Non-opoids analgesics(NSAIDS) (1).pptx a

Non steroidal anti inflammation medicine 💊 is

1. Dr. Haji Bahadar, Phd , Assistant Professor KMU-IPMS Drugs Used to treat pain and Inflammation

2. What is inflammation ? Inflammation is the body's protective response to injury. Physical: Burns, Frostbite, Physical injury Biological: Infection by pathogens Chemical: toxin or toxicant Immune system activation Types: Acute and chronic

3. Signs of inflammation Pain  - the inflamed area is likely to be painful .Chemicals that stimulate nerve endings are released, making the area much more sensitive. Redness  - this is because the capillaries are filled up with more blood than usual. Immobility  - there may be some loss of function. Swelling  - caused by an accumulation of fluid. Heat  - more blood in the affected area makes it feel hot to the touch.

4. Rheumatoid arthritis

5. Chemicals involved Cytokines Histamine Prostaglandins (pain sensitizing)

6. Analgesics Non-opioid analgesics or NSAIDs Opioid analgesics

7. Eicosanoids Eicosanoids  are signaling molecules made from arachidonic acid. They are prostaglandins, leukotriens etc Synthesis of prostaglandins: Arachidonic acid is the primary precursor of the prostaglandins and related compounds. Arachidonic acid is present as a component of the phospholipids of cell membranes. Free arachidonic acid is released from tissue phospholipids by the action of phospholipase A2 via a process controlled by hormones and other stimuli. There are two major pathways in the synthesis of the eicosanoids from arachidonic acid, the cyclooxygenase and the lipoxygenase pathways

8. Cyclooxygenase pathway COX-1 is an enzyme that regulates normal cellular processes, such as gastric protection , vascular homeostasis, platelet aggregation, and reproductive and kidney functions COX-2 is constitutively expressed in tissues such as the brain, kidney, and bone. Its expression at other sites is increased during states of chronic inflammation

9. Lipoxygenase pathway Lipoxygenase pathway: Alternatively, several lipoxygenases can act on arachidonic acid to form leukotrienes

10. prostaglandins Prostaglandins  are lipid autacoids derived from arachidonic acid They generally act locally on the tissues in which they are synthesized, and they are rapidly metabolized to inactive products Prostaglandins, thromboxanes , and prostacyclins ) are synthesized via the cyclooxygenase pathway COX-1 is a constitutive enzyme that regulates normal cellular processes, such as gastric cytoprotection , vascular homeostasis, platelet aggregation, and reproductive and kidney functions. COX-2 is constitutively expressed in tissues such as the brain, kidney, and bone COX-2 is expression is induced by inflammatory mediators like TNF-α and IL-1

11. Actions of prostaglandins Thromboxane A2 (TXA2) is involved in platelets aggregation Prostacyclin ( PGI2), produced by endothelial cells, has opposite effects, inhibiting platelet aggregation PGE1: Prostaglandin F2 α

12. Alprostadil : alprostadil can be used to treat erectile dysfunction Misoprostol:is used to protect the mucosal lining of the stomach during chronic NSAID treatment. Bimatoprost : it is indicated for the treatment of open-angle glaucoma. It also is approved for the treatment of eyelash hypotrichosis .

13. Nonsteroidal anti-inflammatory drugs (NSAIDs ) TRADE NAMES (DRUG MANNUAL) 1. Non selective COX inhibitors Aspirin Diclofenac Indomethacin Ketorolac Meloxicam Piroxicam Fenoprofen Flurbiprofen Ibuprofen Ketoprofen Naproxen Paracetamol (no anti inflammatory) 2. COX-2 inhibitors Selective COX-2 inhibitors are a type of non-steroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration. Drugs are celecoxib ,  rofecoxib

14. Steroidal anti inflammatory drugs Steroid is an organic compound with four rings. The steroid core structure is composed of seventeen carbon atoms, bonded in four "fused" rings.

15. Difference between non steroid and steroid structures Aspirin Dexamethasone

16. Mechanism of action During inflammation prostaglandins are produced which stimulate peripheral nerve endings producing pain impulses that are carried to the CNS. NSAIDs cause the inhibition of COX-1/2, decreasing prostaglandin synthesis . Aspirin irreversibly inhibit cyclooxygenase. The other NSAIDs are all reversible inhibitors of cyclooxygenase.

17. Indications Headache ( nonmigraine ) Muscle aches and pain Toothache Dysmenorrhea Joint Pain  ( osteoarthritis) Inflammation Removal of acne(salicylic acid) Salicylic acid 6 % topical gel

18. Side effects Nausea due to erosion of stomach lining Decrease cytoprotective mucus secretion.

19. Side effects Vomiting Peptic ulcer disease Gastrointestinal bleeding Prolong bleeding time (Aspirin) Hepatotoxicity (elevated serum enzymes like alkaline phosphatase , serum glutamic-pyruvic transaminase SGPT or ALT )(Paracetamol) Hypersensitivity (in sensitive patients)- rash, laryngeal edema, asthma (Aspirin) Kidney damage

20. Contraindications Severe hepatic diseases (Aspirin, diclofenac, paracetamol )  Vitamin K deficiency (Aspirin)   Hemophilia (bleeding disorder) (Aspirin) Children (Aspirin) causing Reye syndrome(self) Patients receiving anticoagulants such as coumarin and heparin (aspirin) Asthma (aspirin)  

21. Analgesics and pain relief in pregnancy and breastfeeding Paracetamol Mefanamic acid