GI pharmacology Flashcards
GORD - management?
PPIs e.g. omeprazole, esomeprazole, rabeprazole, pantoprazole, lansoprazole
if incomplete response, add H2RA then fundoplication
Gastritis - treatment for erosive, non erosive and autoimmune causes
erosive - stop irritants, PPI or H2RA
non erosive - triple therapy: PPI, amoxicillin, clarythromycin/metronidazole
autoimmune - cyanocobalamin treatment
PID - treatment for H pylori +ve and -ve
h pylori - h pylori eradication regime, test using carbon 13 urea breath test
non h pylori - stop NSAIDs, consider COX2, PPI, if NSAIDs needed then consider misoprostol which decreases proton pump activity
what are gastric prostaglandins and what do they do?
PGE2 and PGI2
potent vasodilators, decrease acid, stimulate mucus and HCO3-, decrease permeability of epithelium to back flow of acid, decreases release of inflammatory mediators
describe parietal cells in non secreting and secreting states
in non secreting states, proton pumps (H,K-ATPase) are located in membrane bound compartment (tubulovesicles), which lack K+ permeability blocking the proton pump. the apical membrane of the parietal cell has K+ channels and involutions (canaliculi) which have microvilli
in secreting states, tubulovesicles fuse with canalicular membrane which moves the proton pump to a position where they can exchange H+ for K+, this involves huge movement of membrane to canaliculi and elongation of microvilli
how do PPIs work, why do they need an enteric coating and what are some adverse effects?
PPIs are weak bases and accumulate in the acidic parietal cell canaliculus giving them a high concentration in the luminal surface of the cell.
they bind covalently to gastric proton pumps and block function
need coating to prevent premature activation in stomach
they are metabolised by CYP450, generally well tolerated but can cause headache, nausea, GI issues. causes increased gastrin which leads to parietal cell and ECL hyperplasia so concern of tumours
increased hip fracture risk due to increased pH
H2 receptor antagonists - name, mechanism, side effects
cimetidine
competitively inhibits binding of histamine to H2 receptors
- indirectly blocks effects of gastrin and ach on parietal cell, and activation of PKA helps change the shape of the parietal cell creating the canaliculi
- metabolised by CYP450
diarrhoea, constipation, muscle ache, fatigue
prostaglandin analogues - use, name, mechanism, side effects, contraindications
for NSAID induced ulcers
misoprostol - acts on PGE2, affects a similar pathway to H2RA
diarrhoea, abdo pain
pregnancy, causes uterine contractions
antacids - use, 4 types and their details
symptom relief for dyspepsia by neutralising HCl as they react with acid to form water and salt
aluminium hydroxide - constipation, can bind phosphate so decreases phosphate levels, and can cause neurotoxicity in renal failure presence.
magnesium hydroxide - diarrhoea, avoid in renal failure as increases Mg levels
sodium bicarbonate - reacts with HCl to form water, CO2 and salt. avoid in hypertension and fluid overload
calcium carbonate - reacts with HCl to form CaCl and CO2
describe step up/ step down therapy for GORD
PPI therapy for best symptom control, some pt’s do well with H2RAs.
start pt’s on H2RAs then PPI if need to step up, start pt’s on PPIs and then see if H2RAs can maintain for step down.
how does h pylori cause damage, and what is the treatment?
thrives in upper GI tract as microaerophlic, has flagella, can attach to gastric epithelia and produces urease. damages epithelium by promoting strong immune response, ammonium hydroxide is toxic to epithelia and endotoxins are produced.
triple therapy approach - PPI with 2 antibiotics
