Drugs used in gastrointestinal disease

Drugs used in Acid Peptic Disease

Drugs that promote upper G.I. motility
Drugs with antiemetic action
Antidiarrheal agent
Laxative agent
Drugs used in Inflammatory Bowel
Disease
 Acid peptic disease
Gastro esophageal reflux disease (GERD)

Peptic ulcer (gastric & duodenal)

Mucosal injury
Aggressive Defensive
factors factors
Acid,pepsin,bile Mucus,bicarbonate,
PG,blood flow,EGF,
FGF
 Principle of treatment
Reduce intragastric acidity

Promote mucosal defense

Antibiotic
Drugs used in acid peptic disease
Antacids
H2 blocker
Proton pump inhibitor
Antimuscarinic
Prostaglandin
Sucralfate
Antibiotic
 Mechanism of action of ANTACIDS
In Stomach

Mg2Si3O8 + 4HCl 2MgCl2 + 3SiO2 + 2H20

In Intestine

MgCl2 + H2CO3 MgCO3 + 2 HCl

 NaHCO3+2HCl NaCl+H2O+CO2
 CaCO3+2HCl CaCl2+H2O+CO2

 Mg(OH)2+2HCl MgCl2+2H2O
 Al(OH)3+3HCl AlCl3+3H2O
 PPI available
 Omeprazole
 Lansoprazole
 Rabeprazole
 Pantoprazole
 esomeprazole
 Properties of PPI
Inactive prodrug (weak base)
Acid labile prodrug
Enteric coated formulation
Absorb at alkaline intestinal lumen
Concentrated in acidic parietal cell
Undergoes to active thiophilic
sulfonamide
Bioav.decrease 50% by food
Half life 1,5 hour; duration 24 hours
Mechanism of action of PPI
 Clinical uses
GERD
Peptic Ulcer Disease
Dyspepsia
Gastrinoma and Hypersecretory
 Adverse Effects
 PPIs are extremely safe
 Diarrhea, headache, abdominal pain

 Do not have teratogenicity in animal

 Reduction of B12 absorption

 Increase risk for enteric infections

 Drug Interaction
 PPIs are metabolized by Cytochroom P450
 CYP2C19 and CYP3A4
 Lanzoprazol enhance CL of Theophyllin
 Sucralfate
In acidic solution it form a viscous paste
Forming a physical barrier
Stimulate mucosal prostaglandin secretion
Stimulate bicarbonate secretion
Enhancing mucosal repair
Not significantly absorbed
 Prostaglandin analogs
(misoprostol)
Acid inhibitory & mucosal protective
Stimulate mucus and bicarbonate
secretion
Enhance mucosal blood flow
Stimulate uterine contraction
 Drugs that promote upper G.I.motility

Mechanism of action of Metoclopramide & Cisapride

CNS

Dopamin antagonist

Metoclopramide & domperidone

Ach fasilitator, dopamin antagonist

Ach
Enteric Nervous System M Intestin

5HT4 Agonist

Cisapride
Clinical use
 GERD (symptomatic),especially in
combination with antiscretory for
treatment of refractory regurgitation &
heartburn
 Delayed gastric emptying
 Nonulcer dyspepsia
 Prevention of vomiting
 Promote postpartum lactation
Adverse effect

 Especially due to central effect of

metoclopramide
central nervous system
extrapyramidal effect
elevated prolactin levels
 Domperidone
Drugs with anti emetic action
Drug used in emesis
 Metoclopramide
 Dexamethasone
 AH1
 Phenothiazine
 5-HT3 inhibitor(ondansetron, granisetron)
 Dronabinol
Antidiarrheal agent
 Diphenoxylate
 Loperamide
 Kaolin & pectate
Loperamide & Diphenoxylate
 Opioid agonist
 Inhibit presynaptic cholinergic nerve in
submucosal and myenteric plexus
 Decreased mass colonic movement
 Increased colonic transit time
 Increased fecal water absorption
Kaolin & Pectin
 Absorbents of bacteria, toxins and fluid
 Decreasing stool liquidity
 Not absorbed
STIMULANT/IRRITANT LAXATIVE

CASTOR OIL

HIDROLYSE

RICINOLEIC ACID

IRRITANT LOCAL

MOTILITY INTESTINAL
 CASCARA, SENNA, ALOES

ABSORB IN INTESTINE

SYSTEMIC CIRCULATION
(CONTAIN EMODINE)

EXCRETED INTO COLON

PERISTALTIC STIMULATED
Mech.of action of bulk-forming laxative
BULKING/BULK FORMING LAXATIVE

HYDROPHYLIC COLLOIDS
(INDIGESTIBLE PART OF FRUITS, VEGETABLES AND
SEEDS)

FORM GEL WITHIN THE LARGE

INTESTINE

DISTENDING THE INTESTINE

STIMULATING PERISTALTIC ACTIVITY

 Stool softening

 Dioctyl sodium sulfosuccinate (docusate)

penetrate of water and lipids

soften stool material

easy to deficate
Lubricating laxative

Mineral oil

Viscous oil that lubricates fecal material

Inhibit water reabsorption

Easy to deficate
Drugs used in inflammatory bowel disease

 Glucorticoid
 Immunosuppressive antimetabolit
 Infliximab
 Aminosalicylate(sulfasalazine,mesalamine
 Glucocorticoids
 Prednison &prednisolone most
commonly used oral
 Hydrocortisone enema,foam,
suppositorie are used to maximize
effect, and minimize systemic
absorption
 Budesonide,potent analog of
prednisolone rapid first pass effect
 Aminosalicylates
5 ASA, work topically
80% readily absorbed in small intestine,
acetylated by gut epithelium and liver (not
active as antiinflamatory)
Small amount reach distal small bowel or
colon (absorption is low)
5 ASA Supp.or enema are useful in patient
(high conc. at active site of disease)
 Sulfasalazine
5 ASA bound to sulfapyridine
Reduce absorption from small intestine
In terminal ileum & colon, azoreductase
enzyme (in bacteria) change sulfasalazine
to active form 5 ASA + sulfapyridine
85% sulfapyridine diabsorbsi di colon
(systemic effect of sulfapyridine)
 Mesalamine
Formulation design of 5 ASA package
(5 ASA formulation)
Time release microgranule
Enteric coated, disolve at pH 7 (distal
ileum & proximal colon). Mesalazine is
available in Indonesia
20-30% 5 ASA from mesalamine absorbed
in small intestine
 Antimetabolite
• Azathioprine & 6 mercaptopurine
immunosupressive effect
can reduce dose of corticosteroid
BM depression & hepatotoxic
metabolism reduces by Allopurinol
• Methotrexate
inhibition of dihydrofolate reductase
antiprolifrative effect may not be seen in low dose
increased release of adenosine (endogenous anti inf)
BM depression, Megaloblastic anemia, Alopecia
 Anti TNFα
• Infliximab
• Administered as an intravenous infusion
• Bind to soluble TNFα, preventing it from
binding to its receptors