Gastrointestinal Flashcards
H2 Blockers
cimetidine, ranitidine, famotidine (most potent), nizatidine (greatest bioavailability)
MECHANISM: Reversible block of histamine H2 receptors –> Dec. H+ secretion by parietal cells
CLINICAL USE: Peptic ulcer, gastritis, mild esophageal reflux - effect most pronounced on nocturnal acid secretion
TOXICITY: Cimetidine is potent inhibitor of cyt P-450 (multiple drug interactions); it also has antiandrogenic effects (prolactin release, gynecomastia, impotence, dec libido in males); can cross blood-brain barrier (confusion, dizziness, headaches) and placenta. Both cimetidine and ranitidine dec renal excretion of creatinine. Other H2 blockers are relatively free of these effects.
Take H2 blockers before you dine. Think “table for 2” to remember H2.
Proton Pump Inhibitors
Omeprazole, lansoprazole, esomeprazole, dexlansoprazole
MECHANISM: Prodrugs activated by protonation in secretory canaliculus of parietal cell –> traps PPI inside cell
CLINICAL USE: Peptic ulcer, gastritis, 1st line for esophageal reflux, Zollinger-Ellison syndrome
TOXICITY: Increased risk of C. difficile infection (dec gastric acid barier) , pneumonia,hip fractures, dec serum Mg2+ with long-term use.
Bismuth
bismuth
MECHANISM: Bind to ulcer base, providing physical protection (“band-aid” for ulcers) an dallowing HCO3- secretion to reestablish pH gradient in the mucous layer.
CLINICAL USE: inc ulcer healing, traveler’s diarrhea
bismuth - has antimicrobial activity against H. pylori and binds enterotoxins
sucralfate
sucralfate
MECHANISM: Bind to ulcer base, providing physical protection (“band-aid” for ulcers) an dallowing HCO3- secretion to reestablish pH gradient in the mucous layer.
CLINICAL USE: inc ulcer healing, traveler’s diarrhea
sucralfate is activated by H+ - do not take H2 blocker/PPI concurrently
Misoprostol
Misoprostol
MECHANISM: A PGE1 analog. Inc production and secretion of gastric mucous barrier. Dec acid production.
CLNIICAL USE: Prevention of NSAID-induced peptic ulcers; maintenance of a patent ductus arteriosus. Also used to induce labor (ripens cervix)
TOXICITY: Diarrhea. Contraindicated in women of childbearing potential (abortifacient)
Triple therapy for H. Pylori ulcer
- PPI BID
- Clarithromycin 500 mg
- Amoxicillin 1g qd or metronidazole 500 mg bid
Octreotide
Octreotide
MECHANISM: Long-acting somatostatin analog. Acts on ECL cell –> dec Histamine release
CLINICAL USE: Acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors, dec secretory diarrhea
TOXICITY: Nausea, cramps, steatorrhea
Antacid use
Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric urinary pH or by delaying gastric emptying.
All can cause hypokalemia.
Overuse can also cause problems.
Antacid use may heal duodenal ulcers, but gastric ulcer healing not demonstrated.
Antacids with alginic acid reduces sx of GERD without bloating –> but does not affect natural Hx of disease.
Aluminum Hydroxide - Side effects
Aluminum Hydroxide (Antacid)
SIDE EFFECTS (overuse) - Constipatoin and hypophosphatemia; proximal muscle weakness, osteodystrophy, seizures
“Alu’minimum’ amount of feces”
Magnesium hydroxide - side effects
Antacid
SIDE EFFECTS (overuse): Diarrhea (Mg2+ cmpds are laxatives), hyporeflexia, hypotension, cardiac arrest
Mg = Must go to the bathroom
Calcium carbonate - Side effects
**Calcium Carbonate **
SIDE EFFECTS (overuse) hypercalcemia, rebound acid inc
Can chelate and dec effectiveness of other drugs (e.g. tetracycline)
Adsorbents
kaolin-pectin, altapulgite
MECHANISM: Absorb GI Fluids, toxins, nutrients to make stools less watery (antidiarrheal)
Osmotic laxatives
Magnesium hydroxide (for constipative IBS), magnesium citrate, polyethylene glycol, lactulose, sorbitol
MECHANISM: Provide osmotic load to draw water out. Lactulose also treats hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion as NH4+, which can’t be absorbed, only NH3+ can.
CLINICAL USE: Constipation.
TOXICITY: Diarrhea, dehydration; may be abused by bulimics.
Infliximab
Infliximab, adalimumab, certolizumab
-mab = monoclonal Ab
MECHANISM: Monoclonal antibody to TNF-alpha.
CLINICAL USE: Moderate/severe Crohn’s disease, ulcerative colitis, rheumatoid arthritis
TOXICITY: Infection due to suppression of Th1 cells (including reactivation of latent TB from breakdown of the granulomas), fever, hypotension.
Sulfasalazine
Sulfasalazine
“-sala-“
MECHANISM: A combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory). [OTHER 5-ASA DRUGS INCLUDE: mesalamine, osalazine, balsalazide. Activated by colonic bacteria.
CLINICAL USE: mild/moderate Ulcerative colitis, Crohn’s disease
TOXICITY: Malaise, nausea, sulfonamide toxicity, reversible oligospermia
Ondansetron
Ondansetron
All 5-HT3 antagonists are “-setrons” (Granisetron, dolasetron, palonosetron, alosetron (for severe IBS w/diarrhea)
MECHANISM: 5HT3 antagonist. Powerfulcentral-acting antiemetic. Also acts peripherally at presynaptic terminals of vagal afferents in GI tract.
CLINICAL USE: Control vomiting postoperatively and in patients undergoing cancer chemotherapy.
TOXICITY: Headache, constipation
- enhanced in combination with corticosteroid and NK1 receptor antagonist (aprepitant)
Metoclopramide
Metoclopramide (Prokinetic agent); Lubiprostone (for chronic idiopathic constipation) –> PGE1 derivative activates type 2 chloride channel –> Chloride-rich fluid softens stool and increases motility.
MECHANISM: D2 receptor antagonist. Inc resting tone, contractility, LES tone, motility. Does not influence colon transport time. Increases esophageal clearance, inc gastric emptying. “Prokinetic agent.”
CLINICAL USE: Diabetic and post-surgery gastroparesis, antiemetic
TOXICITY: Extrapyrimidal symptoms (Parkinsonian effects) Restlessness, drowsiness, fatigue, depression, nausea, diarrhea. Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel obstruction or Parkinson’s disease.
Orlistat
Orlistat
MECHANISM: Inhibits gastric and pancreatic lipase –> dec breakdown and absorption of dietary fats
CLINICAL USE: Weight loss
TOXICITY: Steatorrhea, dec absorption of fat-soluble vitamins
Antidiarrheal agents
Diphenoxylate, loperamide
Opioid agonists inhibit ACh release by binding presynaptic opioid receptors in enteric nervous system (ENS)
- Diphenoxylate has CNS effects, addictive (combined with atropine to dec abuse)
- Loperamide (“slow”peramide) does not cross the BBB, is non-addictive
Glucocorticoids for IBD
**prednisone, prednisolone, hydrocortisone (enema), budesonide **(controlled release oral formulation)
- For mild/moderate class IBD
Inti-Integrins for IBD
natalizumab
Antibody against integrin alpha4-subunit, blocks leukocyte transmigration
- mod/severe Crohn’s in patients with OUT polyoma virus!
Antimetabolites for IBD
- *Azothioprine, 6-mercaptopurine (6-MP) **
- purine antimetabolites with immunosuppressive effects
- moderate IBD, induction/maintenance of remission
Methotrexate maintains remission in Crohns, but efficacy in UC is uncertain
H1 blockers
diphenhydramine, dimenhydrinate, meclizine
prevents motion sickness, meclizine is less sedating
Neurokinin (NK) Receptor antagonists
Aprepitant, fosaprepitant
Block NK1-R
- used with 5HT-3 antagonists and corticosteroids to prevent acute and delayed nausea/vomiting from chemotherapy
