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Drug in muskuloskeletal Hikmawan Wahyu S1Sign of inflammation

AUTACOIDS THAT PLAY A ROLE IN INFLAMMATIONHistamineBradykininSerotonin (5-Hydroxytryptamine, 5-HT)Lipid derived Autacoids (Eicosanoid and Platelet Activating Factors/PAF)Cytokines

Histamine functions in many physiological and pathological processes in the human body, such as, in urticaria, allergy, hipersensitivity, etc.Bradykinin and kalidin (peptide autocoids) occurs in tissue damage, allergic reaction, virus infection and in inflammatory events cause by other things, which activates the proteolytic process. These peptides are autocoids which works locally in causing pain, vasodilatation, and an increase in vascular permeability. 5-hydroxytryptamine (5 HT, serotonin)is a regulator of smooth muscle function in the cardiovascular and gastrointestinal tract, a regulator in platelet function and a neurotransmitter in the central cnervous sytem (CNS). The lipid cell membrane supplies substrate for the synthesis of eicosanoid and the platelet activating factor (PAF). Eicosanoid is an arachidonic metabolite, it includes prostaglandins, prostacyclines, thromboxane A2 and leukotriens, all are not stored in the cell yet produced by most cells. Cytokines are soluble (glyco)proteins, nonimmunoglobulin in nature, released by living cells of the host, which act nonenzymatically in picomolar to nanomolar concentrations through specific receptors to regulate host cell function.

Translate :1. Fungsi Histamin dalam banyak proses fisiologis dan patologis dalam tubuh manusia, seperti, di urtikaria, alergi, Hipersensitivitas, dll2. Bradykinin dan kalidin (autocoids peptida) terjadi kerusakan jaringan, reaksi alergi, infeksi virus dan peristiwa inflamasi menyebabkan oleh hal-hal lain, yang mengaktifkan proses proteolitik. Peptida ini adalah autocoids yang bekerja secara lokal dalam menyebabkan nyeri, vasodilatasi, dan peningkatan permeabilitas pembuluh darah.3. 5-hydroxytryptamine (5 HT, serotonin) adalah pengatur fungsi otot polos saluran kardiovaskular dan pencernaan, regulator fungsi trombosit dan neurotransmitter di Sytem cnervous pusat (SSP).4. lipid pasokan membran sel substrat untuk sintesis eicosanoid dan platelet activating factor (PAF). Eicosanoid adalah metabolit arakidonat, itu termasuk prostaglandin, prostacyclines, tromboksan A2 dan leukotriens, semua tidak disimpan dalam sel belum diproduksi oleh sebagian besar sel.5. Sitokin yang larut (glyco) protein, nonimmunoglobulin di alam, yang dirilis oleh sel-sel hidup dari tuan rumah, yang bertindak nonenzymatically di picomolar konsentrasi nanomolar melalui reseptor spesifik untuk mengatur fungsi sel inang.34

Physiologic functionInflammation Non selective NSAID/ tNSAID COX-2 SELECTIVE INHIBITOR NSAIDClassification of NSAID by chemical similarityGROUPS EXAMPLES 1Salicylic acidAspirin, sodium salicylate, diflunisal 2Acetic acidsKetorolac, indomethacin, tolmetin, nabumethone, sulindac, etodolac, diclofenac, lumiracoxib3Propionic acid Flurbiprofen, ketoprofen, fenoprofen, naproxen, ibuprofen4Fenamic acid Meclofenamate 5Diarylheterocyclics Celecoxib, valdecoxib, rofecoxib, etoricoxib6Enolic acidsPiroxicam, meloxicam7Other Acetaminophen (paracetamol)Black : non selective/ tNSAIDRed : COX-2 selective inhibitor

PHARMACOKINETICS ABSORPTION: Most of NSAIDs are rapidly absorbed following oral ingestion, and peak plasma concentration usually are reach within 2-3 hoursFood intake may delay absorption and sometimes decreases systemic availability (i.e. fenoprofen, sulindac)PHARMACOKINETICSDISTRIBUTION:95-99% NSAIDs bound to plasma protein, usually albuminMost NSAIDs are distributed widely throughout the body and readily penetrate arthritic joints, yielding synovial fluid concentration in various range of plasma concentrationDirect transport of topically applied NSAIDs into inflamed tissues and joints appears to be minimal, and detectable concentrations in synovial fluid of some agent (i.e diclofenac) following topical use are primarily attained via dermal absorption and systemic circulation

PHARMACOKINETICSMETABOLISM:Acetaminophen, at therapeutic dose, is oxidized only to small fraction to form highly reactive metabolites, N-acetyl-p-benzoquinone imine (NAPQI)When overdosed (usually >10 g of acetaminophen) the principal metabolic pathway are saturated and hepatotoxic NAPQI concentration can be formedEXCRETION:Hepatic biotransformation and renal excretion is the principal route of elimination of the majority of NSAIDs

THERAPEUTIC USESAntipyretic (all NSAIDs)Analgesic (all NSAIDs)Anti inflammatory (all NSAIDs except acetaminophen)Fetal circulatory system/ to close inappropriate patent ductus arteriosus in neonates (tNSAID)Cardio protection (aspirin)ADVERSE EFFECT OF NSAID THERAPYSYSTEMMANIFESTATION1GITAbdominal pain, nausea, diarrhea, anorexia, GI hemorrhage , gastric erosion/ ulcer (15-30%), anemia, perforation2Platelet Inhibited platelet activation, increased risk of hemorrhage3Renal Salt and water retention, edema, decreased effectiveness of antihypertensive and diuretic medication 4CVSClosure of ductus arteriosus, stroke, trombosis5CNSHeadache, vertigo, dizziness6Uterus Prolongation of gestation, inhibition of labor7Hypersensitivity Urticaria, asthma, shockRed: side effect decreased with COX-2 selective NSAIDsGreen : with exception of low dose aspirin