GORD Flashcards
What are the two main categories of drugs used to treat GORD?
PPIs
Histamine receptor antagonist
Name examples of PPIs
Omeprazole
Lansoprazole
Name an example of H2 receptor antagonist
Rantidine
What is the drug target of PPIs
H+/K+ ATPase (‘proton pump’)
What is the drug target of H2 receptor antagonist?
Histamine H2 receptor
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
Proton pump inhibitors inhibit basal and stimulated gastric acid secretion by >90%.
Mechanism of action of H2 antagonist
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%.
Side effectcs of PPIs
Uncommon:
– headache, diarrhoea, bloating, abdominal pain & rashes.
– 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.
Side effects of H2 receptor antagonist
Uncommon:
– 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.
Extra information on PPIs
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.
Generally given orally but degrade rapidly at low pH so administered as capsules containing enteric-coated granules.
Extra information on H2 receptor antagonists
Ranitidine plasma half-life approx. 2-3 h – well tolerated so twice daily dosing effective. Undergo 1st pass metabolism (50% bioavailability).
Low dose over-the-counter formulations available from pharmacies for short term use without prescription.
Mechanism of action of NSAIDs
NSAIDS inhibit the enzyme cyclo-oxygenase (COX) which is the rate-limiting step for the production of all prostanoids (prostaglandins & thromboxanes) from the parent arachidonic acid.
Prostanoids act through a large number of prostanoid receptors to produce a highly complex array of actions.
It is thought that the anti-inflammatory actions, and probably most of the analgesic & antipyretic actions, of the NSAIDs are related to inhibition of COX-2, while their unwanted effects are largely a result of inhibition of COX-1
Drug Target of NSAIDs
COX2 enzyme
Mechanism of action of paracetamol
Still not totally clear.
At peripheral sites, may inhibit a peroxidase enzyme which is involved in the conversion of arachidonic acid to prostaglandins (1st step in this pathway involves the enzyme, cyclooxygenase). The ability of paracetamol to inhibit peroxidase can be blocked if excessive levels of peroxide build up (as is commonly seen in inflammation)
Activation of descending serotonergic pathways possibly via 5HT3 receptor activation.
Inhibits reuptake of endogenous endocannabinoids, which would increase activation of cannabinoid receptors - this may contribute to activation of descending pathways.
Drug Target of Paracetamol
Unclear.
5HT3 receptors/Cannabinoid reuptake proteins/Peroxidase
