GI Drugs

Question 1

What is Gastric mucosa? What is it’s importance?

Answer 1

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

Question 2

How does hyperacidity happen?

Answer 2

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

Question 3

Peptic Ulcer Bleeding prevalence:

Answer 3

5% of emergency admissions

80% stop spontaneously

10% of pt’s die

Rebleeding increases mortality by 10x

Question 4

What are Antacids?

Answer 4

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

Question 5

What is NaHCO3?

Answer 5

This is quick, easy, and effective in the SHORT TERM to reduce stomach acid

Question 6

What are the problems w/ NaHCO3?

Answer 6

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

Question 7

What are non-systemic antacids?

Answer 7

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)

Question 8

What is the proton pump - the parietal cell?

Answer 8

?

Question 9

What are Anticholinergics?

Answer 9

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

Question 10

What are Cytoprotectives?

Answer 10

Mucosal protection

Drugs which protect cells from acidic damage, either directly or through stimulation of mucous

Question 11

What are the 2 major Cytoprotective drugs?

Answer 11

Sucralfate - used to coat & protect ulcer

Misoprostol - increase slime in gut to protect lining

Question 12

What is Sucralfate?

Answer 12

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

Question 13

What is Misoprostol?

Answer 13

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

Question 14

What are the Histamine H2 receptor blockers?

Answer 14

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

Question 15

What is H2 blockers: Cimetidine?

Answer 15

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

Question 16

What is H2 blockers: Ranitidine?

Answer 16

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

Question 17

What is H2 Blockers: Famotidine?

Answer 17

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

Question 18

What are Proton Pump inhibitors (PPIs)?

Answer 18

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

Question 19

What is Helicobacter pylori Infection?

Answer 19

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

Question 20

How do you test for the H. pylori infection?

Answer 20

Testing for infection
- Breath test for urea
- Serological
- Culture
- Histology

Antisecretory or antibiotic treatments alone are not as effective as combination therapy.

Question 21

What is the Triple and quadruple therapy?

Answer 21

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)

Question 22

What is Gastroesophogeal reflux disease (GERD)?

Answer 22

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

Question 23

What is the tx for GERD?

Answer 23

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.

Question 24

Diarrhea =

Answer 24

frequent liquid stool – sign of an intestinal disorder

Question 25

What are the multiple causes of diarrhea?

Answer 25

foods, bacteria, virus, drug side effect, laxative abuse, malabsorption syndrome, stress, bowel tumor.
Very mild to life threatening - dehydration

Question 26

What is the simple tx for diarrhea?

Answer 26

= clear liquids (gatorade, pedialyte), (BRAT diet)

Question 27

What are the GI agents - Antidiarrheals?

Answer 27

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