OBAT LOKAL SALURAN

CERNA
Dimas P.Nugraha
Departement Farmakologi dan Terapi
FK-UR
 Acid Peptic disease
includes:
Peptic ulcer (gastric & duodenal)
 Peptic Ulcer Disease
Imbalance between mucosal defensive factors and aggressive factors
 Defensive factors
Prevent the stomach and duodenum from being harmed (self-digestion
Netter s, Atlas of Physiology
Aggressive factors
NSAIDS inhibit the production of prostaglandins
Drugs That May Cause Gastrointestinal
Injury
 Physiological and pharmacological regulation of
gastric secretion: the basis for therapy of acid-peptic
disorders

Goodmand and Gilmans, The Pharmalogical Basis of Therapeuticed ,2011

Drugs used to neutralize gastric acid

(Luellman,Color Atlas of Pharmacology2005)

Drugs used to lower gastric acid
production

(Luellman,Color Atlas of Pharmacology2005)

 Antacids
Antacids are weak bases that react with gastric hydrochloric acid to for
 Antacids
Al(OH)3 (Aluminum hydroxide)
Calcium carbonate (Tums, Os-Cal)
is less soluble and reacts more slowly
than sodium bicarbonate with HCl to
form carbon dioxide and calcium
chloride (CaCl2).
Like sodium bicarbonate, calcium
carbonate may cause belching or
metabolic alkalosis
Excessive doses of either sodium bicarbonate or calcium carbonate
 Antacids may alter the absorption and excretion
of drugs when administered concomitantly
Important interactions may occur when antacids
are administered with :
- iron supplements,
- tetracycline,
- warfarin,
- digoxin,
- quinidine,
- isoniazid,
- ketoconazole,
- fluoroquinolones

(Dipiro,200
Most interactions can be avoided by sep
 Gastric Antisecretory
drugs
H
 Histamine 2-receptor
antagonists
Therapeutic uses
ulcers,
GERD,
Zollinger-ellison syndrome,
aspiration pneumonitis,
heartburn,
indigestion
 MOA
H2 antagonists acid secretion stimulated
by histamine as well as by gastrin and
cholinomimetic agents through 2
mechanisms :
First, histamine released from ECL cells by
gastrin or vagal stimulation is blocked from
binding to the parietal cell H 2 receptor
Second, direct stimulation of the parietal
cell by gastrin or acetylcholine has a
diminished effect on acid secretion in the
presence of H2-receptor blockade.
 PK
Four H
 PD
The H
 Ranitidine
More potent than
Clinical Comparisons of H2-Receptor Blockers

Katzung,ed.11, 2009
 Adverse Effects

Cimetidine inhibits binding of

dihydrotestosterone to androgen receptors,
inhibits metabolism of estradiol, and
increases serum prolactin levels
When used long-term or in high doses, it
may cause gynecomastia or impotence in
men and galactorrhea in women
These effects are specific to cimetidine and
do not occur with the other H2 antagonists
 Although there are no known harmful
effects on the fetus, H2 antagonists
cross the placenta
Therefore, they should not be
administered to pregnant women
unless absolutely necessary. The H2
antagonists are secreted into breast
milk and may therefore affect
nursing infants
 Proton Pump Inhibitors
The most potent suppressors of gastric acid se
 To prevent degradation of proton pump inhibitors
by acid in the gastric lumen, oral dosage forms
are supplied in different formulations:
enteric-coated drugs contained inside gelatin
capsules (omeprazole, dexlansoprazole,
esomeprazole, and lansoprazole)
enteric-coated granules supplied as a powder for
suspension (lansoprazole)
enteric-coated tablets (pantoprazole, rabeprazole,
and omeprazole)
powdered omeprazole combined with sodium
bicarbonate (ZEGERID) contained in capsules and
formulated for oralsuspension
 Pharmacokinetics
Because an acidic pH in the parietal cell acid
Adverse Effects
 Drug Interactions
Proton pump inhibitors have been
observed to interact with warfarin
(esomeprazole, lansoprazole,
omeprazole, and rabeprazole),
diazepam (esomeprazole and
omeprazole), and cyclosporine
(omeprazole and rabeprazole).
 Therapeutic Uses
gastric and duodenal ulcers
gastroesophageal reflux disease
(GERD),
Erosive esophagitis,
Zollinger-Ellison syndrome
In children, omeprazole is safe and
effective for treatment of erosive
esophagitis and GERD
Twenty-four-hour intragastric acidity and plasma gastrin concentration
before and during treatment with either ranitidine or omeprazole.
 Mucosal Protective Agents:
SUCRALFATE (complex of aluminum hydroxide and sulfated sucrose)

BARRIER TO ACID, PEPSIN & BILE

Form sticky gel that coats ulcer portion
DIRECTLY ABSORB BILE SALTS
STIMULATE ENDOGENOUS PROSTAGLANDIN
SYNTHESIS
BE EFFECTIVE IN THE HEALING OF DUODENAL
ULCERS
1 g 4 TIMES DAILY ON AN EMPTY STOMACH (AT
LEAST 1 HOUR BEFORE MEALS)
REQUIRES AN ACID pH TO BE ACTIVATED
SHOULD NOT BE ADMINISTERED SIMULTANEOUSLY
WITH ANTACIDS, H2-RECEPTOR ANTAGONIST, OR
PPIs
 Therapeutic Uses
sucralfate has been used in several other
conditions associated with mucosal
inflammation/ulceration that may not
respond to acid suppression, including
oral mucositis (radiation and aphthous
ulcers) and bile reflux gastropathy.
Administered by rectal enema, sucralfate
also has been used for radiation proctitis
and solitary rectal ulcers.
Sucralfate
 Adverse Effects

The most common side effect of sucralfate

is constipation
Sucralfate forms a viscous layer in the
stomach that may inhibit absorption of
other drugs, including phenytoin, digoxin,
cimetidine, ketoconazole, and
fluoroquinolone antibiotics.
Sucralfate therefore should be taken at
least 2 hours after the administration of
other drugs
 Bismuth chelate
(Colloidal Bismuth subcitrate,
tripotassium dicitratobismuthate)

Coating & protecting it from acid

& pepsin
inhibition of pepsin activity
stimulation of mucus production
increase prostaglandin synthesis
have some antimicrobial activity
against H. Pylori (mainly when
combined with metronidazole &
tetracycline)
 Misoprostol (a stable analog of PGE1)

Replacement for endogenous prostaglandins

Inhibit gastric acid secretions, both basal and in
response to food, histamine, pentagastrine and
caffein (direct action on the parietal cell)
Increase mucosal bloodflow & augment the
secretion of mucus and bicarbonate
Prevention of ulcers induced by the administration
of NSAIDs (NSAIDs gastropathy)
(Luellman,2005
 Adverse Effects
Misoprostol can cause clinical
exacerbations of inflammatory bowel
disease and should be avoided in
patients with this disorder.
Misoprostol is contraindicated during
pregnancy because it can increase
uterine contractility.
Algorithm.Guidelines for the evaluation and management of a
patient who presents with dyspeptic or ulcer-like symptoms
(Luellman,2005
 Oral Drug Regimens Used to Heal
Peptic Ulcers or Maintain Ulcer Healing
Management of gastroesophageal reflux disease
Goodman and Gilmans, Manual Pharmacology and therapeutic
 SEKIAN
TERIMA KASIH !!

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