Pharmacology of GORD Flashcards
What is the primary 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.
What is the drug target of NSAIDs and examples?
Cyclo-oxygenase (COX) enzyme is target. Examples: ibuprofen, naproxen, diclofenac.
What are the main 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.
Aspirin has been linked with a rare but serious post-viral encephalitis (Reye’s syndrome) in children.
What are some extra facts about NSAIDs?
The main uses of NSAIDs are as analgesics for the relief of mild to moderate pain (e.g. musculoskeletal pain, headache, dysmenorrhoea); as antipyretics to reduce fever; as anti-inflammatory drugs for chronic control of inflammatory diseases (e.g. rheumatoid arthritis, osteoarthritis); and (aspirin only) as an anti-aggregatory agent to inhibit platelet aggregation in patients who are at risk of stroke or myocardial infarction.
What is the 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 (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 is the drug target of PPIs and examples?
H+/K+ ATPase (‘proton pump’). Omeprazole, lansoprazole.
What are common 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 2 facts about 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.
What is the primary 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 is the drug target of histamine receptor antagonists and what are some examples?
Histamine H2 receptors. Ranitidine.
What are side effects of histamine receptor antagonists?
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.
What are facts about histamine 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.
What is the mechanism of action of paracetamol?
Its actions appear to be largely restricted to nervous tissue but its mechanism of action is unclear. Current hypotheses suggest both a central and peripheral action possibly involving interaction with a COX-3 isoform (inhibition of PG synthesis), cannabinoid receptors or the endogenous opioids. Interactions at 5HT & adenosine receptors have also been proposed.
What is the drug target of paracetamol?
Not yet well defined. COX-3 isoform?
What are the side effects of paracetamol?
Generally a very safe drug with few side-effects at therapeutic doses. It does not cause gastric irritation but in overdose serious hepatotoxicity may occur. Occasional allergic skin reactions.
