Drugs to Treat GI Disorders Flashcards
________ drugs are relatively weak inhibitors of acid secretion b/c they act at only one site (M3 receptor mediated by acetylcholine), used as adjuncts to other therapies
anti-muscarinic
- family of peptide hormones formed by gastric mucosal cells
- stimulates gastric motility, HCl and pepsin secretion
- no direct antagonists
gastrin
- reduce gastrin secretion
- block histamine induced cAMP and proton pump activation
H2 antagonists
- irreversibly inhibit the parietal cell H/K ATPase
- all prodrugs that are inactive at neutral pH, activation requires acid environment (take w/ meals so food can stimulate acid secretion)
- unstable at low pH –> have enteric coated granules that dissolve only at alkaline pH
- prodrug absorbed in intestines, carried to circulation to parietal cells, accumulates in secretory canaliculi
- activated at acid pH and bind sulfhydryl groups on H/K ATPase
proton pump inhibitors
PPIs retain efficacy with chronic use b/c intracellular canaliculi are ________ from the proton pump target at the luminal membrane
upstream
- prazoles
- currently most effective drugs for suppressing gastric acid secretion b/c gastric response to all stimuli is inhibited
PPIs
adverse effects of this drug:
- GI effects: colic, flatulence, constipation, diarrhea
- CNS
- skin rash
- prolonged use - diarrhea due to GIT bacteria overgrowth from removal of natural acid barrier
- hepatic metabolism
PPIs adverse effects
cimetidine, famotidine, nizatadine, ranitidine
H2 receptor antagonists
- OTC preps that inhibit acid secretion for <6 hours
- block H2 receptors selectively to reduce gastric acid and pepsin secretion without affecting H/K ATPase, H1, or other receptors
- effective against noctural secretion which is largely driven by histamine
H2 receptor antagonists (-dines)
side effects of this drug
- extremely safe, minor and infrequent adverse effects
- don’t give to pregnant or nursing women
- diarrhea, headaches, fatigue, myalgias, constipation, bradycardia
- confusion, hallucinations, agitation with IV admin in hepatic dysfunction
H2 receptor antagonists
- this drug causes gynecomastia or impotence in men, galactorrhea in women
- endocrine effects b/c it inhibits binding of dihydrotestosterone to androgen receptors, inhibits estradiol metabolism, increases serum prolactin
- interferes with CYP450 paths
cimetidine (H2 receptor antagonist)
- all equally effective for healing and preventing recurrence of PUD
- given 1X daily at bedtime to suppress nocturnal acid secretion
- use declined following PPIs
H2 antagonists (-dines)
- 20% failure in ulcer patients who smoke and in the elderly
- don’t use in combo with PPIs, reduce efficacy by reducing acid activation
- combined with abx and bismuth for treatment of Hpylori
uses of H2 antagonists
- aluminum hydroxide
- calcium carbonate
- combo aluminum hydroxide and magnesium hydroxide
antacids
- act by reducing gastric acidity, inactivating pepsin
- weak bases that neutralize gastric HCl to form salt and water, may interfere with absorption of other drugs
- may provide mucosal protection by stimulating PG synthesis
antacids
- aluminum or magnesium hydroxide
- single dose given 1 hr after eating neutralizes for 2 hours
- side effects: diarrhea for magnesium, constipation for aluminum
- used as needed to relieve pain in esophagitis, peptic ulcer, and GERD
- not recommended for treatment of active peptic ulcers
antacids
- protective coating on peptic ulcers, limits exposure to acid and pepsin
- sucralfate binds selectively to necrotic ulcer tissue and acts as barrier
mucosal protective agents
- polymerizes to produce viscous gel that adheres strongly to epithelial cells and ulcer craters in acid environment
- effective in healing duodenal ulcers
- side effect: constipation
- requires acid pH for activation, don’t give with antacids/H2 antagonist/PPI
sucralfate
- methyl analog of PGE1
- binds PG receptors on parietal cells to inhibit acid secretion
- because NSAIDS inhibit PG formation, it’s used to prevent NSAID induced ulcers
- adverse: diarrhea, abdominal pain
- may cause abortion by stimulating uterine contractions
misoprostol
- colloidal bismuth
- protective coating of ulcers, antibacterial against Hpylori
- darken tongue and stool
bismuth subsalicylate (pepto bismol)
antibiotic regimen for Hpylori?
clarithromycin + amoxicillin + PPI
- nonabsorbable salts containing magnesium cations (magnesium citrate) or phosphate anions (sodium phosphate)
- act by osmotic force to hold water inside intestines –> distended intestines –> stimulate peristalsis
- intensely bitter taste masked by citrus
- avoid in renal insufficiency, heart disease, electrolye imbalance, diuretic co treatment
saline laxatives
-trihydroxy alcohol that acts in the rectum as lubricant and hygroscopic agent –> water retention –> stimulate peristalsis
glycerin
- nonabsorbable sugars
- hydrolyzed to organic acids - acidify luminal contents - draw water into lumen - increase colonic propulsive motility
lactulose, sorbitol, mannitol
- poorly absorbed, retain added water by their high osmotic pressure
- colonoscopy prep, drink 3-4 liters over 3-4 hours to produce watery diarrhea and remove solid wastes
PEG-electrolyte solutions
- act directly on enterocytes, enteric neurons, and muscle
- induce low grade intestinal inflammation, water and electrolytes accumulate, increase intestinal motility
stimulant or irritant laxatives
- a diphenylmethane derivative, available as enteric coated tablets taken at bedtime to take effect next morning
- swallow to avoid activation in stomach
bisacodyl
- stimulant/irritant laxative
- poorly absorbed in small intestine and require activation in colon with effects 6-12 hours later
- long term use: melanomic pigmentation of colon, cathartic colon (dilated, ahaustral)
anthraquinones - aloe, cascara sagrada, senna
-stimulant/irritant: increases intestinal secretion and motility, seldom used due to unpleasant taste and toxic potential
castor oil (ricinoleic acid)
methylcellulose, lactulose, polycarbophil
bulk forming laxatives
mineral oil, glycerin suppositories, docusate sodium
stool softeners - facilitate expulsion
often prescribed to prevent straining in hospitalized patients
docusate
loperamide, diphenoxylate, difenozin, bismuth salicylate, kaolin/pectin
antidiarrheal drugs
act on intestinal opioid receptors - inhibit Ach release - decrease motility (peristalsis)
loperamide, difenoxin, diphenoxylate
- 40-50X more effective than morphine for diarrhea, does not cross BBB
- relief of acute nonspecific diarrhea
- effective against traveler’s diarrhea
- more effective than diphenoxylate
loperamide
- act by absorbing compounds and presumably binding potential intestinal toxins
- antidiarrheal
kaolin and pectin
-antidiarrheal that inhibits intestinal secretions, management of infectious diarrhea
bismuth salicylate
- antidiarrheal: inhibits secretion of gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, 5-HT
- reduces intestinal fluid and pancreatic secretion
- slows GI motility and inhibits gallbladder contraction
- reduces portal and splanchnic bloodflow
somatostatin/octreotide
- first generation H1 blockers
- produce sedation and antimuscarinic activity
- prevent motion sickness
- dimenhydrinate, diphenhydramine, cyclizine, meclizine
anti-emetics: histamine H1 antagonists
metoclopramide, trimethobenzamide
D2 antagonists (anti-emetic)
ondansetron, granisetron, dolasetron
5-HT3 antagonists, chemotherapy anti-emetics
aprepitant, fosaprepitant, rolapitant
NK-1 antagonists, anti-emetic
chorpromazine, prochlorperazine
phenothiazines, anti-emetic
THC, dronabinol
marijuana derivatives - anti-emetic
- low doses of amitriptyline or desipiramine
- treatment of abdominal pain
tricyclic antidepressants - treat IBS
anticholinergics (dicyclomine, hyoscyamine)
antispasmodics - IBS treatment
- tegaserod
- emergency treatment only
- CV effects
5-HT4 partial agonist, IBS treatment
- 5HT3 antagonist, for IBS treatment
- diarrhea prominent IBS
- serious CV events can occur
alosetron
- diarrhea prominent IBS treament
- opioid agonist/antagonist
- reduces neuronal drive on peristalsis
- spasm in sphincter of Oddi can cause pancreatitis
eluxadoline
- diarrhea prominent IBS treatment
- synthetic antibiotic similar to rifampin
- may alter bacterial content of GI tract
rifaximin
- pancreatic insufficiency can lead to steatorrhea, azotorrhea, vitamin malabsorption, weight loss
- enzyme supplements _______ and _______ treat enzyme insufficiency
- administer with each meal and snack
- can lead to hyperuricosuria and renal stones
pancreatin, pancrelipase
- antiobesity
- targets gut, GI lipase inhibitor
- reduces absorption of fats since triglycerides not split
- toxicity: flatulence, steatorrhea, fecal incontinence
orlistat
- target CNS, SERT and NET inhibitor
- reduces appetite
- CV effects: tachycardia, hypertension
sibutramine
targets CNS, a CB1 receptor antagonist, reduces appetite
-toxicity: depression, anxiety, nausea
rimonabant
