Drugs Used In Drugs Used In

Gastrointestinal DiseasesGastrointestinal Diseases

Peptic Ulcers

OBAT ULKUS PEPTIKUMOBAT ULKUS PEPTIKUMPatogenesis ulkus peptikum• 1. Sekresi asam lambung yang berlebih• 2. Menurunnya efek proteksi dari mukosa• 3. Infeksi Helicobacter Pylori ( HP)

1. Antasida1. Antasida

• Basa lemah : Mg(OH)2 , MgSiO3 , Al(OH)3 CaCO3 Ca(HCO3)2 NaHCO3

• Mekanisme kerja: netralisasi asam

lambung→mengurangi keasaman lambung→mengurangi aktivitas pepsin

2. Gastric antisecretory drugs2. Gastric antisecretory drugs2. H2-R antagonists 2.1 mechanism: block H2-R→ reduce the secretion of

gastric acid→↓the volume of gastric acid & acidity

2.2 clinical uses: • peptic ulcer • zollinger-ellison syndrome • gastroesophageal reflux

2.3 adverse reaction2.3 adverse reaction::

• ) Antiandrogenic effect : gynecomastia, impotency, galactorrhea

• ) Inhibit cytochrome P450 catalyzed oxidative drug metabolism pathway→ reduce clearance of other drugs

• Cimetidine: 400 mg bid 4W→80% healing • Ranitidine 1) Antisecretive effect is 10 times that

of Cimetidine . 2)Less effect on hepatic microsomal

metabolism system. 3)Longer duration and less

antiandrogenic effect

• Famotidine, Nizatidine: 1) Antisecretive effect is 30 times that

of Cimetidine . 2) Have no effect on hepatic

microsomal metabolism system.• Ebrotidine: 1) ↑Expression of EGF and

PDGF→stimulate proliferation of epithelium

2) increase mucus secretion

2.2. M1- R antagonist:M1- R antagonist: Pirenzepin Pirenzepin

3. Proton pump inhibitors Omeprazole, lansoprazole, rabeprazole, pantoprazole.

Mechanism of actionMechanism of action

• Require activation in the acid environment of the secretory canaliculus of the parietal cell

• Inhibit H+-K+ ATPase irreversibly and inhibit over 95% of gastric acid secretion

• Clinical uses: superior to H2-R antagonists.

• Adverse reactions: 1) inhibits gastric secretion→overgrowth

of bacteria. 2) hypergastrinemia.

4. gastrin-receptor antagonists: 4. gastrin-receptor antagonists: - proglumide - proglumide

Mucosal protective agents prostaglandins: Misoprostol1) inhibit gastric secretion 2) promote mucus secretionclinical uses: NSAID-induced ulcer adverse reactions: dose-dependent

diarrhea, stimulate uterus

2. sucralfate2. sucralfate

3. bismuth potassium citrate mechanism of action: 1) selective binding to an ulcer, coating

it and protecting it from acid and pepsin. 2) Inhibit pepsin activity

3) stimulate mucous production

mechanism of action: 4) increase prostaglandin synthesis. 5) antimicrobial activity against H pylori clinical use: when combined with antibiotics

(metronidazole and tetracycline), ulcer healing rates of up to 98% have been seen.

Antibacterial agentsAntibacterial agents

• metronidazole, • tetracycline

Cerebral Centers Affecting Vomiting

antiemetic drugsantiemetic drugs

• 1. 5-HT3 inhibitor ondansetron : used in the prevention of chemotherapy-

induced and postoperative nausea and vomiting

2. dopamine antagonists:2. dopamine antagonists:

• Metoclopramide mechanism block D2-receptor in CTZ adverse reaction: extrapyramidal symptoms, especially dystonias

DomperidoneDomperidone

• block gastrointestinal D-receptor • difficultly penetrate BBB, have no

extrapyramidal symptoms

laxativeslaxatives

• bulking laxatives: MgSO4, • irritant or stimulant laxatives: castor oil• stool softeners: liquid paraffin, glycerin

Antidiare

• Tipe of antidiare– Opiates and opiate-related agents– Diphenoxylate with atropine– Adsorbents; Kaopectate– Antidiarrheal combinations