Pharmacology of GORD Flashcards
What drugs are used to treat GORD?
- NSAIDs
- PPIs
- H2 receptor antagonists
What are examples of NSAIDs?
- Ibuprofen
- Naproxen
- Diclofenac
What is the drug target of NSAIDs?
Cyclo-oxygenase (COX) enzyme
What is the primary mechanism of action of NSAIDs?
Inhibit the enzyme 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.
What are the main side effects of NSAIDs?
Common
gastric irritation
ulceration
bleeding
Extreme cases
perforation
reduced creatinine clearance nephritis
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.
Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children.
What are the uses of NSAIDs?
Analgesics for the relief of mild to moderate pain (e.g. musculoskeletal pain, headache, dysmenorrhoea); Antipyretics to reduce fever; as anti-inflammatory drugs for chronic control of inflammatory diseases
What are examples of PPIs?
omeprazole, lansoprazole
What is the drug target for PPIs?
H+/K+ ATPase (‘proton pump’)
What is the mechanism of action for 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
(omeprazole plasma half-life approx. 1 h but single daily dose affects acid secretion for 2-3 days). Proton pump inhibitors inhibit basal and stimulated gastric acid secretion by >90%.
What are the side effects of PPIs?
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 is the drug target of histamine 2 receptor antagonists?
Histamine H2 receptor
What are examples of histamine receptor antagonists?
Ranitidine
What is the mechanism of action of histamine 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%.
What are the side effects of histamine receptor antagonists?
Diarrhoea, dizziness, muscle pains & transient rashes have been reported.
Cimetidine inhibits cytochrome P450 and may retard the metabolism and potentiate the effects of a range of drugs incl. oral anticoagulants and TCAs.
What form do PPIs exist in?
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.
