GI Drugs

GI Drugs

1. GERD & Peptic Ulcer Disease

   • Inhibit gastric acid secretion
     • proton pump inhibitors
       • Benzamidazole compounds that irreversibly inhibit H/K-ATPase
         • bind to sulfhydrl group on H/K-ATPase
       • Pro-drug; inactive @ neutral pH; require acid for activation
         • enteric coating dissolves at alkaline pH; absorbed in intestine --> circulation carries to parietal cells
       • -prazole
         • side effects include GI, CNS, skin rashes, diarrhea w/ prolonged use d/t bacterial overgrowth
       • most effective drug for suppressing gastric acid secretion
         • single dose daily
         • effects last after stopping drug; require synthesis of new proton pumps
       • doesn't affect pepsin secretion or gastric motility
     • H2 Antagonists
       • -tidine
         • potency varies famotidine > nizatidine = ranitidine > cimetidine
       • all OTC preparations now
         • inhibit secretion for < 6 h
           • or ~ 60-70% of 24h total secretion
           • block H2 receptors, reducing gastric acid & pepsin secretion
       • useful at night when vagal drive is higher
         • once daily; can fail in elderly & smokers
       • DON'T use w/ PPIs
       • SE: diarrhea, headache,fatigue, myalgias, constipation, bradycardia
         • 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
   • Neutralize gastric acid
     • antacids
       • weak bases that neutralize gastric HCl to form salt & water
       • reduce gastric acidity & inactivate pepsin
         • can interfere w/ absorption of other drugs
         • rapid action but can lead to acid oversecretion
       • may also provide mucosal protection by stimulating PG synthesis
       • aluminum hydroxide, calcium carbonate, combination aluminum hydroxide & magnesium hydroxide
         • SE: magnesium --> diarrhea; aluminum --> constipation
           • In renal pts., cation absorption & systemic alkalosis
       • single dose 1 h after eating neutralizes for 2 h; 2nd dose extend to 4 h
         • generally weak; not recommended for PUD
           • commonly used for esophagitis, GERD, some peptic ulcer
   • Form acid barrier in necrotic tissue
     • mucosal protective agents
       • limit exposure to acid & pepsin
       • sucralfate
         • binds selectively to necrotic ulcer & acts as barrier
           • viscous, sticky gel adheres to epithelial cells
           • SE: constipation
           • can use for duodenal ulcers
         • need acidic pH to activate
       • misoprostol
         • binds to PG receptors on parietal cells to inhibit acid secretion
           • used to prevent NSAID-induced ulcers
         • SE: diarrhea & abdominal pain
           • !! can cause abortion via stimulation of uterine contractions
       • bismuth subsalicylate
         • protective coat of entire GI tract
           • darkens tongue & stools
         • abx against H. pylori
   • Eradicate H. pylori
     • Antimicrobial drugs
       • use triple or quadruple therapy
         • 10-14 d of clarithromycin, amoxicillin, & PPI
           • metronidazole if allergic to penicillin

2. Motility Disorders

   • Constipation
     • Osmotically Active Laxatives
       • Saline Laxatives
         • nonabsorbable salts w/ Mg cations or phosphate anions
         • draw water into intestinal lumen --> distended intestines --> stimulation of peristalsis
         • very bitter; mix them
         • Avoid if renal insuff., heart dz, electrolyte imbalance, or diuretics
         • magnesium citrate sodium phosphate
       • Non-digestable sugars & alcohols
         • glycerin
           • alcohol that lubricates
           • hygroscopic agent --> water retention --> peristalsis
         • lactulose, sorbitol, & mannitol
           • non-absorbable sugars
             • hydrolyzed to organic acids --> acidification of luminal contents --> draw water in --> colonic propulsive motility
       • polyethylene glycol (PEG) - electrolyte solutions
         • poor absorption --> retention of water
         • mixtures of sodium sulfate, sodium bicarb, sodium chloride, potassium chloride
         • typical for colonoscopy
     • Stimulant/Irritant Laxatives
       • Act directly on enterocytes, enteric neurons & muscle
         • Induce low-grade inflammation --> accumulation of water & electrolytes --> increased intestinal motility
       • diphenylmethane derivatives
         • bisacodyl
           • tablet @ bedtime, bowel movement in morning
           • don't chew/crush; avoid stomach activation
         • phenolphtalein
           • carcinogen; no longer used
       • anthraquinones
         • 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
         • ricinoleic acid (castor oil)
           • local irritant that increases intestinal secretion & motility
           • unpleasant taste & toxic potential
     • bulk-forming laxatives
       • supplements that add bulk & hold water to expant intestinal contents
       • require adequate hydration, otherwise brick gets bigger
       • methylcellulose, lactulose & polycarbophil
     • stool softeners
       • facilitate expulsion
       • mineral oil & glycerin given orally or rectally
       • docusate sodium given in hospitalized to prevent straining
   • Diarrhea
     • Mu agonists
       • loperamide
         • 40-50x more effective than morhpine
         • relief of acute, non-specific diarrhea (traveler's diarrhea too)
         • more effective than diphenoxylate
         • does not cross BBB
       • difenoxin & dephenoxylate
       • inhibit ACh release --> decreases motility (peristalsis)
       • specific for intestinal opioid receptors
     • kaolin/pectin
       • kaolin (clay) absorbs compounds & presumably binds toxins
       • pectin increases viscosity
     • bismuth subsalicylate
       • inhibits intestinal secretions
       • manage infectious diarrhea
     • somatostatin/octreotide
       • inhibits secretion of gastrin, CCK, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, and 5-HT
         • slows GI motility & inhibits GB contraction
         • reduces portal & splanchnic blood floow
         • BIG GUN! Not used in outpt.
       • reduces intestinal fluid & pancreatic secretion
   • Nausea & Vomiting
     • Histamine H1 Antagonists
       • 1st gen H1 blockers
         • sedation & anti-muscarinic
         • prevent motion sickness
       • dimenhydrinate, diphenhydramine, cyclizine, meclizine
     • dopamine D2 antagonists
       • metoclopramide
       • trimethobenzamide
     • 5-HT3 antagonists
       • odansetron, granisetron, dolasetron
       • serotonin antagonists
       • used in cancer chemo pts
     • NK-1 antagonists
       • aprepitant, fosaprepitant, rolapitant
       • substance P also used in cancer
     • phenothiazines
       • chlorpromazine, prochlorperazine
     • benzodiazepenes
       • lorazepam, alprazolam
         • anxiety
     • marijuana derivatives
       • THC or dronabinol
       • PPx during chemo
       • AE: increased central sympathomimetic activity: mood changes, laughing, paranoia, thinking abnorm