Download - Antiinflamatory Drug
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ANTIINFLAMATORY DRUG
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PROSTAGLANDIN
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OBAT-OBAT ANTIINFLAMASI NONSTEROID
• BEKERJA DGN MENGHAMBAT ENZIM SIKLO-OKSIGENASE• YG PLG SERING DIGUNAKAN ADLH ASPIRIN
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ANTI INLAMATORY DRUGSACETAMINOPHEN
ANTI INLAMATORY DRUGS ACETAMINOPHEN
ASPIRIN OTHER NON SELECTIVE NSAID
COX-2 SELECTIVEINHIBITOR
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ANALGESIK
ANTIINLAMASI KUAT
ANTIINFLAMASI SEDANG/RINGAN
ANTIINFLAMASI (-)
SALICYLATE(aspirin)
PYRAZOLONE(dipyrone)
INDOL(indomethacine)
PROPIONIC ACID(Ibuprofen)
ANTHRANICIL ACID(Mefenamic acid)ARYLACETIC ACID
(Diclofenac)
ANILINE(Paracetamol)
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MECHANISM OF ACTON
DISTURBANCE OF CELL MEMBRANES
PHOSPOLIPIDS
ARACHIDONIC ACID
ENDOPEROXIDASE
PROSTAGLANDIN
ASPIRIN CYCLOOXIGENASE
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EFFECTS• ANALGESIC• REDUCE THE MANIFESTATIONS
OF INFLAMATION• ANTIPYRETIC• HOMEOSTATIC FUNCTION • REDUCE PROSTAGLANDIN-MEDIATED CYTOPROTECTION IN THE
GASTROINTESTINAL TRACT
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PHARMACOKINETICS AND CLINICAL USE
Aspirin• Pharmacokinetics
- The salicylates Rapidly absorbed from the stomach and upper small intestine- yielding a peak plasma level with 1-2 hours- Rapidly hydrolyzed to acetic acid and salicylat by esterases- excreted unchanged
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Mechanisms of Action1. Anti-inflammatory Effects
- Aspirin is nonselective inhibitor of both COX isoform- Irreversibly, inhibits platelet aggregation- Inhibiting the granulocytes adherence to damaged vasculature, stabilizing lysosome,
and inhibiting the chemotaxis of leucocytes and macrophages- High doses (2400-4000 mg/d)
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2. Analgesic Effects- Most effective in reducing pain of mild to moderate intensity- Intermediate (300-2400 mg/d) have antipyretic dan analgesic
3. Antipyretic Effects- Reduces elevated temperature- Probably mediated by both COX inhibition and inhibition of IL-1
4. Antiplatelet Effects- Single low doses (81 mg daily)
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Clincal UsesAnalgesia, Antipyresis, and Anti-inflammatory Effects- For mild to moderate pain- Combined with opioid analgesics for treatment of cancer pain- High-dose for treatment of rheumatic fever, rheumatoid arthritis and other inflammatory join conditions
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Adverse EffectsUsual dosage
Gastric upset (intolerance), gastric and duodenal uncers, hepatotoxicity, asthma, rashes, and renal toxicity
Higher dosesSalicylism, tinnitus, decreased hearing and vertigo (rever), hyperpnea, metabolic acidosis
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COX-2 SELECTIVE INHIBITOR
1. Celecoxib- As effective as other NSAID- Fewer endoscopic ulcer than NSAID- No more edema or renal effects
2. Etoricoxib- a second-generation COX-2- 60 mg once daily for acute osteoarthritis- 120 mg for acute gouty arthritis
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3. Meloxicam- Therapeutic dose 7,5 mg/d- For treatment of rheumatic diseases, osteoarthritis, rheumatoid arthritis
4. RofecoxibFor treatment of rheumatic diseases, osteoarthritis, rheumatoid arthritis, analgesic and antipyretic
5. ValdecoxibA new highly selective cox-2 inhibitorDosage is 20 mg twice dailyNo effect on platelet aggregation or bleeding time
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NON SELECTIVE COX INHIBITORS
1. DiclofenacPhenylacetic acid derivateA preparation diclofenac combining and misoprostol decreases gastrointestinal ulceration. Another combination of diclofenac and omeperazol for prevention of recurrent bleeding.
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0,1 % diclofenac for prevention of postoperative ophthalmic inflammationA topical gel containing 3 % diclofenac for solar keratosesSuppository form for preemptive analgesis and postoperative nausea
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2. DiflunisialDiflunisial is derived from salicylat acidIt undergoes an enterohepatic cycleEffective for cancer painA 2 % diflunisial for pianful oral lession
3. EtodolacAcetic acid derivateMore Cox-2 selective than most other NSAID, with a cox-2:cox1 about 10For post operative painLess gastric toxicity
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4. FlurbibiprofenPropionic acid derivateOral : 200-400 mg/d for gout, rheumatoid arthritis, ankylosing spondylitis, osteoarthritisIV: for perioprative analgesia in minor ear, neeck and nose surgeryTopical: intraoperative miosis
5. IbuprofenPhenylpropionat acid derivateDoses: < 240 mg daily for analgesic but anti-inflammatory efficacy400 mg efficacy in postsurgical dental painUsed to treat patent ductus arteriosus Anti-inflammatory effect = aspirinGI irritation and bleeding< aspirin
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6. IndomethacinPotent cox inhibitor, inhibit phospholipase A and C, reduce neutrophil migration, decrease T cell and B cell proliferation
Clinical useGout, ankylosing, patent ductus arteriosus, juvenile rheumatoid, nephrotic syndrom, diabetes insipidus, postepisiotomy pain, conjunctival inflammatory, gingival inflammatory
Adverse Effectsabdominal pain, headache, dizziness, confusion, trombocytopenia, aplastic anemia
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7. KetoprofenPropionic acid derivate With probenecid elevates ketoprofen level and prolongs its plasma half-lifeThe effectiveness at dosages 100-300 mg/d
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8. KetorolacFor systemic use mainly as an analgesicUsed to replace morphineMild to moderate pain
9. Mefenamic acidless effective than aspirinNot be used for longer than 1 weekShould not be given to children
10. NabumetoneAcetic acid derivateProdrug, half-life more than 24 hoursIt may be less damaging to the stomach, SE mirror of other NSAID
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11. NaproxenNaphthylpropionic acid derivate effective for the usual rheumatologic indicationsGastrointestinal bleeding is lowRare case of allergic pneumonitis, leukocytoclastic vasculitis and pseudoporphyria
12. OxaprozinPropionic acid derivateVery long half-life (50-60 hours)Can be given once a day
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13. PhenylbutazonePyrazolone derivateIts toxicities, particularly the hematologic effect (aplastic anemia)Rarely used today
14. PiroxicamOral: dosages 20 mg/dUsed for the usual rheumatic indicationHigh concentration also inhibits polymorphonuclear leukocyte migration, decrease oxygen radical production and inhibits lymphocyte funtionDosages higher than 20 mg/d, an increased incidence of peptic ulcer and bleeding
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15. SulindacSulfoxide prodrug
IndicationRheumatic diseaseSuppresses familial intestinal polyposis
Adverse effectsReversible renal failure and nephrotic syndrome, trombocytopenia, agranulocytosis
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2. Other NSAID - Are well absorbed after oral administration
- Ibuprofen a half-life of about 2 hour- Indomethacin is potent NSAID- Naproxen and piroxicam half-life 12-24 hours
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NONSELECTIVE COX INHIBITOR
Used for the treatment of mild to moderate painCOX-2 inhibitors are primarily used in anflammatory disordersSelected NSAID are also used to treat other conditions
(dysmenorrhea)
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TOXICITY
1. AspirinHypersensitivity,Gastrointestinal disturbance, nepritis, tinitus, vertigo
2. COX-2-selective inhibitorHave reduce risk of gastrointestinal, hypersensitivity
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LEARNING TASK1. Jelaskan sintesa prostaglandin dan dimana
obat NSAID bekerja !2. Jelaskan farmakokinetik, farmakodinamik
dan toksisitas dari aspirin !3. Jelaskan farmakokinetik, farmakodinamik
dan toksisitas dari non selective NSAID !4. Jelaskan farmakokinetik, farmakodinamik,
dan toksisitas dari COX-2 selective inhibitors !
5. Jelaskan mekanisme kerja dan toksisitas dari acetaminophen !
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