Pharmacology of Antacids, H2 Blockers/Antagonists

Question 1

When should antacids be taken?

Answer 1

at the onset of heartburn symptoms (effects last up to 2 hrs) because onset of action will occur within minutes.
*FASTEST ACTING

Question 2

What are some antacids?

Answer 2

• sodium bicarbonate (Alka-Seltzer)
• calcium carbonate (Tums, Os-Cal)
• magnesium + aluminum hydroxide (Gelusil, Maalox, Mylanta)

Question 3

What should you not take calcium carbonate with?

Answer 3

tetracyclines, iron, fluoroquinolones, or itraconAZOLE (anti-fungal) bc it chelates them and decreases their effectiveness

Question 4

What is an ADR of magnesium and an ADR of aluminum hydroxide?

Answer 4

aluminum salts= constipation, magnesium salts= diarrhea, but together they cancel each other out :)
*long term use is contraindicated in renal insufficiency

Question 5

What are some ADRs of calcium carbonates (Tums…)?

Answer 5

metabolic alkalosis, renal insufficiency, and hypercalcemia

Question 6

How do the Antihistamine H2 blockers work?

Answer 6

inhibit NOCTURNAL release of acid and are better suited for duodenal over gastric ulcers.

Question 7

What are the specific antihistamine H2 blockers?

Answer 7

• cimetiDINE
• ranitiDINE
• famotiDINE
• nizatiDINE

Question 8

What is important to know about Cimetidine?

Answer 8

• antihistamine H2 blocker that undergoes 1st pass metabolism and BLOCKS the ANDROGEN RECEPTOR. (decreasing metabolism of estradiol, and increases prolactin levels) :(
• absorption may be decreased by antacids
• inhibits cytochrom P-450 enzymes
• can cause impotency and gynecomastia in men or galactorrhea in women.

Question 9

What is unique about Nizatidine?

Answer 9

• H2 blocker with fastest onset, no 1st pass metabolism, and best bioavailability.
• negligible P-450 inhibition
• NO ANDROGEN BLOCKING :)

Question 10

What is unique about Ranitidine (Zantac)?

Answer 10

• H2 blocker with minimal P-450 inhibition and NO ANDROGEN BLOCKING :)

Question 11

What is unique about Famotidine (Pepcid)?

Answer 11

• most potent H2 blocker with negligible P-450 inhibition and NO ANDROGEN BLOCKING :)

Question 12

What are some drug interactions involving the P-450 system with H2 blockers?

Answer 12

• benzodiazepines, phenytoin, and warfarin

Question 13

What are the MOST EFFECTIVE reducers of HCl secretion?

Answer 13

Proton Pump Inhibitors (PPIs) by IRREVERSIBLY inhibiting the H+/K+ ATPase

Question 14

When are PPIs used?

Answer 14

Zollinger-Ellison syndrome (gastrin-secreting tumors), gastric/duodenal ulcers, and gastroesophageal reflux disease (GERD).

Question 15

What are the specific PPIs?

Answer 15

• OmePRAZOLE (Prilosec)= only one that causes P450 inhibition.
• EsomePRAZOLE (Nexium)
• LansoPRAZOLE
• PantoPRAZOLE
• RaberPRAZOLE
• all should be taken on empty stomach and all undergo 1st pass metabolism.

Question 16

What are some ADRs of PPIs?

Answer 16

headache, rash, HYPERGASTRINEMIA (due to gastrin trying to stimulate more H+ production from negative feedback), and colonic cell hyperplasia.

Question 17

Are PPIs superior to H2 blockers with H. pylori infection, hemorrhagic ulcers/bleeding, and when pt is using NSAIDS?

Answer 17

YES

Question 18

When are H2 blockers better?

Answer 18

safer in pregnancy (except cimetidine), and have lower incidence of ADRs

Question 19

What is Sucralfate?

Answer 19

• cytoprotective agent that interacts with HCl to form a VISCOUS PASTE that binds to proteins in ulcers or erosions.
• claims to stimulate mucosal PG synthesis
• think of it like a band-aid for the stomach

Question 20

What must you remember with sucralfate regarding antacids, H2 blockers and PPIs?

Answer 20

administer 2 hrs prior to any of these drugs because it will inhibit the absorption of them.

Question 21

What is Misoprostol?

Answer 21

PGE1 analog the increases mucus/NO/HCO3- secretion, cell proliferation, and decreases acid secretion (via EP3 receptor).

Question 22

What are some important points about Misoprostol?

Answer 22

• must be taken 3-4x daily
• contraindicated in pregancy
• cramps are common side effect
• not used frequently

Question 23

What is Bismuth subsalicylate (Pepto-Bismol)

Answer 23

• colloidal preparation of bismuth (heavy metal, not absorbed) and salicylate (absorbed). Bismuth binds mucus glycoproteins, coats/protects GI, and increases mucus/HCO3- secretion, PG synthesis, and decreases intestinal secretions.
• indicated for dyspepsia (indigestion) and acute diarrhea.
• also has some bacteriocidal properties to H. pylori

Question 24

How do we treat Helicobacter pylori?

Answer 24

triple therapy of:

• PPI
• Clarithromycin
• amoxicillin or metronidazole
• using a PPI will increase the pH of the stomach, thus increasing the effectiveness of antibiotics (especially amoxicillin).

Question 25

How do we treat GERD?

Answer 25

- lifestyle modification - prokinetic agents - acid suppression - antireflux surgery

Question 26

What are the prokinetic drugs given for GERD?

Answer 26

- Metoclopramide= blocks enteric GI presynaptic dopamine D2 receptors, thus increasing ACh activity (cholinomimetic), which increases upper GI tone/motility. Also has anti-emetic effects - Bethanechol= muscarinic (M3) actions, which increases lower esophageal sphincter pressure and GI motility (rarely used) - Erythromycin (antibiotic)= motilin agonist

Question 27

What other drugs besides prokinetic drugs are given for GERD?

Answer 27

acid suppressors (H2 blockers, PPIs)

Question 28

What surgical approach can be taken for overproduction of stomach acid?

Answer 28

vagotomy to prevent vagal ACh secretion and thus acid production.