Anti-ulcer drugs used to treat excess acid secretion.

1. TREATMENT OF
PEPTIC ULCER

2. 3. Describe the therapy of the following
➢ Anti-Helicobacter Pylori infection
➢ Gastroesophageal reflex disease (GERD)
At the end of the session:
LEARNING OBJECTIVES
2. Describe the Pharmacological actions, mechanism of action, therapeutic uses,
interactions and adverse effects of following drugs
➢ H2 Blockers
➢ Proton pump inhibitors (PPIs)
➢ Antimuscarinic drugs
➢ Mucosal protective drug
➢ Gastro-protective Prostaglandin
➢ Antacids
1. Enumerate the drugs used for treatment of peptic ulcer.

3. Physiological Regulation of Gastric Acid Secretion

4. Pathophysiology of Peptic Ulcer
Imbalance between Aggressive & Defence factors:
MUCUS
HCO3-
PGs
NO
BLOOD FLOW
TO MUCOSA
Defence factors
Aggressive factors
ACID
PEPSIN
BILE
H. PYLORI
NSAIDs

5. Deep-fried food
Contaminated water
Spicy food
Environmental
Pollutants
Chemicals
Medications
Individual Behaviour
Diet
Stress
Age
Genetics
High fat diets

6. Relief of
Pain
Preven
-tion of
Compli
-cation
Ulcer
Healing
Preven
-tion of
Relapse
Goal of Antiulcer Therapy

7. Decrease acid secretion in the stomach
Increase protective factors → Mucus & Bicarbonate
Protect the ulcer by forming a layer over the mucosa
Stimulate the healing of the ulcer
Neutralize gastric acid → Antacids
Killing H.Pylori associated with PUD
Major strategies employed for Treatment of PUD

8. Classification of Peptic
Ulcer Drugs

9. Antimuscarinic
Drugs
CRRFN
TOPP
OLD PERSON DIE
Telenzepine
Oxyphenonium
Pirenzepine
Propantheline
Inhibition/ Reduction of Acid
Secretion
Proton Pump
Inhibitors (PPIs)
H2 Receptor
Blockers
Omeprazole
Lansoprazole
Dexlansoprazole
Pentoprazole
Rabeprazole
S-Pantoprazole
Dexrabeprazole
Ilaprazole
Esomeprazole
Cimetidine
Ranitidine
Roxatidine
Famotidine
Nizatidine

10. PG analogues
❑ Misoprostol
❑ Enprostil
❑ Erbaprostil
❑ Rioprostil
TCS PG
MEER or REEM
❑ Tripotassium dicitratobismuthate
(Colloidal bismuth subcitrate (CBS))
❑ Carbenoxolone
❑ Sucralfate
❑ PG analogues
Mucosal
Protective
agents

11. Systemic Non-systemic
SS CAM3
Calcium carbonate (CC)
Aluminium hydroxide (AH)
Magnesium hydroxide (MH)
Magnesium trisilicate (MT)
Magnesium carbonate (MC)
Sodium bicarbonate (NaHCO3),
Sodium citrate
Neutralization of acid

12. GERD
❑ PPIs
❑ Prokinetic drugs
❑ Antacids
❑ Sodium alginate
CAMTT
Clarithromycin
Amoxicillin
Metronidazole
Tinidazole
Tetracycline
Anti H.pylori
drugs

13. Mechanism of Action of Peptic Ulcer Drugs

14. Pirenzepine Misoprostol
PGE2
Histamine
Cimetidine
_
ACh
+ _ Gastrin
M3
PGE2
+ receptor
_ Adenyl
+
H2
cyclase Gastrin
+ receptor
Ca++
+
ATP cAMP
+
Ca++
+
K+
+ H+
Parietal cell
_
Omeprazole
Proton pump
Lumen of stomach
Antacid
Protein Kinase
(Activated)
_
Gastric acid

15. H2 BLOCKERS

16. Propranolol, Cimetidine
Sir James Whyte Black, OM, FRS, FRSE,
FRCP (born 14 July 1924) is a Scottish
doctor & Pharmacologist who invented
synthesized &
was awarded the Nobel Prize for Medicine
in 1988 for these discoveries

17. ❑ Competitive H2 antagonist → C, R, R & N
❑ Non-Competitive H2 antagonist → F
❑ Highly selective to H2 receptor
❑ No action on H1 or H3 receptors
CRRFN ❑ Very effective → Inhibit nocturnal acid secretion
❑ Modest effective → Meal stimulated acid secretion (Ach, Gastrin & H)
H2 Receptor Blockers
Cimetidine
Ranitidine
Roxatidine
Famotidine
Nizatidine

18. H2 Receptor Blockers
Pharmacological Action:
1. H2 antagonist:
❑ Block histamine induced gastric acid secretion
❑ Cardiac Stimulation (Isolated preparation → Guinea Pig)
❑ Uterine Relaxation (Rat)
❑ Bronchial Relaxation (H2 blockers potentiate H induced bronchospasm)
❑ Fall in BP → due to H, late phase response seen with high doses
❑ No effect on H1 R mediated response / other transmitters & Autocoids

19. H2 Receptor Blockers
Pharmacological Action:
2. Gastric Secretion:
❑ Block all phases secretion by dose dependent → Gastric, Basal, Psychic & Neurogenic
❑ Basal nocturnal acid secretion → suppressed more completely
❑ Not only Histamine also suppressed → Ach, Gastric, Insulin, Alcohol, Food
❑ Also reduced volume, Pepsin content & Intrinsic factor secretion → Mainly acid
❑ Vit B12 absorption is not interfered
❑ After prolonged use → No Vit B12 deficiency

20. H2 Receptor Blockers
Pharmacological Action:
2. Gastric Secretion:
❑ Usual doses → 60-70% inhibition of 24 hr acid output
❑ Gastric ulcer due → Stress & Drugs (NSAIDs, Cholinergic & Histaminergic) is prevented
❑ No effect on Gastric or esophageal motility or Lower esophageal sphincter (LES) tone.

21. H2 Receptor Blockers
Pharmacokinetics:
Cimetidine:
❑ Absorbed orally → Bioavailability is 60-80% due to FPM
❑ Absorption not affected by presence of food in stomach
❑ Crosses Placenta & reaches to Milk
❑ Penetration in brain is poor → Hydrophilic in nature
❑ About 2/3 dose → excreted unchanged in Urine & Bile→ rest as oxidized metabolites
❑ Elimination Half life → 2-3 hr
Contraindication:
❖ Renal failure→ Dose reduction is needed

22. H2 Receptor Blockers
Adverse drug reaction:
Cimetidine well tolerated by most patients: ADR occur in < 5%
❑ Headache, Dizziness
❑ Dry mouth, Rashes, Bowel upset
❑ Anti-androgenic effect → Plasma prolactin & inhibits degradation of Estradiol (liver)
❑ Gynaecomastia (High doses given for long periods)
❑ Loss of Libido
❑ Impotence & Temporary in sperm count
❑ Transient elevation of plasma aminotransferases → Hepatotoxicity is rare

23. H2 Receptor Blockers
Interaction:
Cimetidine:
❑ Inhibit Cytochrome P-450 isoenzyme → Hepatic blood flow
❑ It inhibits the metabolism of many drugs & can accumulate to toxic levels
Theophylline,
Carbamazepine,
Phenytoin,
Phenobarbitone,
Sulfonylureas,
Warfarin,
Imipramine,
Metronidazole,
Lidocaine,
Quinidine,
Nifedipine
JK OR UV
IJKLMNOPQRSTUVW

24. H2 Receptor Blockers
Interaction:
Cimetidine:
❑ Alteration of Metabolism of Propranolol & Diazepam → Clinically insignificant
❑ Antacids → reduce absorption of all H2 blockers (2hr gap)
❑ Ketoconazole absorption is decreased by H2 blocker → reduced gastric acidity

25. H2 Receptor Blockers
Cimetidine Dose:
❑ Ulcer healing → 400mg BD or 800mg at bed time orally: Maintenance → 400mg
at bed time
❑ Stress ulcer → 50mg / hr I.V. infusion
Contraindication:
❑ Rapid or Higher dose I.V. injection cause → Confusional state, Hallucinations,
Convulsions, Bradycardia, Arrhythmias, Coma or Cardiac arrest

26. Drug
Bioavail
ability (%)
t1/2 (h) Duration of
Action (h)
Inhibition of
CYP450
affinity
Cimetidine 80 1.5-2.3 6 1
Ranitidine 50 1.6-2.4 8 0.1
Famotidine 40 2.5-4.0 12 0
Nizatidine >90 1.1-1.6 8 0
Pharmacokinetics of H2 Blockers

27. H2 Receptor Blockers
Clinical Uses:
❑ Duodenal ulcer
Rapid & Marked pain relief (within 2-3 days)
60-85 % of ulcers heal at 4 weeks
70-95% of ulcers heal at 8 weeks
Single high dose → suppression of Nocturnal secretion
About ½ of patients relapse within 1 year of healing
Maintenance therapy with bed time dose reduce relapse rate to 15-20% / year
❑ Gastric ulcer
Healing rate is lower → 50-70% at 8 weeks
It can heal NSAIDs associated ulcers → Effects are less than PPIs or Misoprostol

28. H2 Receptor Blockers
Clinical Uses:
❑ Stress ulcer & Gastritis
Stressful situation like →
Hepatic coma,
Severe burns,
Trauma,
Prolonged surgery,
Prolonged intensive care,
Renal failure,
Asphyxia neonatorum etc…. → associated with gastric erosions & bleeding
Mucosal ischaemia + Acid → Causative
I.V. Infusion of H2B → prevent gastric erosions & bleeding & promotes healing of erosions

29. H2 Receptor Blockers
Clinical Uses:
❑ Zollinger-Ellison syndrome
Gastric hyper secretory state due to a rare tumour secreting Gastrin
High doses control hyperacidity & symptoms in many patients
DOC→ Proton Pump Inhibitors (PPIs)
Definitive treatment is surgical
❑ Gastroesophageal reflux disease (GERD)
Symptomatic relief & facilitate healing of esophageal erosions
H2 blockers less effective than PPIs
Used in Mild or Stage-1 cases of GERD

30. H2 Receptor Blockers
Clinical Uses:
❑ Prophylaxis of aspiration pneumonia
Preoperatively (evening) reduce the risk of aspiration of acidic & gastric contents
during Anaesthesia & Surgery
❑ Other Uses
Adjuvant beneficial action in certain cases of Urticaria → who do not respond to
H1 blocker alone

31. BID → twice daily; HS → Bedtime
Drug
Relative
Potency
Dose to
Achieve >
50% acid
inhibition for
10 hrs
Usual Dose
for Acute
Duodenal or
Gastric ulcer
Usual Dose
for
GERD
Usual Dose
for
Prevention of
Stress
Related
Bleeding
Cimetidine 1 400-800 mg 800 mg HS or
400 mg BID
800 mg BID 50 mg / h con.
infusion
Ranitidine 4-10 150 mg 300 mg HS or
150 mg BID
150 mg BID 6.25 mg / h
con. or
50 mg I.V.
every 6-8 h
Nizatidine 4-10 150 mg 300 mg HS or
150 mg BID
150 mg BID NA
Famotidine 20-50 20mg 40 mg HS or
20 mg BID
20 mg BID 20 mg I.V.
every 12h
Clinical Comparisons of H2 Receptor Blockers

32. ✓ Treatment for intractable nausea & vomiting
✓ Benign duodenal ulcer
✓ Gastric ulcer
✓ Inflammation of the oesophagus
✓ Acid peptic disease
✓ Treatment for symptoms associated with Idiopathic or Diabetic gastroparesis
Combination of Ranitidine + Domperidone

33. PROTON PUMP INHIBITORS (PPIs)

34. Omeprazole
Lansoprazole
Dexlansoprazole
Pentoprazole
Rabeprazole
S-Pantoprazole
Dexrabeprazole
Ilaprazole
Esomeprazole
OLD PERSON DIE
PROTON PUMP INHIBITORS (PPIs)

35. PROTON PUMP INHIBITORS (PPIs)
❑ Most effective drugs in Antiulcer therapy
❑ Irreversible inhibitor of H+K+ ATPase enzyme
❑ Prodrugs requiring activation in acid environment
❑ Weakly basic drugs → so accumulate in canaliculi of parietal cells
❑ Activated in Canaliculi & Binds covalently to extracellular domain of H+K+ ATPase
❑ Acid secretion resumes only after synthesis of new molecules

36. PROTON PUMP INHIBITORS (PPIs)
❑ In a fasting state → only 10% of proton pumps are actively secreting acid &
susceptible to inhibition.
❑ Upon parietal cell stimulation → the inactive tubulovesicles are immediately
transformed into active secretory canalicular membranes.
❑ Proton pumps are recycled back into inactive state, once parietal cell stimulation
terminates.

37. PROTON PUMP INHIBITORS (PPIs)
Clinical Implication:
Other acid suppressing drugs are not co-administered
Clinical implication:
Proton pump inhibitors should be given 1 hr before a meal (usually breakfast) →
so that peak serum concentration coincides with the maximal activity of proton
pump secretion.

38. Acidic pH in
Parietal
cell canaliculi
Absorption & Secretion of
PPI In parietal cell takes
around 30 min
Not given after
meals
Converts PPI to
active form
Maximum PPI conc.
when proton pump is
working maximally
PPIs are produce more efficacy
Food decreases
absorption of PPIs
Food stimulates Proton
Pump (H+ K+ - ATPase)
Food stimulates
Acid secretion
PPIs given 30 min before Meals

39. QD → Once daily
Drug pKa Bioavaila
bility (%)
t1/2 (h) Tmax (h)
Usual Dose for
Peptic ulcer or
GERD
Omeprazole 4 40-50 0.5-1.0 1-3 20-40 mg QD
Esomeprazole 4 >80 1.5 1.6 20-40 mg QD
Lansoprazole 4 >80 1.0-2.0 1.7 30 mg QD
Dexlansoprazole 4 NA 1.0-2.0 5.0 30-60 mg QD
Pantoprazole 3.9 77 1.0-1.9 2.5-4.0 40 mg QD
Rabeprazole 5 52 1.0-2.0 3.1 20 mg QD
Pharmacokinetics of PPIs

40. Pharmacokinetics of PPIs
❑ Food decreased 50% of bioavailability
Clinical Implication:
❑ PPIs should be administered on an empty
stomach
❑ Half life → 1.5 hrs & inhibit acid secretion for
more than 24 hrs
❑ Oral → Administered as an enteric coated
granules in capsule or tablets
❑ I.V. → Pantoprazole, Esomeprazole &
Lansoprazole
PPIs acid labile drugs→ it
destroyed in acidic pH in
lumen → enteric coating
dissolves in alkaline medium
(duodenum)
Mixture of PPIs + Sodium
bicarbonate → it neutralizes
the stomach acid & improving
the absorption of PPIs.

41. Half life of proton pump inhibitors is 1.5 hours only and these drugs are
generally given once daily. How this can be justified ?
Answer :
✓ P.P.I → Hit and run drugs → Irreversible inhibitors of H+ K+ ATPase.
✓ Acid inhibition is present up to 24 hrs → Due to irreversible
inactivation of the Proton Pump
✓ Synthesis of new H+ K+ ATPase requires at least 18 -20hrs → So
acid secretion resumes only after new pump molecules are
synthesized.
Answer ?????

42. Clinical Uses:
1.Peptic ulcer (NSAID induced ) → DOC
2.Bleeding peptic ulcer
3.Stress ulcers
4.GERD → DOC
5.Zollinger – Ellison syndrome → DOC
6.Aspiration pneumonia
PROTON PUMP INHIBITORS (PPIs)

43. ADR of PPIs
❑ Nausea
❑ Diarrhoea
❑ Dizziness
❑ Headache
❑ Osteoporosis (due to reduced calcium absorption )
❑ Erectile dysfunction → prolonged use

44. ADR of PPIs (Cont…)
❑ PPIs → A minor reduction in oral cyanocobalamin absorption
❑ PPIs may reduce calcium absorption or inhibit Osteoclast function → Prolonged use
❑ Hypomagnesemia
❑ PPIs→ Increases in gastric bacterial concentration → both community acquired
respiratory infections & Nosocomial pneumonia

45. ADR of PPIs (Cont…)
❑ Increased serum gastrin level→ may stimulates hyperplasia of ECL & Parietal
cells→ transient rebound acid hypersecretion with increased dyspepsia &
heartburn after drug discontinuation.
❑ Long term PPI therapy development of small benign gastric fundic-gland
polyps→ in a small number of patients.

46. ❑Decreased absorption of certain drugs which need gastric acidity for absorption
→ Ketoconazole, Itraconazole, Digoxin, & Atazanavir.
❑Enzyme inhibition → Omeprazole & Esomeprazole inhibit CYP3A4 & CYP2C19
→ it inhibit the metabolism of Diazepam, Phenytoin & Warfarin.
❑ Inhibits activation of Clopidogrel by inhibition of CYP2C19 → If needed → may
give Pantoprazole or Rabeprazole
❑ Clarithromycin inhibits Omeprazole metabolism & Increases its plasma
concentration
❑ Lansoprazole may enhance clearance of theophylline
❑ Rabeprazole & Pantoprazole have no significant drug interactions
Interactions of PPIs

47. ❑Esomeprazole has higher oral bioavailability as compared to Omeprazole
❑Lansoprazole as compared to Omeprazole is
→ More potent → More bioavailable → Faster acting → Longer half life
❑ Pantoprazole is available as I.V. formulation
❑ Rabeprazole is considered to be Rapid/ fastest acting PPIs.
❑ PPIs are DOC → PUD (help in healing ulcer as well as prevent the relapse)
❑ PPIs → No harmful effects during pregnancy → but avoid pregnancy having GERD
condition.
Advantages of PPIs in PU

48. Tenatoprazole:
❑ Half life is 9 hrs
❑ Produce stronger acid suppression → with a longer period of intragastric
pH greater than 4.
Vonoprazan:
❑ Novel potassium competitive acid blocker → reduced gastric acid secretion
❑ It effective in acid peptic disease
❑ As a component of anti H.pylori triple drug regimen
Newer Reduction of Acid Secretion Drugs

49. ANTIMUSCARINIC DRUGS

50. Telenzepine, Oxyphenonium, Pirenzepine & Propantheline:
❑ Antimuscarinic drugs → reduce the volume of gastric juice without raising its pH
❑ Unless, there is food in stomach to dilute the secreted acid.
❑ It less completely inhibit by stimulated gastric secretion
❑ Effective doses invariably produce intolerable side effects
❑ Introduction of H2B & PPIs has sent them into oblivion.
ANTIMUSCARINIC DRUGS

51. ANTIMUSCARINIC DRUGS
Pirenzepine:
❑ Selective M1 antagonist → Used in Europe for PU
❑ Gastric secretion reduced by 40-50% without producing intolerable side effects
❑ Inhibit secretion of gastrin, mucus & bicarbonate
❑ If doses slightly increase → produce side effects
❑ It does not cross the BBB→ no CNS side effects

52. ANTIMUSCARINIC DRUGS
Pirenzepine:
❑ Dryness of mouth & Blurred vision
❑ It is used as an adjuvant
❑ Not used in India & USA.
Telenzepine:
❑ Telenzepine is more potent than Pirenzepine

53. TCS PG
MUCOPROTECTIVE ANGENTS

54. MUCOPROTECTIVE ANGENTS
❑ Mucosal PGs appear to important in stimulating mucus & Bicarbonate
secretion & Mucosal blood flow
❑ Agents that potentiate these mucosal defence mechanisms & prevention &
treatment of acid-peptic disorders

55. MUCOPROTECTIVE ANGENTS
Sucralfate:
❑ Salt of sucrose complexed to sulfated aluminium hydroxide (sucr + ulfate)
❑ In water or acidic solutions it forms a viscous, tenacious paste → that binds selectively to
ulcers or erosions for up to 6h
❑ It has limited solubility → breaking down into sucrose sulfate (strongly negative charge)
+ aluminium salt
❑ Less than 3 % of intact drug & aluminium is absorbed from the intestinal tract →
remainder excreted in feces

56. MUCOPROTECTIVE ANGENTS
Pharmacodynamics:
❑ The precise mechanism of action is unclear
❑ Believed that negatively charged sucrose sulfate binds to positive charged proteins in
the base of ulcer or erosion → forming a physical barrier → that restricts further caustic
damage & stimulates mucosal PG & bicarbonate secretion

57. MUCOPROTECTIVE ANGENTS
ADR:
❑ It is not absorbed → virtually devoid of systemic ADR
❑ Inducing hypophosphatemia by binding phosphate ions in the intestine
❑ Constipation (2%) → due to aluminium salt
❑ Long term uses → may cause aluminium toxicity
Contraindication :
❑ Avoid kidney patients → prolonged use

58. MUCOPROTECTIVE ANGENTS
Interaction :
❑ May bind to Tetracycline, Digoxin, Cimetidine & Phenytoin → impairing their
absorption
❑ It should not be given with antacids → neutralize gastric acid & raises pH →
At pH > 4, Sucralfate cannot polymerize & thus not able to protect ulcer
Use:
❑ Ulcer protective in peptic ulcer
❑ Stress ulcer → prophylaxis
❑ Bleeding in critically ill patient
❑ Gastritis
❑ Bile reflux

59. MUCOPROTECTIVE ANGENTS
Colloidal bismuth subcitrate (CBS) & Bismuth subsalicylate :
❑ It forms an acid resistant coating over the ulcer
❑ It dislodges H.pylori from the surface of gastric mucosa and kills it
❑ It stimulate the production of mucus & PGs → they promote ulcer healing in 4-8 weeks
❑ Bismuth subsalicylate → Bismuth (excreted through the gut) + salicylate (absorbed)
❑ Constipation, Black stools, Blackening of tongue & bismuth toxicity (Osteodystrophy &
Encephalopathy)
❑ It combination regimens for H.pylori infection
❑ Used for prevention of Traveller's diarrhoea

60. Stool frequency
Secretions
Salicylate moiety inhibit COX Bismuth moiety kills E.coli
& Binds to enterotoxins
Bismuth subsalicylate
Prevention & Treatment of
Traveller’s Diarrhoea
PGs and Cl- Secretion

61. PG ANALOGUES

62. PG Analogues
❑ PGE2 & PGI2 synthesized by gastric mucosa → inhibit gastric secretion, enhance
mucus production, mucosal blood flow & exert a cytoprotective effect
❑ They act by binding to PG receptor (EP3) on parietal cells & inhibit CAMP production
❑ Misoprostol → synthetic PGE1 analogue
❑ Enprostil, Erbaprostil & Rioprostil → PGE2 analogue

63. PG Analogues
Misoprostol:
❑ NSAIDs induced ulcer
❑ Prophylactic use → moderate to high risk of NSAIDs induced ulcer → Elderly patients &
those with previous ulcers
❑ It contraindicate in Pregnancy → it can stimulate uterine contractions (Ecbolic) & cause
miscarriage
❑ Dose-related diarrhoea, muscles cramp & nausea

64. HCl
Remove inflammatory
mediators
Less damage to
Stomach Mucosa
Protection to
Stomach Mucosa
Less damage to
Gastric Mucosa
Mucosal
blood flow
Mucus & HCO3−
Secretion
Inhibit Proton Pump
Misoprostol

65. Enprostil & Rioprostil:
❑ More stable & longer acting compared to natural PGs
❑ It contraindicate in Pregnancy → it can stimulate uterine contractions
PG Analogues

66. ANTACIDS

67. Antacids
❑ Weak basic substances
❑ Given orally → neutralize the gastric acid & raise the pH of gastric contents
❑ It reduce the peptic activity → as pepsin is active only below pH 4
❑ It provide rapid relived of symptoms in hyperacidity as they chemically neutralize the acid
❑ It do not reduce the acid secretions
❑ pH rises > 5 there could be rebound hyperacidity due to raised gastrin level

68. Antacids
Acid Neutralizing Capacity (ANC):
❑ It express by potency of an antacid
❑ As number of mEq of 1N HCl that are brought to pH 3.5 in 15 min (or 60 min in some
tests) by a unit dose of antacid preparation
❑ Rate at which the antacid dissolves & reacts with HCl
❑ Single dose taken in empty stomach acts for 30-60 min only
❑ Taken with meals antacids may act for at most 2-3 hrs

69. Antacids
Sodium bicarbonate:
NaHCO3 + HCl → NaCl + H2O + CO2
❑ It rapid & short acting antacid
❑ It gets absorbed from intestines leading to systemic alkalosis
❑ There is rebound hyperacidity as gastrin levels increase due to raised gastric pH
❑ Sodium load may increase → contraindicate to CVS patients
❑ ANC → 12 mEq HCl / g

70. Antacids
Sodium bicarbonate:
Milk – Alkali syndrome
→ Higher dose sodium bicarbonate or calcium carbonate with calcium rich dairy
product cause milk alkali syndrome.
→ Characterized by Hypercalcaemia, metabolic alkalosis & renal dysfunction
→ It not preferred for long term use → produce above side effects

71. Antacids
Sodium citrate:
❑ It is absorbed systemically
❑ It can be used in place of sodium bicarbonate
❑ ANC → 10 mEq HCl/g
Uses:
❑ Sodium bicarbonate + other antacid in PU → hyperacidity for short periods
❑ To alkalinise the urine in the treatment of Acidic drug poisoning
❑ To treat metabolic acidosis

72. HCO3− HCO3− reacts
with H2O to
liberate CO2
More Symptoms
Aggravates Oedema
&
Symptoms of CHF
➢ Distention of stomach
➢ Belching
➢ Risk of rupture of PU
Sodium bicarbonate in Peptic Ulcer
If absorbed lead to
Metabolic Alkalosis
Acid Rebound
May lead to
retention of H2O
Short action
Sodium

73. Antacids
Nonsystemic antacids:
❑ Insoluble in nature
❑ It react in stomach HCl to form a chloride salt & water
❑ They are not absorbed in stomach
CaCO3 + 2HCl → CaCl2 + H2O + CO2
Mg(OH)2 + 2HCl → MgCl2 + 2H2O
Al(OH)3 + 3HCl → AlCl3 + 3H2O

74. Antacids
Calcium carbonate:
❑ It acts quickly & has prolonged action but liberates CO2 which may cause discomfort
❑ It is chalky taste
❑ It may cause constipation & hypercalcaemia
❑ Increased plasma calcium levels → result in rebound hyperacidity
❑ Long term use → renal calcium stones & milk alkali syndrome
❑ ANC → 20 mEq HCl/ g → but commercial preparation is less

75. Antacids
Magnesium Salts:
❑ Magnesium hydroxide, Magnesium trisilicate, Magnesium oxide & Magnesium carbonate
❑ Magnesium salts → osmotic purgatives→ because MgCl2 is formed in the stomach →
which is act as an osmotic purgative
❑ Dose used as antacid may cause mild diarrhoea
❑ Antacid action is quick & prolonged
❑ Rebound acidity is mild
❑ A small percentage of Mg. trisilicate gets absorbed systemically
❑ Prolonged use → Hypomagnesaemia in presence of renal dysfunction

76. Antacids
Magaldrate :
❑ It is a Hydroxy Magnesium Aluminate hydrated complex (Mag- al- drate)
❑ The complex reacts with acid to release aluminium hydroxide → prolong effect
❑ Magaldrate cannot be equated to a physical mixture of Mg. & Al. hydroxides
❑ Good antacid with prompt & sustained neutralizing action
❑ ANC → 28 mEq HCl/g
❑ Aqueous suspension of magnesium hydroxide → Milk of magnesia

77. Antacids
Aluminium hydroxide:
❑ It is slowacting
❑ Food further slows its neutralizingcapacity
❑ Astringent & demulcent effect → forms aprotective coating over the ulcers
❑ Aluminium ion relax SM→ delayed gastric emptying & constipation
❑ It binds with phosphate → prevents its absorption → hypophosphatemia on prolonged use
❑ ANC → 1-2.5 mEq HCl / g
Aluminium = Constipation → AC
Magnesium = Diarrhoea → MD

78. Antacids
Antacid Combinations:
Antacid 1 Antacid 2 Combination beneficial
Effect
Magnesium hydroxide (fast) Aluminium hydroxide (slow) Prompt as well as sustained
effect
Magnesium salts (laxative) Aluminium salts
(constipating)
Bowel movement may be
least affected
Magnesium or calcium
salts (tend to hasten it)
Aluminium salts
(tend to delay)
Gastric emptying is least
affected
Dose of individual compound
is reduced
Dose of individual compound
is reduced
Systemic toxicity is
minimized (dependent on
fraction absorption)

79. ANTI H.PYLORI DRUGS

80. Anti H.pylori:
❑ Gram negative bacterium
❑ It is adapted to living in the stomach
❑ Infection associated with gastroduodenal disease → gastritis & PUD → major
risk factor for stomach cancer
❑ Eradication of H.Pylori with drugs → reduce acid secretion has shown to reduce
the relapse rate
❑ Various combination regimens of 2-4 drugs → produced up to 95% efficacy
ANTI H.PYLORI DRUGS

81. Anti H.pylori:
❑ Amoxicillin & clarithromycin are pH dependent
❑ Various combination regimens of 2-4 drugs → produced up to 95% efficacy
ANTI H.PYLORI DRUGS

82. ✓ PPIs
✓ H2 blockers
✓ Amoxycillin
✓ Bismuth salts
✓Clarithromycin
✓ Tetracycline
✓ Metronidazole
DRUGS USED TO ERADICATE H.PYLORI

83. TRIPLE ANTI H.PYLORI THERAPY
The BEST among all the Triple therapy regimen is
DRUG DOSE
Lansoprazole (or)
Omeprazole (or)
Rabeprazole (or)
Esomeprazole (or)
30 mg PO bid
20 mg PO bid
20 mg PO bid
40 mg PO qd
Amoxicilline 1000 mg PO bid
Clarithromycin 500 mg PO bid
LORE+A+C
Given for 14 days followed by PPIs for 4 –6 weeks.

84. TRIPLE ANTI H.PYLORI THERAPY
Alternate Triple therapy regimen is
DRUG DOSE
Lansoprazole (or)
Omeprazole (or)
Rabeprazole (or)
Esomeprazole (or)
30 mg PO bid
20 mg PO bid
20 mg PO bid
40 mg PO qd
Metronidazole 500 mg PO bid
Clarithromycin 500 mg PO bid
LORE+M+C
Given for 14 days

85. ❑Lansoprazole 30 mg PO bd
❑Amoxycillin 1g PO bd
❑Clarithromycin 500 mg PO bd
For 14 days / 2 week
FDA RECOMMENDED DOSE

86. TRIPLE THERAPY –TREATMENT FAILURE
➢ Most common → Diarrhea (due Amoxicillin)
➢ Nausea & Vomiting (Metronidazole)
➢ Most serious → Pseudomembranous colitis
➢ Most common cause →Antibiotic resistant strains
TRIPLE THERAPY -ADR

87. Given when Triple Therapy fails
PPIs standard dose or Ranitidine → 20 / 30 mg or 150mg PO bid
Bismuth subsalicylate → 525mg PO qid
Metronidazole → 500mg PO qid
Tetracycline → 500mg PO qid
QUADRUPLE ANTI H.PYLORI THERAPY

88. Proton Pump Inhibitors
(Omeprazole or Lansoprazole)
Clarithromycin
Amoxycillin
Metronidazole
Rationale for Triple Drug Therapy
CAM-POL
Helps in
ulcer healing
✓ Fast ulcer healing
✓ Lower risk of relapse
More efficacy of
Antimicrobials
MIC of
Antimicrobials
Acidity
Combination of drugs
Possess anti H. Pylori
activity but
❖ Single drug less effective
❖ Risk of emergence of drug
resistance

89. GATRO ESOPHAGEAL REFLUX DISEASES
(GERD / GORD)

90. Drugs used in GERD:
❑ PPIs
❑ H2 Blockers
❑ Antacids
❑ Sodium alginate
❑ Prokinetic drug → Metoclopramide, Cisapride
GATRO ESOPHAGEAL REFLUX DISEASES

91. STAGE 1 STAGE 2 STAGE 3
Occasional heartburn
(<3 episodes/ week),
Precipitating factor,
Mild symptoms,
No esophageal lesion
Moderately severe
symptoms
(≥3 episodes/ week),
Nocturnal awakening
due regurgitation,
Esophagitis present or
absent
Daily / chronic
symptoms,
Disturbed sleep,
Esophagitis/ Erosions/
Stricture/ Extra
esophageal symptoms
like Laryngitis,
Hoarseness, Dry
cough, Asthma.
Symptoms recur soon
after treatment stopped
GERD Grades

92. GATRO ESOPHAGEAL REFLUX DISEASES
❑ Reflux of acidic gastric contents into the oesophagus → heart burn due to oesophagitis
❑ Reflux due to anatomical (hiatus hernia) or functional causes
❑ Most cases are functional & result from loss of tone of lower oesophageal sphincter (LES)
❑ Reflux of acidic contents → Inflammation, erosion & ulcers in the oesophagus
❑ In chronic oesophagitis → changes in oesophageal mucosa → premalignant condition
(Barrett’s oesophagus)

93. GATRO ESOPHAGEAL REFLUX DISEASES
❑ Severity may vary from mild nonerosive GERD with occasional heart burn to severe ones
with regular disturbing oesophagitis & erosive GERD
❑ Uncomplicated, mild GERD with occasional dyspepsia → treated with antacids
❑ They may combined with sodium alginate → reacts with acid to form a layer & floats on
the top of contents in the stomach→ act as a mechanical barrier → prevents contact of
the oesophageal mucosa with acids→ thus protects the mucosa
❑ H2 blockers may used → but less efficacious in more severe GERD

94. GATRO ESOPHAGEAL REFLUX DISEASES
❑ In moderate to severe GERD→ PPIs are DOC
❑ They afford rapid relief of symptoms & promote healing of oesophageal lesions in 4-8
weeks
❑ Treatment may have to be continued for long period → may be years
❑ Prokinetic agents are used as adjuvants.
❑ Non pharmacological measures → Avoiding – Heavy meals, late night dinner, smoking &
alcohol.

95. ANSWER THE QUESTIONS??????

96. 1. Metoclopramide in GERD
Rationale Questions
2. Combination of Aluminium hydroxide with Magnesium hydroxide in Antacid gel
3. Pirenzepine for PU
4. PPIs or H2 blockers for shortterm management in PU (DOC → PPIs)
5. Omeprazole or Pantoprazole as suitable PPIs for therapy (DOC → Pantoprazole)
6. Triple therapy or Quadruple therapy as Anti H. Pylori regiment (DOC → Quadruple therapy)
7. Systemic or non-systemic antacids in therapy of PU (DOC → Non-systemic)
8. H2 blockers / PPIs in stage II & III of GERD (DOC → PPIs)
9. PPIs monotherapy / PPIs with H2 blockers co-administration for suppressing Nocturnal
acid breakthrough in GERD (DOC → PPIs + H2 blockers)
10. Famotidine / Cimetidine for long-term maintenance to suppress nocturnal acid secretion in PU
(DOC → Famotidine)

97. 1. Essentials of Medical Pharmacology, 7th Edt., K D Tripathi
2. Lippincott Illustrated Reviews Pharmacology, 6th Edt., Richard A. Harvey
3. Exam Preparatory Manual for Undergraduates Pharmacology, 1st Edt., Gobind Rai Garg & Sparsh
Gupta
4. Pharmacology for MBBS, 1st Edt., S.K. Srivastava
5. Medical Pharmacology, 5th Edt., Padmaja Udaykumar.
REFERENCES