NONSTEROIDAL ANTIINFLAMATORY DRUGS(NSAIDS)
Definition :Non steroidal anti inflammatory drugs is a class of analgesic medication that reduces pain, fever & inflammation . Pain: It is a neurophysiological sensation arising from noxious stimulus. Fever : It is a elevation of body temperature. Inflammation : It is a localized physical condition in which part of the body becomes reddened , swollen ,hot & often pain full ,especially as a reaction to infection
Classification: Non selective Preferential Selective Cox3 Cox inhibitors cox2 inhibitors cox2inhibitors inhibitors
Non selective COX inhibitors: Salicylates : aspirin Propionic acid derivatives : ibuprofen Anthranillic acid derivative : mephenamicacid Aryl acetic acid derivatives : diclofenac
Preferential cox2 inhibitors : nimesulide , meloxicam nabumetone Selective cox2 inhibitors :celecoxib , etoricoxib Cox3 inhibitors : para acetamido phenol
Mechanism of action: Cell wall phospholipids phospho lipase A2 Arachidonic acid COX enzyme cyclo endo Hydroxy acid peroxides of arachdonic acid prostaglandins leuko trienes
Cox 1:This activity is constitutively present in nearly all cell types at constant level . Cox 2: This activity is normally absent from cells except those of kidneys & brain but it is inducible by bacterial lyposaccharides IL2 &TNF in activated leucocytes &other inflammatory cells. Cox 1 is a physiological while Cox 2 is usually pathological
SALICYLATES: Aspirin: it is a acetyl salicylic acid it is rapidly converted in the body to salicylic acid which is responsible for most of the actions . Other actions are the result of acetylation of certain macro molecules including COX it is the of the oldest analgesic, anti inflammatory drugs & is still widely used
Pharmacological actions: Analgesic , anti pyretic , anti inflammatory actions of aspirin: aspirin is weaker analgesic than morphine like drugs aspirin 600mg similar to codeine 60mg .how ever it effectively relives anti inflammatory action.
Respiration: the effects are dose dependent . at anti inflammatory doses , respiration is stimulated by peripheral ¢ral actions further rising of Salicylate level causes respiratory depression , death is due to respiratory failure Acid base electrolyte balance: anti inflammatory doses produce significant changes in the acid base &electrolyte composition of body fluids. initially respiratory stimulation predominates &tends to wash out CO2
CVS: aspirin has no direct effect in therapeutic doses larger dose increase in cardiac output and increased oxygen levels and cause direct vasodilation . GIT: aspirin and released salicylic acid irritate gastric mucosa BLOOD: Aspirin having anti coagulent property .long term intake of large dose decreases synthesis of clotting factors in liver
USES: Its is used as analgesic, anti pyretic &treatment of acute rheumatic fever &rheumatoid arthritis & osteoarthritis Adverse effects: Ibuprofen & all its congeners are better tolerated than aspirin . side effects are milder and their incidence is lower gastric discomfort , nausea ,and vomiting , though less than aspirin or indomethacin. CNS side effects include headache, dizziness.
Precautions : aspirin is contraindicated in patients who are sensitive to it and in peptic ulcer ,bleeding tendencies In children suffering from chicken fox or influenza. In chronic liver disease cases of hepatic necrosis have been reported . Aspirin should be stopped one week before electric surgery Given during pregnancy it may be responsible for low birth weight babies It should be avoided by breast feeding methods &also in diabetics
Conclusion: Inhibition of COX-1& COX-2 by NSAIDS in gastro intestinal track has been associated with both adverse and beneficial effects. The effects of NSAIDS & COX-2 inhibitors in patients with inflammatory bowel disease are still unclear. New nitric oxide-NSAIDS derivates, may prevent the colon cancer.
References: Abenavoli L, capasso R ,Millic N ,et al A Book on pharmacology by NM agarwal