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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
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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
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H2 receptor stimulation causes...
Increased HCl production from parietal cell
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Where are H2 receptors found in stomach?
parietal cell
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H2 receptor antagonist causes
decrease in HCl production
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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
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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
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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
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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
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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
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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
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Sucralfate
- mucousal protective agent, give prophylactically with NSAIDs or glucocorticoids
- GIVE 1-2 H AFTER OTHER PO DRUGS
- 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
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pantoprazole
- IV proton pump inhibitor, faster effect
- dilute, give over 20 minutes
- human
-
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
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triple therapy for Helicobacter pylori
- amoxicillin, metronidazole, acid decreaser (H2 antagonist, *omeprazole inhibits)
- Can use clithromycin (sp) instead of amoxicillin
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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)
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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
-
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)
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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
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receptors in emetic center
- a2 adrenergic (esp in cats)
- serotonin 5-HT1A
- Neurokinin-1
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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
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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
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Apomorphine
- stimulates D receptors in CTZ, no good in cats
- Can cause protracted vomiting, excitement/sedation, OD=cardio/resp depression (naloxone reversal)
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alpha2-adrenergic agonists
- xylazine, dexmedetomidine, causes vomiting in 90% of cats
- lower doses for emesis than tranquilization
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Home emetic remedies
- 3% hydrogen peroxide (esophagitis, gastritis, DEATH IN CATS)
- table salt (salt toxicosis, seizures).
- ipecac
- None safe for cats
-
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.
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Prochlorperazine
- antiemetic, phenothiazine derivative
- antagonizes dopamine at CTZ
- mild histamine antagonist
- high doses block a2 at emetic center
- tranquilizer effect
- contra in seizure Hx
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Dimenhydrinate (antiemetic)
- H1 antagonist.
- block input form vestibular apparatus to CTZ, control vomiting due to motions sickness/inner ear
- sedative-hypnotic
- anticholinergic
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Odansetron
- antiemetic, 5-HT3 receptor antagonist
- block seratonin at CTZ and vagal afferents in intestine
- usually treats for chemo in cancer
-
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
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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
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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
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loperamide
- immodium, opioid.
- interacts with mu receptors in enteric NS, decreases ACh release, inhibit peristalsis, increase transit time.
- controversial in cats, watch for MDR1
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paregoric
- opioid. interacts with mu receptors in enteric NS, decreases ACh release, inhibit peristalsis, increase transit time.
- controversial in cats, watch for MDR1
-
laxative
- increases bulk of intestines to strech mucosa and stimulate peristalsis.
- increase fluid volume for same reason.
- Cause flatulance, cramping, diarrhea
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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)
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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)
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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
-
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
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antihelmintic
drugs used to eliminate helminth parasites from a host. (cestodes, nematodes, trematodes)
-
Fenbendazole
- benzoimidazoles
- microtubules
- broad spectrum for round, hook, whip, tape, lung, strongyles, pinworm, giardia, ovicidal
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albendazole
- benzoimidazoles
- microtubules
- broad spectrum for round, hook, whip, tape, lung, strongyles, pinworm, giardia, ovicidal
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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)
-
pyrantel
- tetrahydropyrimidine
- nicotinic receptor agonist, like organophosphate.
- Round, hook. strongyles, pinworm.
- cats and kittens okay
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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
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drontal plus
- praziquantel, pyrantel, febentel
- Broad spectrum
- tape, hook, round, whip
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heartgard plus
- ivermectin and pyrantel
- heart, round, hook
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milbemycin
- related ot avermectins, but not one.
- heartworm, round, hook, whip
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