pharm gi 2
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First-line H.pylori eradication combo therapy?
PPI + clarithromycin (500mg) + amoxicillin (1000mg) BID
Gastrointestinal Cycloprotectants -- prostaglandin analogues drugs
misoprostol (prostaglandin E1 [PGE1])
prostaglandin analogues MOA
mimics endogenous prostaglandins, acting on prostaglandin E receptor 3 (EP3) on parietal cells that cause reduced activity of proton pumps. also stimulates the secretion of mucus and bicarbonate and enhancing mucosal blood flow, helping to enhance the mucous barrier that protects the lining of the stomach.
prostaglandin analogues kinetics (T 1/2)
short half-life, so must be administered frequently (3-4 times daily)
prostaglandin analogues indications
prevention of NSAID-induced ulcers (NSAIDS inhibit the production of endogenous prostaglandins via COX inhibition)
prostaglandin analogues contraindications
pregnancy (cat x -- prostaglandins stimulate uterine contractions)
prostaglandin analogues side effects
severe diarrhea and abdominal cramping (prostaglandins stimulate GI smooth muscle contraction)
Gastrointestinal Cycloprotectants -- coating agents drugs
coating agents MOA
sucralfate is a complex of sucrose and aluminum hydroxide that forms a negatively-charged viscous paste in the acidic gut, which binds to positively charged proteins found in ulcers and forms a protective barrier for up to 6 hours. bismuth salts also form a protective barrier on ulcers, and additionally inhibit the growth and adherence of H.pylori to the mucosa. both also enhance secretion of prostaglandins, mucus, and bicarbonate.
coating agents pharmacokinetics (T 1/2)
sucralfate = has a short half-life and must be administered frequently (QID), take 1h ac because it is activated by acid (effectiveness can be decreased by antacids).
coating agents indications
sucralfate = ulcers. bismuth = H.pylori eradication, acute diarrhea, heartburn.
coating agents contraindications
bismuth = not used in children or teens with viral infections (because its combined with ASA, can lead to Reye's syndrome)
coating agents interactions
sucralfate = decreases concentrations of tetracycline, quinolone, levothyroxine, digoxin, and others by binding to them in the gut (separate dosing)
coating agents side effects
sucralfate = same as AlOH3. bismuth = black tarry stool, blackening of tongue, constipation, tinnitus.
dopamine antagonists (prokinetics) drugs
dopamine antagonists MOA
dopamine has an inhibitory effect on GI motility (D2 receptors inhibit ACh release), so antagonists will enhance motility. this includes increasing lower esophageal sphincter tone, and stimulating peristalsis. also act as antinauseants by central inhibition.
dopamine antagonists pharmacokinetics (availability)
domperidone = low oral bioavailability (extensively metabolized in first pass of liver), bioavailability increased with food, does not cross blood-brain barrier as easily as metoclopramide.
dopamine antagonists indications
disorders of GI motility (gastroparesis, nausea, vomiting), GERD, diagnostic procedures
dopamine antagonists contraindications
pts with obstruction or perforation
dopamine antagonists interactions
metaclopramide = increased concentrations of SSRI (serotonin storm, neuroletptic malignant syndrome)
dopamine antagonists side effects
hyperprolactinemia (dopamine inhibits prolactin release, so antagonism leads to increased prolactin which can result in gyynecomastia, galactorrhea, dysmenorrhea). metoclopramide = extrapyramidal issues (movement issues such as abnormal muscle tone, Parkinson-like sx, tardive dyskinesia), other CNS (drowsiness, restlessness, insomnia, anxiety, agitation), in infants rare methemoglobinemia.
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