Antiulcer Agents
Tomáš Goněc 26.11.2012
Peptic ulceration
 Mucose degradation
Mechanism of acid secretion
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
Long-term NSAID administration
Therapy
 acids and digestives
 direct antacids
 indirect antacids
 mucoprotective drugs
 drugs for Helicobacter pylori eradication
Mechanism of action
Acids
 achlorhydria – low or no HCl secretion
 increased pH damages mucosa
 citric acid, betaine hydrochloride
OH
O
OH
OH
O
OH
O
N
+
O
OH
Cl
citric acid betaine hydrochloride
Digestives
 insufficient digestion – longer pass through of
food – gastritis, ulceration risk
 recombinant enzymes:
pepsine, pancreatine, trypsine
chymotripsine, amylase, lipase
Direct antacids
 Carbonates:
NaHCO3,
CaCO3,
MgCO3
- quick pH increase may lead to increased
gastrine levels and excessive HCl secretion
- absorbtion of Mg2+, Ca2+ and Na+ leads to ion
dysballance
Direct antacids
Magnesium oxides and hydroxides:
MgO,
MgO2,
Mg(OH)2
- forming MgCl2 has laxative effect
Direct antacids
Aluminium compounds:
AlPO4,
Al(OH)3 (algeldrate),
Al5Mg10(OH)31(SO4)2.H2O (magaldrate)
- both antacide and protective effect
- long-term administration of aluminium salts
may cause obstipation
Antimuscarinic agents
 Pirenzepine
N
N
H
N
O
O
N
N
Pirenzepine synthesis
Selective H2 histamine receptor
antagonists
SAR of H2 antagonists:
N
H
N
NH2
S
NH
NH
NH
R
R
histamine
Har
Cimetidine
N
NH
S N
H
N
H
CNcimetidine
Cimetidine synthesis
Ranitidine
O
S N
H
N
H
NO2
N
ranitidine
Ranitidine synthesis
Nizatidine
S
N
S N
H
N
H
NO2
N
nizatidine
Nizatidine synthesis
Famotidine
S
N
S
NH2
N
NH2
NH2
N S
O
NH2
O
famotidine
Famotidine synthesis
Proton pump inhibitors
Omeprazole synthesis
Mechanism of action
Mucoprotective agents
 misoprostol
Mucoprotective agents
 alginic acid, pectines (natural drugs)
 sucralfate
Sucralfate synthesis
Drugs for Helicobacter pylori
eradication
 metronidazole
 azithromycine, clarithromycine
 amoxyciline
 tetracycline
 bismuth salts: subcitrate, subsalicylate