1. strategies for treating GI ulcers (5)
    • decrease acid production: H2 antagonists, proton pump inhibitors
    • increase mucus production: PGE1 analog
    • Protect damaged areas from secreted acid: coating
    • neutralize secreted acid: antacids
    • antibacterial agenst to treat Helicobacter pylori: controversial
  2. 2 ways histamines are released in stomach with GI ulcer
    • histamine released from enterochromaffin-like cell in gastric epithelium
    • Histamine released from mast cells in submucosa of epithelial wall when touched by acid (ulcer removes protection
    • Binds to H2 receptor, activates proton pump, lowers pH of stomach
  3. H2 receptor stimulation causes...
    Increased HCl production from parietal cell
  4. Where are H2 receptors found in stomach?
    parietal cell
  5. H2 receptor antagonist causes
    decrease in HCl production
  6. H2 receptor antagonists (list 3)
    • Not antacids!
    • cimetidine (Tagamet): prototype. inhibits hepatic microsomal, slows biotransformation of other drugs.
    • famotidine (Pepcid): very little hepatic biotransformation
    • Ranitidine (Zantac): mild prokinetic effect
  7. cimetidine
    • H2 receptor antagonist prototype, used in gastric ulcers to decrease production of HCl. Not effective in NSAID or glucocorticoid ulcers.
    • *Significantly inhibits hepatic microsomal enzymes, slows biotransformation of other drugs.
    • Tagamet
    • Rapid IV causes histamine release, bradycardia, hypotension
  8. Famotidine
    • H2 receptor antagonist, used in gastric ulcers to decrease production of HCl. 
    • very little hepatic biotransformation
    • Pepcid
    • DILUTE IV, Rapid IV causes HISTAMINE release, bradycardia, hypotension
    • Cats: IV famotidine can cause hemolytic anemia, SLOW AND DILUTE
  9. Ranitidine
    • H2 receptor antagonist, used in gastric ulcers to decrease production of HCl. 
    • mild PROKINETIC effect (Ach)
    • Zantac
    • Rapid IV causes histamine release, bradycardia, hypotension
  10. Proton pump inhibitor
    • Omeprazole
    • Irreversibly inhibit H+, K+-ATPase, decrease production of HCl
    • After plasma drops, continue to have effects
    • Any dog undergoing gen anaesthesia get omeprazole night before and 4 hours after to prevent reflux
    • Unstable in acid, don't split enteric-coat
    • Inhibits P-450 (like cimetidine), drug interactions (slows biotransformation)
    • q24h, may take days for max effect
    • well tolerated, GI side effects like VD
  11. Misoprostol
    • Mucus producer (PGE1 analog)
    • increases mucus, high doses decrease gastric acid and gastrin production.
    • GI ulcers DUE TO NSAIDS, PREVENTION, not for steroids
    • diarrhea, not in pregnant or nursing
  12. Sucralfate
    • mucousal protective agent, give prophylactically with NSAIDs or glucocorticoids
    • binds to ulcerated tissue in esophagus, stomach, duodenum, forming protective barrier, inactivates pepsin who breaks down proteins, breaks down bile acids
    • stimulates synthesis of PGs and growth factors, protect gastric mucosa, promote healing
    • constipation
    • HAS ALUMINUM, can't give with antacids, tetracycline, floroquinolones
  13. pantoprazole
    • IV proton pump inhibitor, faster effect
    • dilute, give over 20 minutes
    • human
  14. antacids
    • aluminum hydroxide (bind phosphates in CRF, too)
    • calcium carbonate
    • Aluminum hydroxide with magnesium hydroxide (maalox/mylanta, mix constipation/diarrhea)
    • constipation, acid rebound.
    • not with sucralfate, tetracyclines or fluroquinolones
  15. triple therapy for Helicobacter pylori
    • amoxicillin, metronidazole, acid decreaser (H2 antagonist, *omeprazole inhibits)
    • Can use clithromycin (sp) instead of amoxicillin
  16. H pylori
    • helicobacter pylori, may or may not play a role in GI ulceration. 
    • Triple therapy to treat, amoxicillin, metronidazole, decrease acid (H2 antagonist or, better, proton pump inhibitor, *omeprazole)
  17. emesis
    • in nonruminant, forceful ejection of contents of stomach and proximal duodenum into mouth
    • Protective reflex that rids stomach and intestine of toxic substances
    • Horse, rabbit, mouse can't vomit
    • coordinated by emetic center in medulla
  18. emetic center
    • causes emesis reflex, in medulla near CTZ.  
    • Impulses from: CTZ, gut (duodenum esp), cerebral cortex (brain), vestibular apparatus in cat (in dog, vestibular apparatus goes to CTZ first)
  19. CTZ
    • chemotriggerzone, no BBB.  Toxins enter CSF and stimulate receptors in CTZ, sends to emetic center. 
    • Serotonin, dopamine (esp dogs), opioid, neurokinin-1 (substance P), histamine (not cats), muscarinic
  20. receptors in emetic center
    • a2 adrenergic (esp in cats)
    • serotonin 5-HT1A
    • Neurokinin-1
  21. sympathetic, somatic, parasympathetic, in emesis
    • parasympathetic: salivate to protect teeth, relax sphincters, retroperistalsis starting from mid small-intestine
    • somatic: abdominal contraction to send ingesta up
    • symp: sweating, HR increases
  22. emetic agents contraindications and limitations
    • give within 30 minutes (best), or 2-3 hours
    • remove 40-60%, toxins often already somewhat absorbed
    • don't use if ingested caustic, don't swallow normally, seizures, unconscious, shock, dyspneic, horse, rabbit, rodent
  23. Apomorphine
    • stimulates D receptors in CTZ, no good in cats
    • Can cause protracted vomiting, excitement/sedation, OD=cardio/resp depression (naloxone reversal)
  24. alpha2-adrenergic agonists
    • xylazine, dexmedetomidine, causes vomiting in 90% of cats
    • lower doses for emesis than tranquilization
  25. Home emetic remedies
    • 3% hydrogen peroxide (esophagitis, gastritis, DEATH IN CATS)
    • table salt (salt toxicosis, seizures).  
    • ipecac
    • None safe for cats
  26. activated charcoal
    • PO to absorb toxins, reduce absorption
    • Don't give other oral drugs for 3 hours !
    • not good at alcohols, caustic alkalis, nitrates, mineral acids, petroleum distillates
    • rapid causes emesis, constipation, diarrhea (black), stains.
  27. Prochlorperazine
    • antiemetic, phenothiazine derivative
    • antagonizes dopamine at CTZ
    • mild histamine antagonist
    • high doses block a2 at emetic center
    • tranquilizer effect
    • contra in seizure Hx
  28. Dimenhydrinate (antiemetic)
    • H1 antagonist. 
    • block input form vestibular apparatus to CTZ, control vomiting due to motions sickness/inner ear
    • sedative-hypnotic
    • anticholinergic
  29. Odansetron
    • antiemetic, 5-HT3 receptor antagonist
    • block seratonin at CTZ and vagal afferents in intestine
    • usually treats for chemo in cancer
  30. maropitant
    • antiemetic, cerenia.
    • neurokinin-1 receptor antagonist (emetic center, CTZ, peripherally through body)
    • IV and PO for acute vomiting, PO for motion sickness
    • 16 weeks at least
    • stinging, VDA
  31. metoclopramide
    • anti-emetic through prokinetic (motility-promoting) agents (Reglan)
    • antagonizes dopamine at CTZ and 5-HT3 at vagal afferents
    • best as CRI, not in obstruction or seizure
    • Prokinetic caused by ACH release (increased) from enteric neurons, increase force of contractions, promote emptying.
    • agitation and anxiety, restlessness, seizures
  32. cisapride
    • prokinetic (motility-promoting), for stomach, small intestine, colon.
    • Absorption varies.
    • gastroesophageal reflux, delayed emptying, small bowel motility disorders, chronic constipation, colonic ileus (postop)
    • removed from market in 2000 due to cardiac in humans.  Can be compounded
    • seratonin agonist 5HT4, antagonist 5HT3, both myenteric.  
    • Enhance Ach release in myenteric plexus
  33. loperamide
    • immodium, opioid. 
    • interacts with mu receptors in enteric NS, decreases ACh release, inhibit peristalsis, increase transit time.  
    • controversial in cats, watch for MDR1
  34. paregoric
    • opioid. interacts with mu receptors in enteric NS, decreases ACh release, inhibit peristalsis, increase transit time.
    • controversial in cats, watch for MDR1
  35. laxative
    • increases bulk of intestines to strech mucosa and stimulate peristalsis.  
    • increase fluid volume for same reason. 
    • Cause flatulance, cramping, diarrhea
  36. Bulk laxatives
    • fiber (cellulose derivatives or psyllium seeds, bran)
    • antidiarrheals to absorb water from intestinal contents
    • laxatives to increase bulk, stretch and stim peristalsis (give with water or constipation)
  37. Lactulose
    • osmotic laxative.  
    • disaccharide (galactose/fructose) mammals can't use. Break down by bacteria in colon, increase osmotic pressure, fluid comes into gut.
    • Also used to reduce blook NH3 in hepatic encephalopathy (acidification causes ion trapping)
    • heat or light may cause prob
    • flatulence, cramping, diarrhea (OD)
  38. lubricant laxative
    • mineral oil, petrolatum
    • decrease fluid absorption in gut, keep fluid in stool
    • careful with aspiration, may not swallow
    • decreased fat-soluble vitamins eventually
  39. docusate sodium (DSS)
    • decrease surface tension and allow more water into stool
    • DISRUPT EPITHELIUM OF INTESTINE, allows other things to be absorbed.  
    • Do not give with lubricant laxatives
  40. antihelmintic
    drugs used to eliminate helminth parasites from a host.  (cestodes, nematodes, trematodes)
  41. Fenbendazole
    • benzoimidazoles
    • microtubules
    • broad spectrum for round, hook, whip, tape, lung, strongyles, pinworm, giardia, ovicidal
  42. albendazole
    • benzoimidazoles
    • microtubules
    • broad spectrum for round, hook, whip, tape, lung, strongyles, pinworm, giardia, ovicidal
  43. tetrahydropyrimidine
    • nicotinic receptor agonist are 100x more potent than Ach (mimic organophosphates, but for bugs)
    • Pyrantel (round, hook, strongyles, pinworm, mature and immature, cats and kittens)
  44. pyrantel
    • tetrahydropyrimidine
    • nicotinic receptor agonist, like organophosphate.  
    • Round, hook. strongyles, pinworm.
    • cats and kittens okay
  45. Avermectins
    • binds and activates glutamate-gated chloride channels (neuromuscular paralysis/death), not in mammal cells, crosses BBB at high doses
    • Ivermectin, selamectin, moxidectin
    • round, strongyles, pinworm, hookworm, heartworm, ectoparasites
  46. drontal plus
    • praziquantel, pyrantel, febentel
    • Broad spectrum
    • tape, hook, round, whip
  47. heartgard plus
    • ivermectin and pyrantel
    • heart, round, hook
  48. milbemycin
    • related ot avermectins, but not one.  
    • heartworm, round, hook, whip
Card Set
GI agents in vet pharm tox