Non steroidal anti-inflammatory drugs.pptx

Nsaids

1. Non steroidal anti-inflammatory drugs By Dr Ayesha Jamil

2. CLASSIFICATION 1) Non-Selective COX inhibitors: Salicylates : Aspirin . Propionic acid derivatives : Ibuprofen,ketoprofen , naproxen. Acetic acid derivatives : Diclofenac . Fenamic acid derivatives: Mefenamic acid. Pyrrolo-pyrrole derivatives : ketorolac Oxicam derivatives : piroxicam , tenoxicam . Indole derivatives : indomethacin , sulindac

3. classification Preferential COX 2 inhibitors: nimesulide , meloxicam . Higly selective COX 2 inhibitors: etoricoxib , parecoxib . Analgesic---Antipyretic with poor anti-inflammatory effect: paracetamol nefopam .

4. COX is an enzyme responsible for the biosynthesis of PG’s. there are two isoforms of COX, COX1 and COX2. Cyclooxygenase-1 (COX-1) : responsible for the physiologic production of prostanoids . It is a constitutive enzyme that regulates normal cellular processes, such as gastric cytoprotection , vascular homeostasis, platelet aggregation, and reproductive and kidney functions.  Cyclooxygenase-2 (COX-2) : causes the elevated production of prostanoids that occurs in sites of chronic disease and inflammation. It  is constitutively expressed in tissues such as the brain, kidney, and bone. Its expression at other sites is increased during states of chronic inflammation

5. Mechanism of action of aspirin Aspirin & most of the other NSAIDS inhibit COX , there by inhibiting the synthesis of PG;s & thromboxanes . The anti-inflammatory effect of all the NSAIDS is mainly due inhibition of COX2 activity. Inhibition of COX by aspirin is irreversible, however others inhibit them reversibly.

6. Pharmacological actions of Aspirin & other NSAIDS Analgesic activity: Nsaids are used for the releive of muscle pain, dysmenorrhea & pain associated with inflammation & tissue injury. Ananlgesic activity is due to the inhibition of PG’s production. Also NSAIDS increase the threshold to pain in the subcortical region. Anti-pyretic activity: NSAIDS reset the hypothalamic thermoregulatory center in fever& reduce the fever. This they do by inhibiting the production of PG’s in the thermoregulatory center. They also reduce temperature by causing cutaneous vasodilatation and sweating.

7. Anti-inflammatory acivity : anti-inflammatory activity is seen with high doses of NSAIDS( 4-6mgs in divided doses). This effect is mainly due to the inhibition of PG’s at the site of tissue damage. They also inhibit the release of other mediators of inflammation. They also inhibit the adherence of leukocytes at the sit e of injury. Anti-thrombotic ( anti-platelet) effect: In low doses (50-325mgs) it reversibly inhibits TXA2 of the platelets & gives anti-platelet effect, this effect last till the regeneration of new platelets. In high doses (2-3mgs)it inhibits both TXA2& PGI2. so the beneficial effect of PGI2 is lost.

8. Acid-base and electrolyte balance . Antiinflammatorydoses produce significant changes. Initially respiratorystimulation predominates and tends to wash out CO 2 despite increased production and the result is respiratory alkalosis , which is compensated by increased renalexcretion of HCO 3 - (with accompanying Na + , K + , and water). Most adults treated with 4–6 g/daily of Aspirin stay in a state of compensated respiratory alkalosis. Still higher doses cause respiratory depression with CO 2 retention, while excess CO 2 production continues to develop respiratory acidosis . To this are added dis-sociated salicylic acid as well as metabolic acid(because there is rebound depression). It develops uncompensated metabolic acidosis . Dehydration occurs in poisoning due to increased water loss in urine.

9. GIT: Due to the inhibition of the cytoprotective PG’s (PGE 2 & PGI 2 ) acid secretion is increased and mucus secretion is decreased leading to gastric ulcers. Also it stimultes the CTZ causing vomiting. CVS: Prolonged use of NSAIDS cause salt 7 water retention leading to HTN further increased load on the failing heart (CCF). Urate excretion: salicylates in therapeutic amount inhibit urate secretion in urine increasing plasma concentration of urates . In high doses it promotes excretion of uric acid leading to uricosuric effect.

10. Adverse effects GIT : Nausea , vomiting , dyspepsia,epigastric pain, acute gastritis, ulceration and GI bleeding. Ulcerogenic effect is the major draw back of NSAIDS. Hypersensitivity reactions: These reactions are more common with ASPIRIN. The menisfestations are skin rashes, urticaria , rhinitis,bronchospasm , angioneurotic edema and rarely anaphylactoid reaction. In G6PD DEFFICIENT patients it causes hemolytic anemia. Prolonged use causes vit K defficiency there by leading to hypoprothrombinemia . Reye’s syndrome : children with viral disease ( mumps etc) leads to severe heptic damage and encephalopathy---Reye’s syndrome. Pregnancy : due to inhibition of PG’s it prolongs labour and increase the incidence of PPH. In neonates deficiency of PG’s laeds to premature closure of ductus arteriosus . Analgesic nephropathy: slowly progresssive renal failure has been observed with chronic use NSAIDS.

11. clinical uses As Analgesic : As anti-pyretic: paracetamol is preferred (as GI symptoms are rare, reye’s syndrome is doesn’t occur with it . Rheumatoid arthrits : NSAIDS only give the symptomatic relief . Acute rheumatic fever: aspirin is the preferred drug as it reeduces fever, relieves swelling & joint pain, but effect the course of disease. Osteoarthritis : In mild cases paracetamol is the drug of choice but in severe cases NSAIDS are the drug of choice. Thrombo -embolic disorders : Antiplatelet effect of aspirin allows It to be used prophylactically for transient ischemic attack (TIA ) myocardial infarction( MI) T o reduce the incidence of (MI) to reduce mortality in post MI attack s.

12. For medical closure of patent ductus arteriosus . Regular use aspirin reduces the risk of colon and rectal cancer. Aspirin reduces the risk of alzheimer’s disease To control pruritis and flushing with the use of nicotinic acid. Low dose of aspirin is useful in preeclampsia.