pharmacology of GORD Flashcards
Drug target of NSAID
cyclo oxygenase 2 but also inhibits COX 1 (adverse effects)
primary mechanism of action of NSAID
By inhibiting COX1, prostaglandin synthesis is reduced. . Prostaglandins sensitise peripheral nociceptor mediators to (eg histamine and bradykinin) which causes pain.
Explain how NSAIDs can lead to stomach injury
COX 1 is also inhibited. COX1 produces prostaglandins . These PGs protect the stomach mucosa by: producing increasing mucus production, increasing bicarbonate production, and increasing blood flow. Those protective mechanisms are decreased if COX 1 is inhibited
Primary mechanism of action of PPIs
Irreversible inhibitors of H+/K+ ATPase in gastric parietal cells. They are weak bases and accumulate in the acid environment of the canaliculi of the parietal cells. This concentrates their actions there and prolongs their duration of action
What and why are PPIs usually coated in
Generally given orally but degrade rapidly at low pH so administered as capsules containing enteric-coated granules.
How are PPIs activated
PPIs are pro-drugs which, at low pH, are converted into 2 reactive species which react with sulphydryl groups in the H+/K+ ATPase responsible for transporting H+ ions out of the parietal cells.
Target of PPIs
H+/K+ ATPase (‘proton pump’)
side effects of PPIs
Unwanted effects are uncommon but may include headache, diarrhoea, bloating, abdominal pain & rashes.
The use of these drugs may mask the symptoms of gastric cancer.
Omeprazole is an inhibitor of cytochrome P2C19 and has been reported to reduce the activity of e.g. clopidogrel, when platelet function is monitored.
What are NSAIDs contra indicated in
asthma as side effect is bronchoconstriction
side effects of NSAIDs
Common unwanted effects include gastric irritation, ulceration and bleeding and, in extreme cases, perforation; reduced creatinine clearance and possible nephritis; and bronchoconstriction in susceptible individuals (contraindicated in asthma). Skin rashes & other allergies, dizziness, tinnitus.
Adverse cardiovascular effects (hypertension, stroke, MI) may occur following prolonged use or in patients with pre-existing CV risk.
Prolonged analgesic abuse over a period of years is associated with chronic renal failure.
Mechanism of action of H2 receptor antagonists
H2 antagonists are competitive antagonists of H2 histamine receptors (structural analogues of histamine). They inhibit the stimulatory action of histamine released from enterochromaffin-like (ECL) cells on the gastric parietal cells. They inhibit gastric acid secretion by approximately 60%.
Target of ranitidine
H2 receptor
Side effects of ranitidine
Incidence of side-effects is low. Diarrhoea, dizziness, muscle pains & transient rashes have been reported.
Cimetidine (but not other H2 antagonists) inhibits cytochrome P450 and may retard the metabolism and potentiate the effects of a range of drugs incl. oral anticoagulants and TCAs
Bioavailability of H2 receptor antagonists
Undergo 1st pass metabolism (50% bioavailability).
plasma half life of ranitidine
Ranitidine plasma half-life approx. 2-3 h – well tolerated so twice daily dosing effective.
