NSAIDs Flashcards
What is the mechanism of action of NSAIDs?
Inhibit prostaglandin biosynthesis by inhibit cyclo-oxygenase (COX)
What is COX?
A key enzyme in the synthesis of prostaglandins and thromboxanes
What is the function of prostaglandins and thromboxanes?
Important mediators of the erythema, oedema, pain, and fever in inflammation
What are the isoforms of COX?
COX-1 (constitutive form)
COX-2 (inducible form)
Where is COX-1 present?
Platelets, stomach, kidneys, and other tissues
Where is COX-2 present?
In inflamed tissues when there is stimulation by cytokines.
Also present to a lesser extent in healthy organs, including the kidneys
What was the intention with the development of selective COX-2 inhibitors?
Reduced gastric toxicity
What is the problem with the development of COX-2 inhibitors?
Several of the developed drugs increased anti-thrombotic events, probably as a class effect related to inhibition of basal prostacyciln biosynthesis.
What is the use of NSAIDs?
Provide symptomatic relief in acute and chronic inflammation
Other kinds of pain, including mild (headaches, dysmennorhoea, muscular sprains) and severe (metastatic bone cancer) might also respond to NSAIDs
Do NSAIDs change the course in chronic inflammatory conditions?
No
How does aspirin differ from other NSAIDs?
It irreversibly inhibits COX-1, and so can be used as an anti-platelet drug, as well as maintaining its mild analgesic effects
What systems might experience adverse effects as a result of NSAID use?
GI, renal, respiratory, CVS, hepatic.
What are the GI adverse effects of NSAIDs?
Gastritis, gastric mucosal ulceration and bleeding
What are the renal adverse effects of NSAIDs?
Vasoregulatory renal impairment, hyperkalaemia, nephritis, interstitial nephritis, nephrotic syndrome
What are the respiratory adverse effects of NSAIDs?
Bronchospasm
What are the CVS adverse effects of NSAIDs?
Cardiac failure with fluid retention, MI
What are the hepatic adverse effects of NSAIDs?
Biochemical hepatitis
How can the adverse effects of NSAIDs on the stomach be reduced?
Co-administration with omeprazole
What are the main prostaglandins produced in the human kidney?
Prostacyclin (PGI2) and prostaglandin E2
In whom do NSAIDs cause functional renal impairment?
Patients with pre-existing glomerular disease, or with systemic disease in which renal blood flow is dependant on the kidneys ability to synthesise vasodilator prostaglandins (PGI2 and prostaglandin E2)
Elderly especially at risk.
What systemic diseases depend on the kidneys ability to synthesise PGI2 and prostaglandin E2?
Heart failure, salt and water depletion, cirrhosis, and necrotic syndrome
Is renal impairment with NSAID use reversible?
Yes, if stopped promptly
What NSAIDs less commonly cause renal impairment?
Aspirin, or low doses of sulindac
What drugs to NSAIDs inhibit with as a result of their effect on renal prostaglandin biosynthesis?
Anti-hypertensive medications (makes them less effective)
What is the result of PGE2 and PGI2 having natriuretic properties on the adverse effects of NSAIDs?
It means that NSAIDs can cause salt and water retention, and so antagonist the effects of diuretics and exacerbate heart failure.
Why should lithium be closely monitored when co-administered with NSAIDs?
Because NSAIDs reduce lithium ion clearance
What effect do NSAIDs have on plasma potassium ion concentration?
Increase it
In whom do NSAIDs worsen bronchospasm?
In aspirin-sensitive asthmatics, who sometimes have a history of nasal polyps and utricaria
What patient group is particularly susceptible to NSAID -induced hepatitis?
Elderly
How does ibuprofen compare to paracetamol?
Ibuprofen has a similar analgesic potency, but also has useful anti-inflammatory activity
What are the indications for ibuprofen?
Painful conditions with an inflammatory component, e.g. sprains and minor soft tissue injury
Useful in dysmenorrhoea
What is naproxen used for?
Rheumatic and musculoskeletal diseases, acute gout, and dysmenorrhoea
How does naproxen compare to aspirin?
It is approx. 20x as potent an inhibitor of COX as aspirin.
An additional property of naproxen is inhibition of leukocyte migration
