GORD/Peptic Ulcer Pharmacology Flashcards
what is the MOA for NSAIDs?
inhibit enzyme cyclo-oxygenase (which generates prostaglandins and thromboxanes)
exibits analgesic effects by reduced prostaglandin effects so less sensitisation to pain
also anti inflammatory via reduced prostaglandin effects
what is the drug target for NSAIDs?
cyclo-oxygenase enzyme (COX-1 &2)
what are the main side effects for NSAIDs?
gastric irritation, ulceration, bleeding, perforation
REDUCED CREATININE CLEARANCE, nephritis,
bronchoconstriction
skin rashes,
dizziness,
tinnitus
what are the risks of long term NSAID use?
CV effects - stroke, MI, hypertension
chronic renal failure/CKD
what is the MOA for proton pump inhibitors?
irreversible inhibitor of H+/k+ATP pump in gastric parietal cells
therefore inhibits basal and stimulated gastric acid secretion by over 90%
what is the drug target for PPIs?
H+/K+ ATP pump
what are the main side effects of PPIs?
headache, diarrhoea, bloating, abdominal pain, rashes
may mask gastric cancer
what is the MOA for H2 receptor antagonists?
competitive antagonists of H2 histamine receptors
inhibit stimulatory action of histamine release from enterochromaffin-like cells on gastric parietal cells
inhibits gastric acid secretin by ~60%
what is the drug target for H2 receptors antagonists?
histamine H2 receptor on gastric parietal cells
stops histamine action after its release from enterochromaffin like cells
what are the main side effects of histamine H2 receptor antagonists?
fairly uncommon diarrhoea, dizziness, muscle pains, transient rashes
give examples of H2 receptor antagonists?
cimetidine, rantidine
give examples of PPIs?
omeprazole
lansoprazole
give examples of NSAIDs?
ibuprofen
naproxen
diclofenac
what is an additional side effect of cimetidine (an H2 receptor antagonist)?
inhibits cytochrome P450 may retard metabolism and effect drugs e.g anticoagulants, TCAs
what is the MOA of paracetamol?
unclear
activation of descending serotinergic pathways possibly via 5HT3 receptor
mild inhibition of cylcooxygenase
inhibits reuptake of endogenous endocannabinoids increasing activation of cannabinoid receptors
what is the drug target for paracetamol?
not yet defined
what are the main side effects of paracetamol?
very few effects
in overdose, severe hepatotoxicity
how should the adverse GI effects for NSAIDs be avoided?
if any upper abdominal discomfort arises, stop any oral or topical use
how do NSAIDs cause GI side effects?
the role of COX-1 includes protection of the stomach lining. this is achieved by increasing bicarbonate release, mucus production and blood flow in gastric mucosa
reducing the stomachs protection may cause discomfort and irritation, ulceration, bleeding, perforation
why should those with osteoporosis not be prescribed PPIs and instead use H2 blockers?
increased risk of osteoporosis related fractures
potentially due to altering pH which calcium absorbance is dependent on normally, decreasing amount of calcium available for bone
first management step of GORD
test for h.pylori first
first line for h.pylori positive
PPI and clarithromycin + amoxicillin (triple therapy)
first line for h. pylori negative
address risk factors e.g NSAIDs
if cant be stopped, consider misoprostol or selective COX2 inhibitor
first line for GORD with no reversible cause long term
PPI
2nd line for no reversible cause long term
H2 receptor antagonist
what condition are NSAIDs contraindicated for?
asthma