Gi 4

Front 1

H2RAs have a higher affinity for H2 but there’s also some attraction to H1. Where on the parietal cell do the H2RAs work?

Back 1

Histamine receptors on the parietal cell express the “H2-type” receptor

Front 2

What’s the mechanism of action for H2RAs?

Back 2

It REVERSIBLY (not irreversible) inhibits gastric acid secretion by competitively antagonizing H2 receptors on parietal cells.

Front 3

This inhibition results in:

Back 3

Decreased acid production, ↓ hydrogen ion content. Inhibits gastric acid release, ↓ hydrogen ion content. Diminish parietal cell responsiveness to other stimulants (e.g., gastrin)

Front 4

What are the 4 multiple dosage forms?

Back 4

Cimetidine (Tagamet®) IV and oral. Ranitidine (Zantac®), IV and oral. Famotidine (Pepcid®), IV and oral. Nizatidine (Axid®), oral NOT IV!!

Front 5

Why do insurance companies like these H2RAs?

Back 5

No new ones have been released lately, so they are all generic/cheaper.

Front 6

Cimetidine - ranitidine - and famotidine undergo first pass metabolism (bioavailability ~50%). What about Nizatidine?

Back 6

Nizatidine’s bioavailability is almost 100%

Front 7

Elimination - Half lives are about 1-4 hours. What’s the duration of action?

Back 7

about 12 hours

Front 8

Hepatic metabolism is primary for which 2 drugs?

Back 8

Cimetidine & Ranitidine

Front 9

Renal excretion is primary for what 2 drugs?

Back 9

Famotidine & Nizatidine

Front 10

NOTE - All H2RAs should be dose adjusted for what?

Back 10

Renal insufficiency. ClCr under 50 ml/min

Front 11

Tachyphylaxis may occur with H2RAs. What is this?

Back 11

Patient’s body adapts with prolonged use.

Front 12

What do you have to remember about pregnancy and H2RAs?

Back 12

they DO cross the placental barrier, and are secreted in breast milk. H2RAs are associated with major teratogenic risk, so use caution! (just use PPIs)

Front 13

What are the 4 adverse effects of H2RAs?

Back 13

CNS: confusion, change in MS, HA, hallucinations, drowsiness - especially in the elderly. (This is very real) Derm: rash. GI: N/V/D, flatulence, dry mouth, diarrhea, constipation. Heme: Thrombocytopenia

Front 14

What are the drug interactions of H2RAs?

Back 14

CYP450 drug-drug interactions. Cimetidine (by competitive inhibition) competes with medications and creatinine for tubular secretion (kidney). Drugs requiring gastric acid for absorption. Ketoconazole and itraconazole (antifungals). Alcohol: All H2RAs may inhibit the action of alcohol dehydrogenase = ↓metabolism ↓ clearance of ethanol

Front 15

TEST - What H2RA has the MOST drug interactions and CNS effects?

Back 15

Cimetidine.

Front 16

List the order of other H2RAs in terms of drug interactiveness.

Back 16

Ranitidine. Famotidine. Nizatidine. (Elderly, kids, & those on a lot of drugs - use Nizatidine)

Front 17

H2RAs are all effective for treatment of:

Back 17

duodenal and gastric ulcers.

Front 18

TEST What % of healing occurs with H2RAs?

Back 18

Overall healing of 70-95% after 4-8 weeks.

Front 19

All H2RAs are equally effective and roughly all well tolerated. The mg-per-mg potency differs widely. Which drug is the most potent and possesses the longest duration of action?

Back 19

Famotidine

Front 20

H2RAs are more effective for:

Back 20

nocturnal acid secretion

Front 21

What about H. pylori associated PUD?

Back 21

H2RAs play no role in treating this (It’s for the PPIs to tackle)

Front 22

The ACG GERD recommendations state that H2RA therapy can be used as:

Back 22

a maintenance option in patients w/o erosive disease if patients experience heartburn relief.

Front 23

The ACG GERD recommendations also state that bedtime H2RA therapy can be:

Back 23

added to daytime PPI therapy in selected patients with objective evidence of night-time reflux if needed but may be associated with the development of tachyphlaxis after several weeks of use.

Front 24

SAMPLE QUESTION - What is the mechanism of H2 antagonists? A - H2 antagonists inhibit histamine binding to parietal cells and subsequent extrusion of hydrogen ions into the gastric lumen B - H2 antagonists inhibit gastrin binding to histamine receptors on parietal cells and subsequent activity of the H+/K+ ATPase pump C - H2 antagonists inhibit histamine-mediated prostaglandin destruction and subsequent destruction of the protective mucus lining D - H2 antagonists inhibit acetylcholine binding to preganglionic receptors and subsequent acetylcholine mediated bicarbonate sequestration

Back 24

A - H2 antagonists inhibit histamine binding to parietal cells and subsequent extrusion of hydrogen ions into the gastric lumen

Front 25

ANTACIDS What is their MOA?

Back 25

They are neutralizers

Front 26

TEST How do antacids neutralize?

Back 26

The are weak bases that react with gastric acid to form a WATER and a SALT. It occurs after ingestion of H+ binding groups.

Front 27

What are antacid’s 2nd MOA?

Back 27

They stimulate mucosal prostaglandin synthesis.

Front 28

TEST How should antacids be administered?

Back 28

BETWEEN meals. Or, after meals, when the stomach is empty.

Front 29

Antacids come in 2 forms - absorbable and non-absorbable. What are non-absorbable antacids?

Back 29

Counter ions are dissolved in gastric acid neutralization.

Front 30

What occurs to the aluminum and magnesium in antacids?

Back 30

Aluminum hydroxide: Aluminum Chloride and H2O. Magnesium hydroxide: Magnesium Chloride and H2O.

Front 31

W/ alkaline pancreatic secretion in the duodenum these antacids are:

Back 31

Precipitated again and LARGELY excreted in feces

Front 32

Absorbable antacids include sodium and calcium. What does sodium bicarb turn into?

Back 32

NaCl, CO2 and H2O.

Front 33

What does calcium bicarb turn into?

Back 33

Calcium chloride, CO2 and H2O

Front 34

W/ alkaline pancreatic secretion in the duodenum these antacids are:

Back 34

Precipitated again and SUBJECT to REABSORPTION (sodium > calcium).

Front 35

What should you keep in mind with these absorbable antacids?

Back 35

The sodium - especially the sodium absorption

Front 36

What are the common therapeutic uses of antacids?

Back 36

Symptomatic treatment in patients with GERD. They are OTC for heartburn and dyspepsia.

Front 37

TEST - What are antacids NOT recommended for?

Back 37

the treatment of active peptic ulcer disease

Front 38

Administration considerations include the multiple daily dosing that’s secondary to the short duration of action. How many times a day?

Back 38

4-7 times/day

Front 39

How should on take antacids?

Back 39

On an empty stomach.

Front 40

Liquid formulations have a more rapid acid-neutralizing onset than tablets. What do some formulation contain that you have to be weary of?

Back 40

sugar. think:DM

Front 41

ABSORBABLE antacids - Sodium bicarbonate and calcium bicarbonate. When sodium bicarb forms carbon dioxide it can produce what effects?

Back 41

bloating and belching.

Front 42

The sodium in the sodium bicarb may be absorbed and exacerbate what?

Back 42

fluid retention, hypertension, kidney disease, heart failure (horrible for heart failure patients)

Front 43

When calcium carbonate forms carbon dioxide it can produce what effects?

Back 43

bloating & belching (like the sodium bicarb). Plus, it may also cause constipation.

Front 44

There’s a potential for hypercalcemia (but requires a lot) and it may induce rebound:

Back 44

acid secretion

Front 45

TEST - NOTE: Balance calcium btwn the antacid and a supplement because:

Back 45

calcium is an acid stimulant.

Front 46

NON-ABSORBABLE antacids - Magnesium and aluminum compounds. Magnesium compounds produce no gas or belching but may lead to:

Back 46

Diarrhea.

Front 47

Magnesium can be absorbed causing sedation and N/V. In which patients should you avoid using magnesium compounds?

Back 47

Patients with severe renal disease.

Front 48

Aluminum compounds also cause no gas or belching but can lead to:

Back 48

Constipation.

Front 49

Aluminum can also be absorbed so it should also be avoided in patients with severe renal disease. Why are magnesium and aluminum often combined in products like Maylox or Mylanta?

Back 49

To balance diarrhea and constipation

Front 50

List the common antacid agents:

Back 50

Maalox: aluminum, magnesium. Mylanta: aluminum, magnesium. Gaviscon: aluminum, magnesium. Tums: calcium carbonate. Rolaids: calcium carbonate, magnesium. Alka-Seltzer: sodium bicarbonate

Front 51

Antacids are often available as chewable tablets or liquid suspensions. In the presence of renal insufficiency - absorption of even small amounts may cause:

Back 51

an increase in plasma levels of counter ions

Front 52

Increased plasma levels of counter ions include:

Back 52

Mg+ intoxication - paralysis / cardiac disturbances. Na+ intoxication- fluid overload worsening CHF, HTN, edema, heart failure. Hypercalcemia- moans, stones, groans, bones

Front 53

Mg(OH)2 produces a laxative effect (osmotic action & release of cholecytokinin). Al(OH)3 produces:

Back 53

constipation

Front 54

Dark stools are another adverse effect of antacid use. What do you have to do as a provider?

Back 54

educate patients that this isn’t bloody stool (black & tarry).

Front 55

How do antacids affect the absorption of other drugs?

Back 55

By binding the drug or by increasing gastric pH

Front 56

Increased gastric pH influences drug absorption of:

Back 56

Digoxin, phenytoin, ketoconazole, itraconazole. Also, enteric coated drugs may release prematurely

Front 57

Antacids reduce the absorption of other drugs due to their ADSORPTION to the surface of antacid. What does adsorption mean?

Back 57

Antacids act like a sponge, so don’t take them with other drugs.

Front 58

Antacids have an effect on the complexation (chelation) of:

Back 58

Fluoroquinolones and tetracyclines.

Front 59

With fluoroquinolones - Administer oral fluoroquinolones either two hours before or two hours after antacids. With Tetracyclines:

Back 59

Administer antacids 2-3 hours after tetracycline administration

Front 60

How effective are antacids in healing duodenal ulcers?

Back 60

Healing of duodenal ulcers in 46-88% after 4 weeks (placebo 24-45%).

Front 61

Disadvantage of taking antacids to treat a duodenal ulcer:

Back 61

Multiple times a day in high doses

Front 62

What are antacids used for?

Back 62

Relief of ulcer pain and dyspepsia as needed (Duration of relief ~2 hrs). Supplement to other therapies!

Front 63

The antacid Gaviscon is an antacid plus:

Back 63

a barrier. Gaviscon is Sodium bicarbonate, aluminum hydroxide, magnesium trisilicate + alginic acid

Front 64

What is the MOA of Gaviscon?

Back 64

Antacids neutralize gastric pH. The reaction between alginic acid and salivary bicarbonate creates a “foam” which floats on top of gastric contents. If reflux occurs, its the antacid solution that emerges.

Front 65

Gaviscon needs to be taken with:

Back 65

sufficient water

Front 66

Sucralfate is octasulfate salt of sucrose + aluminum hydroxide. What is its MOA?

Back 66

It undergoes cross-linking in gastric juice, forming a viscous gel/paste that adheres to mucosal defects and exposed deeper layers. Does so in an acid environment (pH 2-2.5)

Front 67

Protected from acid + from pepsin - trypsin - and bile acids the mucosal defect can heal more rapidly. The “band-aid.” It’s NOT:

Back 67

an antacid because it fails to lower the overall acidity of gastric juice

Front 68

What are the therapeutic uses of Sucralfate?

Back 68

“Treatment” of gastric and duodenal ulcers (less effective & not really used). Prevention of stress ulcers for patients at risk.

Front 69

Sucralfate is Not for:

Back 69

GERD (doesn’t stay in esophagus & requires acid to work)

Front 70

The dose of sucralfate is tablet or suspension four times daily. How should it be taken?

Back 70

On an empty stomach (one hour before meals)

Front 71

What are the adverse effects of Sucralfate?

Back 71

sorbitol in suspension = diarrhea. It contains numerous AI(OH)3 residues released Al3 +'ions, and so must be used cautiously in renal impairment. Aluminum hydroxide can cause constipation.

Front 72

What are the drug interaction of Sucralfate?

Back 72

altered absorption of other PO medications (take other meds 1 hour before or 2 hours after sucralfate)

Front 73

MISOPROSTOL is a semisynthetic prostaglandin (PGE1 analog) that inhibits gastric acid secretion and increases:

Back 73

mucus and HCO3 secretion.

Front 74

Misoprostol is cytoprotective - making it an effective:

Back 74

prophylaxis for drug-induced peptic ulcer caused by long term NSAIDs & corticosteroids (FDA).

Front 75

What are the adverse effects of misoprostol?

Back 75

Frequent (but self-limiting) diarrhea, cramps (up to 30% of pts) seen after ~ 2wks, resolves spontaneously in 1 wk.

Front 76

Why is misoprostol contraindicated during pregnancy?

Back 76

it increases uterine contractility. Women can’t even touch it!! Packs can’t be broken. Residue on drug trays.

Front 77

Colloidal Bismuth Compounds (Bismuth Subsalicylate) is Pepto-Bismol [Kaopectate d/c’d in US] What is it’s MOA?

Back 77

Coats ulcers and erosions, offering a protective layer against acid and pepsin. May stimulate prostaglandin, mucus and bicarbonate secretion

Front 78

What other uses are Colloidal Bismuth Compounds used for?

Back 78

Anti-diarrheal = Salicylate (like aspirin) inhibition of intestinal prostaglandin and chloride secretion. Antimicrobial activity = Bismuth activity against H. pylori and binds enterotoxins (traveler’s diarrhea)

Front 79

Colloidal Bismuth Compounds (Bismuth Subsalicylate) pharmokinetics. How much of the bismuth and subsalicylate is absorbed?

Back 79

Bismuth <1%. Subsalicylate >90%

Front 80

Bismuth subsalicylate is converted to salicylic acid and insoluble bismuth salts in the GI tract. How are they excreted?

Back 80

Bismuth: feces. Salicylate: slow renal excretion

Front 81

Adverse effects of Colloidal Bismuth Compounds?

Back 81

Blackening of stool (may be confused with GI bleeding). Darkening of the tongue. Encephalopathy. Use only short term and avoid in renal insufficiency. Salicylate toxicity in high doses.

Front 82

What precautions/warnings are there with Colloidal Bismuth Compounds?

Back 82

Caution in patients taking aspirin. Contraindicated with warfarin (Coumadin). Contraindicated with salicylate (aspirin) allergy

Front 83

SAMPLE QUESTION - Sucralfate alleviates the symptoms of peptic ulcer disease by: A. Preventing the secretion of gastric acid. B. Neutralizing gastric acid. C. Forming a viscous gel that coats and protects gastric epithelial cells. D. Preventing the secretion of gastrin

Back 83

C. Forming a viscous gel that coats and protects gastric epithelial cells