GI Flashcards
Cimetidine (Tagamet)
. Ranitidine (Zantac)
Famotidine (Pepcid)
Nizatidine (Axid).
Their effect is most pronounced on nocturnal acid secretion, which depends largely on histamine.
May be taken prophylactically before meals to reduce likelihood of heartburn
Nocturnal acid suppression by H2 antagonists affords effective ulcer
healing in most patients with uncomplicated gastric and duodenal ulcers
Cimetidine slows the hepatic metabolism of many drugs
CLINI CAL USE Peptic ulcer, gastritis, mild esophageal reflux.
ADVERSE EFFECTS Cimetidine is a potent inhibitor of cytochrome P-450 (multiple drug interactions); it also has
ANTIANDROGENIC effects (prolactin release, gynecomastia, impotence, decrease libido in males); can
cross blood-brain barrier (confusion, dizziness, headaches) and placenta. Both cimetidine and
ranitidine decrease renal excretion of creatinine. Other H2 blockers are relatively free of these effects.
Prazoles
prodrugs, since they require activation (via protonation) in the acid environment of the secretory canaliculus of the gastric parietal cell.
• The activated drug then forms a covalent disulfide bond with the H+,K+ ATPase
(a.k.a., the proton pump), thereby irreversibly inactivating the enzyme
PPIs markedly suppress both fasting and meal-stimulated acid secretion, the latter effect being significantly more pronounced than that of H2 antagonists.
PPIs are the most effective agents for the treatment of nonerosive and erosive
GERD.
• Once-daily dosing
PPIs afford more rapid symptom relief and
faster ulcer healing for duodenal ulcers and, to a lesser extent, gastric ulcers.
• All the PPIs heal >90% of duodenal ulcers within 4 weeks and a similar
percentage of gastric ulcers within 6-8 weeks
ADVERSE:
• Increases in gastric bacterial concentrations have been reported in patients taking
PPIs, due to suppression of the gastric acid barrier to ingested bacteria. - Patients taking PPIs have a 2-fold to 3-fold higher risk for C. difficile infection.
PPIs may reduce calcium absorption and inhibit osteoclast function.
= All agents carry an FDA-mandated warning of a possible increased risk of
hip, spine, and wrist fractures
CLINICAL USE Peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome, component of therapy for
H pylori, stress ulcer prophylaxis.
ADVERSE EFFECTS increase risk of C difficile infection, pneumonia, acute interstitial nephritis. decrease serum Mg2+ with long-term
use; decrease serum Mg2+ and decrease Ca2+ absorption (potentially leading to increased fracture risk in elderly).
Triple therapy for H.pylori associated ulcers
Crows Among Pigions and Men
- A PPI twice daily
- Amoxicillin (1 g) twice daily
- Either clarithromycin (500 mg) or metronidazole (500 mg) twice daily
“Quadruple therapy” with both antibiotics is proving more effective for
eradication of H. pylori, and is now recommended for initial treatment due to resistance towards clarithromycin and metronidazole.
Antacids in genera
Aluminum hydroxide
Calcium carbonate
Magnesium hydroxide l
weak bases that react with gastric HCl to form a salt
and water.
• Their usefulness lies in their ability to reduce gastric acidity as well as
peptic activity (pepsin is inactive in solutions above pH 4.0).
used for treatment of intermittent heartburn
Can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and
urinary pH or by delaying gastric emptying.
All can cause HYPOKALEMIA
Overuse can also cause the following problems.
Aluminum hydroxide Constipation and hypophosphatemia; proximal
muscle weakness, osteodystrophy, seizures
Aluminimum amount of feces.
Calcium carbonate Hypercalcemia (milk-alkali syndrome), rebound
acid increase
Can chelate and decrease effectiveness of other drugs
(eg, tetracycline).
Magnesium hydroxide Diarrhea, hyporeflexia, hypotension, cardiac
arrest
Mg2+ = Must go to the bathroom.
Sucralfate
drug that promotes mucosal defense
Thought to selectively bind necrotic ulcer tissue, where it acts as a barrier to
acid, pepsin, and bile.
• May stimulate the synthesis of prostaglandins, which, in turn, stimulate the
secretion of mucus and HCO3
• Effective in preventing and healing duodenal ulcers.
• Requires acidic conditions to be activated and thus should not be taken
together with antacids, H2
-receptor antagonists, or PPIs.
Bind to ulcer base, providing physical protection and allowing HCO3
– secretion to reestablish
pH gradient in the mucous layer. Require acidic environment; usually not given with PPIs/H2
blockers.
CLINI CAL USE increase ulcer healing, travelers’ diarrhea (bismuth).
Bismuth Subsalicylate
Bismuth Subcitrate Potassium
Bismuth appears to work by selectively binding to an ulcer, coating it, and
protecting it from acid and pepsin.
-have direct antimicrobial activity against H. pylori and
bind enterotoxins
Bismuth subsalicylate reduces stool frequency and liquidity in acute
infectious diarrhea, due to salicylate inhibition of intestinal prostaglandin and
chloride secretion.
• OTC bismuth subsalicylates (Pepto-Bismol and Kaopectate) are widely
used for the nonspecific treatment of dyspepsia and acute diarrhea.
Bismuth subcitrate is only available as a
combination prescription product with
tetracycline and metronidazole
Bind to ulcer base, providing physical protection and allowing HCO3
– secretion to reestablish
pH gradient in the mucous layer. Require acidic environment; usually not given with PPIs/H2
blockers.
CLINI CAL USE ulcer healing, travelers’ diarrhea (bismuth).
Misoprostol
a methyl analog of prostaglandin E1
(PGE1 and
is approved for the prevention of NSAID-induced ulcers.
• It has both mucosal protective and acid inhibitory properties.
• Its mucosal protective effects stem from stimulation of mucus and HCO3
secretion as well as enhancement of mucosal blood flow.
• It also reduces histamine-stimulated cAMP production, resulting in modest
acid inhibition.
• Misoprostol causes dose-dependent diarrhea and is contraindicated in
women with childbearing potential, due to its stimulant effect on the uterus.
PGE1 analog. increase production and secretion of gastric mucous barrier, decrease acid production.
CLINICAL USE: Prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production). Also used off-labelfor induction of labor (ripens cervix).
ADVERSE EFFECTS Diarrhea. Contraindicated in women of childbearing potential (abortifacient).
Psyllium, methylcellulose
Bulk forming laxatives
They are indigestible, hydrophilic colloids that absorb water, forming a bulky, emollient gel that distends the colon and promotes peristalsis.
• Common preparations include the natural plant products psyllium
and methylcellulose and the synthetic fiber polycarbophil
• Bacterial digestion of plant fibers in the colon can lead to bloating and flatus.
Soluble fibers draw water into gut lumen, forming a viscous liquid that promotes peristalsis Adverse: Bloating
Docusate, glycerin suppository
Stool softeners - emolients
soften stool material, permitting water and lipids to penetrate.
• They may be administered orally or rectally.
• Common agents include docusate (Colace®) and glycerin suppository.
• Mineral oil lubricates fecal material, retarding water absorption from the
stool.
Promotes incorporation of
water and fat into stool
Adverse: Diarrhea
Magnesium hydroxide,
magnesium citrate,
polyethylene glycol
lactulose
Osmotic Laxatives
Magnesium hydroxide is milk of magnesia
Polyethylene glycol is miralax
soluble but non-absorbable compounds that result in
increased stool liquidity due to an obligate increase in fecal fluid.
Provides osmotic load to draw water into GI lumen Lactulose also treats hepatic encephalopathy: gut flora degrade lactulose into metabolites (lactic acid, acetic acid) that promote nitrogen excretion as NH4 \+ ADVERSE: Diarrhea, dehydration; may be abused by bulimics
Stimulant Laxatives (Cathartics)
Senna
Stimulant Laxatives (Cathartics)
• Induce bowel movements through mechanisms that include stimulation of the
enteric nervous system and secretion of colonic electrolytes and fluid.
• They typically produce a bowel movement in 6-12 hours when given orally and
within 0.5-2 hours when given rectally.
Enteric nerve stimulation
> colonic contraction
ADVERSE: Diarrhea, melanosis coli
Metoclopramide
Hastens esophageal clearance, raises lower esophageal sphincter pressure,
and accelerates gastric emptying.
• Antagonism of dopamine D2
-receptors is thought to underlie its prokinetic
properties.
• Can produce symptomatic relief in patients with gastric motor failure due to
diabetes and post-surgical disorders.
• Sometimes used in combination with antisecretory agents, for the treatment
of refractory heartburn.
• Also effective as an antiemetic agent (prevention of vomiting).
ME CHANISM D2 receptor antagonist. increase resting tone, contractility, LES tone, motility, promotes gastric emptying.
Does not influence colon transport time.
CLINICAL USE Diabetic and postsurgery gastroparesis, antiemetic, persistent GERD.
ADVERSE EFFECTS increase parkinsonian effects, tardive dyskinesia. Restlessness, drowsiness, fatigue, depression, diarrhea.
Drug interaction with digoxin and diabetic agents. Contraindicated in patients with small bowel
obstruction or Parkinson disease (due to D2-receptor blockade).
ADVERSE: tardive dyskinesia, parkinson like symptoms, hyperprolactinemia
Diphenoxylate
Loperamide
SLOWERS!
Both drugs act by activating m-opioid receptors in the enteric nervous system, leading to increased colonic transit time and fecal fluid absorption.
• Neither drug has analgesic properties at standard doses.
• Diphenoxylate has the potential for CNS effects at high doses, and prolonged
use can lead to dependence.
• For this reason, Lomotil® contains a small amount of the anticholinergic agent
atropine as an abuse deterrent and to discourage overdosage.
• Loperamide does not cross the blood-brain barrier and has little or no potential
for CNS effects or addiction
Loparamide
ME CHANISM Agonist at μ-opioid receptors; slows gut motility. Poor CNS penetration (low addictive potential).
CLINI CAL USE Diarrhea.
ADVERSE EFFECTS Constipation, nausea.
Eluxadoline
agonist at m- and k-opioid receptors and as an
antagonist at d-opioid receptors.
• It acts locally in the enteric nervous system to decrease abdominal pain and
reduce diarrhea, with minimal potential for CNS effects and addiction.
• It is approved for the treatment of Irritable Bowel Syndrome with Predominant
Diarrhea (IBS-D).
• Most common adverse reactions are constipation and nausea.
• A rare, but more serious, side effect is
sphincter of Oddi spasm that can result
in abdominal pain and pancreatitis.
• Risk increases with blockage or
absence of a gallbladder
Octreotide
Octreotide is a synthetic octapeptide with actions similar to somatostatin.
• It has numerous physiologic effects that give rise to its antidiarrheal properties:
➢ It inhibits the secretion of multiple hormones and neurotransmitters, such
as gastrin, secretin, vasoactive intestinal peptide (VIP), and histamine.
➢ It reduces intestinal fluid secretion and pancreatic secretion.
➢ It slows GI motility and inhibits gallbladder contraction.
• It is useful for treating secretory diarrhea caused by GI neuroendocrine tumors,
like carcinoid tumors and VIPoma.
• It is also useful for the treatment of diarrhea due to
vagotomy, dumping syndrome, or short bowel
syndrome
Adverse effects include:
➢ Nausea, abdominal pain, and flatulence.
➢ Impaired pancreatic secretion can lead to steatorrhea and fat-soluble
vitamin deficiency.
➢ Inhibition of gallbladder contractility and alteration in fat absorption can
cause gallstones with long-term use.
➢ Prolonged treatment can also cause hypothyroidism.
Treats
Acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices.
ME CHANISM Long-acting somatostatin analog; inhibits secretion of various splanchnic vasodilatory hormones.
CLINI CAL USE Acute variceal bleeds, acromegaly, VIPoma, carcinoid tumors.
ADVERSE EFFECTS Nausea, cramps, steatorrhea. increased risk of cholelithiasis due to CCK inhibition > gallbladder hypomotility
