GI Drugs Flashcards
What is Gastric mucosa? What is it’s importance?
is secreted from mucosal epithelial cells. This mucous layer protects the cells of the stomach from the acid and enzymes in the lumen of the stomach (otherwise, the stomach would eat itself).
Loss of this mucous layer, for any reason, will allow acid to reach the cells and cause an ULCER
How does hyperacidity happen?
PARITAL CELLS in the stomach make hydrochloric acid (HCl)- one of the strongest acids known
This acid environment kills bacteria, viruses, and other parasites, NOT PRIMARILY FOR DIGESTION (does facilitate protein digestion)
Overproduction of this acid can overwhelm the mucous layer and buffer systems, and lead to ulcers
Peptic Ulcer Bleeding prevalence:
5% of emergency admissions
80% stop spontaneously
10% of pt’s die
Rebleeding increases mortality by 10x
What are Antacids?
Systemic antacids- NaHCO3
Dissociates into Na+ and HCO3-
(bicarbonate – Alka Seltzer)
The bicarb ion is absorbed into the blood and SLIGHTLY INCREASES pH (alkalosis)
Elevates the pH of the stomach
What is NaHCO3?
This is quick, easy, and effective in the SHORT TERM to reduce stomach acid
What are the problems w/ NaHCO3?
Alkalotic urine can increase the deposition of calcium and phosphate to form a KIDNEY STONE (cranberry juice does the opposite)
This increases blood sodium, thus exacerbating HYPERTENSION
ACID REBOUND due to feedback regulation
What are non-systemic antacids?
CaCO3 (Tums), Al(OH)3, Mg(OH)2
These do NOT effect extracellular or blood pH (more efficient neutralization)
Aluminum and calcium antacids are CONSTIPATING, thus are often combined with magnesium (Maalox, Mylanta)
What is the proton pump - the parietal cell?
?
What are Anticholinergics?
Recall: MUSCARINIC RECEPTORS in parietal cells stimulate HCl secretion from these cells.
Inhibition of these receptors reduces acid secretion (but not by much)
Muscarinic acetylcholine type 1 receptor (M1R) blockers (PIRENZEPINE) may reduce acid by up to 40%
Side effect: dry mouth, vision problems, sedation, etc. VERY NON-SELECTIVE
Thus, lots of side effects, limited acid reduction – rarely used now
What are Cytoprotectives?
Mucosal protection
Drugs which protect cells from acidic damage, either directly or through stimulation of mucous
What are the 2 major Cytoprotective drugs?
Sucralfate - used to coat & protect ulcer
Misoprostol - increase slime in gut to protect lining
What is Sucralfate?
Aluminum base sucrose salt
- Binds to hydrogen ions to form a GOOEY paste, increasing pH (decreasing acidity)
- ALSO binds to degenerating cells (at ulcer), forming a protective layer
- “Artificial” mucous
- It is not absorbed into the bloodstream, but can inhibit absorption of other drugs
- Works for 8-12 hrs, specifically protects damaged tissue as well as reducing acidity
What is Misoprostol?
From NSAIDS lecture! Recall Cox inhibition causes PGE inhibition, and PGE is critical for mucous production in stomach - this is why NSAIDS cause stomach problems
*Misoprostol is a PGE1 analogue - STIMULATES PROTECTION of the mucosal barrier
Short half-life so 3-4 treatments per day
What are the Histamine H2 receptor blockers?
Stimulation of H2 receptors in parietal cells increases HCl production
COMPETITIVE inhibition of H2 receptors highly effective in a number of acid- related disorders
VERY SPECIFIC to the organ, to the receptor type (do not cross to H1, H3 or PGE) and NO ADVERSE EFFECT on mucosa
What is H2 blockers: Cimetidine?
50-60% reduction in acidity (moderate)
Binds to Cyt p450 to cause drug interaction (non-selective inhibition)
Binds to androgen receptors: gynecomastia, reduced LIBIDO, impotence…..Over the counter med Tagamet
What is H2 blockers: Ranitidine?
More effective at reducing acid than Cimitidine (65-70%)
Less drug interaction (only binds p450 at high doses)
*Does not bind androgen receptors
Also over-the-counter drug Zantac
What is H2 Blockers: Famotidine?
More effective than Ranitidine – MOST POTENT
Does not bind cyt p450 at all
Very FEW ADVERSE side effects
Over-the-counter- Pepcid (with antacid)
This drug is the most effective at reducing acid secretion, and has the best safety profile
What are Proton Pump inhibitors (PPIs)?
Inhibits gastric H+/K+ ATPase (proton pump)
Especially good for RAPID REDUCTION of acid
Bind to H+ extrusion sites, and block the release of H+ and Cl-
Effective – most commonly used
(something)-Prazole
*Omeprazole (prilosec), *esomeprazole (nexium), lansoprazole, pantoprazole, rabeprazole
Especially good for gastroesophogeal reflux disease (GERD), as well as other acid-dependent disorders
Generally safe and cheap
PPIs enter the secretory CANALICULUS of the parietal cell which opens when acid secretion occurs
The pro-drug is converted to the active drug here
PPIs bind IRREVERSIBLY to the channel, thus have a LONG half-life
Rabeprazole also increases mucous secretion
What is Helicobacter pylori Infection?
Better and better drugs were developed to reduce acidity - however, recurrence rates were 60-100%
In the early 1980’s (against a strong resistance) *H. pylori infection was found to be a major cause of ulcers
H. pylori (HP) is present in 95% of duodenal ulcers, 80% of gastric ulcers
To escape gastric acid, HP BURROWS INTO THE GASTRIC MUCOSA
HP then produces UREASE, the enzyme that converts urea to ammonia and CO2
This KILLS MUCOSAL epithelial cells, leaving the gut unprotected
How do you test for the H. pylori infection?
Testing for infection
- Breath test for urea
- Serological
- Culture
- Histology
Antisecretory or antibiotic treatments alone are not as effective as combination therapy.
What is the Triple and quadruple therapy?
Triple: a PPI to control acid and 2 effective antibiotics to kill the HP
Quadruple: Add bismuth (coating of ulcer)
These are the most effective treatments for ulcers caused by HP (which may account for nearly 90% of ulcers)
What is Gastroesophogeal reflux disease (GERD)?
The most prevalent type of ulceration - 5X more common than gastric ulcers
Lower esophageal sphincter (LES) defect allows acidic contents to contact the esophageal lining
A number of drugs reduce LES pressure (allow reflux) - beta blockers, Ca channel blockers, nicotine
What is the tx for GERD?
Treatment- pharmacological treatments (PPIs) are not nearly as effective as BEHAVIOUR CHANGE
Avoid fat, caffeine, chocolate, peppermint and alcohol (chocolate- coated coffee beans and peppermint schnapps)
Avoid large meals, especially immediately before bed, stop smoking.
Diarrhea =
frequent liquid stool – sign of an intestinal disorder
What are the multiple causes of diarrhea?
foods, bacteria, virus, drug side effect, laxative abuse, malabsorption syndrome, stress, bowel tumor.
Very mild to life threatening - dehydration
What is the simple tx for diarrhea?
= clear liquids (gatorade, pedialyte), (BRAT diet)
What are the GI agents - Antidiarrheals?
Decrease hypermotility
Opiates, opiate related agents, adsorbents antidiarrheal combos
Opiates - decrease intestinal motility
tincture of opium, paregoric, codeine
Side effects- CNS depression, constipation (duration = 2 hrs)
Opiate-Related Agents - diphenoxylate (Lomotil), loperamide (Imodium) - synthetic drugs chemically related to the opioid meperidine
Side effects- drowsiness and distention
Adsorbents - coat the wall of the GI tract and adsorbing the bacteria or toxins causing diarrhea (substance takes in toxin)
- Kaopectate (kaolin & pectin) OTC
- Pepto-Bismol adsorbs bacterial toxin & for GI discomfort, OTC
