NON STEROIDAL ANTI INFLAMMATORY NSAID

Transcription

1 NON STEROIDAL ANTI INFLAMMATORY DRUGS NSAID

2 inflammation Normal, protective response to tissue injury 1-physical trauma 2-noxious chemical 3-microbial agent

3 NSAIDs act by inhibiting the synth. Of prostaglandins PGs.(20 carbon unsaturated fatty acid ) PGs. Produced in minute quantities by all tissues. PGs. Act locally on tissues in which they are Synth. and rapidly metabolized.

4 Many action of PGs. mediated by Binding cell membrane receptors that operate Via G protein which subsequently activate or inhibit adenylyl cyclase Or stimulate phospholipase C, this cause Or stimulate phospholipase C, this cause formation diacylglycerol and IP3.

5 PGF2,LTs,TXA2=activation phosphatidyl inositol metabolism causing Increase intracellular Ca++. NSAIDs ; Group of chemically dissimilar agents That differ in their antipyretic,analgesic,and anti-inflammatory effects.

6 NSAIDs inhibiting COX that lead to decrease PGs. Synth. 1-salicyclic acid derivatives 2-propionic acid derivatives 3-acetic acid derivatives 4- oxicam derivatives

7 5-fenamate group 6- heteroaryl acetic acid 7- nabumetone 8-celecoxib 9-acetaminophen

8 *Salicylic acid derivatives and salicylate Aspirin example of salicylic acid derivative Salicylates example; Mg.choline salicylate Sod.salicylate Salicylsalicylate

9 Aspirin, weak acid,that is irreversibly acetylate and inactivate COX enzyme. it de acetylated by esterase producing salicylate which has anti-infl., analgesic, antipyretic effects. Antipyretic and anti- infl., effects due to block synth. Of PGs. Aspirin in also depress pain stimuli at subcortical sites (thalamus and hypothalamus).

10 Action of aspirin NSAIDs and aspirin have; 1-reducing inflammation 2-reduce pain 3-reduce fever

11 *Anti- inflammatory of aspirin Asp. Inhibit COX activity so it diminished formation of PGs. *Analgesic action of aspirin PGE2 is sensitize the nerve ending to the action of bradykinin, histamine and other mediator. By decreasing PGE2 synth. By aspirin this will depress sensation of pain ( low to moderate).

12 *Antipyretic action of aspirin fever occur when PGE2 elevate set point of anterior hypothalamus thermoregulatory center Aspirin re sets the thermostat toward normal and rapidly lower body temperature.

13 *Respiratory action of aspirin Aspirin increase the alveolar ventilation at high dose by acting directly to respri.center in the medulla, also causes rep. alkalosis. *GI.T. action of aspirin PGs. Inhibit acid secretion, while PGE2, PGF2, Stimulate synth. Of mucus in stomach and intestine.

14 Aspirin inhibit prostanoid synth. So result in increase acid secretion and decrease In mucus protection. Buffered and enteric coated aspirin preparation are used Misoprostol (PGE1) and proton pump inhibitors drug,are used for prevention ulcer of NSAIDs.

15 *effect of aspirin on platelets TXA2 enhance platelets aggregation, low dose of aspirin ( mg ),inhibit TXA2 production in the platelets *Action of aspirin on the kidney In kidney PGI2 is responsible for maintaining renal blood flow.

16 So decrease synth. Of PGs. By aspirin Can result In water and sodium retention and may cause edema and hyperkalemia. NSAIDs causes nephritis, but not aspirin.

17 Therapeutic uses of aspirin 1- anti-inflammatory 2-external uses 3-cardiovascular uses a- reduce TIA and stroke b-reduce risk of death of MI c-reduce risk recurrent non fatal MI d-reduce sudden death in unstable angina+ MI e-reduce risk in patient undergo revascularization

18 Pharmacokinetic of aspirin Oral administered of aspirin, the non ionized form passively absorbed from stomach and intestines. Rectal absorption is slow and unreliable Aspirin and salicylate must avoided in child under 15 years old and infected with viral.

19 Fate of aspirin Aspirin is hydrolyzed to salicylic acid by esterase enzyme in tissues and blood. t1/2 of aspi. 3.5 hrs. and cleared by kidney Asp. Cross BBB and placenta. Aspi. Show zero order kinetic in a dose above 4 gm /day and it t1/2 =15 hrs.

20 Adverse effects of aspirin 1- G.I.T 2-blood 3-respiration 4-hypersensitivity 5-Reye syndrome

21 *Drug interaction Aspi. Displace other highly protein binding drugs like warfarin, phenytoin,valproic acid. *pregnancy and aspirin Aspirin avoided in pregnancy due it excreted in breast milk.

22 Aspirin toxicity Mild form called salicylism Nausea, vomiting,hyperventilation,headache, Mental confusion,dizziness,tinnitus. Severe form intoxication All above symptoms followed by restlessness, delirium,convulsion, coma,respi. And metabolic acidosis and death.

23 *Treatment of aspirin intoxication Mild form symptomatic treatment and change the PH of urine to alkaline. Severe form hemodialysis or peritoneal Severe form hemodialysis or peritoneal dialysis and correcting acid base and electrolytes balance.