(NSAIDS)
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) play a crucial role in managing inflammation by blocking inflammatory mediators. This includes the inhibition of enzymes like PLA2 & Cox, as well as the selective or non-selective inhibition of COX-1 and COX-2. NSAIDs have various pharmacological actions such as analgesic, antipyretic, and anti-inflammatory effects, making them valuable in treating conditions like fever, headache, arthritis, and more. Explore the mechanisms of action and therapeutic uses of NSAIDs in this informative content.
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Presentation Transcript
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) Dr Sasan Zaeri (PharmD, PhD) Department of Pharmacology
Inflammatory cascade Triggers Infection Tissue and/or vessel damage Inflammatory Mediators Acute Inflammatory Response Note this is a common & non-specific response - Redness - Heat - Swelling - Pain
Drugs block production or effect of inflammatory mediators Tissue and/or vessel damage Infection Inflammatory Mediators o Vasoactive peptides: Histamine,serotonin o The kinin system o Coagulation cascade o The complement system NSAIDs Corticosteroids o Arachidonic Acid metabolites
Inflammatory Enzymes: PLA2 &COX 3. Zileuton Montelukast, zafirlukast 2.NSAIDS 1. Steroids Phospholipase A2 Arachidonic acid (AA) Cyclooxygenase (COX) Lipoxygenase Lipoxygenase products (leukotrienes) Prostaglandins & thromboxanes Inflammatory effects (inducible) Homeostatic Functions (stomach mucus) Inflammatory effects (esp. in asthma)
NSAIDS- MECHANISM OF ACTION Non Selective NSAIDs inhibit both COX-1 & COX-2 reversibly Ibuprofen, Diclofenac, Indomethacin, Naproxen, Mefenamic acid etc. Aspirin (irreversible COX inhibitor) Selective NSAIDs inhibit only COX-2 reversibly Celecoxib
Pharmacological Actions of Non- Selective NSAIDs Analgesic Antipyretic (Drug that lowers the elevated body temperature to normal) Anti-inflammatory Anti-platelet Exceptions: celecoxib, non-acetylated salicylates
THERAPEUTIC USES SHARED BY NS- NSAIDs Fever Analgesic Headache Migraine Dental pain Common cold
THERAPEUTIC USES SHARED BY NS- NSAIDs Rheumatoid arthritis Osteoarthritis Myositis or other forms of inflammatory conditions Dysmenorrhea
ADVERSEEFFECTSSHAREDBY NS-NSAIDS GIT upsets ( nausea, vomiting) GIT bleeding & ulceration Bleeding Hypersensitivity reaction Inhibition of uterine contraction Salt & water retention
DOSE DEPENDENT THERAPEUTIC EFFECTS OF ASPIRIN Anti-inflammatory Antipyretic, Analgesic Antithrombotic 0 1 2 3 4 5 Daily dose of aspirin (g)
Blood Vessel Wall Endothelial Cell (COX-2) Platelet (COX-1) Arachidonic acid Arachidonic acid PGH2 PGH2 Prostacyclin (PGI2) Thromboxane (TXA2) cAMP/vessel smooth muscle relaxes Ca2+ aggregation cAMP aggregation Ca2+/vessel smooth muscle constricts Normal physiologic interaction between PGI2 and TXA2 in platelet and endothelial cell biology
ADDEDCLINICALUSES Antiplatelet/Antithrombotic effect Decreases platelet production of TXA2 by COX-1 irreversibly to limit platelet aggregation and vasoconstriction Cardioprotective (reducing the risk of MI)
Acute rheumatic fever Prevention of pre-eclampsia Chronic gouty arthritis with large doses Chronic use of small doses , reduce the incidence of cancer colon
Adverse Effects Related to : (A) Therapeutic Doses Of Aspirin Aspirin asthma Reye's syndrome Syndrome of hepatic injury & encephalopathy in kids treated with aspirin after a viral illness
Aspirin-induced asthma
Adverse Effects Related to ( B) LARGEDOSESORPROLONGED USEOFASPIRIN Salicylism ( ringing of ear( tinnitus) , vertigo) Hyperthermia GI ulcer and bleeding Metabolic acidosis
CONTRAINDICATIONS Children with viral infections Patients with GI ulcer or upper GI bleeding Patients with hemophilia Patients with Aspirin-induced asthma
PARACETAMOL (acetaminophen) Commonly used as analgesic antipyretic drug
CLINICALUSESOFPARACETAMOL Can be used safely in patients with: Peptic or gastric ulcers Bleeding tendency Allergy to aspirin Viral infections in children Pregnancy
ADVERSE EFFECTS Mainly on liver due to its active metabolite ( N-acetyl-p-benzoquinone) Large doses cause liver necrosis Treatment Of toxicity of paracetamol: N- acetylcysteine : SH- donor to neutralize the toxic metabolite
ACETAMINOPHEN TOXICITY Acetaminophen UDP glucuronosyl- transferase Sulfotransferase glucuronide sulfate CYP2E1 induction alcohol Acetylcysteine (antidote) Glutathione-S- transferase Liver failure protein glutathione
DICLOFENAC Clinical uses o Treatment of rheumatoid arthritis , osteoarthritis (accumulates in synovial fluid in Long-term use ) o Analgesic o Antipyretic o Acute gouty arthritis o Locally to prevent post-operative ophthalmic inflammation
SELECTIVE COX-2 INHIBITORS General advantages : o Adverse effects are slighter than other NSADs o No effect on platelet aggregation (COX-1) o Long-term studies of the incidence of clinically significant gastrointestinal ulcers and bleeding are not yet completed
ADVERSEEFFECTS Renal toxicity Cardiovascular (high risk of MI) Rofecoxib and valdecoxib were withdrawn
GENERAL CLINICAL USES Rheumatoid arthritis Osteoarthritis Acute musculoskeletal pain Dysmenorrhea They can also be used in patients with gastric ulcer , haemophilia for the above indications
