Cyclooxygenase inhibitors, NSAID - General features
Cyclooxygenase inhibition produces beneficial and adverse effects. The consequences of administration of a NSAID, taking into account the different cyclo-oxygenases and their different tissue distribution are necessarily complex. Schematically one can distinguish useful and harmful effects but the same effect can be both: thus an antiplatelet effect is useful to avoid thromboembolic disorders but can be harmful by causing bleeding.
Useful effects in therapeutics:
anti-inflammatory effect
antalgic effect
antipyretic effect
inhibition of platelet aggregation and decrease of thromboembolic risk (well-known with aspirin at low doses)
hypocalcemic effect (during hypercalcemia.)
inhibition of colic tumor development
Adverse effects:
O gastralgia, gastroduodenal ulcerations and digestive bleeding due primarily to COX-1 inhibition
prolongation of pregnancy (if the NSAID is taken by the pregnant woman in late pregnancy)
premature closure of the ductus arteriosus
aggravation of renal impairment by insufficient vasodilator prostaglandin synthesis to counter the vasoconstrictive effect of catecholamines and angiotensin, retention of salt and water and increase of blood pressure
aggravation of a heart failure
decrease of the resistance of the body with respect to an infectious agent (microbe, parasite, etc). The prescription of a NSAID during an infectious state not controlled by an antibiotic does not seem desirable
increase of the risk of bleeding
delay possible, in the event of sustained administration in large doses, of the osseous consolidation after fracture.
Concerning pharmacokinetics, NSAID are usually administered by oral route, have a good bioavailability, bind to plasma proteins with 90% on average. Their plasma half-life is about a few hours, except for piroxicam and tenoxicam where it is approximately 48 hours. Drugs containing active principles whose half-life is short can, when formulated in sustained-release forms, have apparent long half-lives. They are called sustained-release NSAID. NSAID undergo many hepatic biotransformations and their metabolites are eliminated primarily by the kidney.
The chemical classification of NSAID is of no interest because it does not have any consequences. A classification according to the preferential inhibition of type I and type II cyclo-oxygenases is currently proposed.
