gi drugs phc 5409b dr. t.c. peterson. drugs for gi tract disorders drugs that reduce gastric...
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GI DrugsGI Drugs
PHC 5409BPHC 5409B
Dr. T.C. PetersonDr. T.C. Peterson
Drugs for GI Tract disordersDrugs for GI Tract disorders
DRUGS THAT REDUCE GASTRIC ACIDITYDRUGS THAT REDUCE GASTRIC ACIDITY CYTOPROTECTIVE DRUGS CYTOPROTECTIVE DRUGS DRUGS FOR DRUGS FOR HELICOBACTER PYLORI HELICOBACTER PYLORI INFECTIONINFECTION DRUGS FOR INFLAMMATORY BOWEL DISEASES DRUGS FOR INFLAMMATORY BOWEL DISEASES PROKINETIC DRUGS PROKINETIC DRUGS LAXATIVES LAXATIVES ANTIDIARRHEAL AGENTS ANTIDIARRHEAL AGENTS ANTIEMETICSANTIEMETICS
Peptic Ulcer diseasePeptic Ulcer disease
Characterized by inflamed lesions and Characterized by inflamed lesions and ulcersulcers
Causes: Causes: Excessive acid productionExcessive acid production Bile acid refluxBile acid reflux Advancing ageAdvancing age IschemiaIschemia Inhibition of PG synthesisInhibition of PG synthesis Infection with Helicobacter pyloriInfection with Helicobacter pylori
Drugs that reduce gastric acidityDrugs that reduce gastric acidity
H2 receptor antagonistsH2 receptor antagonists Proton pump inhibitorsProton pump inhibitors Muscarinic antagonistsMuscarinic antagonists ProstaglandinsProstaglandins AntacidsAntacids SucralfateSucralfate
Cytoprotective DrugsCytoprotective Drugs
SucralfateSucralfate
MisoprostolMisoprostol
Drugs for H.pylori infectionDrugs for H.pylori infection
Multi-drug therapy is usually usedMulti-drug therapy is usually used Common combination:Common combination:
Gastric acid secretion inhibitor Gastric acid secretion inhibitor
(PPI or H2 blocker) (PPI or H2 blocker)
and two of the following:and two of the following:
Amoxicillin, Bismuth, Clarithromycin, Amoxicillin, Bismuth, Clarithromycin, Metronidazole, TetracyclineMetronidazole, Tetracycline
Inflammatory Bowel DiseaseInflammatory Bowel Disease
Chronic Inflammatory disease:Chronic Inflammatory disease: Crohn's Disease (CD) - full thickness - full thickness
inflammation anywhere in gastrointestinal tract inflammation anywhere in gastrointestinal tract Ulcerative Colitis (UC) - inflammation of superficial - inflammation of superficial
layers, continuous from rectum layers, continuous from rectum Lymphocytic Colitis - collections of lymphocytes Lymphocytic Colitis - collections of lymphocytes
without granulomas without granulomas Collagenous Colitis - collagenous deposition in Collagenous Colitis - collagenous deposition in
subepithelial zone, rectum and colon subepithelial zone, rectum and colon Diagnosis is clinical but requires tissue biopsy for Diagnosis is clinical but requires tissue biopsy for
confirmation and classification confirmation and classification
IBD - Treatment IBD - Treatment
Acute Moderate to Severe ExacerbationAcute Moderate to Severe Exacerbation - Usually in - Usually in patients with known disease, now active patients with known disease, now active – Glucocorticoids Glucocorticoids – Broad spectrum antibioticsBroad spectrum antibiotics (including metronidazole) (including metronidazole) – Intravenous cyclosporineIntravenous cyclosporine may be used after 7-10 may be used after 7-10
days if responses are poor days if responses are poor
Chronic Therapy (Remission Maintenance) Chronic Therapy (Remission Maintenance) – 5-aminosalicylate (5-ASA)5-aminosalicylate (5-ASA)– Azathioprine, 6-mercaptopurine (6-MP) and Azathioprine, 6-mercaptopurine (6-MP) and
methotrexatemethotrexate
IBD drugsIBD drugs
SulfasalazineSulfasalazine– First line therapy in most patients with acute or chronic IBD First line therapy in most patients with acute or chronic IBD – Congener of sulfapyridine and 5-aminosalicylic acid linked by an Congener of sulfapyridine and 5-aminosalicylic acid linked by an
azo bond azo bond – Attenuates inflammation in the large bowel only Attenuates inflammation in the large bowel only – Compound is cleaved to composite groups by colonic bacteria Compound is cleaved to composite groups by colonic bacteria
(azoreductase) (azoreductase) – Requires 5-28 days for efficacy Requires 5-28 days for efficacy – Contradindicated in patients with sulfa allergy; 15% of patients Contradindicated in patients with sulfa allergy; 15% of patients
will discontinue drug will discontinue drug – Side effects: cytopenias, pancreatitis, hepatitis, rash, diarrhea, Side effects: cytopenias, pancreatitis, hepatitis, rash, diarrhea,
male infertility male infertility
IBD drugsIBD drugs
OlsalazineOlsalazine– Dimer of 5-ASA linked by azo bond which is split by Dimer of 5-ASA linked by azo bond which is split by
colonic bacteria colonic bacteria – Contraindicated in patients with salicylate allergy; no Contraindicated in patients with salicylate allergy; no
sulfa moiety sulfa moiety – Main side effect is diarrhea (~25% of patients) Main side effect is diarrhea (~25% of patients) – Main use is in patients who cannot tolerate Main use is in patients who cannot tolerate
sulfasalazine sulfasalazine
Appears to be as effective as sulfasalazine for Appears to be as effective as sulfasalazine for mild to moderate IBD mild to moderate IBD
IBD drugsIBD drugs
MesalamineMesalamine
– Delayed release 5-ASA (ie. coated with acrylic-based Delayed release 5-ASA (ie. coated with acrylic-based resin) dissolves at pH 6 resin) dissolves at pH 6
– Mainly released in distal ileum and colon; Mainly released in distal ileum and colon;
IBD drugsIBD drugs
AzathioprineAzathioprine– Side Effects: Pancreatitis (~5%), Bone marrow Side Effects: Pancreatitis (~5%), Bone marrow
suppression (~2%), hepatitis suppression (~2%), hepatitis – Mildly effective as single agent, does prevent Mildly effective as single agent, does prevent
flares of disease and maintain remissions flares of disease and maintain remissions – Usually permits reduction in glucocorticoid Usually permits reduction in glucocorticoid
dose required for suppression of disease dose required for suppression of disease – Note: this drug is metabolized to 6-MP Note: this drug is metabolized to 6-MP
IBD drugsIBD drugs
6-Mercaptopurine (6-MP)6-Mercaptopurine (6-MP) – Effective in prevention of relapses and possibly in Effective in prevention of relapses and possibly in
active disease active disease – Most patients require >17 weeks to see initial effect Most patients require >17 weeks to see initial effect – 6-MP and AZA are effective in 50-70% of patients with 6-MP and AZA are effective in 50-70% of patients with
IBD IBD – Side effects include bone marrow suppression and Side effects include bone marrow suppression and
pancreatitis, hepatitis pancreatitis, hepatitis
IBD drugsIBD drugs
MethotrexateMethotrexate – 20-25mg/week given i.m. in refractory Crohn's disease 20-25mg/week given i.m. in refractory Crohn's disease
disease disease – Extremely well tolerated Extremely well tolerated – Allowing lowering of steroid doses and control of Allowing lowering of steroid doses and control of
disease disease – Recommended now in nearly all patients requiring Recommended now in nearly all patients requiring
higher dose prednisone higher dose prednisone
IBD drugIBD drug
CyclosporineCyclosporine – Good response initially to iv form, usually within 48 Good response initially to iv form, usually within 48
hours hours – Relapses common when drug is stopped Relapses common when drug is stopped – This agent shows most rapid onset of activity in This agent shows most rapid onset of activity in
steroid refractory disease steroid refractory disease – Reduces need for surgical resection in fulminant UC Reduces need for surgical resection in fulminant UC – Dose must be monitored closely Dose must be monitored closely
Novel Therapies for IBD Novel Therapies for IBD
Specific Cytokine Blockers Specific Cytokine Blockers – IL-1 receptor antagonist (IL-1RA) IL-1 receptor antagonist (IL-1RA) – TNFTNF blockers blockers
Other immunosuppressive agents may be effective Other immunosuppressive agents may be effective – Cyclosporine Cyclosporine – Rapamycin Rapamycin – FK506 and other immunosuppressives FK506 and other immunosuppressives
Fish Oil (EPA) Fish Oil (EPA) – May reduce production of inflammatory leukotrienes and May reduce production of inflammatory leukotrienes and
thromboxanes thromboxanes – Suppresses IL-1 and TNF production Suppresses IL-1 and TNF production – Reduced CD exacerbations at 1 year Reduced CD exacerbations at 1 year
IBD drugsIBD drugs
Tumor Necrosis Factor Alpha (TNFTumor Necrosis Factor Alpha (TNF) ) BlockadeBlockade
– Activity predicted on the basis of certain Activity predicted on the basis of certain animal models animal models
– Has good activity in Crohn's Disease, Has good activity in Crohn's Disease, including fistula healing including fistula healing
Prokinetic DrugsProkinetic Drugs
Drugs used to increase GI motilityDrugs used to increase GI motility Increase activity of smooth muscle in the Increase activity of smooth muscle in the
esophagus, stomach and intestineesophagus, stomach and intestine examples:examples:
– Cisapride: stimulates 5-HT receptorsCisapride: stimulates 5-HT receptors– Metoclopramide: blocks dopamine D2 receptorsMetoclopramide: blocks dopamine D2 receptors
Antidiarrheal AgentsAntidiarrheal Agents
Bismuth subsalicylate, diphenoxylate, Bismuth subsalicylate, diphenoxylate, kaolin-pectin, loperamide, and polycarbophil kaolin-pectin, loperamide, and polycarbophil
Opioid DrugsOpioid Drugs
Antiemetic drugsAntiemetic drugs
Dopamine D2 receptor antagonistsDopamine D2 receptor antagonists
Serotonin 5HT3 receptor antagonistsSerotonin 5HT3 receptor antagonists
Other antiemetics Other antiemetics
• • Dimenhydrinate and scopolamine Dimenhydrinate and scopolamine
Review of drugs for GI DisordersReview of drugs for GI Disorders
DRUGS THAT REDUCE GASTRIC ACIDITY DRUGS THAT REDUCE GASTRIC ACIDITY
Histamine 2 receptor antagonists Histamine 2 receptor antagonists
• • Cimetidine, famotidine, and ranitidineCimetidine, famotidine, and ranitidine
Proton pump inhibitors Proton pump inhibitors
Lansoprazole and omeprazole Lansoprazole and omeprazole
Muscarinic receptor antagonists Muscarinic receptor antagonists
• • Atropine and pirenzepineAtropine and pirenzepine
Gastric antacids Gastric antacids
Aluminum and magnesium hydroxides and calcium Aluminum and magnesium hydroxides and calcium carbonate carbonate
Review of drugs for GI DisordersReview of drugs for GI Disorders
Cytoprotective drugsCytoprotective drugs
Misoprostol and sucralfateMisoprostol and sucralfate
Drugs for Drugs for Helicobacter pylori infection Helicobacter pylori infection
• • Amoxicillin, bismuth, clarithromycin, metronidazole, and Amoxicillin, bismuth, clarithromycin, metronidazole, and tetracyclinetetracycline
DRUGS FOR INFLAMMATORY BOWEL DISEASES DRUGS FOR INFLAMMATORY BOWEL DISEASES
• • .Azathioprine, infliximab, mercaptopurine, mesalamine, .Azathioprine, infliximab, mercaptopurine, mesalamine, metronidazole, prednisolone, and sulfasalazine metronidazole, prednisolone, and sulfasalazine
Review of drugs for GI DisordersReview of drugs for GI Disorders
PROKINETIC DRUGSPROKINETIC DRUGS
• • Cisapride and metoclopramide Cisapride and metoclopramide ANTIDIARRHEAL AGENTS ANTIDIARRHEAL AGENTS
• • Bismuth subsalicylate, diphenoxylate, kaolin-pectin, Bismuth subsalicylate, diphenoxylate, kaolin-pectin, loperamide, and opiates loperamide, and opiates
ANTIEMETICSANTIEMETICS
Serotonin 5-HT3 receptor antagonists Serotonin 5-HT3 receptor antagonists
• • Granisetron and ondansetron Granisetron and ondansetron
Dopamine D2Dopamine D2 receptor antagonistsreceptor antagonists • • Metoclopramide Metoclopramide