DRUG USED IN GASTRO

INTESTINAL DISEASE

DR.dr.Asep Sukohar, M.Kes

Department of Pharmacology, Faculty Of Medicine,
Lampung University

Many Drugs
Have

applications in the treatment of

gastro intestinal disease
-

motility
digestion
secretion
absorption

- peptic ulcers
- delayed gastric emptying in adequate propulsion
- diarrhea
- infections and inflammation

DRUG USED IN PEPTIC ULCERS

DISEASE
Pathogenesis of peptic ulcers not
completely understood
Secretion

of acid by gastric parietal cells

regulated by
- Histamin
- Asetylcholine
- Gastrin

AGENT FOR CONTROL OF

GASTRIC ACIDITY AND
TREATMENT OF PEPTIC ULCERS
-

Antacids
H2 Receptor antagonists
Mucosal protective agents
Others agents

Antacids
-

Alumunium hydroxide
Calcium carbonate
Magnesium hydroxide
Sodium bicarbonate
Magnesium trisilikate

H2 Histamin receptor-blockers
-

Cimetidine
Ranitidine
Famatidine
Nizatidine

 Mucosal
-

protective agents

Sucralfate

Studies in human subjects and with animal models of ulcer disease have
shown that sucralfate forms an ulcer-adherent complex with proteinaceous exudate at the ulcer site.
In vitro, a sucralfate-albumin film provides a barrier to diffusion of hydrogen ions.
In human subjects, sucralfate given in doses recommended for ulcer therapy inhibits pepsin activity in gastric juice
by 32%.
In vitro, sucralfate adsorbs bile salts.

Colloidal bismuth

Inhibitors
-

of proton pump

Omeprazol
Lansoprazol

Prostaglandins
-

Misoprostal: inhibiting the secretion of gastric acid via G-protein coupled receptor-mediated inhibition of adenylate cyclase,
which leads to decreased intracellular cyclic AMP levels and decreased proton pump activity at the apical surface of the
parietal cell

 Antimicrobial
-

agents

Amoxicillin
Bismuth compounds
Claritromycin
Metronidazole
Tetracycline

 Antacids
Sodium

Bicarbonat
NaHCO3 + HCl NaCl + H2O + CO2
-

Active ingredient in backing soda

Highly soluble
absorbed rapidly from the gut

promote systemic alkalosis and fluid retention

Not recommended for long-term use

Aluminium Hydroxide
Al(OH)3 + 3 HCl

AlCl3 + H2O

Onset

of action
: Late
Duration of action : Long
-

Often causes constipation

Binds certain drugs : eg, tetracycline

Phospate

Used to therapeutic advantage in patients with chronic renal

failure and bone dis.

Calcium Carbonate
Ca Co3 + 2 Hcl CaCl2 + H2O + Co2
-

More slowly than sodium bicarbonate

Very effective in neutralyzing in gastric acid
10% produced is absorbed

potensial
- hypercalcemia
- milk alkali syndrome
- acid rebound

not recommended for long term use

Magnesium Hydroxide
= Milk of Magnesia
Mg(OH)2 + 2 HCl MgCl2 + 2 H2O
-

Prolonging its neutralizing effect

Magnesium salts cathartic effect
A small absorbed renal insufficiency

Magnesium Trisilikate
Mg2 Si308(nH2O) +4HT 2 mg++ +
3S1O2+(n+2)H2O
-

S1O2 - adsorbent
Siliceous nephroliths

H2 HISTAMIN RECEPTOR
ANTAGONITS

Cimetidine }
Ranitidine } 2 major drugs in use
Capable of over 90% reduction in based food
stimulated, and nocturnal secretion of gastric
acid after a single dose
Promoting the healing of duodenal and gastric
ulcers and preventing their recurrence.
Famotidine
Nizatidine

Pharmacological Properties
- H2 Rec An. Competitively inhibit the interaction of
histamine
with H2 receptor
- Highly selective
- Absorption, Fate and Excretion
- H2 Rec. An. . rapidly and well absorbed after oral
ad.
. peak C : 1 or 2 hours
. bioavailability Niz : 91%
. t : 2-3 hours
1-3 hours : nizatidine
. Exc : urine

- Adverse effects :

- headache
- dizziness and nausea
- myalgia, skin rashes
- itching

- Drug interactions :

- Antacid
- Ketakenazole
- cyt. P.450

Sitokrom P450 sistem oksidase

4 sub-famili utama: CYP1,CYP2, CYP3, dan CYP4 6
isoform (CYP1A2, CYP2C9, CYP2C19, CYP2D6,
CYP2E1, dan CYP3A4)
Aktivitas dimodulasi oleh genetik dan faktor lain (umur,
etnik, jenis kelamin, diet, konsumsi alkohol atau
tembakau) juga kondisi patologis

Inbitors of H+, K+ ATP ase

Omeprazole
Lansoprazole

Inhibition of gastric acid secretion

Do not affect gastric motility
Absorption : rapidly
Bioavailability : 70%
95% bound to plasma protein
t : 30-40
Metabolism : hepatic
Exc
: urine
Adverse effects - gastrointestinal
- C.N.S

Sucralfate
-

Cytoprotective agents
Alumunium sucrose sulfate
Recently developed for use in peptic ul. dis.
selective binding toneocrotic ulcer tissue
Effective in healing of duodenal ulcers
Not absorbed systemically
Few side effects have been reported
Ig 4 times daily on an empty stomach

PROSTAGLANDIN ANALOGS
PG E2}
}

PGI2 }
-

Predominant PG synthesized the gastric mucosa

Inhibit the secretion acid
Stimulate the secretion of mucus and
bicarbonat

Misoprostol
-

1.5 deoxy 16 hydroxy 16-metyl PGE1

Available in the U.S
Effective in treating - duodenal and
gastric ulcers
inhibits gastric acid secretion
produce cyproprotective effects

Pancreatic Enzime
Replacement Product
Two mayor types of preparation in use
-

Pancreatin

}
}
}

- Pancrelipase
- Pepsime
- Pancreatime
- Dyastase
- Dehidrocyolate acid

amylase
trypsim
lipase

Laxatives
Irritant or stimulant laxatives

Castor oil
Cascara }
Senna }
Aloes
}

Phenolphtalien

- Bisacodyl

Difenilmetane

}
} Anthrakinon
}

peristalsis is stimulated

Bulk Laxative
- Methylcellulose
- Psyllium seed
- Agar
Hydrophylic colloids
:USES: This medication has been used to treat common constipation, diarrhea, irritable bowel syndrome, spastic
colon, diverticulitis, and hemorrhoids. Bulk-forming laxatives, also called fiber laxatives, work by increasing the
amount of water in the stool, making it softer and easier to pass. These are generally the preferred laxatives for
most ages

Stool softeners
- Mineral oil
- Glycerin suppositories
- Dioctyl sodium sulfosuccinate
Agents that become emulsified with stool serve to soften it
make possage easier

Drugs promoting
Gastrointestinal motility

* Bethanecol cholinergic agonist

* Metoclopramide
-

Facilitating small bowel inhibition

Gastric motor failure
Particularly diabetic gastroporesis
After vagotomy
Disorders of gastric emptying
Gastroesophageal reflux disease
cancer chemotherapy

- Rapidly absorbed
- Peak C : 40 120
- t : 4 hours
- Excretion : kidneys
- 10 mg 4 times daily - neal
- bed time

Antidiarrheal Drugs
Most widelly used prescription drugs
1. Diphenoxylate (with atropine)
analog of meperidine
2. Loperamide
haloperidol
mechanisme of action : similar to that of the opioids
Kaolin } adsorbents
Pectin }
also widely used

Drugs Used in The Treatment of Bowel Chranic

Inflammatory Bowel disease
ulcerative collitis
chrohms disease
-

Corticosteroids
Other immunosuppressive agents

Sulfasalazine

combines sulfapyridine
- 5 aminosalicylic acid
poorly absorbed from the intestine
MOA unknown
cytoprotective role ?
3-4g daily individed doses

Azodisalicylate

How to formulate drugs?

GG 979

Clinical Summary

GG 980