GI Drugs

GI Drugs

GERD & Peptic Ulcer Disease
1. Inhibit gastric acid secretion
  1. proton pump inhibitors
    1. Benzamidazole compounds that irreversibly inhibit H/K-ATPase
      1. bind to sulfhydrl group on H/K-ATPase
    2. Pro-drug; inactive @ neutral pH; require acid for activation
      1. enteric coating dissolves at alkaline pH; absorbed in intestine --> circulation carries to parietal cells
    3. -prazole
      1. side effects include GI, CNS, skin rashes, diarrhea w/ prolonged use d/t bacterial overgrowth
    4. most effective drug for suppressing gastric acid secretion
      1. single dose daily
      2. effects last after stopping drug; require synthesis of new proton pumps
    5. doesn't affect pepsin secretion or gastric motility
  2. H2 Antagonists
    1. -tidine
      1. potency varies famotidine > nizatidine = ranitidine > cimetidine
    2. all OTC preparations now
      1. inhibit secretion for < 6 h
        or ~ 60-70% of 24h total secretion
        block H2 receptors, reducing gastric acid & pepsin secretion
    3. useful at night when vagal drive is higher
      1. once daily; can fail in elderly & smokers
    4. DON'T use w/ PPIs
    5. SE: diarrhea, headache,fatigue, myalgias, constipation, bradycardia
      1. If IV: confusion, hallucinations & agitation in those w/ renal or hepatic dysfunction
        Cimetidine only: gynecomastia or impotence; galactorrhea d/t inhibition of DHT binding to androgen receptors; also interferes w/ P450
2. Neutralize gastric acid
  1. antacids
    1. weak bases that neutralize gastric HCl to form salt & water
    2. reduce gastric acidity & inactivate pepsin
      1. can interfere w/ absorption of other drugs
      2. rapid action but can lead to acid oversecretion
    3. may also provide mucosal protection by stimulating PG synthesis
    4. aluminum hydroxide, calcium carbonate, combination aluminum hydroxide & magnesium hydroxide
      1. SE: magnesium --> diarrhea; aluminum --> constipation
        In renal pts., cation absorption & systemic alkalosis
    5. single dose 1 h after eating neutralizes for 2 h; 2nd dose extend to 4 h
      1. generally weak; not recommended for PUD
        commonly used for esophagitis, GERD, some peptic ulcer
3. Form acid barrier in necrotic tissue
  1. mucosal protective agents
    1. limit exposure to acid & pepsin
    2. sucralfate
      1. binds selectively to necrotic ulcer & acts as barrier
        viscous, sticky gel adheres to epithelial cells
        SE: constipation
        can use for duodenal ulcers
      2. need acidic pH to activate
    3. misoprostol
      1. binds to PG receptors on parietal cells to inhibit acid secretion
        used to prevent NSAID-induced ulcers
      2. SE: diarrhea & abdominal pain
        !! can cause abortion via stimulation of uterine contractions
    4. bismuth subsalicylate
      1. protective coat of entire GI tract
        darkens tongue & stools
      2. abx against H. pylori
4. Eradicate H. pylori
  1. Antimicrobial drugs
    1. use triple or quadruple therapy
      1. 10-14 d of clarithromycin, amoxicillin, & PPI
        metronidazole if allergic to penicillin
Motility Disorders
1. Constipation
  1. Osmotically Active Laxatives
    1. Saline Laxatives
      1. nonabsorbable salts w/ Mg cations or phosphate anions
      2. draw water into intestinal lumen --> distended intestines --> stimulation of peristalsis
      3. very bitter; mix them
      4. Avoid if renal insuff., heart dz, electrolyte imbalance, or diuretics
      5. magnesium citrate sodium phosphate
    2. Non-digestable sugars & alcohols
      1. glycerin
        alcohol that lubricates
        hygroscopic agent --> water retention --> peristalsis
      2. lactulose, sorbitol, & mannitol
        non-absorbable sugars
        hydrolyzed to organic acids --> acidification of luminal contents --> draw water in --> colonic propulsive motility
    3. polyethylene glycol (PEG) - electrolyte solutions
      1. poor absorption --> retention of water
      2. mixtures of sodium sulfate, sodium bicarb, sodium chloride, potassium chloride
      3. typical for colonoscopy
  2. Stimulant/Irritant Laxatives
    1. Act directly on enterocytes, enteric neurons & muscle
      1. Induce low-grade inflammation --> accumulation of water & electrolytes --> increased intestinal motility
    2. diphenylmethane derivatives
      1. bisacodyl
        tablet @ bedtime, bowel movement in morning
        don't chew/crush; avoid stomach activation
      2. phenolphtalein
        carcinogen; no longer used
    3. anthraquinones
      1. aloe, cascara sagrada, senna
        poor absorption in SI
        activated in colon; BM in 6-12 h
        long-term use --> pigmentation of colonic mucosa & cathartic colon
      2. ricinoleic acid (castor oil)
        local irritant that increases intestinal secretion & motility
        unpleasant taste & toxic potential
  3. bulk-forming laxatives
    1. supplements that add bulk & hold water to expant intestinal contents
    2. require adequate hydration, otherwise brick gets bigger
    3. methylcellulose, lactulose & polycarbophil
  4. stool softeners
    1. facilitate expulsion
    2. mineral oil & glycerin given orally or rectally
    3. docusate sodium given in hospitalized to prevent straining
2. Diarrhea
  1. Mu agonists
    1. loperamide
      1. 40-50x more effective than morhpine
      2. relief of acute, non-specific diarrhea (traveler's diarrhea too)
      3. more effective than diphenoxylate
      4. does not cross BBB
    2. difenoxin & dephenoxylate
    3. inhibit ACh release --> decreases motility (peristalsis)
    4. specific for intestinal opioid receptors
  2. kaolin/pectin
    1. kaolin (clay) absorbs compounds & presumably binds toxins
    2. pectin increases viscosity
  3. bismuth subsalicylate
    1. inhibits intestinal secretions
    2. manage infectious diarrhea
  4. somatostatin/octreotide
    1. inhibits secretion of gastrin, CCK, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, and 5-HT
      1. slows GI motility & inhibits GB contraction
      2. reduces portal & splanchnic blood floow
      3. BIG GUN! Not used in outpt.
    2. reduces intestinal fluid & pancreatic secretion
3. Nausea & Vomiting
  1. Histamine H1 Antagonists
    1. 1st gen H1 blockers
      1. sedation & anti-muscarinic
      2. prevent motion sickness
    2. dimenhydrinate, diphenhydramine, cyclizine, meclizine
  2. dopamine D2 antagonists
    1. metoclopramide
    2. trimethobenzamide
  3. 5-HT3 antagonists
    1. odansetron, granisetron, dolasetron
    2. serotonin antagonists
    3. used in cancer chemo pts
  4. NK-1 antagonists
    1. aprepitant, fosaprepitant, rolapitant
    2. substance P also used in cancer
  5. phenothiazines
    1. chlorpromazine, prochlorperazine
  6. benzodiazepenes
    1. lorazepam, alprazolam
      1. anxiety
  7. marijuana derivatives
    1. THC or dronabinol
    2. PPx during chemo
    3. AE: increased central sympathomimetic activity: mood changes, laughing, paranoia, thinking abnorm

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	Created by Amanda Curl almost 7 years ago