These category drugs do not cause any physical dependence. Those drugs have no opioid/steroid activity but they have anti inflammatory action, called non-steroid anti-inflammatory drugs.NSAIDs are class of drugs which have some common properties – 1) They are analgesic 2) They have antipyretic property and most of them are antiinflamatory3) They are non-steroid.These class of drugs are do not depress Central nervous system (CNS) and also do not occur any physical dependence.You Might Like It- Analgesic Non Steridal Antiinflammatory Drugs Narcotic Opioid Analgesia Opioid ReceptorPathology of inflammation:Acute inflammation is due to release of mediators i.e. autocoides such as 5 HT prostaglandin (Leucotrines), bradykinine (produce vasodilation), chemotaxic and pain of acute inflammation some of them including prostaglandine produced fever in acute inflammation.Pathology of COX pathway:Prostaglaandin, Thromboxin and Prostacycline are produced by cyclooxtgenase pathway. They mediators are produced by cyclooxygenase and COX enzyme. There are two iso form of COX :- COX 1 & COX 2.COX 1 Mechanism:COX 1 is constitutive. it is always present. its product have pro-inflammatory action with some other action like protection of gastric mucosa. COX-1 involve in physiological functions such as haeosatsis, maintenance of renal function and secretion of mucus for protection of gastric mucosa.Lack of COX-1 enzyme inhibit inflammation but can cause gastric ulcer.COX-2 Mechanism:COX-2 is a inducible enzyme. it can be induced by cytokine and growth factor. Inhibit the inflammation because synthesis or prostaglandin is inhibited.You Might Like It- Screening Methods of Antidiarrheals and Laxatives On Animal ModelPathology of Pain:Interleukin & Bradykine are Librtaed at the site of injury. these substance produced prostaglandin E2 (PGE2). PGE2 is a pain producing substance (PPS). contact of PPS with peripheral pain receptor than nerve terminal produce pain sensation.NSAIDs PREVENT PGE2 SYNTHESIS BY INHIBITING COX ENZYME.Classification of NSAIDs Drugs: 1) Nonselective COX Inhibitors (Conventional NSAIDs) a) Salicylates:                              Aspirin, Didlunisal b) Pyrazolone derivatives:          Phenylbutazone, Oxyphenylbutazone c) Propionic acid derivatives:    Ibuprofen, Naproxen, Ketoprofen, flurbiprofen d) Indole derivatives:                  Sulindac, Indomethacin e) Aryl acetic acid derivative:    Diclofenace  f) Anthranilic acid derivative:    Mephenamic acid g) Pyrrolo-pyrrole derivative:    Ketorolac h) Oxicam derivative:                 Piroxicam, tenoxicam2) Selecive COX-2 InhibitorsCelecoxib, Rofecoxib, Valdecoxib3) Preferential COX-2 InhibitorsNimesulide, Meloxicam, Nabumetone4) Analgesic-antipyretics with poor antiinflammatory actiona) Paraaminophenol derivative: Paracetamol (Acetaminophenol)b) Pyrazolone derivative:            Metamizol (Dipyrone), Propiphenazonec) Benzoxazocine derivative:     Nefapam  Meachanisms of Action Of NSAIDs: NSAIDs mechanim involve in Analgesia:Prostaglandins induce sever pain (Hyperalgesia). NSAIDs do not block directly pain induced by Prostaglandin, but block the pain mechanism induced by interleukins, bradykinin and other anlgesic substances. NSAIDs are more effective againest inflammatory associated pain.You Might Like It- How does the CARDIOVASCULAR SYSTEM work part and functionNSAIDs mechanim involve in Antiinflammatory: NSAIDs is supress or inhibition of prostaglandin synthesis at site of injury. NSAIDs inhibit inflammation by block Cyclooxygenase enzyme but they do not block inflammation cause by interleukines (ILs), cytokines etc. NSAIDs mechanim involve in Antipyresis:fever cause during infection called infectious fever. Infectious fever cause by production of pyrogens, ILs and interferon’s which raised prostaglandin production in hypothalamus — temperature raises (Fever). That fever cause by production of prostaglandin. However, fever can also cause by non-prostglandin mediators mechanism, so supression of COX enzyme does not completely explain the antipyretic activity of NSAIDs. NSAIDs also reduce raised body temperature by heat loss through sweating, vasodilatation and cutaneous but it does not supress the heat production.NSAIDs mechanim involve in Antiplatelet aggregatory:Thromboxane synthase (TXA2) is most potent inducer of aggregation of platelets. NSAIDs inhibit both aggregatory and antiaggregatory activity by blocking TXA2 and PGI2 synthesis. NSAIDs are block TXA2 synthesis predominate. NSAIDs mechanim involve in gastric mucosal damage:COX 1 pathway is mediated many gastricprotective protsglandin synthesis such as PGE2 & PGI2 that protect the gastric wall. NSAIDs are blocks both pathway COX 2 as well as COX 1. NSAIDs cause deficiency of mucus and HCO3- secretion & induce back diffusion of H+ in gastric mucosa which leads to enhance acid secretion that cause mucosal erosion or ulceration, mucosal ischaemia and gastric pain.     NSAIDs mechanim involve in Dysmenorrhoea:Dymenorrhoea is known as painful menstruation or menstrual crimps. Prostglandins and its metabolites in circulation are raised  dysmenorrheaic women. NSAIDs reduced the prostaglandin production and it also relieved ancillary symptoms including headache, nausea and muscle ache. NSAIDs may also normalized excess flow in menstruation.NSAIDs mechanim involve in Ductus Arteriosus closure:Ductus arteriosus is blood vessle that connecting the pulmonary artery to descending arota. its recives most of blood from right ventricle and bypass fetus nonfunctioning lungs. this blood vessle collect blood from right ventricle and blood supply to descending arota. Ductus arteriosus is completely close after birth by natural mechanism when Ductus Arteriosus is not closed completely than called patent Ductus Arteriosus (PDA). PGE2 librated locally by COX2 pathway in Ductus Arteriosus that kept help to open the vessel. NSAIDs is block the COX2 pathway completely and supress prostaglandin secretion. NSAIDs treat patent Ductus Arteriosus.You Might Like It- Screening Methods of Diuretic Activity On Animal Model In Vitro Methods In Vivo MethodAspirin:Aspirin is one of most effective and oldest analgesic, Anti inflammatory drug. it is acetyl salicylic acid and rapidly converted to salicylic acid in the living body which are responsible for various pharmacological action. Pharmacological Action of Asiprin:Pharmacological action of Aspirin on Antipyretic effect:Aspirin rapidly reduce fever by promoting heat loss through sweating, vasodilatation and cutaneous but it does not suppress the heat production. Pharmacological action of Aspirin on Anti inflammatory Effect:Aspirin suppress inflammation like pain, swelling, leucocyte infiltration and tenderness but it exert anti inflammatory action at high dose up-to 3-6 gm/day or 100 mg/kg/day.Pharmacological action of Aspirin on Analgesic Effect:Aspirin effectively relieves inflammatory associated pain. aspirin suppress pain cause by tissue injury and inflammation but it is ineffective in visceral and ischemic pain. Aspirin have least analgesic activity than morphine. Pharmacological action of Aspirin on Metabolic Effect:Aspirin at anti inflammatory doses (3-6 gm/day or 100 mg/kg/day) produce metabolic effect.aspirin stimulate the uncoupling of oxidative phosphorylation which increase cellular metabolism in skeletal muscles. this process increase production of heat in body than utilization of glucose is enhance. blood sugar is decrease especially in diabetes patient than liver glycogen is finished (depleted)Pharmacological action of Aspirin on Respiration:Aspirin at anti-inflammatory dose is stimulate both peripheral and central action. In peripharal action, overproduction of carbon di oxide and in central action, increase sensitivity of respiratory center to carbon di oxide. when excess carbon di oxide produce in body that stimulate respiratory system.Aspirin on RespirationSalicylate poisoning (excess salicylic acid present in body) cause hyperventilation.Aspirin on RespirationHigh salicylate level cause respiration depression that cause respiratory system failure and last death.Aspirin on RespirationPharmacological action of Aspirin on Cardiac vascular system (C.V.S.):Larger dose aspirin is increase peripheral oxygen demond which increase cardiac output cause vasodilation.Aspirin on Cardiac vascular systemToxic dose of aspirin is inactive vasomotor center and increase sodium and water retention which cause low blood pressure.Aspirin on Cardiac vascular systemPharmacological action of Aspirin on gastrointestinal tract:Aspirin metabolites in salicylic acid that irritate gastric mucosa and cause gastric distress/bleeding/ulceration/nausea/vomiting. High dose of aspirin stimulate vomiting center especially chemo-receptor trigger zone (CTZ) which induce vomiting.Aspirin on gastrointestinal tractIn body aspirin present in two form at body i.e. ionized and unionized. unionzied aspirin is diffused in the acid (gastric juice) but it also enter into the mucosal cell. ionized aspirin is in-difusible.Pharmacological action of Aspirin Aspirin breakdown into the salicylic acid which come contact to the gastric mucosal wall and promote back diffusion of gastric juice (acid) that cause necrosis in mucosal cells and ulcer, erosive gastritis etc take place.AspirinPharmacological action of Aspirin on Blood:Small dose of aspirin is decrease synthesis of thromboxane A2 (TXA2) which prolonged bleeding time.Pharmacological action of AspirinLong term high dose aspirin is suppress synthesis of clotting factor in liver.         Pharmacological action of Aspirin