this class gives brief discussion for under graduate examination

1. Dr. RAGHU PRASADA M S
MBBS,MD
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
SSIMS & RC.
1

2. DRUGS NEUTRALISE GASTRIC ACID (ANTACIDS)
SYSTEMIC ANTACIDS-SODIUM BICARBONATE
NONSYSTEMIC ANTACIDS
BUFFER TYPE- ALUMINIUM HYDROXIDE, MAGNESIUM
TRISILICATE, MAGALDRATE
NON- BUFFER TYPE- MAGNESIUM HYDROXIDE
CALCIUM CARBONATE
MISCELLANEOUS- ALGINATES, SIMETHICONE

3. DRUGS WHICH REDUCE GASTRIC ACID SECRETION
H2 RECEPTOR ANTAGONISTS- CIMETIDINE,
RANITIDINE, NIZATIDINE, ROXATIDINE
PROTON PUMP INHIBITORS- OMEPRAZOLE
PANTOPROZOLE, RABEPRAZOLE
ANTICHOLINERGICS-PROPATHELINE, OXYPHENONIUM,
PIRENZEPINE, TELENZEPINE
PROSTAGLANDIN ANALOGUES-MISOPROSTOL,
ENPROSTIL,

4. MUCOSAL PROTECTIVES
 SUCRALFATE, COLLOIDAL BISMUTH SUBCITRATE,
RANITIDINE BISMUTH CITRATE
ULCER HEALING DRUGS-CARBENOXOLONE
ANTI-HELICOBACTER PYLORI DRUGS-AMOXICILLIN,
CLARITHROMYCIN, TETRACYCLINE, METRONIDAZOLE,
RANITIDINE BISMUTH CITRATE

8. Promote the gastric mucosal defense mechanisms:
 Secretion of:
-Mucus: Protective barrier against HCl.
-Bicarbonate: Helps buffer acidic properties of HCl.
-Prostaglandins: Prevent activation of proton pump.
Antacids DO NOT prevent the over-production of
acid.
Antacids NEUTRALIZE the acid once it’s in the
stomach.

9. Reduction of pain associated with acid-related
disorders.
Raising gastric pH from 1.3 to 1.6 neutralizes 50%
of gastric acid.
Raising gastric pH point from 1.3 to 2.3 neutralizes
90% of the gastric acid.

10. Sodium Bicarbonate:
Highly soluble.
Quick onset, but short duration.
Raises gastric ph 7.4 rebound acidity
Hcl+ NaHco3  co2+ Nacl  co2belching
Unreacted alkali  cause metabolic alkalosis.
NaclNa load HTN, CCF
Sodium content may cause problems in patients
with hypertension or renal insufficiency.
Can heal duodenal ulcer longer duration

11. Poorly absorbed, do not disturb systemic acid balance
Magnesium salts:
Forms: carbonate hydroxide, oxide, trisilicate.
 Commonly cause a laxative effect.
 Usually used with the other agents to counteract this
effect.
 Dangerous when used with renal failure-the Failing
kidney cannot excrete magnesium, resulting in
accumulation.
 Example :combination products such as aluminium &
magnesium.

12. Aluminum hydroxide, magnesium trisilicate and
magaldrate salts:
Raise gastric PH to 3-4pepsin activity is inhibited around
4
They neutralise gastric HCL to form magnesium chloride
and aluminium chloride react with bicarbonates  Al
and Mg carbonate
 Bicarbonate not available for systemic absorption
 Nacl formed in this process account for chloride loss
Forms: carbonate, hydroxide, phosphate.
 Have constipating effects.
 Often used with magnesium to counteract constipation.
Example: aluminum carbonate

13. Calcium carbonate and magnesium hydroxide
Powerful, fast acting
CaCo3 Cacl2 CACo3+Cl. Stearate+Nacl
May cause constipation.
Serum calciummay result in kidney stones.
Long duration of acid action may cause increase of
gastric acid secretion (hyperacidity bound)
Often advertised as an extra source of dietary calcium.

14. Simethicone:
 Silicon polymer and water repellant
 Decrease surface tension thereby reduce bubble
formation - added to prevent reflux
 Foaming agent, prevents hiccups and reduces
flatulence
 Used topically for bed sores
Sodium Alginates: hydrophobic colloidal carbohydrate
from brown sea weed
Form a layer of foam on top of gastric contents &
reduce reflux
Oxethazaine: Surface anaesthetic

15. Minimal and depend on the compound used:
 Aluminum and Calcium:-Constipation
Magnesium:-Diarrhea
Calcium carbonate: Produce gas and belching;
often combined with simethicone.

16. Cimetidine, Ranitidine, Famotidine, Nizatidine
Reversible competitive inhibitors of H2 receptor
Highly selective, no action on H1 or H3 receptors
All phases of gastric acid secretion
Very effective in inhibiting nocturnal acid secretion
(as it depends largely on Histamine )
Modest impact on meal stimulated acid secretion
(as it depends on gastrin, acetylcholine and
histamine)
Volume of pepsin content and IF are also reduced
Volume reduced by 60 – 70% - anti ulcerogenic
effect

17. All drugs are absorbed orally adequately
Bioavailability upto 80 %
Absorption is not interfered by presence of food
Can cross placental barrier and reaches milk
Poor CNS penetration
2/3rd of the drugs are excreted unchanged in bile
and urine
Preparations: available as tablets, injections

18. Duodenal ulcer – 70 to 90%
Gastric Ulcer – 50 to 75% (NSAID ulcers)
Stress ulcer and gastritis
GERD
Zollinger-Ellison syndrome
Prophylaxis of aspiration pneumonia
Urticaria

19.  Overall, less than 3% incidence of side effects.
Cimetedine may induce impotence and
gynecomastia.

Drug Interactions:
Cimetedine: Binds with P-450 microsomal oxidase
system in the liver, resulting in inhibited oxidation of
many drugs and increased drug levels.
All H2 antagonists may inhibit the absorption of
drugs that require an acidic GI environment for
absorption.

20.  Smoking has been shown to decrease the
effectiveness of H2 blockers.
Assess for allergies and impaired renal or liver
function.
 Use with caution in patients who are confused,
disoriented or elderly.
 Taken one hour before or after antacids.
 Ranitidine may be given intravenously.

21. Substituted Benzimidazole derivatives
Lansoprazole, Omeprazole, Rabeprazole
Pantoprazole, Esomeprazole
Mechanism of action:
The parietal cells release positive hydrogen ions
(protons) during HCl production Proton Pump
Protonated within canaliculus henderson-hassel
batch trapping
PPI(prodrugs) active entity is SULFENAMIDE
forms covalent disulfide bond with H/K-ATP ase 
Irreversible inactivation

22. Irreversibly bind to H+/K+ ATPase enzyme prevents
the movement of hydrogen ions from the parietal
cell into the stomach Achlorhydria  gastric acid
secretion is blocked
 In order to return to normal acid secretion, the
parietal cell must synthesize new H+/K+ ATPase.
 ME-TOO DRUGS
 PRO-DRUGS
 SUICIDAL INHIBITORS
 HIT AND RUN DRUGS

23. Proglumide

24.  Oral acid resistant formulations  release the drug
in the intestine parietal cell canaliculi
 They irreversibly inactivate the proton pump
molecule – but half life only 1-2 Hrs
 Still action persists for 24 Hrs to 48 hrs after a single
dose – irreversible inhibition of PPI
 New PP synthesis takes time (24 to 48 hour
suppression of acid secretion, despite the much
shorter plasma half-lives of the parent compounds)
 Action lasts for 4-5 days

25.  Given 30 minutes to 1 hour before food intake
because an acidic pH in the parietal cell acid
canaliculi is required for drug activation, and food
stimulates acid production
 Concomitant use of other antisecretory drugs - H2
receptor antagonists – reduces action
 Highly protein bound and rapidly Metabolized by the
liver by CYP2C19 and CYP3A4 – dose reduction
necessary in severe hepatic failure
 Excreted in Kidneys minimally (no dose reduction
needed in renal failure and elderly)

26. Therapeutic uses:
 GERD maintenance therapy.
 Erosive esophagitis
 Short-term treatment of active duodenal and begin
gastric ulcers.
 Zollinger-Ellison syndrome.
 Treatment of H.Pylori-induced ulcers.

27.  The most common are GIT troubles in the form of
nausea, abdominal pain, constipation, flatulence,
and diarrhea
 Subacute myopathy, arthralgias, headaches, and skin
rashes
 Prolonged use:
 Leucopenia and hepatic dysfunction
 Vitamin B12 deficiency->6-8wks
 Hypergastrinemia which may predispose to
rebound hypersecretion of gastric acid
 May promote the growth of gastrointestinal
tumors (carcinoid tumors )

28.  Assess for allergies and history of liver disease.
Drug interaction-
 Decrease gastric acidity decrease absorption of
digoxin and ketoconazole
 Inhibit CYP 2Cincrease serum levels of diazepam,
phenytoin, and warfarin.

29.  Quaternary drugs-Propantheline, Oxyphenonium
 MOA-Muscarinic receptor inhibitiondecrease
gastrointestinal motility and secretion
 Adjuncts in the management of peptic ulcer disease
and Zollinger-Ellison syndrome,
 Refractory to standard therapies.
S/E- blurred vision, dry mouth
Pirenzepine Telenzapine-- Prevent recurrences

30. Inhibit cAMPInhibits secretion of gastric acid and
stimulate secretion of mucus and bicarbonate.
Dilate blood vessel of mucous membrane.
Prevention of gastric ulcers induced by NSAIDs.
Less effective than H2-receptor antagonists for acute
treatment of peptic ulcers.
S/E-diarrhoea, colic pain
Produces uterine contractions and is contraindicated
during pregnancy.

31. Sucralfate
In water or acidic solutions it forms a viscous,
tenacious paste that binds selectively to ulcers or
erosions for up to 6 hours.
Also stimulates prostaglandin release and mucus and
bicarbonate output.
Inhibit H.PyloriNeeds acid environment; affects
absorption of other drugs

32. Colloidal bismuth subcitrate
Bismuth coats ulcers and erosions protecting them
from acid and pepsin and bicarbonate production
Binds to an ulcer crater, coating it and protecting it
from acid and pepsin Inhibits the activity of pepsin
Increases mucous secretion
Increase prostaglandin synthesis
Helps to eradicate H. pylori

33.  Endoscopy
 Barium meal – contrast x-
ray
 Biopsy – bacteria &
malignancy
 H.Pylori:
 Endoscopy cytology
 Biopsy – Special stains
 Urease Breath test.
MARSHALLAND WARREN

34. Is a bacteria that causes chronic inflammation of the inner
lining of the stomach.
 Produce enzymes (tissue damage), inflammation – ulcer.
 Duodenal ulcer - Gastric ulcer
 Risk factor for esophagus and stomach cancers.
 Eradication is important to prevent recurrence
of ulcer.
No HP No ulcer
NEW TESTAMENT
Eradication Of H Pylori

35. Triple Therapy
The BEST among all the Triple therapy regimen is:
Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxicillin / Metronidazole - 1gm / 500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks
Short regimens for 7 – 10 days not very effective
Ranitidine Bismuth citrate - 400 mg bd
Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd

36. Omeprazole - 20mg OD
Bismuth subsalicylate – 2 tab qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
Uses
Duodenal ulcer and peptic ulcer
MALT type lymphoma
Non-ulcer dyspepsia