medicinal chemistry

1. ANTI-SECRETORY
DRUGS

2. INTRODUCTION:
Antisecretory drugs inhibit or reduce gastric acid secretion. It is used
in the treatment of peptic ulcer. A peptic ulcer is a sore in the lining of
Stomach or duodenum, the first part of the small intestine. A burning
Stomach pain is the most common symptom. When the acids that help
To digest food damage the walls of the stomach or duodenum peptic
Ulcer occurs. The most common cause is infection with a bacterium
Called Helicobacter pylori. Another cause is the long term use of NSAIDs.

3. CLASSIFICATION OF ANTIULCER DRUGS
DRUGS USED TO NEUTRALIZE THE ACID – ANTACIDS:
Aluminium hydroxide, magnesium hydroxide.
DRUGS USED TO DECREASE HCL SECRETION:
*H2 receptor antagonist: ranitidine, cimetidine, famotidine.
*proton pump inhibitors: omeprazole, rabeprazole,
lansoprazole, pantoprazole.
MUCOSAL PROTECTIVE AGENTS OR CYTOPROTECTIVE AGENTS:
sucralfate, misoprostol ( PG analogue)
ANTIBIOTIC REGIMENS FOR Helicobacter pylori ERADICATION:
amoxycillin, clarithromycin.

8. MECHANISM OF ACTION OF H2 RECEPTOR
ANTAGONIST:
• Acid is generated by the carbonic anhydrase mediated catalysis of CO2
and H2O to form H+ and HCO3.
• H+ ions are then exchanged for K+ by the H+K+-ATPase pump and later
coupled with Cl ions entering the parietal cell from the blood in
exchange for HCO3.
• There are 3 regulatory molecules that stimulate acid secretion
( Ach, histamine and gastrin)
• One regulatory molecule that inhibits acid secrtion
(Somatostatin).

9. • The 3 regulatory molecules raise intracellular levels of cAMP, Inositol
triphosphate, diacylglycerol and calcium.This sequence of events
induces H+K+ ATPase to Secrete, protons directly into the lumen of
the parietal cell and gastric gland.
• When the pH of the stomach gets too low, somatostatin secretion is
stimulated inhibits acid secretion.
• H2 receptors on the parietal cell increase adenylate
cyclase activity and generate cAMP.
• H2 blockers bind with the H2 receptors of the parietal
cells and produce competetive drug antagonism, thus
inhibit acid secretion.

10. STRUCTURE ACTIVITY RELATIONSHIP:
Study of structural features of cimetidine confirms that,
• Imidazole ring is not required for competetive antagonism of histamine
H2 receptor other heterocyclic, which enhance the potency and
selectivity of H2 receptor antagonism can be used.
• The ring and terminal nitrogen should be seperated by 4 C atom for
optimum activity. Isosteric thio ether link is also present in certain
drugs.
• The terminal nitrogen- conatining functionality should be a polar, non
basic substituent for maximal antagonist activity.

11. It is used in the gastric and duodenal ulcer.
CIMETIDINE (Tagamet)
ADR: Head ache, dizziness,drowsiness,depression
skin rash, diarrhoea,nausea,constipation.

12. FAMOTIDINE: (Pepcid)
Used in the treatment of duodenal and gastric ulcers,
Zolinger-Ellison syndrome and heart burn.
ADR: Fatigue, dizziness, weakness,mood changes,
Headache,insomnia, muscle pain,dry mouth, nausea,
vomiting.

13. RANITIDINE:(Zantac)
It is used in treating duodenal ulcer.
ADR:Constipation, diarrohea, nausea, vomiting,
stomach pain, headache, insomnia, tender breast.

14. PROTON PUMP INHIBITORS

15. • Proton pump inhibitors are weak bases that act as prodrugs
and need an acidic environment in order to inhibit H+K+ATPase.
• All these compounds share a common structure consisting of
substituted pyridyl methyl sulfinyl benzimidazoles that varies in terms
of the substitutions on either the pyridine or the benzimadazole rings.
• These drugs become protonated and converted into the active
sulfonamide species, which forms disulfide bonds with cysteine
residues in the α- subunit of the H+K+ATPase and thus inhibit the
enzyme system of the gastric parietal cells.
• This results in an inhibitory mechanism that is independent of
histamine, Ach or gastrin stimulus for acid secretion.

16. OMEPRAZOLE:(Prilosec,Zegerid)
It is used in the treatment of duodenal ulcer, gastric ulcer
And pathological hypersecretory conditions.
ADR: Head ache, nausea,vomiting, stomach pain, fever,
Cold symptoms.

17. PANTOPRAZOLE:(Protonix)
It is used in gastric hypersecretory disorders.
ADR:Head ache, dizziness, nausea, vomiting, joint pain
Fever, rash or cold symptoms.