Obat anti inflamasi non steroid

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Obat anti inflamasi non steroid

• Nurina H, dr

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Inflammation
injurious stimulus
inflammatory process
Calor Dolor Rubor Tumor Functiolesa
noxious agents Infection Antibodies Physical
injuries
Phase acute subacute chronic proliferative
inflammatory response
Essential for survival in the face of
environmental pathogens and injury
may be exaggerated sustained without apparent
benefit w/ severe adverse consequences
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Inflammation
Therapeutic Strategies
Relief of pain
Slowing or-in theory-arrest of the tissue
damaging process
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NSAIDS NONSTEROIDAL ANTIINFLAMMATORY DRUGS

• Chemistry Pharmacokinetics
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Grouped in several chemical classes
Varied pharmacokinetic characteristics
But NSAIDs have some general properties in common
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NSAIDS NONSTEROIDAL ANTIINFLAMMATORY DRUGS

• Chemistry Pharmacokinetics

Weak organic acids except nabumetone
Most are well absorbed Food doesnt substantially
change bioavalability
Most are highly metabolized phase I II
phase II alone
Elimination most important route renal
excretion nearly all undergo enterohepatic
circulation
Most are highly protein bound, usually to albumin
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NSAIDS NONSTEROIDAL ANTIINFLAMMATORY DRUGS

• PHARMACODYNAMICS

antiinflammatory
analgesic
antipyretic
Except paracetamol w/ very low anti inflammatory
effect
Inhibition of Prostaglandin Biosynthesis
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Cyclooxygenase (COX)

• 2 forms cyclooxygenase-1 (COX-1)
  cyclooxygenase-2 (COX-2)
• COX-1 primarily constitutive isoform
• found in most normal cells and tissues kidney,
  GIT, platelet homeostasis
• COX-2 induced during inflammation facilitate
  the inflammatory response

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• Origin
• Effects
• of Prostaglandin

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Classification of NSAIDs

• NON SELECTIVE COX INHIBITORS
• 1. SALICYLIC ACID DERIVATIVES
• - ASPIRIN, SODIUM SALICYLATE, SALSALATE,
• 2. PARA AMINOPHENOL DERIVATIVES
• - ACETAMINOPHEN ( PARACETAMOL )
• 3. INDOLE INDENE ACETIC ACIDS
• - INDOMETHACIN, SULINDAC
• 4. HETEROARYL ACETIC ACIDS
• - TOL METIN, DICLOFENAC, KETOROLAC

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Classification of NSAIDs - cont

• 5. ARYL PROPIONIC ACIDS
• -IBUPROFEN, NAPROXEN, FLURBIPROFEN,
• KETOPROFEN, FENOPROFEN, OXAPROZIN
• 6. ANTHRANILIC ACIDS ( FENAMATES )
• - MEFENAMIC ACID, MECLOFENAMIC ACID
• 7. ENOLIC ACIDS
• - OXICAM ( PIROXICAM, MELOXICAM )
• 8. ALKANONES
• - NABUMETONE

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Classification of NSAIDs - cont

• II SELECTIVE COX 2 INHIBITOR
• DIARYL SUBTITUTED FURANONES
• - ROFECOXIB
• DIARYL SUBTITUTED PYRAZOLES
• - CELECOXIB
• INDOLE ACETIC ACIDS
• - ETODOLAC
• SULFONANILIDES
• - NIMESULIDE

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Clinical uses of NSAIDs

• For analgesia (e.g. headache, dysmenorrhoea,
  backache, bony metastases, postoperative pain)
• For anti-inflammatory effects (e.g. rheumatoid
  arthritis and related connective tissue
  disorders, gout and soft tissue disorders)
• To lower temperature (antipyretic)

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NSAIDs group-specific adverse effects
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Adverse Effects of NSAID Therapy

• Gastrointestinal anorexia, nausea, dyspepsia,
  abdominal pain, diarrhea
• ? gastric or intestinal ulcers (? with
  COX-2-selective drugs)
• Cardiovascular
• COX-2-selective- ? risk of heart attack and
  stroke
• Analgesic Nephropathy

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Adverse Effects of NSAID Therapy

• Pregnancy Prolongation of gestation, postpartum
  hemorrhage, closure of the ductus arteriosus and
  impaired fetal circulation in utero
• Hypersensitivity bronchial asthma, urticaria,
  shock
• Platelets ?risk of hemorrhage
• Cox -2 selective- ?risk of thrombosis

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Aspirin (acetylsalicylic acid)

• the oldest NSAID
• Is given orally and is rapidly absorbed 75 is
  metabolised in the liver
• Also inhibits platelet aggregation ? ? CHD
• Unwanted effects gastric bleeding dizziness,
  deafness and tinnitus ('salicylism) postviral
  encephalitis (Reye's syndrome) in children
  respiratory alkalosis followed by metabolic
  acidosis

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Paracetamol/Acetaminophen

• potent analgesic and antipyretic actions but
  rather weaker anti-inflammatory effects
• administered orally
• mild to moderate pain headache,
• myalgia, postpartum pain
• preferred to aspirin in children with viral
  infections

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Paracetamol/Acetaminophen

• Adverse Effects
• therapeutic doses?a mild increase in hepatic
  enzymes
• larger doses?dizziness, excitement,
  disorientation
• 15 g? severe hepatotoxicity acute renal tubular
  necrosis

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DIPIRON

• analgesic , antipyretic , anti inflammatory
  (weak)
• Administered orally parenteral
• Adverse Effects agranulositosis, anemia
  aplastik, trombositopeni, hemolisis

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