What is the pathogenesis of gastroduodenal ulcers?
Excess gastric acid secretion, breakdown of mucosal cytoprotection, Helicobacter pylori infection
What are the goals of ulcer treatment?
reduce ulcerogenic factors, enhance defensive factors, or eradicate any infectious causes
What are pro-ulcerogenic factors?
Acids (HCl, VFA, bile acids), pepsin, infections
What are antiulcerogenic factors?
mucosal cytoprotection, epithelial renewal, external protection
How does one increase the gastric pH to greater than 4 to promote healing?
H2-Histamine receptor blockade, stimulation of gastric PGE receptors, gastric H+-K+-ATPase inhibition (proton pump inhibitors)
Famotidine
H2-Histamine antagonist, decreases acid secretion which decreases pepsin. As treatment continues effectiveness decreases due to an increased secretion of gastrin. Low oral biovalibility and renal clearance
What are examples of H2-histamine antagonists?
famotidine, ranitidine, cimetidine
What are the side effects and indications of H2-histamine antagonist?
Renal disease patients need lower dose, treatment of ulcers due to gastritis, stress, NSAID terapies, gastrinomas
Misoprostil
PGE analogue, po administration, needs frequent administration due to rapid hepatic metabolism. Decreases acid secretion stimulated by histamine or gastrin. Less effective than H2-HR antagonists or PPI, increases gastric cytoprotection
How do PGE and PGI promote cytoprotection?
Mucus production (coats surface of the gastric mucosa), bicarb production (neutralizes HCl), intrinsic mucosal barrier (resist back-diffusion of acid), and gastric blood flow (flushes away acid, prevents buildup, maintains tissue pH in normal range)
Indications/side effects/contraindications of misoprostil?
NSAIDs-induced ulcers, increased mast cell influx. Side effects include diarrhea due to prokinetic action. Contraindications include IBD, pregnancy
What is an example of a proton pump inhibitor?
Omeprazole
What is the action of proton pump inhibitors?
Irreversibly inactivate H+/K+ ATPase, so effects extend longer than the drug’s presence in the body. Reduce acid secretions
Omeprazole
Proton pump inhibitor. Oral paste that is a weak base that decreases the release of HCl
Sucralfate
Binds to ulcerated tissue to form a seal after oral administration, heals existing ulcers not prevent new ones. Short duration of action. Binds and inactivates bile acids, increases local prostanoid formation.
Antacids
Either systemic or non-systemic, non-systemic only affects stomach. Maalox and Mylanta examples. Relieve clinical signs, no healing.
Na or Ca carbonate antacids onset
rapid
Mg salts (sulfate, hydroxide) onset
intermediate with laxative effect
all hydroxide antacids onset
slow
What is the best type of drug to use to treat an ulcer: PPIs, H2-histamine antagonists, or cytoprotectants?
PPIs
What are examples of locally-acting emetic agents?
warm water, sodium chloride, 3% hydrogen peroxide, syrup of ipecac (emetine akaloid substance)
Apomorphine
centrally acts on D2 dopamine receptors, produces vomiting in 2-10 minutes
Xylazine
simulates alpha2-adrenergic receptors to produce emesis in cats
Indications of anti-emetic drugs
motion sickness, uremia, liver disease, cancer chemo, parvo, trauma
Famotidine
H2-histamine antagonist that lessens irritating effects of acid on the stomach
muscarinic acetylcholine antagonist anti-emetic effects
decrease vagal afferent transmission to vomiting center to decrease vomiting
kaolin-pectin and other coating agents anti-emetic efficacy
not very effective
Metoclopramide
Simulate gastric motility, block CNS dopamine receptors and 5-HT3 receptors
Action of diphenhydramine, meclizine
may reduce motion sickness by blocking histamine and muscarinic cholinergic receptors
Ondanestron
blocks type three serotonin receptors on gastric vagal fibers and are effective at inhibiting emesis in dogs associated with chemo or parvo
Maropitant
Blocks type 1 neurokinin (substance P) receptors present in vomiting center, broad spectrum anti-emetic
What effect do mAChR antagonists have on the GI tract?
increased peristalsis
What affect do opiods have on the GI tract?
increased segmentation
What affect do opiod antagonists or mAChR antagonists have on the GI tract?
inhibit increased segmentation
Bethanechol
mAChR agonist that is a cholinomimetric that increases GI motility
Neostigmine
anticholinesterase drug that increases GI motility
Ranitidine and Nizatidine
weak cholinesterase inhibitors that can increase upper GI motility
Metoclopramide
Acts on upper GI tract to increase smooth muscle contractions, blocks D2 dopamine receptors and is an agonist at the 5-HT4 serotonin receptors
Cisapride
Partial agonist at 5-HT4 receptors, increase acetylcholine release from enteric neurons to stimulate motility, indicated by chronic constipation, ileus in dogs
Erythromycin
agonist at receptors in smooth muscle and gastroenteric nerves for motilin, stimulates motility of stomach and upper SI (not colon). Metabolized by CYP450 and eliminated in bile
Lidocaine
Blocks voltage-gated Na+ channels in enteric nerves, stimulates intestinal motility although mechanism unclear
What are contraindications of prokinetic drugs?
GI tract obstructions and post-surgical anastomoses
What are the major types of laxatives and cathartics?
Osmotic, bulk, lubricants/surfactants, and irritants
What are examples of osmotic laxatives?
Mannitol, sorbitol (draws water into intestinal tract)
What is an example of a irritant laxative?
Bisacodyl- stimulates enteric sensory nerves to increase intestinal motility and decrease water absorption
What is an example of a bulk laxative drug?
Canned pumpkin- increase mass of non-digestible matter
What is an example of a lubricant/surfactant laxative drug?
Mineral oil, docusate sodium- coat fecal surface with hydrophobic film
Bismuth subsalicylate
breaks down to salicylic acid (NSAID) and bismuth oxychloride (bacteriocide?), bismuth salts absorb enterotoxins
Kaolin-Pectin
Aluminum silicate, changes fecal consistency (maybe??) but clinical efficacy questionable
Propantheline, Isopropramide, N-butylscopolammonium bromine
Types of quarternary ammonium anticholinergic drugs (act through intestinal mAChR) that do not enter CNS and inhibit intestinal motility and secretion as antidiarrheal drugs
Naloxone
antagonize opiod actions in GI tract (opiods inhibit GI propulsion)
What are examples of opiate antidiarrheal drugs?
Loperamide (no abuse) and codine (acts at perif and CNS cites too)
What are examples of opiod antagonists that are peripherally-specific?
Alvimopan and methynaltrexone
