This slide consists of details related to Peptic ulcers and what can be the possible drugs to be used with their overview. I hope this will be helpful for all readers.

1. Drugs Acting on the GI Tract:
Peptic Ulcer
Dr. Khalid Ghaznavi
Doctor of Physiotherapy
(USA)

2. Dr.Khalid Ghaznavi
(DPT)

3. Acid-Peptic Disease
A group of disorders involving erosion or ulceration of mucosal lining of GIT;
includes
 GERD (Gastro-Esophageal Reflux Disease)
 Gastric and Duodenal ulcers
 Dyspepsia
 Stress related gastritis
Dr.Khalid Ghaznavi
(DPT)

4. Gastro-Esophageal Reflux Disease (GERD)
Esophageal irritation and inflammation due to reflux of stomach acid
Also known as heart-burn
Dr.Khalid Ghaznavi
(DPT)

5. Peptic Ulcers
 “Peptic ulcers results from imbalance between
◼ acid – pepsin secretion and
◼ mucosal defense”
Common in present days
Dr.Khalid Ghaznavi
(DPT)

6. Peptic ulcer contd
Peptic ulcer are the sores that develop in
◼ the lining of stomach ,
◼ lower esophagus ,
◼ small intestine
They are usually formed as a result of…
 inflammation caused by H APYLORIC
 AS WELL as erosion from stomach acid.
Dr.Khalid Ghaznavi
(DPT)

7. Peptic ulcer symptoms
 Pain in the stomach, chest and upper abdomen
 Severity after eating
 Nausea or vomiting.
 Passing excessive of gas
 Burping or Acid reflux.
 Heart-burn, (which is a burning sensation in the chest)
Dr.Khalid Ghaznavi
(DPT)

8. PHYSIOLOGY OF PAREITAL WALL
The factors that prevent the mucosa are :
Its ability to secrete
◼ Mucous
◼ Bicarbonate
◼ Prostagladilins
Dr.Khalid Ghaznavi
(DPT)

9. Physiology of HCl production
Gastric Acid Secretion is controlled by
3 pathways;
1. Vagus
2. Gastrin
3. Local release of histamine
Dr.Khalid Ghaznavi
(DPT)

10. Dr.Khalid Ghaznavi
(DPT)

11. Three Pathways
1. Histamine acts through H2 receptors on parietal cells
2. Acetylcholine acts through M1 receptors
3. Gastrin through G receptors on parietal cells
 These activates H+ K+ ATPase on the parietal cells
resulting in secretions of H+ into gastrin lumen….
 This combines with Cl drawn from plasma and
HCL is secreted.
Dr.Khalid Ghaznavi
(DPT)

12. Classification of drugs used in
Peptic Ulcer
1. Drugs that neutralize gastric acid (Antacids)
2. Drugs that inhibit gastric acid secretion
3. Ulcer protectives
4. Anti- H. pylori drugs

13. Classification (Contd..)
Drugs that neutralize gastric acid (Antacids)
Systemic:
 Sodium bicarbonate
 Sodium citrate
Non-systemic:
 Magnesium hydroxide
 Magnesium Trisilicate
 Aluminium hydroxide gel
 Calcium carbonate
Drugs that inhibit gastric acid secretion
H2 Receptor Blockers:
 Cimetidine, Ranitidine, Famotidine, roxatidine,
nizatidine.
Proton Pump Inhibitors:
 Omeprazole, Pantoprazole, Esomeprazole ,
lansoprazole, rabeprazole
Anti-cholinergics/ Muscarinic Antagonists:
 Pirenzepine ,Telenzepine
Prostaglandin Analogues:
 Misoprostol
Dr.Khalid Ghaznavi
(DPT)

14. Classification (Contd..)
Ulcer protectives..
 Sucralfate
 Colloidal Bismuth Sulfate (CBS)
Anti H. pylori drugs..
 Amoxicillin
 Clarithromycin
 Metronidazole
 Tinidazole
 Tetracycline
Dr.Khalid Ghaznavi
(DPT)

15. Classification (Contd..)
Other drugs:
Carbenoxolone
Cisapride
prostaglandins
Dr.Khalid Ghaznavi
(DPT)

16. ANTACIDS

17. Antacids
 Weak bases that neutralize acid
 Given orally they neutralize gastric acid
and raise pH of gastric contents
Pepsin activity is also reduced above pH4
The antacids differ mainly in their
absorption and stool consistency
Dr.Khalid Ghaznavi
(DPT)

18. Systemic Antacids
Sodium Bicarbonate:
 Potent neutralizing capacity and acts instantly
 Also used to alkalinize urine in poisoning and to treat metabolic acidosis
DEMERITS:
 Systemic alkalosis
 Rebound hyperacidity
 Abdominal Distension
 Discomfort and belching – CO2
 Sodium overload Dr.Khalid Ghaznavi
(DPT)

19. Non-Systemic Antacids
Insoluble and poorly absorbed basic compounds
React in stomach with HCl to form corresponding chloride salt and
water
Dr.Khalid Ghaznavi
(DPT)

20. Aluminium Antacids/Hydroxide
 Slow acting
 Food further slows its neutralizing capacity
 Forms protective coating over ulcers
 Causes gastric emptying
 Aluminium ions relax smooth muscles mainly intestinal muscles ,also results
in constipation
 It also binds phosphate and prevents its absorption resulting in
hypophosphatemia on prolonged use
Dr.Khalid Ghaznavi
(DPT)

21. Magnesium Hydroxide
 Aqueous suspension is called
Milk of magnesia
 Action is quick and prolonged
 Rebound acidity is mild
 Magnesium salts are osmotic purgatives
 The dose used as antacids may cause mild diarrhea
Dr.Khalid Ghaznavi
(DPT)

22. Non systemic antacids
Duration of action :
 30 min when taken in empty stomach and
 2 hrs when taken after a meal
Adverse effects:
Aluminium antacids
✓ Constipation
✓ Also hypophosphatemia and osteomalcia
Mg2+ antacids
 Osmotic diarrhoea
Dr.Khalid Ghaznavi
(DPT)

23. Antacids in combination
To obtain maximum effects with
least adverse effects
Dr.Khalid Ghaznavi
(DPT)

24. Quick and prolonged effects
Fast acting- magnesium hydroxide
Slow acting- aluminum hydroxide
Dr.Khalid Ghaznavi
(DPT)

25. Neutralizing side effects
Magnesium salts cause diarrhea
Aluminum salts are constipating
Combination neutralizes each others side effects
Dr.Khalid Ghaznavi
(DPT)

26. Drug interactions
 By raising gastric pH & forming insoluble complexes
◼ ↓ absorption of many drugs
 Antacids form complexes with
◼ Tetracycline’s,
◼ iron salts,
◼ H2 Blockers,
◼ diazepam,
◼ phenytoin,
◼ isoniazid,
◼ ethambutol
Dr.Khalid Ghaznavi
(DPT)

27. Instructions
Gels are more effective than tablets
To avoid drug interactions,
antacids should be taken
◼2 hours before or
◼2 hours after other drugs
Dr.Khalid Ghaznavi
(DPT)

28. Uses of Antacids
Hyper-acidity
Peptic ulcer
Reflex esophagitis
Dr.Khalid Ghaznavi
(DPT)

29. H2
RECEPTOR BOCKERS

30. H2 RECEPTOR BOCKERS
CIMETIDINE
RANITIDINE
FAMOTIDINE
NIZATIDINE
ROXATIDINE
Dr.Khalid Ghaznavi
(DPT)

31. Mechanism of action
 Competitively block H2 receptors on parietal cell &
inhibit gastric acid production
 Suppress secretion of acid in all phases
 but mainly nocturnal acid secretion
 Also reduce acid secretion stimulated by Ach, gastrin, food, etc.
Dr.Khalid Ghaznavi
(DPT)

32. Pharmacokinetics
 Absorption is not interfered by food
 Can cross placental barrier and reaches milk
 Poor CNS penetration
Dr.Khalid Ghaznavi
(DPT)

33. H2 antagonists - Uses
Promote the healing of gastric and duodenal ulcers
NSAID induced ulcers
Stress ulcer and gastritis
GERD
Zollinger-Ellison syndrome
Dr.Khalid Ghaznavi
(DPT)

34. Adverse effects
Headache
Dizziness
Bowel upset
Dry mouth
CNS: Confusion
Restlessness
Arrhythmia
Cimetidine has anti-androgenic actions Dr.Khalid Ghaznavi
(DPT)

35. Proton
Pump Inhibitors

36. Proton Pump Inhibitors
Omeprazole
Pantoprazole
Lansoprazole
Esomeprazole
Dr.Khalid Ghaznavi
(DPT)

37. MECHANISM OF ACTION
PPIs are lipophilic weak bases that diffuse into parietal cell
canaliculi
There they undergo conversion to compounds that ir-reversibly
in-activate the parietal cell H+/K+ATPase ,
The transporter that is mainly responsible for producing HCL
Dr.Khalid Ghaznavi
(DPT)

38. Actions of PPIs
 Pro-drugs with an acid resistant enteric coating to protect them from
premature degradation by gastric acid.
 The coating is removed in the alkaline duodenum
 Prodrug, a weak base, is absorbed and transported to the parietal cell
canaliculus.
Dr.Khalid Ghaznavi
(DPT)

39. Omeprazole
 Omeprazole in itself is not the active inhibitor of the H+ / K+ - ATPase.
 It needs transformation in acid media to an intermediate compound, a sulphenamide, that
effectively inhibits the H+ / K+ ATPase
 The sulphenamide interacts covalently with the sulphydryl groups of cysteine residues in the
extracellular domain of the H+ / K+ - ATPase, thereby inhibiting its activity.
 Oral formulation of these drugs are enteric coated to prevent acid inactivation in the stomach
 After absorption in the intestine, they are rapidly metabolized in liver
 Half life 1-2 hrs.
 Duration of action approximately 24 hrs.
Dr.Khalid Ghaznavi
(DPT)

40. Pharmacokinetics PPI
 Available as enteric coated tablets
 They should be given 30 minutes to 1 hour before food intake
 Half life is very short and only 1-2 Hrs
 Still the action persists for 24 Hrs to 48 hrs after a single dose
 Action lasts for 3-4days even after stoppage of the drug
Dr.Khalid Ghaznavi
(DPT)

41. Adverse Effects
Nausea, headache , Muscle & joint pain, dizziness, rashes
Omeprazole is well tolerated
Prolonged acid suppression may allow bacterial overgrowth in
the smooth muscles
Dr.Khalid Ghaznavi
(DPT)

42. Long term administration may result in :
 Vitamin B12 deficiency due to its reduced absorption/oral bioavailability
 Atrophic changes in the stomach have been noticed
 Increase gastrin level..
 Also reduces oral bioavailability of many drugs that require acidic medium for
their absorption
 Like digoxin ketoconazole
Dr.Khalid Ghaznavi
(DPT)

43. PPI – cont.
Therapeutic uses:
1. Peptic Ulcer – 20-40 mg daily
2. Severe Gastroesophageal reflux disease (GERD) (not responding to h2 blockers)
 Ulcers heal fast and pain is relieved
 It is given for 4-8 weeks
3. Zollinger Ellison Syndrome
(a condition in which a gastrin-secreting tumor or hyperplasia of the islet cells in the pancreas causes
overproduction of gastric acid, resulting in recurrent peptic ulcers. )
4.Prevention of recurrence of NSAID associated gastric ulcers in patients who continue NSAID use.
5. Reducing the risk of duodenal ulcer recurrence associated with H. pylori infections
Dr.Khalid Ghaznavi
(DPT)

44. Drug interactions
 Omeprazole inhibits the metabolism of
◼ warfarin,
◼ phenytoin,
◼ diazepam, and
◼ cyclosporine.
 However, drug interactions are not a problem with the other PPIs.
Dr.Khalid Ghaznavi
(DPT)

45. PPI – Dosage schedule
DOSAGE SCHEDULE
Omeprazole 20 mg o.d.
Lansoprazole 30 mg o.d.
Pantoprazole 40 mg o.d.
Rabeprazole 20 mg o.d.
Esomeprazole 20-40 mg o.d
Dr.Khalid Ghaznavi
(DPT)

46. Proton Pump Inhibitors
 Lansoprazole :
✓ Partly reversible
✓ More potent
✓ Slightly more against H pylori
✓ Higher BA
 Rapid onset
 Pantoprazole: More acid stable, I.V
 Rabeprazole: Claimed to most rapid
 Esomeprazole: Better intra-gastric pH , higher healing rates.
Dr.Khalid Ghaznavi
(DPT)

47. Muscarinic antagonists
 Block the M1 class receptors
 Reduce acid production
 Abolish gastrointestinal spasm
 Pirenzepine and Telenzepine
 Reduce meal stimulated HCl secretion by reversible blockade of muscarinic (M1)
receptors present in stomach
 Unpopular as a first choice
 Because of high incidence of anticholinergic side effects :
✓ Dry mouth
✓ Blurred vision
Dr.Khalid Ghaznavi
(DPT)

48. Prostaglandin analogues (Misoprostol)
Misoprostol
 Inhibit gastric acid secretion
 Enhance local production of mucus or bicarbonate
 Exerts protective effect
 Special value in preventing NSAIDs gastric ulceration
Dr.Khalid Ghaznavi
(DPT)

49. Therapeutic use Of Misoprostol
Prevention of NSAID-induced mucosal injury
(rarely used because it needs frequent administration – 4 times
daily)
Dr.Khalid Ghaznavi
(DPT)

50. Misoprostol’s ADRs:
Diarrhea and abdominal cramps
Contraindications:
1. Pregnancy (may cause abortion)
Dr.Khalid Ghaznavi
(DPT)

51. Sucralfate – Ulcer Protective
 Aluminum salt of sulfated sucrose
 MOA:
 In acidic environment ( pH <4) it polymerizes by cross linking molecules to
form sticky viscous gel that adheres to base of ulcer
 It remains there for over 6 hours
 Astringent action and acts as physical barrier
 Dietary proteins get deposited on this layer forming another coat
 Prevents contact with acid and pepsin
Dr.Khalid Ghaznavi
(DPT)

52. Sucralfate – contd.
 Concurrent antacids avoided, (as it needs acid for activation)
Uses:
 Prophylaxis of Stress ulcers
Dose:
 1 gm 1 Hr. before 3 major meals and one at bed time for 4-8 weeks
 Continued for 6 months to prevent reoccurrence
 Unfortunately, sucralfate must be taken 4 times daily
Dr.Khalid Ghaznavi
(DPT)

53. ADRs:
Constipation
Hypophosphatemia
Drug interactions :
Adsorbs many drugs and interferes with their absorption
Dr.Khalid Ghaznavi
(DPT)

54. Colloidal Bismuth Subcitrate (CBS)
Mechanism of action
CBS and mucous form glycoprotein bicomplex which coats ulcer
↑ secretion of mucous and bicarbonate, through stimulation of
mucosal PGE production
Detaches H.pylori from surface of mucosa and directly kills them
Dr.Khalid Ghaznavi
(DPT)

55. Colloidal Bismuth subcitrate
Dose:
 120 mg 4 times a day promotes ulcer healing in 4-8 weeks
Adverse effects
 Blackening of tongue
 Black Stool
 Constipation
 Headache
 Dizziness
Dr.Khalid Ghaznavi
(DPT)

56. Eradication of H.pylori
Dr.Khalid Ghaznavi
(DPT)

57. HELICOBACTER. pylori
 Gram (-) rod
 Associated with gastritis, gastric & duodenal ulcers, gastric adenocarcinoma
 Transmission route fecal-oral
 Higher prevalence in Low SES
Dr.Khalid Ghaznavi
(DPT)

58. Triple Therapy
The BEST among all the Triple therapy regimen is:
1. Omeprazole / Lansoprazole - 20 / 30 mg bd
2. Clarithromycin - 250 mg bd
3. Amoxycillin / Metronidazole - 1gm / 400 mg bd
 Given for 14 days followed by P.P.I for 4 – 6 weeks
 Short regimens for 7 – 10 days not very effective
Dr.Khalid Ghaznavi
(DPT)

59. Other 2 weeks regimen(mg)
 Amoxicillin 750/ + Tinidazole 500 +omeprazole 20 mg/ lansoprazole 30 mg BD
 Carithromycin 250 + Tinidazole 500/amoxicillin 1000 + lansoprazole 30 mg BD
Dr.Khalid Ghaznavi
(DPT)

60. .From.
Dr.Khalid Ghaznavi
(DPT)