DRUGS USED IN GASTROINTESTINAL

DISEASES
Dr. Francisca Diana A,M.Sc
Outline
 Drugs used in acid-peptic diseases
 Prokinetic agent
 Antiemetic
 Antidiarrheals
 Laxatives
 Antispasmodic
 Drug used for miscellaneous GI disorder
DRUG USED IN ACID-PEPTIC DISEASE

 Acid neutralizing agents

 Acid production inhibitor
 H2 antagonist
 Proton-pump inhibitors
 Mucosal protective agents
 Other acid suppressant
GASTER
 Terdiri atas
 Bodi
 Kardia
 Fundus
 Korpus
 Pilorus
 Cekungan
 Kurvatura minor
 Kurvatura mayor
 Mukosa lambung dibagi menjadi tiga
daerah ekskresi:
Area glandula kardia mensekresi mukus dan
pepsinogen.
 Area glandula oksintik (parietal) mensekresi ion H,
pepsinogen dan bikarbonat.
 Area glandula pilorik mensekresi gastrin dan
mukus.
 Pepsinogen dikatalisis oleh HCl jadi pepsin, yaitu enzim
proteolitik
 Ulkus peptik di esofagus, lambung dan duodenum terjadi
apabila produksi asam lambung dan pepsin tidak berimbang
dgn sietem pertahanan gastroduodenal
Schematic model for physiologic control of hydrogen ion (acid)
secretion by the parietal cells of the gastric fundic glands
Acid neutralizing agents: Antacids
 Antacid tidak mengurangi volume HCl yang dikeluarkan
lambung tetapi peninggian Ph akan menurunkan aktivitas
pepsin.
 Antasid dibagi dlm 2 golongan :
a. Antasid sistemik : Natrium bikarbonat (NaHCO3)
diabsorpsi di dlm usus halus sehingga menyebabkan
urin bersifat alkalis.
b. Antasid nonsistemik : Al(OH)3, Mg(OH)2, CaCO3
hampir tidak diabsorpsi dlm usus sehingga
tidak menimbulkan alkalosis metabolik.
Acid neutralizing agents: Antacids
Combination of Al(OH)3, Mg(OH)2, CaCO3
(+simethicone)
Pharmacodynamics:
 Form salt and water
 Promote mucosal defense by stimulation of PG
production
Drug interaction:
 Inhibit absorption of digoxin, phenytoin, cimetidine,
fluoroquinolone
 Some Al can be absorbed
Acid neutralizing agents: Antacids
H2 receptor antagonists
Cimetidine, ranitidine, nizatidine, famotidine

Pharmacodynamic:
 Reduce acid secretion in 2 ways: competitive
inhibition H2 receptor & modulate PC’s
response to gastrin & Ach
 Reduce 90% (at night) and 60-80% (daytime)
H2 receptor antagonists
Pharmacokinetic:
 rapidly absorbed in intestinal lumen
 Undergo 1st pass metabolism  F = 50%
 T1/2: 1-4 hrs, and d.o.a depend on dose, 10 hrs in
recommended dose
 Elimination: hepatic metab., glomerular filtration
filtration & renal tubular secretion
 Cross the placenta, secreted into breast milk
H2 receptor antagonists
Safety:
 Extremely safe
 SE:
 diarrhea, constipation, headache, fatigue, myalgia
 Gynaecomastia
 Blood dyscrasi
 Avoid from pregnant and nursing women
Drug interaction:
 cimetidine prolong half-lives drugs that are substrate for CYP:
warfarin, theophylline, phenitoin, lidocaine, quinidine, b-blockers,
Ca-channel blockers, benzodiazepines
 Compete with procainamide for renal tubular secretion
H2 receptor antagonists
Proton-pump inhibitors
Omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole
Pharmacodynamic:
 Protonated & concentrated in PC canaliculi
 The reactive cation binds covalently with H/K
ATPase
 Reduce 80-95%, needs 3-4 days to return
 Proton-pump inhibitors
Pharmacokinetic: absorbed in intestinal lumen
(available in enteric coated)
 An acid-labile lipophylic prodrug: need acid
environment to be activated  easily diffuse into
acidified compartment (PC canaliculi)
 To be administered 1 hour before meal
 Highly protein bound
 Undergo 1st pass & hepatic metabolism
 T1/2: 1,5 hr but acid inhibition last up to 24 hr
 No renal elimination
Proton-pump inhibitors
Safety:
 Extremely safe
 SE: due to highly reduction acid
 Reduction in cyanocobalamin
absorption
 Food-bound minerals (?)
 Increase risk of enteric infections
 Drug interaction
 Alter absorption of certain drugs
 Hanya omeprazol yg dpt menghambat
aktivitas enzim CYP2C19 serta menginduksi
CYP1A2 (meningkatkan klirens beberapa
obat antipsikotik, takrin dan teofilin)
 Proton-pump inhibitors
OBAT BIOAVAILABILITAS T ½ (JAM) Dosis lazim untuk peptic ulcer
(%) atau GERD
OMEPRAZOL 40-65 0,5 – 1,5 20-40 mg 1 kali sehari
ESOMEPRAZOL > 80 1,2 – 1,5 20 – 40 mg 1 kali sehari
LANZOPRAZOL 80 1,5 30 mg 1 kali sehari
PANTOPRAZOL 77 1,0 – 1,9 40 mg 1 kali sehari
RABEPRAZOL 52 1-2 20 mg 1 kali sehari
Mucosal protective agents
Sucralfate: A complex of sucrose salt + sulfated AlOH 
forms a paste that selectively cover ulcers/erosions
Pharmacokinetic:
 Almost unabsorbed
 Breaking down into sucrose sulfate & Al salt
Pharmacodynamic:
 Forming physical barrier so that prevent further caustic
damage  stimulate mucosal PG & HCO3 secretion
 Enhancing mucosal repair
Drug interaction:
 Inhibit absorption of digoxin, phenytoin, cimetidine,
fluoroquinolone
 Some Al can be absorbed
Mucosal defense enhancing agents
Bismuth compounds
Pharmacodynamic: = sucralfate
 Stimulate PG, mucus, bicarbonat secretion
Prostaglandin analog: misoprostol
A methyl analog of PGE1
Pharmacokinetic:
 T1/2: 30 mnts  3-4 times daily
Pharmacodynamic: stimulates mucus and bicarbonat secretion
SE: diarrhea, abdominal cramp (10-20%), stimulate
uterine contraction
Dosis : oral, dewasa 200 mg 4 kali/sehari atau 400 mg 2
kali/hari.
Indikasi : usia lanjut atau perdarahan saluran cerna akibat
AINS
Mechanism of action of drug used in acid peptic disease
PROKINETIC AGENTS
Agents that enhance coordinated GI motility and transits
material in the GI tract
 Cholinomimetic
 Bethanechol
 Neostigmin methylsulfate
 Dopamine receptor antagonist
 Metoclopramide
 domperidon
 Serotonin (5-HT4) receptor agonist
 Cisapride, prucalopride
 Motilin agonist
 Macrolides: erythromycin
 PROKINETIC AGENTS
Side effects:
 Metoclopramide
 Extrapyramidal effect
 Elevated prolactin level galactorrhea, gynaecomastia,
menstrual disorder
 methaemoglobinemia
 Domperidone
 No extrapyramidal effect
 Cisaprid
 Fatal cardiac arrythmia (occasionally) – torsades de
pointes due to induced EAD
PROKINETIC AGENTS
Therapeutic use:
 GERD
 Impaired gastric emptying
 Postvagotomy
 Diabetic gastroparesis
 NGT-ed patients
 Dyspepsia syndrome (non-ulcers)
 Antiemetic
 Persistent hiccup (metoclopramide)
LAXATIVES
Stimulant laxatives
 Merangsang mukosa, saraf intramural atau otot polos usus
sehingga meningkatkan peristaltik dan sekresi lendir usus.
 Castor oil
 Kerjanya pada usus halus sehingga efek terlihat setelah 3 jam
 ES : kolik, dehidrasi yg disertai gangguan elektrolit
 Dianjurkan untuk diberikan pada pagi hari waktu perut
kosong.
 Dosis : dewasa : 15-60 mL, Anak : 5 -15 mL
 Dosis lebih besar tidak menambah efek pencahar
 Stimulant laxatives
• Diphenylmethane derivatives:
a. bisacodyl
 Dosis : supp 10 mg, oral : dewasa 10-15 mg; anak 5– 10 mg
 ES : kolik usus, perasaan terbakar pd penggunaan rektal
 Efek pencahar terlihat setelah 6 -12 jam pd pemberian oral
 Pada pemberian rektal efek setelah ¼ - 1 jam
• Anthraquinone derivatives: Aloe, senna, cascara
 Efek pencahar golongan ini bergantung pada antrakinon yg
dilepaskan dari ikatan glikosidanya.
 Efek muncul setelah 6 jam
 Zat aktif bisa ditemukan pada ASI (cascara)
ES : pigmentasi kolon, penggunaan kronis menyebabkan kerusan
neuron mesenterik
 Bulk forming laxatives
 Pembentuk massa tinja
 Bekerja dengan meningkatkan massa tinja, karena
kemampuannya menarik air dan ion dalam lumen kolon,
sehingga membentuk hidrogel.
 Contoh : sediaan semi sintetik : metilselulosa dan natrium
karboksimetilselulosa; sedangkan sediaan alami : agar-agar, biji
psyllium dan kulit padi
PELEMBEK TINJA
 Bekerja dengan meningkatkan ukuran tinja dan melembekkan
tinja tanpa merangsang peristaltik usus baik langsung maupun
tidak langsung sehingga mudah dikeluarkan.
 Contoh : Parafin cair, Na dokusat , glycerin supp, parafin cair
(mineral oil)
 Osmotic laxatives
 Osmolalitas lumen usus meningkat dan
pergerakan cairan terjadi karena tekanan
osmotik.
 Terbagi 2 Jenis :
 saline laxatives:
 unabsorbable sugars: sorbitol, lactulose
 SALINE LAXATIVES
 Merupakan garam non organik yang mengandung kation atau
anion dan tidak segera diabsorpsi mukosa usus karena
cenderung bertahan di saluran cerna.
 Peristaltik usus meningkat disebabkan pengaruh tdk langsung
karena daya osmotiknya.
 Air ditarik ke dlm lumen usus dan tinja menjadi lembek
setelah 3 – 6 jam.
 Absorpsi pencahar garam melalui usus berlangsung lambat dan
tidak sempurna.
 Contoh : magnesium citrate, sodium phosphate
Mechanism of action of laxatives
ANTIEMETIC

1. Serotonin (5-HT3) receptors antagonist

 Ondansetron, granisetron, ramosetron, palanosetron,
dolasetron
2. Dopamine antagonist: Metoklopramide, domperidon
3. H1-antagonist : Cyclizine, Promethazine,
prochlorperazine, CPZ
4. Antikolinergics: Scopolamine
5. Cannabioid antagonist: Dronabinol
ANTIDIARRHEA

1. Opioid agonist
2. Colloidal bismuth compound
3. Kaolin (hydrated Mg-Al silicate) & pectin
(indigestible KH)
4. Bile salt-binding resin
5. Octreotide
 Pharmacodynamic
Opioid
antidiare
(Loperamide,
 Inhibit presynaptic cholinergic
nerve, reduce peristaltic activity
Diphenoxylate, codein)  Increase transit time
 Decrease mass colonic movements
Colloidal bismuth compound  direct antimicrobial effects and binds
enterotoxins
Kaolin & pectin  adsorbents of bacterial toxins and
fluid, thereby decreasing stool liquidity
and number.
Bile salt-binding resin  binds bile salts and increases fecal
(Cholestiramine, excretion of bile acids
Colestipol, colesevalam)
Somatostatin-like  reduces intestinal fluid secretion &
(Octreotide) pancreatic secretion
 slows GI motility, inhibit gallbladder
contraction
Side effects
 constipation, cramps, drowsiness,
paralytic ileus, abdominal bloating.
 Diphenoxylate, but not loperamide,
produce euphoria dan respiratory
depression
 Dark stools, black staining of the tounge
 Have no significant adverse effect except
constipation.
 Should not be taken within 2 hours of
other medication
 Bloating, flatulence, constipation
 Fat malabsorption
 Should not be taken within 2 hours of
other medication
 Steatorrhea, nausea, bloating
 Fat-soluble vitamin deficiency
 Gallstone formation,
hypo/hyperglycemia
ANTIPASMODIC
1. Anticholinergic
• Hyoscyamine, Dicyclomine
2. Serotonin (5-HT3) receptor antagonist
• Alosetron
Indication:
 to prevent the pain and fecal urgency in
patient with IBS
 treatment of diarrhea-predominant IBS
Drug used for miscellaneous GI disorder

1. Pancreatic enzymes: pancreatin,

pancrelipase
 Chronic pancreatitis
 Malabsorption
2. Bile acids: ursodeoxycholic
 Gallstone dissolution
3. Antiflatulance: simethicone, herbal prep.
(antifoaming agent)
References
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p. 1309-21.
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