Presentation on Peptic ulcer for Medical students and postgraduates

1. PEPTIC ULCER
DISEASE
Dr. Noopur Vyas
1st Year
Pharmacology Resident

2. CONTENT
 Acid peptic disease
 Gastric anatomy and gastric physiology
 What is Peptic ulcer?
 Epidemiology
 Etio-pathophysiology
 History of drug development
 Pharmacological agents used in treatment- MOA, Pharmacokinetics,
Clinical uses, Adverse drug reactions
 Eradication of Helicobacter Pylori
 Principles of medical treatment of Peptic ulcers
 Other related disorders
 Newer drugs and future developments
 Summary

3. ACID PEPTIC DISEASE
 Excessive secretion of acid and pepsin on a weakened stomach
mucosal defense is responsible for damage to the delicate mucosa
and the lining of the stomach, oesophagus and duodenum resulting
in ulceration which is known as “Acid Peptic Disease”.
 Acid peptic disease is a collective term used to include many
conditions such as, gastritis, gastric ulcer, duodenal ulcer, gastro-
oesophageal reflux disease (GERD) and Zollinger Ellison Syndrome
(ZES)

4. GASTRIC ANATOMY

5. GASTRIC ANATOMY
Glands
Gastric cardia:
 Comprises <5% of the gastric glands
 Contain mucous and endocrine cells
Oxyntic gland /fundus:
 The 75% of gastric glands
 Contain mucous neck, parietal, chief,
endocrine and enterochromaffin cells.
 The parietal cell, also known as the oxyntic
cell, is usually found in the neck, or isthmus, or
in the oxyntic gland.
Antrum:
 Pyloric glands contain mucous and endocrine
cells, including gastrin cells

6. PHYSIOLOGY OF GASTRIC SECRETION
 H2 receptor activation increases cAMP, which
activates protein kinase A
 M3 and CCKB receptor activation stimulates
release of Ca2+ and activates protein kinase
 Protein kinase activation results in
translocation of cytoplasmic tubulovesicles
containing inactive H+ /K + ATPase to the
apical membrane
 Fusion of tubulovesicles with the apical
membrane activates H+ /K+ ATPase, which
pumps H+ ions into the stomach lumen
 An apical membrane, Cl- channel couples Cl-
influx to H + efflux
 K+channel recycles K + out of the cell.
 The net result of this process is the rapid
extrusion of HCl into the stomach lumen

8. WHAT IS PEPTIC ULCER?
 What is peptic ulcer?
An ulcer is defined as disruption of the mucosal integrity due
to active inflammation of the stomach and/or duodenum
leading to a local defect or excavation.
 The break can involve the mucosa, muscularis mucosa,
submucosa, and in some cases, the deeper layers of the
muscle wall
 Gastritis is the precursor to peptic ulcer disease (PUD)
 PUD includes:
 Stomach (called gastric ulcer)
 Duodenum (called duodenal ulcer)

9. DUODENAL ULCERS GASTRIC ULCER
AGE (YEARS) 35-40 50-60
GASTRIC SECRETION Increased gastric acid
secretion between meals,
after meals and at night
Reduced gastric secretion
PAIN Pain 2-3 hours after meal
,at night and awakens the
patient between 1-2
Pain occurs ½-1 hour after
the meal, rarely at night.
RELIEF ON TAKING
FOOD
Relieved by taking food Not relieved by taking food
BLEEDING Melena is more common
than hematemesis
Hematemesis is more
common than melena
GASTRIC CARCINOMA Less chances of gastric
carcinoma
More chances of converting
to gastric carcinoma

10. EPIDEMIOLOGY OF PUD
 APD (GERD and PUD) is more common in 18-59 years age group
 According to the WHO data published in May 2014 Peptic Ulcer
Disease Deaths in India reached 85,487 or 0.96% of total deaths.
 India #26 in the world in PUD.
 In a study in 2016 about 39.2% and 37.1% patients had reported GERD
and PUD respectively with incidence of ulcers as:
i. Duodenal ulcer: 10.5%
ii. Gastric ulcer: 9.9%
iii. Peptic ulcer-non specified: 16.7%

11. WHY DOES PEPTIC ULCER DISEASE
OCCUR?
 PROTECTIVE FACTORS
 Mucus
 Mucosal blood flow
 Bicarbonate
 Prostaglandin E
 Growth factors such as
epidermal and transforming
growth factors
 Competent pyloric sphincter
 DAMAGING FACTORS
 Helicobacter Pylori
 NSAID
 Acid hypersecretion
 Hereditary factors
 Diminished gastric mucosal blood flow leading
to stress ulcers.
 High gastric acid output
 Smoking
 Glucocorticosteroids
 Alcohol
 Incompetent pyloric sphincter

12. WHY DOES PEPTIC ULCER DISEASE
OCCUR?
Protective factors
Mucus, Mucosal
blood flow
Formation of
HCO3,PGE2
Damaging factors
Acid , Pepsin ,
NSAIDS,
Helicobacter
Pylori
IMBALANCE BETWEEN
DAMAGING AND
PROTECTIVE FACTORS

14. WHEN DID IT ALL START?
 John Abercrombie provided the first full pathological description of
ulcer in 1828
 Moynihan also cites Abercrombie as the first to describe the patients
history with duodenal ulcer when he wrote “The leading peculiarity of
disease the duodenum, so far as we are presently acquainted with it,
seems to be that the food is taken with relish, and the first stage of
digestion is not impeded; but the pain begins about the time when the
food is passing out of the stomach or from two to four hours after a
meal.”
 Ulceration, rarely reported uptil the nineteenth century, began to
increase dramatically in prevalence in young and middle-age males
and, by 1900, was more common
 The treatment of peptic ulceration changed after the pronouncement
of the dictum 'no acid, no ulcer' in 1910 by the Croatian, Karl Schwarz

15. 1915
Antacids
1960
Stilbesterol
1962
Carbenoloxne
1966
Histamine
receptor
1970
H2 receptor
antagonist
1979
Proton Pump
Inhibitor
WHEN DID IT ALL START?

16. DISCOVERY OF HELICOBACTER PYLORI
 In 1981 when a second-year medical internist, Barry Marshall, began a
clinical research project with Robin Warren, a histopathologist, in the
Royal Perth Hospital, Western Australia.
 Their research led to the discovery of the pivotal role of H. pylori in
gastroduodenal disease association of these bacteria with gastritis .
 It was first presented at the Royal Australian College of Physicians on
22 October 1982 and published in letter form in 1983 .
 Initially named Campylobacter but later a new genus was added and
named Helicobacter in 1987.

17.  In 1994, H. pylori was recognised as a
grade I (definite) carcinogen.
 The National Institutes of Health
Consensus Development Conference
Statement recommended that all
patients who are found to have gastric or
duodenal ulceration and concurrent H.
pylori infection should receive treatment
aimed at eradicating the bacterium.
 In 2005, Barry Marshall and Robin Warren
were awarded the Nobel prize in
Physiology for their pioneering work
on Helicobacter pylori. In the words of
the Nobel Committee, they were honored
“for their discovery of the
bacterium Helicobacter pylori and its role
in gastritis and peptic ulcer disease.”
Barry J MarshallJ. Robin Warren

18. HELICOBACTER PYLORI
 Gram negative rod with flagella.
 Colonizes stomach and duodenum
 Acquired by feco-oral route
 Attaches to epithelial cells
 It secretes:
Urease
 Urea CO2 +NH3
Producing alkaline environment for survival
 Exotoxin which damages the epithelial cells
 Present in nearly all patients with duodenal ulcer and 80% of patients with
gastric ulcer.
 Causes chronic gastritis and implicated in pathogenesis of gastric
carcinoma and lymphoma

19.  H.Pylori can be confirmed by:
 Detection of IgG antibody against H.Pylori in the serum and antigen
 Carbon labelled urea breath test
 Rapid urease breath test
 Histopathological examination of biopsy and gastric antral mucosa at
endoscopy

20. NON STEROIDAL ANTI-INFLAMMATORY
DRUGS (NSAID)
 The gastrointestinal tract is the most common target for the
adverse effects of NSAID use
 Most NSAIDs are weak organic acids
 They cause
 Systemic effects
 Topical injury

21.  SYSTEMIC EFFECTS:
 Inhibition of cyclooxygenase leading to
decreased prostaglandin
 Mucosal damage due to neutrophil derived
free radicals and proteases
 TOPICAL INJURY:
 In the acidic environment of the stomach,
these drugs are neutral compounds that can
cross the plasma membrane and enter
gastric epithelial cells.
 In the neutral intracellular environment, the
drugs are re-ionized and trapped
 The resulting intracellular damage is
responsible for the local gastrointestinal
injury associated with NSAID use.

22. TREATMENT OF PEPTIC ULCER
DRUGS WHICH
NEUTRALIZE GASTRIC
ACID(ANTACIDS)
 SYSTEMIC ANTACIDS:
Sodium Bicarbonate
 NON SYTEMIC ANTACIDS:
• BUFFER TYPE: Aluminium
Hydroxide ,magnesium
trisilicate, Magaldrate
• NON BUFFER TYPE:
Magnesium hydroxide,
Calcium carbonate
• MISCELLANEOUS :
Alginate, Simithicone
DRUGS WHICH REDUCE
GASTRIC ACID SECRETION
 H2 RECEPTOR ANTAGONIST
Cimetidine,Ranitdine,Famotidine,
Nizatidine,Roxatidine,Loxatidine
 PROTON PUMP INHIBITORS:
Omeprazole ,Lansoprazole ,
Pantoprazole ,Rabeprazole,
Esomeprazole
 ANTICHOLINERGICS:
Propantheline , Oxyphenonium,
Pirenzepine ,Telenzepine
 PROSTRAGLANDIN ANALOGUES:
Misoprostol , Enprostil ,Rioprostil
MUCOSAL
PROTECTIVE
DRUGS
 Sucralfate
 Colloid bismuth
subcitrate
 Ranitidine
bismuth
citrate
ANTI
HELICOBACTER
PYLORI DRUGS
Given in combinations
 Amoxicillin
 Clarithomycin
 Tetracycline
 Metronidazole
 Ranitidine bismuth
citrate
 Bismuth
subsalicylate
 PPI

23. PRINCIPLES OF ANTI ULCER THERAPY
1.Controlling gastric acidity , hypermotility and promoting
ulcer healing
2.Treatment of H.Pylori infection
3.Prevention of complications
4.Prevention of recurrence

24. REGULATION OF GASTRIC ACID SECRETION
AND PHARMACOLOGICAL TREATMENT

25. PROTON PUMP INHIBITORS
 Most effective drugs in peptic ulcer disease
 Prodrugs, require activation at an acid pH
 Most potent suppressors of gastric acid secretion are inhibitors of the
gastric H+, K+-ATPase (proton pump)
 Prototype: Omeprazole
 Examples:
 Lansoprazole
 Pantoprazole
 Rabeprazole
 Esomeprazole

26. OMEPRAZOLE :MECHANISM OF ACTION
 Substituted Benzimidazole
 MOA:
Prodrugs,activated in acidic environment and absorbed
into systemic circulation
Diffuse into parietal cells and accumulates in acidic
secretory canaliculi
Drug activated and trapped by Proton catalyzed
formation of tetracyline sulfonamide
Activated form binds irreversibly with sulfhydryl groups
of cysteines H+K+ATPase and block acid secretion

28. PHARMACOKINETICS
 PPI’s are acid labile and can be destroyed by gastric acid
 They should be given uncrushed and unbroken or taken as enteric
coated granules.
 Presence of food decreases their absorption
 Should be given 30 mins before meals for best results
 Provide a prolonged (up to 24- to 48-hour) suppression of acid
secretion, despite the much shorter plasma half-lives (0.5-2 hours) of
the parent compounds
 Highly protein bound
 Rapidly metabolized by the liver by CYP2C19 and CYP3A4 – dose
reduction necessary in severe hepatic failure
 Takes 3-4 days for return of normal acid secretion after PPI
withdrawal

29. CLINICAL USES
 Omeprazole is used over the counter(OTC) for heart burn
 Duodenal and gastric ulcer
 GERD
 NSAID Induced ulceration
 Prevention of ulcer recurrence
 Zollinger Ellison Syndrome although definitive treatment is surgical
 H.Pylori associated ulcers:
 Use in Children:
 Safe and effective for treatment of erosive esophagitis and GERD.
 Increased metabolic capacity and so there is need for higher
dosages
PPI’s promote eradication of H.Pylori by raising intragastric pH
Lowers minimal inhibitory concentration of antibiotics

30. DOSAGE SCHEDULE
DRUG BIOAVALIBILITY
%
DOSE mg/day
OMEPRAZOLE 40-65 20-40
PANTOPRAZOLE 77 40
LANSOPRAZOLE 80-90 30
RABEPRAZOLE 52 20-40
ESOMEPRAZOLE 50-89 20-40

31. ADVERSE REACTIONS
 Well tolerated and few incidences of side effects
 GI disturbances ,dizziness ,drowsiness is seen
 EFFECTS OF CHRONIC USE :
 Decreases absorption of Vit B12
 Increased incidence of osteoporotic fractures
 Hypergastrinemia may predispose to rebound hypersecretion of
gastric acid upon discontinuation of therapy and may promote the
growth of gastrointestinal tumors (carcinoid tumors )
DRUG INTERACTIONS
 Inhibits hepatic microsomal enzymes and prolongs half life of
diazepam, disulfiram, phenytoin, carbamazepine, warfarin

32. H2 RECEPTOR ANTAGONISTS
 Landmark discovery
 Safety and efficacy lead to availability without prescription
 Being replaced by Proton pump inhibitors
 Reversible competitive inhibitors of H2 receptor
 DRUGS:
 Cimetidine
 Ranitidine
 Famotidine
 Roxatidine
 Nizatidine
 Loxatidine

33. H2 ANTAGONISTS

34. MECHANISM OF ACTION:CIMETIDINE
 Inhibit acid production
 It acts by reversibly competing with
histamine for binding to H2 receptors on
the basolateral membrane of parietal
cells
 Inhibit basal acid secretion
 Effective in suppressing nocturnal acid
secretion
 Suppress 24-hour gastric acid secretion
by ∼70%
 Less potent than proton pump inhibitors

35. PHARMACOKINETICS
 Rapidly absorbed after oral administration
 Reaches peak serum concentrations within 1-3 hours
 Therapeutic effect of a single dose lasts for 5-8 hours
 Bioavailability is 80%
 Drugs undergo metabolism in the liver, but liver disease per se is not
an indication for dose adjustment.
 Absorption may be enhanced by food or decreased by antacids
 Excreted unchanged in the urine within 24 hours
 Crosses placenta and secreted in the milk

36. Comparison of H2 antagonists
FEATURES CIMETIDINE RANITIDINE FAMOTIDINE
BIOAVAILABILITY(%) 80 50 50
RELATIVE POTENCY 1 5 30
CYTOCHROME P450
INHIBITION
++++ + 0
DURATION OF
ACTION
(Hours)
5-8 8-12 24
HALF LIFE (Hours) 1.5-2.3 1.6-2.4 3-4

37. CLINICAL USES
 Cimetidine use is obsolete now
 Ranitidine famotidine ,nizatidine, roxatidine,
loxatidine are used
 Used in duodenal and gastric ulcer, more
effective in duodenal ulcer
 Zollinger Ellison syndrome
 Gastro oesophageal disease reflux disease (GERD)
 Prevention of acute erosive gastritis in acutely
stressed patients
 NSAID induced ulcers
 Stress ulcers
 Prevention of ulcer recurrences

38. DOSAGE FOR PETIC ULCER
Cimetidine 800mg HS 400mg BD
Ranitidine 300 mg HS 150 mg BD
Famotidine 40 mg HS 20 mg BD
Roxatidine 150 mg HS 75 mg BD
Nizatidine 300 mg HS 150 mg BD

39. ADVERSE REACTIONS
 Well tolerated, with a low (<3%) incidence of adverse effects
 Minor side effects include diarrhoea, headache, drowsiness, fatigue,
muscular pain, and constipation.
 Less common side effects include those affecting the CNS confusion,
delirium, hallucinations, slurred speech, and headaches-Given IV
 Associated with various blood dyscrasias, including
thrombocytopenia.
 H2 receptor antagonists cross the placenta and are excreted in
breast milk.
 No major teratogenic risk but should be used with caution in
pregnancy

40. ADVERSE REACTIONS
 Inhibits binding of DHT to androgen receptors-----Impotence
 Inhibits oestradiol metabolism, Sr. Prolactin level----Gynecomastia
(enlarged breasts) in men and, rarely, galactorrhoea (discharge of
milk) in women

41. DRUG INTERACTIONS
 Cimetidine inhibits CYP3A4 and CYP1A2 and reduces hepatic blood
flow
 It inhibits the metabolism of many drugs so that they can accumulate
to toxic levels, e.g. theophylline, phenytoin, carbamazepine,
phenobarbitone, sulfonylureas, metronidazole, warfarin, imipramine,
lidocaine, nifedipine, quinidine.
 Hepatotoxicity of INH and Paracetamol is enhanced
 Antacids reduce absorption of all H2 blockers so when used
concurrently a gap of 2 hr should be allowed.
 Ketoconazole absorption is decreased by H2 blockers due to reduced
gastric acidity.

42. OTHERS
 RANITIDINE
 Nitroethane derivative
 More potent than cimetidine
 More selective and longer
lasting
 ADR:
Skin rash ,constipation and
fecal concretions
 Does not inhibit hepatic drug
metabolism
 Less anti androgenic effects
 Little central effects
 FAMOTIDINE
 Thiazole ring
 Longer acting
 ADR:
Headache ,dizziness and GI
symptoms
 Cost effective
 Generic preparations are the
cheapest drugs

43. Tolerance
and
rebound
with acid
suppressing
medication
Diminished
therapeutic
effect
Develops
within 3 days
Resistant to
increase
dosage
Secondary
hypergastrin
emia to
stimulate
histamine
release from
ECL cells.
PPI do not
cause this
phenomenon
Rebound
acidity may
occur with
withdrawal of
the drugs
May require
gradual drug
taper or
alternative
medication

44. ANTI MUSCARINIC DRUGS
 ATROPINE
 In use before H2 antagonists
and PPI’s- Propantheline and
oxyphenonium used
 MOA: Block basal and
maximum acid secretion
 Increase gastric emptying time
Prolongs exposure of ulcer bed
to acid
 Unsuitable for treatment of
Peptic ulcer
 Anticholinergic side effects like
blurred vision, dry mouth ,
constipation and urinary
retention are seen
 PIRENZEPINE AND
TELENZEPINE
 Used in Canada and Europe
 MOA: Act by selectively blocking
M1 receptors at paracrine
cells in gastric mucosa
 Are being used for treatment of
peptic ulcer (not in India)
 Incidence of anticholinergic side
effects are low

45. PROSTAGLANDIN ANALOGUES
MOA
Enhances
mucosal blood
flow
PGE2 Inhibits
acid secretion
by inhibiting
cAMP and
gastrin
Stimulates
secretion of
mucus and
bicarbonates
Misoprostol(PGE1) and newer drugs like Enprostil and Rioprostil(PGE2)

46.  PHARMACOKINETICS:
 Rapidly absorbed orally
 De-esterified to form misoprostol acid, the principal and active
metabolite of the drug
 Single dose inhibits acid production within 30 minutes
 The therapeutic effect peaks at 60-90 minutes and lasts for up to
3 hours
 Food and antacids decrease absorption
 Excreted mainly in the urine, with an elimination t1/2 of 20-40
minutes
 CLINICAL USES:
 No widespread use because of adverse effects ,need for multiple
daily dosing and expense
 Used in healing of peptic ulcer in patients using NSAID’s and
chronic heavy smokers

47.  Dose: 200 mcg four times
 ADR:
 Commonest is diarrhoea and colicky pain
 Nausea ,vomiting and flatulence
 Headache and dizziness
 Causes clinical exacerbation of Inflammatory Bowel disease
 The cost of these drugs is high
 Contraindicated in patients who are pregnant or
contemplating pregnancy as it causes uterine
contractions

48. MUCOSAL PROTECTIVE DRUGS
 SUCRALFATE:
 Complex of sulphated sucrose and aluminium hydroxide
 MOA:
Undergoes extensive cross-linking to
produce a viscous, sticky polymer in
acidic environment
Adheres to epithelial cells and ulcer
craters for up to 6 hours after a single
dose
Inhibits hydrolysis of mucosal proteins
by pepsin
Stimulates local production of
prostaglandins and epidermal growth
factor

49.  CLINICAL USES
 Use has diminished
 Used in prophylaxis of stress ulcers
 Due to its unique mechanism of action used in oral mucositis
(radiation and aphthous ulcers) and bile reflux gastropathy.
 Administered by rectal enema, sucralfate also has been used for
radiation proctitis and solitary rectal ulcers
 DOSE
 Taken on an empty stomach 1 hour before meals
 The use of antacids within 30 minutes of a dose of sucralfate
should be avoided.
 The usual dose of sucralfate is
 1 g four times daily -For active duodenal ulcer or
 1 g twice daily -For maintenance therapy

50.  ADR:
 Constipation, dryness of mouth ,abdominal discomfort
 Rarely causes hypophosphatemia and aluminium toxicity
 Drug interactions:
 Interferes with absorption of ciprofloxacin , phenytoin ,digoxin
and aminophylline
 Other uses:
 Glycerine paste used for stomatitis
 Burn dressing and bed sores
 Used to prevent phosphate stones in kidney

51. CBS and mucous form glycoprotein bi complex which coats ulcer crater
↑ secretion of mucous and bicarbonate, through stimulation of mucosal PGE
production
Detaches H. Pylori from surface of mucosa and directly kills them
 Colloidal bismuth subcitrate and bismuth subsalicylate
 Mechanism of action
 Dose: 120 mg 4 times a day
 Adverse effects
 Constipation ,blackening of stool and darkening of tongue
 Bismuth toxicity-Osteodystrohy and encephalopathy
 Antacids decrease efficacy
 Ranitidine bismuth citrate: Upon hydrolysis releases bismuth as well
as ranitidine
BISMUTH SALTS

52. ULCER HEALING DRUGS
 Carbenoxolone
 One of the first drugs used
 Outdated anti ulcer drug
 ADR:
 Hypertension
 Sodium and water retention
 Hypokalaemia
 Not used because of side effects and availability of better drugs

53. ANTACIDS
 Antacids were the primary drugs earlier
 Produce symptomatic relief of pain ,
muscle spasm and reduce acidity
 MOA: Weak bases that neutralize gastric
hydrochloric acid
 Acid neutralising capacity(ANC):
 Potency of an antacid
 Expressed in terms of Number of mEq
of 1N HCl that are brought down to pH
3.5 in 15 minutes by unit dose of a
preparation
MOA
Neutralize
hydrochloric
acid
Weak
bases
Reduce
activity of
pepsin
Raise pH
of
stomach
contents

54. SYSTEMIC ANTACIDS: Sodium bicarbonate
 White water soluble absorbable antacid
 Effective and rapidly acting antacid with short duration of action
 ANC: 1 gm = 12 mEq
 Sodium bicarbonate + gastric acid H20 + CO2
 Eructation of carbon dioxide liberated during the process provides
relief from abdominal discomfort
 ADR:
 Belching ,flatulence ,feeling of fullness, nausea and
exacerbation of oesophageal reflux
 Systemic alkalosis and edema due to sodium retention

55.  Therapeutic Uses:
 As an antacid
Dose:1-5g
 Metabolic acidosis
 Alkalinisation of urine
 Topical use
Antipruritic solution as an eye wash , mouth wash ,douche and
loosen ear wax

56. NON SYSTEMIC ANTACIDS
 Insoluble and poorly absorbed basic compounds
 React in stomach to form corresponding chloride salt
 Hydroxide or carbonate or trisiliacate base combined with
Mg++,Al++,Ca++
 The chloride salt again reacts with the intestinal HCO3-, regenerates
HCO3- and so no net gain or loss .

57. ALUMINIUM
HYDROXIDE GEL
• White suspension or dry
gel
• Forms a protective layer
over the ulcer
• 1 ml neutralizes 1.2-2.5
mEq of acid
• ADR:
• Constipation,rarely
osteomalacia and
encephalopathy
• DOSE:
• Gel 4-8ml every 24
hours
• 0.5g tablets 1-2
tablets qid
MAGNESIUM
TRSILICATE
• Fine white tasteless
powder
• Forms hydrated silicon
dioxide
• Forms gelatinous coating
over ulcer crater-
hydrated silica gel
• 1gm neutralizes 9-11
mEq of gastric acid
• ADR:
• Mild diarrhea
• In renal failure CNS
depression
• DOSE: 2-4 g every1-4
hours
MAGALDRATE
• Hydrated complex of
aluminium–magnesium
hydroxide sulfate
• Reacts with HCl to
release AL(OH)3 and
Mg(OH)2
• AL(OH)3 released is more
reactive
BUFFER TYPE

58. NON BUFFER TYPE
MAGNESIUM HYDROXIDE
• Oxide combines with water
to form hydroxide
• 1gm of Mg oxide neutralizes
50 mEq of acid
• Mg hydroxide is available as
‘Milk of Magnesia’
• 1ml neutralizes 2.7 mEq of
acid
• Adverse reactions similar to
magnesium salts
• DOSE:
• 4ml as antacid
• 15 ml as laxative
CALCIUM CARBONATE
• White ,tasteless odourless
powder with chalky taste
• Reacts with gastric acid to
form calcium carbonate
• Acts quickly
• 1gm neutralizes 21 mEq of
acid
• ADR:
• Constipation and fecal
concretions
• Prolonged therapy causes
hypercalcemia
• DOSE: Powder or tablets
• 2-4g

59. DRUG INTERACTIONS
ANTACID DECREASE IN
BIOAVAILIBILITY OF
ALUMINIUM COMPOUNDS
Phosphates , iron salts ,
tetracyclines , antimuscarinic
drugs, phenothiazines, digoxin ,
indomethacin , prednisolone ,
ranitidine, sulfadiazine, fat
soluble vitamins
CALCIUM CARBONATE Anti muscarinic agents , iron ,
phenothiazines, quinidine ,
tetracycline
MAGNESIUM SALTS Digoxin and tetracyclines

60. ANTACID THERAPY
 Easily available over the counter
 Most abused drugs
 Should be prescribed in optimal dose at 1 and 3 hours after each meal
and at bed time and as needed for pain
 Invitro buffering effect of an antacid may not necessarily correlate
with its in vivo effect
 Quantity of an antacid required to produce buffering varies from one
patient to another
 Antacid tablets though more convenient are less effective buffers
 Antacid may interfere with absorption of other drugs
 Persistent reduction in gastric acidity by antacids may increase
susceptibility to intestinal pathogens
 Choice of an antacid depends on adequate dose, frequency of
administration and cost

61. MISCELLANEOUS DRUGS
 SIMETHICONE
 Silicon polymer having water repellant properties
 Antifoaming agent
 Aids proper dispersion of antacids , coats ulcer surface ,reduces
flatulence
 SODIUM ALGINATE
 Hydrophilic colloidal carbohydrate derivatives
 Used along antacids ad H2 receptor antagonist
 Forms viscous gel along with gastric acid
 Foam acts as mechanical barrier to reduce effects of gastric reflux

62. ERADICATION OF H.PYLORI
No acid
No ulcer
OLD TESTAMENT
No HP No ulcer
NEW TESTAMENT

63. ANTIHELICOBACTER PYLORI DRUGS
 H. pylori, a gram-negative rod
 Has been associated with gastritis ,gastric and duodenal ulcers,
gastric adenocarcinoma, and gastric B-cell lymphoma
 All H. pylori positive ulcer patients should receive H. pylori
eradication therapy.
 In absence of H. pylori testing cases with failed conventional ulcer
therapy and relapse cases must be given H. pylori eradication
 For faster ulcer healing and to prevent ulcer relapse:
 Eradication of H. pylori drugs –Antibiotics
 Concurrently with H2 blocker/PPI therapy
 Antimicrobials and anti secretory drugs are given for 10-14 days
followed by anti secretory therapy alone for 6-8 weeks

64. ANTIBIOTICS
Antibiotics used against H. Pylori eradication are:
Amoxicillin,
Clarithromycin
Tetracycline and
Metronidazole/tinidazole.
Chances of developing resistance
Hence ,a single antibiotic is ineffective

65. ACID SUPRESSION BY PPI’S/H2
BLOCKERS
Enhances effectiveness of anti-H. pylori antibiotics
Optimum benefits are obtained when gastric pH is kept
>5 for at least 16–18 hours per day
Benefit by altering the acid environment for H. pylori as
well as by direct inhibitory effect
One of the PPIs is an integral component of all anti-H.
pylori regimens along with 2 (triple drug) or 3 (quadruple
drug) antimicrobials

66. TRIPLE THERAPY
 Given for 14 days
 Greater efficacy compared to 7-10 day routine
DRUG COMBINATION DOSE AND FREQUENCY
Omeprazole
+Clarithromycin
+Amoxicillin or metronidazole
20mg BD
500 mg BD
1g BD or 500 mg BD
Ranitidine Bismuth Citrate
+Tetracycline
+Metronidazole or Clarithromycin
400 mg BD
500 mg BD
500 mg BD or 500 mg BD
OR

67. QUADRUPLE THERAPY
 In case of resistant organism and failure to respond to triple therapy
quadruple therapy is the next step
 Given for a period of 14 days
DRUG COMBINATIONS DOSE AND FREQUENCY
Omeprazole
+Bismuth Subsalicylate
+Metronidazole
+Tetracycline
20 mg BD
2 Tabs(525 mg)QID
500 mg TDS
500 mg QID
Famotidine
+Bismuth subsalicylate
+Metronidazole
+Tetracycline
20 mg
525mg
250 mg
500 mg
OR

68. SEQUENTIAL THERAPY
 Introduced recently
 Demonstrated 90% eradication rate with good patient tolerance
DRUG COMBINATIONS DOSE AND FREQUENCY
FOR 1-5 DAYS
Omeprazole
+ Amoxicillin
20 mg BD
1g BD
FOLLOWED BY DAYS 6-10
Omeprazole
+Clarithromycin
+Tinidazole
20 mg BD
500 mg BD
500 mg BD

69. CURRENT GUIDELINES FOR TREATMENT
OF H.PYLORI
STRONGLY
RECOMMENDED
FOR
• Duodenal and gastric ulcer
• Gastric lymphoma
• Atrophic gastritis
• Recent resection of gastric cancer
MAY BE USEFUL
FOR
• Functional dyspepsia
• First degree relatives of patients with gastric
cancer

70. PRINCIPLES OF MEDICAL TREATMENT OF
ULCERS-GASTRIC AND DUODENAL
A. NON PHARMACOLOGICAL MEASURES:
 Rest and sedative in acute stage
 Advice and reassurance about lifestyle
 Dietary modification –irritants like chilly ,spices and fried food
should be avoided
 Avoiding heavy meals and lying down for 3 hours after
 Weight reduction in obese patients
 Withdrawal of offending agent like smoking ,avoidance of NSAID,
alcohol and caffeine containing beverages

71. B. ANTI SECRETORY DRUGS
DRUG ACTIVE ULCER MAINTANENCE THERAPY
1)H2 RECEPTOR
ANTAGONISTS
Cimetidine 800mg at bedtime 400 mg at bedtime
Famotidine 40 mg at bedtime 20 mg at bedtime
Ranitidine/Nizatidine 150 mg twice daily 150 mg at bedtime
2)PPI’S
Lansoprazole 15 mg for DU
30 mg for GU
Omeprazole 20 mg daily
Rabeprazole 20 mg daily
3)PROSTAGLANDIN
ANALOGUES
Misoprostol 200 mcg four times daily

72. C.THERAPY FOR TREATMENT OF HELICOBACTER
PYLORI INFECTION:
 Triple therapy x 14 days
 Quadruple therapy x 14 days
D.PREVENTION OF RECURRENCE:
 Cimetidine(400 mg daily ) and ranitidine ( 150 mg daily ) used
prophylactically reduce ulcer recurrence and prevent
complications
 Lifestyle changes
 Dietary changes
 Avoid offending agents

73. DRUGS TO BE AVOIDED IN PUD
NSAID
Clopidogrel
Caffeine ,theophylline
Glucocorticoids in pharmacological doses
Some iron salts
Biphosphonates
Mycophenolate mofetil
Potassium chloride

74. FAILURE TO RESPOND TO MEDICAL
TREATMENT
Surgery is
indicated
when
Malignancy is
suspected in GU
DU becomes chronic
and refractory to
treatment
Complication such as
obstruction or
perforation is present
Patient suffers from
repeated attacks of GI
Bleeding

75. RELATED DISORDERS:
GASTROESOPHAGEAL REFLUX DISEASE
(GERD)
 It is a common GIT motility disorder.
 Several mechanism operate to prevent reflux of
gastric contents into the esophagus.
 When these mechanisms fail, gastric contents
reflux into the esophagus and this is called as
GERD.
 Commonly presents with heart burn and
regurgitation of contents into the mouth.
 It can lead to oesophagitis ,ulcers ,Barret's
oesophagus and strictures.
 Treated is by lifestyle modifications and medical
treatment.

76. GERD
 Non pharmacological measures
 Proton pump inhibitors( high dose)
 Effective
 Promote healing of oesophageal lesions
 Maintenance therapy upto 1 year
 H2 receptor antagonists
 Less effective than PPI’s
 Cost effective in long term management
 Antacids to relieve mild reflux and symptoms
 Prokinetic drugs not recommended for routine use
 Routine H.Pylori therapy is not indicated in GERD

77. •Gastric/pancreatic
gastrinomas
•Excessive acid secretion
•DOC-PPI’s
• Therapeutic goal of
reducing acid secretion
to 1-10 mmol/hour.
•Gastritis due to NSAID
or H.pylori
•Ulcer like symptoms
•Acid suppressive
treatment
•Caused due to profound
illness or trauma
•IV preparation of PPI
and H2 receptor
antagonists
•Sucralfate used to
prevent risk of
secondary pneumonia
•Caused by large doses
and long term
treatment
•Misoprostol 400 mcg bid
•PPI’s equally effective
•H2 receptor antagonists
NSAID
INDUCED
ULCERS
STRESS
ULCERS
ZOLLINGER
ELLISON
SYNDROME
NON
ULCER
DYSPEPSIA

78. NEWER DRUGS AND FUTURE DEVELOPMENTS
Histamine Type 2 Receptor Antagonists
 LAFUTIDINE:
 This is a novel second generation H2RA. The drug has been primarily
used as an antisecretory agent in Japan.
 However, lafutidine and rabeprazole provided a similar rate of symptom
relief in patients with heartburn-predominant uninvestigated dyspepsia
 LAVOLTIDINE(AH234844)
 Also known as loxtidine
 Potent noncompetitive H2RA
 Increased incidence of carcinoid tumors observed in rats and mice after
loxtidine treatment, the drug was suspended in 1988.
 Lavoltidine has shown rapid onset of action, high potency, and prolonged
duration of effect after a single dose
 GlaxoSmithKline recently conducted 2 clinical trials with the drug

79. NEWER DRUGS
Extended Release Proton Pump Inhibitors
 DEXALAMSOPRAZOLE MR
 Dual delayed-release formulation of dexlansoprazole (R-
enantiomer of lansoprazole)
 Contains 2 types of granules that release the drug at different pH
levels (5.5 and 6.8)
 Can be administered without regard to meals
 88% of GERD patients requiring twice daily PPI to fully control
their symptoms were able to step down to once daily
dexlansoprazole MR 30 mg.

80.  TENATOPRAZOLE :
 Imidazopyridine backbone with substantially prolonged plasma
half-life
 Tenatoprazole (40 mg once daily) demonstrated better night time
acid control than esomeprazole (40 mg once daily) in healthy
subjects
 AGN201904-Z (Alevium)
 AGN201904-Z (Alevium) is a prodrug of omeprazole.
 It is acid-stable and therefore requires no enteric coating.
 This drug has a long plasma half-life due to slow absorption
throughout the small intestine.
 After absorption, the drug is rapidly hydrolyzed in the systemic
circulation to omeprazole.

81.  ILAPRAZOLE
 Ilaprazole is a benzimidazole compound
 Is extensively metabolized to the major metabolite ilaprazole
sulfone.
 The drug's antisecretory activity, half-life, and safety profile have
all been shown to be superior to omeprazole.
 ESOMEPRAZOLE STRONTIUM DELAYED RELEASE
 Esomeprazole strontium delayed-release (Esomezol) is an
incrementally modified drug (IMD) manufactured by a
pharmaceutical company from South Korea.
 Tentative approval from FDA

82. NEWER DRUGS
PPI COMBINATIONS
 PPI’s-VB101 (Vecam)
 PPI-VB101 (Vecam) is the co administration of a PPI with a ligand
that activates proton pumps in the parietal cells. The rationale
behind this combined therapy is to increase the efficacy of the PPI
by maximizing activation of proton pumps.
 OX17:
 Is an oral tablet containing a combination of omeprazole and
famotidine (doses are unclear).
 NMI-826
 NMI-826 is a nitric-oxide (NO)-enhanced PPI. The drug has been
shown to be more effective than a PPI alone in healing gastric
ulcers.

83. NEWER DRUGS
Potassium-competitive Acid Blockers
 Potassium-competitive acid blockers (P-CABs) share the same final
mechanism of action
 Inhibits gastric H+/K+-ATPase in a K+ competitive but reversible
mechanism
 Do not require prior proton pump activation to achieve their
antisecretory effect.
 Exhibit an early onset of acid-secretion inhibition due to rapid rise in
peak plasma concentration.
 Linaprazan (AZD8065)
 Soraprazan
 Revaprazan
 TAK438

84. FUTURE DEVELOPMENTS
 TRANSIENT LOWER ESOPHAGEAL SPHINCTER RELAXTION REDUCERS
 It is the main mechanism of gastroesophageal reflux, both acidic and
nonacidic, accounting for all reflux episodes in healthy subjects and the
majority of reflux episodes in GERD patients
 Cannabinoid Receptor-agonists-Rimonabant
 Cholecystokinin/Gastrin Receptor antagonist-Spiroglumide, itriglumide
and loxiglumide.
 PAIN MODULATORS: AZD1386 is a transient receptor potential vanilloid
antagonist under trial
 MUCOSAL PROTECTANTS
 Rebamipide
 An amino acid derivative of 2-(1H)-quinolinone with an anti-inflamatory
function and thus may be effective as an esophageal mucosal protectant

85. SUMMARY
 Proton pump inhibitors are superior for acid suppression in most clinically
significant acid-peptic diseases, including gastroesophageal reflux disease,
peptic ulcers, and NSAID-induced ulcers.
 Used in combination with antibiotics to eradicate infection with H. pylori
and prevent recurrent peptic ulcers.
 PPI’s have largely have replaced the use of misoprostol and sucralfate,
although sucralfate is still a low-cost alternative for prophylaxis against
stress ulcers.
 PPI’s delay maximal inhibition of acid secretion making them less suited for
use on an as-needed basis for symptom relief.
 H2 receptor antagonists are used in this situation
 They are less effective than proton pump inhibitors in suppressing acid
secretion
 However,have a more rapid onset of action that makes them useful for
patient-directed management of mild or infrequent symptoms