Drugs Used in Gastrointestinal Disorders

Drugs Used in Acid-Peptic DiseaseDrugs Used in Acid-Peptic Disease

Antacid React with proton in the lumen of the gut. The most popular antacid : Mg(OH)2; Al(OH)3 Mg(OH)2 has a strong laxative effect Al(OH)3 has a constipating action These drugs are available as single-ingrediant product & as combined preparation The others : calcium carbonate (CaCO3)& natrium bicarbonate (NaHCO3), but they have a systemic effects (hypercalcemia, nefrolithiasis, sistemic alkalosis)

Histamin H2 blocker Prototype : cimetidine, ranitidine, famotidine, and nizatidine Mechanism of action : pharmacologic antagonists at H2 receptors Effects : reduction of gastric acid secretion Clinical use : - acid peptic disease - prevent recurrences of gastric peptic ulcers - Zolinger-Ellison syndrome (acid hypersecretion, severe recurrent peptic ulcer, GI bleeding, diarrhea) - gastroesophageal reflux disease (GERD) Tox : Inhibitor of hepatic drug-metabolizing enzymes and reduce hepatic blood flow, Antiandrogen effects

Antimuscarinic Drugs Prototype : atropine, methscopolamine, propantheline, pirenzepin Mechanism : reduce acid secretion, reduce cramping and hypermotility in transient diarrhea Pirenzepin, the M1 selective inhibitor is available for the treatment of peptic ulcer Tox : blockade of thermoregulatory sweating, salivation, and lacrimation

Sucralfat (alumunium sucrose sulfat) Binds to injuried tissue and forms a protective coating over ulcus bed Accelerate the healing of peptic ulcers and to reduce the recuurence rate Toxicities is very low Prostaglandin Misoprostol, a PGE2 analog use in peptic ulcer association with NSAID Tox : diarrhea, uterine stimulant effects (contraindicated to pregnancy women)

Proton pum inhibitor Prototype : omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole Mechanism : inhibitors of the proton pump of gastric parietal cells Clinical use : peptic ulcer disease associated with H.pylori and with NSAID treatment, ZollingerEllison syndrome, GERD Tox : diarrhea, abdominal pain, headache. They can reduce absorption of B12 and certain drugs (digoxin, ketoconazole) Antibiotics Prototype : Bismuth (Pepto-bismol), tetracycline, and metronidazole or amoxicillin+clarithromycin Clinical use : recurrent peptic ulcer associated with chronic infection of H.pylori

Drugs that Promote Upper GI Motility

Prototype : Metoclopramide, cisapride

Mechanism : stimulate motility GI via

cholinergic stimulation (Metoclopramid act as an acetylcholin facilitator and Dopamine D2 antagonist; Cisapride act as 5-HT4 agonist ) Clinical use : diabetic gastroparesis Tox : - parkinsonis, extrapyramidal effects & hyperprolactinemia (metoclopramide) - arrhythmias (cisapride)

Antiemetic Drugs
Prorotype : metoclopramide, dexamethasone, H1

antihistamine, 5-HT3 inhibitor (ondansetron, granisetron, dolasetron) Mechanism : Metoclopramide blocking D2 receptor in the area postrema Clinical use : prevention and treatment of vomiting, especially cancer chemotherapyinduced vomiting and post operation

Laxative
The drugs that increase bowel movement Mechanism :

- irritant or stimulant action on the bowel wall (castor oil, cascara, senna, phenolphtalein, bisacodyl) - bulk-forming action on the stool that evokes reflex contraction of the bowel (saline cathartics (Mg[OH]2; psyllium, methylsellulose) - Softening action on harding or impacted stool (dioctyl sodium sulfosuccinate[docusate]) - Lubricating action that eases passage of stool through rectum (mineral oil, glycerin)

Antidiarrheal Agents
The most effecctive antidiarrheal drugs are Opioid

and derivatives opioid Prototype : Diphenoxylate, loperamide Diphenoxylate is formulated with antimuscarinic alkaloids (eg;atropin) to reduce the likelihood of abuse

Drugs that Inhibit the Formation of Gallstone

Prototype : chenodiol, ursodiol

Mechanism : chenodiol reduce the secretion of

bile acid by the liver

Drugs Used in Inflammatory Bowel Disease

5-aminosalicylates Prototype : sulfasalazine, balsalazine, mesalamine, olsalamine Mechanism : they release 5-aminosalicylate acid (5-ASA) in the large intestine, which inhibits the synthesis of prostaglandine & inflammatory leukotrients Corticosteroids Effect : anti inflammatory

Immunosuppressive agents Prototype : 6-mercaptopurine, azathioprine, methotrexate & cyclosporine They are an antimetabolite immunosuppressive They are the second line agents in the treatment of severe IBD or patient with steroid-resistent or dependent Tox : bone marrow suppression Immunosuppressive Response Modifire Prototype : infliximab Mechanism : infliximab is a immunoglobulin that binds to TNF and neutralizes its activity (TNF, a product of monocyte, macrophage & T-cells, is though to be a critical cytokine in the pathogenesis of inflammation

Supportive Therapy Analgesics, anticholinergic and antidiarrheal agents reducing patients symptoms and improving quality of life Oral iron, folate, vitamin B12