□
Antiulcer Agents
TomasGonec 28.11.2011
Peptic ulceration
□ Mucose degradation
11
Mechanism of acid secretion
H+
Histamine      PGE2 Acetylcholine Gastrin
Peptic ulceration
□ multifactorial disease:
□ increased acid production and enzyme activity
□ decreased acid production and enzyme activity
□ Helicobacter pylori infection
□ long-term NSAID medication
□ leads to damage of mucose protective layer and ulcer formation
Helicobacter pylori infection
Divergent mucosal and secretory responses to H. pylori infection
Chronic H. pyiori Infection
10-15%
Antra l-pradomlnant diffuse Gastritis U Acid, f Gastrin, little or no atrophy low risk of Gastric Carcinoma
2-5%
Corpus-predominant Multifocal Atrophic Gastriti s (MAG), J. Aci d,t Gastrin high risk of Gastric Carcinoma
Ml Id/Mixed Chronic Gastritis <*«tik
Uker/ÖPi-rtf
1
Normal or Reduced Acid
Duodenal ulcer
Gastric Ulcer/Cancer
No significant disease
? Bacterial ? Environment ? Host
B
Long-term NSAID administration
Therapy
□ acids and digestives
□ direct antacids
□ indirect antacids
□ mucoprotective drugs
□ drugs for Helicobacter pylori eradication
Mechanism of action
ACh
K+
cAMP-dependent
GASTRIN
dependent pathway
parietal cell
H* K i
ATPase) X" proton PumP mh'b«tors *■ H30* X-antacids
H. pylori X
bismuth
metronidazole
tetracyclines
clarithromycin
amoxicillin
PGE PGI2
ACh
I
+
<
superficial epithelial cell
mucus
cyto-
protection
HCO
Mucus layer pH7
sucralfate
Gastric Lumen pH2
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Acids
□ achlorhydria - low or no HCl secretion
□ increased pH damages mucosa
□ citric acid, betaine hydrochloride
11
Digestives
□ insufficient digestion - longer pass through of food - gastritis, ulceration risk
□ pepsine, pancreatine, trypsine chymotripsine, amylase, lipase
11
Direct antacids
□ Carbonates: NaHC03, CaC03, MgC03
□ Oxides and hydroxides: MgO, Mg02, Mg(OH)2
□ aluminium compounds: A1P04, Al(OH)3(algeldrate), Al5Mg10(OH)31(SO4)2.H2O (magaldrate)
Antimuscarinic agents
B
- 11
Selective H2 histamine receptor antagonists I^tT^V^3
Drug Trade Name R X Y
Burimamide Cimetidine Metiamide	Tagamet	H                 CH, S CH3                 s n-on CH3                 S S
		H ,N^NHCH3 h'c*no2
Drug	Trade Name	Ar
Ranitidine Nizatidine	Zantac Axid	N~S02NH2
Famotidine	Pepcid	H2N N-^g^
Proton pump inhibitors
Table 33.10. H /K-ATPase Proton Pump Inhibitors
'chiral center
Drugs	Trade Name	Ri	R2	R3	R4
Omeprazole	Prilosec	OCH3	CH3	CH3	CH3
Esomeprozole	Nexium	OCH3	CH3	CH3	CH3
(S-enantiomer)					
Lansoprazole	Prevacid	H	CH3	CH2CF3	H
Rabeprazole	Aciphex	H	CH3	(CH2)30CH3	H
Pantoprazole	Protonix	0CHF2	OCH3	CH3	H
Mechanism of action
Mucoprotective agents
□ misoprostol
Misoprostol
Prostaglandin £^
Mucoprotective agents
□ alginic acid, pectines (natural drugs)
□ sucralfate
ROCH2
ro' ro
O  ROHaC   O CHaOR
h X ro;
or "0' )—'h or
Sucralfate    R = S03{AI2(OH)5]
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Drugs for Helicobacter pylori eradication
□ metronidazole
□ azithromycine, Clarithromycine
□ amoxyciline
□ tetracycline
□ bismuth salts: subcitrate, subsalicylate