pharm gi 1
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calcium carbonate (CaCO3), aluminum hydroxide (AlOH3), magnesium hydroxide (MgOH2)
buffers are bases that directly react with and neutralize stomach acid (increase pH)
Buffers pharmacokinetics (absorption, formulation)
Calcium, aluminum, and magnesium are typically poorly absorbed by the gut (unless given in very high doses). suspensions (dissolved in liquid) work better than powders.
hyperacidity (including reflux), indigestion
Buffers interactions x2
cations may chelate other drugs, interfering with their absorption. Can also change gut pH, interfering with drugs that require a certian pH (true of all antacids! examples: decreased concentrations of tetracyclines, quinolones, biphosphonates). *both of these issues can be overcome by separating administration*
should you combine magnesium and Kalexate?
Buffers side effects x3
CaCO3 = hypercalcemia, gas (carbon dioxide liberation from carbonate), constipation. Al = hypophosphatemia (binds to phosphate in gut, not absorbed), constipation. Mg = diarrhea (magnesium salt draws water into the gut).
Buffer combinations x2
Aluminum (slow reacting, constipation) often combined with magnesium (fast reacting, diarrhea). Simethicone is a surfactant often added to buffers to decrease bloating.
Milk alkali syndrome?
hypercalcemia and alkalosis caused by ingestion of large amounts of calcium antacids
H2 (histamine) Antagonists drugs
"idines" -- ranitidine, cimetidine, famotidine, nizatidine
H2 Antagonists MOA
binding of histamine to H2 receptors on parietal cells stimulates the secretion of H+ (sodium/potassium pump) via second messengers and cAMP. antagonists competitively block histamine binding, and therefore decrease acid secretion (particularly nocturnal acid secretion).
H2 Antagonists indications
too much acid (GERD, PUD, dyspepsia, gastritis), gastric protection in pts on life support
H2 Antagonists interactions
cimetidine inhibits CYP450 so numerous potential interactions (used less frequently because of this, also has to be prescription)
H2 Antagonists side effects
common diarrhea, HA, drowsiness, fatigue, muscle pain, constipation. rare confustion, delerium, slurred speech, thrombocytopenia.
cimetidine additional side effects
gynecomastia and galactorrhea
Can H2 antagonist tolerence occur?
Proton Pump Inhibitors (PPIs) (antisecratory agents) drugs
"prazoles" -- omeprazole, pantoprazole, lansoprazole, esomeprazole, rabeprazole
bind to active proton pumps, resulting in an irreversible inactivation of the pump and reducing the amount of H+ produced (increases pH). stomach has to make new pumps, which can take up to 48 hrs.
PPIs are prodrugs and access the proton pumps via the systemic circulation. Tablet is protected by an enteric coating until it reaches the small intestine, where it is absorbed and travels through the blood stream back to the stomach. Once it reaches the acidic stomach via this backdoor root, the prodrug PPI is activated by the acidic environment of the parietal cells. Take 30-60 mins ac for maximal activation and best results.
acid issues (GERD, ulcers, hypersecretory conditions like Zollinger-Ellison). also upper GI bleeding.
omeprazole is an inducer of CYP1A2, but an inhibitor of CYP2C19 (effects of this include increased concentrations of warfarin, diazepam, phenytoin, digoxin, and carbamazepine).
PPI side effects
GI (N/D, constipation, pain, gas). Less common hypergastrinemia (gastrin hormone levels elevated because it is upstream of the acid suppression) -- can lead to rebound acidic hypersecretion with abrupt cessation of PPIs. Possible link between PPIs and C.diff.
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