Upper GI Pharmacology Flashcards
Antacid pharmacokinetics
tablets/powder, suspension Poorly absorbed (unless poor renal function), thus minimal undesired systemic side effects Di/tri-valent cations; may chelate other drugs, separate dosing
Antacid MOA
Locally buffer H+ to increase pH
Antacid indications
heartburn, dyspepsia
Antacid SE
Mg-containing: osmotic diarrhea (explosive)
Ca-containing: constipation, hypercalcemia, calculi, bloating, nausea (due to CO2 liberated)
Al-containing: constipation, hyperphosphatemia
H2 antagonist prototypes
ranitidine, cimetidine
H2 antagonist PK
po; some iv and im
rapidly absorbed
renal elimination (filtration and secretion) - adjust dosing in renally impaired patients
Cimetidine: notorious CYP450 blocker
H2 antagonist MOA
H2 receptors on parietal cells mediate basal, nocturnal, and meal-stimulated release of acid (histamine binding stimulates H/K ATPase via cAMP)
Reversible blockage
H2 antagonist indications
GERD
PUD
Dyspepsia
Prevention of bleeding from stress-related gastritis
H2 antagonist SE
generally well-tolerated
diarrhea/constipation, headache, fatigue, MSK pain
Cimetidine only: gynecomastia and galactorrhea
PPI prototypes
omeprazole, pantoprazole
PPI PK
must be absorbed into systemic circulation
act locally on GI tract cells (parietal cells)
Prodrugs: activated in acidic canaliculi of parietal cells
hepatic clearance - adjust dosing in liver impaired patients
PPI MOA
antagonist of proton-secreting pump in stomach (K/H pump) on parietal cells
irreversible
PPI indications
gastric and duodenal ulcers, NSAID-induced ulcers
GERD
Pathological hypersecretory conditions (Zollinger-Ellison, where levels of hormone are increased due primarily to gastrinoma tumour of non-beta islet cells in the pancreas)
PPI SEs
generally well-tolerated short term
nausea, ab pain, constipation/diarrhea, flatulence (alteration in intestinal flora due to pH change)
less common: hypergastrinemia, due to rebound secretion of gastric acid if PPI is stopped after short-term use
Misoprostol PK
short half-life
Misoprostol MOA
PG analogue
endogenous PGE2 binds EP3 on parietal cells –> reduces activity of proton pump and stimulates mucin and bicarb secretion to bolster mucosal barrier
endogenous PGE2 is made by COX1
PGE-1 analogues (misoprostol) given as adjuncts in patients on NSAIDs
Misoprostol indications
NSAID-induced gastric ulcer
Misoprostol SEs
diarrhea, abd cramping (stimulates smooth muscle contraction in GI and uterus)
Sucralfate PK
local GI action, minimal absorption (fecally excreted)
activated by acid
contains Al, which is excreted renally - adjust for renal impaired patients
Sucralfate MOA
complex of sucrose and AlOH –> viscous paste in acid aqueous media (direct
stimulates PG synthesis of mucus and bicarb secretion (indirect)
Sucralfate indications
Tx and prevention of gastric and duodenal ulcer
Sucralfate SE
constipation (Al)
minimal systemic effects due to poor absorption
Bismuth MOA
form protective barrier on ulcer
enhance PG, mucus, bicarb secretion
inhibit H. pylori growth and adherence
Bismuth indications
Adjunctive therapy in H. pylori eradication
acute diarrhea