

39. Proton-pump inhibitors (PPIs)
Proton-pump inhibitors such as omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), esomeprazole (Nexium), and rabeprazole (Aciphex) are more potent than H2 blockers in suppressing acid secretion.
The different proton-pump inhibitors are very similar in action and there is no evidence that one is more effective than the other in healing ulcers.

40. Proton-pump inhibitors (PPIs)
While proton-pump inhibitors are comparable to H2 blockers in effectiveness in treating gastric and duodenal ulcers.
They are superior to H2 blockers in treating esophageal ulcers.

41. Proton-pump inhibitors (PPIs)
Esophageal ulcers are more sensitive than gastric and duodenal ulcers to minute amounts of acid. Therefore, more complete acid suppression accomplished by proton-pump inhibitors is important for esophageal ulcer healing.

42. Proton-pump inhibitors (PPIs)
Proton-pump inhibitors are well tolerated. Side effects are uncommon; they include headache, diarrhea, constipation, nausea and rash.
Interestingly, proton-pump inhibitors do not have any effect on a person's ability to digest and absorb nutrients.

43. Proton-pump inhibitors (PPIs)
Proton-pump inhibitors have also been found to be safe when used long term, without serious adverse health effects.
Although they may promote loss of bone (osteoporosis) and low magnesium levels, both of these side effects are easily identified and treated.

44. Sucralfate (Carafate) and misoprostol (Cytotec)
Sucralfate (Carafate) and misoprostol (Cytotec) are agents that strengthen the gut lining against attacks by acidic digestive juices.
Sucralfate coats the ulcer surface and promotes healing. Sucralfate has very few side effects.

45. Sucralfate (Carafate) and misoprostol (Cytotec)
The most common side effect is constipation and the interference with the absorption of other medications.
Misoprostol is a prostaglandin-like substance commonly used to counteract the ulcerogenic effects of NSAIDs.

46. Sucralfate (Carafate) and misoprostol (Cytotec)
Studies suggest that misoprostol may protect the stomach from ulceration among people who take NSAIDs chronically.
Diarrhea is a common side effect. Misoprostol can cause miscarriages when given to pregnant women, and should be avoided by women of childbearing age.

47. H. pylori treatment
Many people harbor H. pylori in their stomachs without ever having pain or ulcers.
It is not completely clear whether these patients should be treated with antibiotics.

48. H. pylori treatment More studies are needed to answer this question.
Patients with documented ulcer disease and H. pylori infection should be treated for both the ulcer and the H. pylori. H. pylori can be very difficult to completely eradicate.

49. H. pylori treatment
Treatment requires a combination of several antibiotics, sometimes in combination with a proton-pump inhibitor, H2 blockers, or Pepto-Bismol.
Commonly used antibiotics are tetracycline, amoxicillin, metronidazole (Flagyl), clarithromycin (Biaxin), and levofloxacin (Levaquin).

50. H. pylori treatment
Eradication of H. pylori prevents the return of ulcers (a major problem with all other ulcer treatment options).
Elimination of this bacteria also may decrease the risk of developing gastric cancer in the future.

51. H. pylori treatment
Treatment with antibiotics carries the risk of allergic reactions, diarrhea, and sometimes severe antibiotic-induced colitis (inflammation of the colon).

52. Diet
There is no conclusive evidence that dietary restrictions and bland diets play a role in ulcer healing.
No proven relationship exists between peptic ulcer disease and the intake of tea ,coffee and alcohol.

53. Diet
However, since coffee stimulates gastric acid secretion, and alcohol can cause gastritis, moderation in alcohol and coffee consumption is recommended.

54. Remember: Management during Haemorrhage includes
Monitor S/S
Determine rate amount of blood loss (Hct/hct),
NGT
Replace blood, fluid and electrolyte loss
saline lavage via NGT
NGT to low intermittent suction
Prevents distension
Assess amount/rate of bleeding,
Medications, oxygen, possible surgery

55. Complications: Perforation
GI contents empty into peritoneal cavity
Manifested by:
Sudden, sharp mid-epigastric pain which can shortly spread to all abdomen
Rigid, tender, board-like abdomen
Patient assumes the fetal position to reduce tension on muscles
Can lead to shock
It is a surgical emergency

56. Remember: Management during perforation includes
NGT to prevent additional spillage of GI contents in peritoneum
Replace blood, fluid, electrolytes
Antibiotics
I & O, NPO
SURGERY: Urgent

57. Complications: Pyloric obstruction
Caused by inflammation or edema of the pylorus
Stomach cannot empty  abdominal bloating, N & V
Persistent vomiting  Hypokalemia and metabolic alkalosis

58. Medical Management of ulcers
Conservative therapy:
Rest: Both physical and emotional
Dietary modifications
Elimination of smoking
Long term follow up care
Pharmaceutical:
Antibiotics
To eradicate H. Pylori infections
Recurrence of ulcer is 75-90% as high with infection
Antiacids
Initial drugs of choice
Histmaine H2 receptor antagonists
Histamine is the final intracellular activator of HCL secretion
Anticholinergic:
Stop the cholinergic stimulation of HCl secretion and slow gastric motility
Not commonly used, if used need to be used with caution in pts with Glaucoma

59. Surgical Management of ulcerations
Gastroduodenostomy (Billroth I)
Removal of the lower portion of stomach and small portion of duodenum and connects remaining of stomach to duodenum

60. Peptic ulcer summary
With modern treatment, patients with ulcer disease can lead normal lives without lifestyle changes or dietary restrictions.
Cigarette smokers have been found to have more complications from ulcers and treatment failure. Eradication of the bacteria H. pylori not only heals ulcers but also prevents the recurrence of ulcer disease.

61. Case 1
I was told I had a peptic ulcer. When I worked lifting, the pain made my work extremely difficult. The pain started in the back above my kidneys and radiated to the front on the sides of my ribcage. You would swear it was a heart attack coming on

62. Case 1
Sometimes I felt it in my chest around my heart. When I ate, the pain would subside and then come back about 30 minutes later. I bought Zantac 75.
Then it would be gone for three or four hours, but come back sooner. I then switched to Zantac 150. That worked a lot better. I found out after trial and error that taking it first thing in morning was better than taking it at lunch.
Now, my work performance is back to normal.