obat anti inflamasi non steroid nurina h, dr. inflammation injurious stimulus inflammatory process...
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Inflammation
injurious stimulus inflammatory process
noxious agents :
Infection
Antibodies
Physical injuries
Calor Dolor
Rubor Tumor
Functiolesa
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
Inflammation
Therapeutic Strategies
Relief of pain
Slowing or-in theory-arrest of the tissue damaging process
NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Chemistry & Pharmacokinetics
Grouped in several chemical classes
Varied pharmacokinetic characteristics
But NSAIDs have some general properties in common
Chemistry & Pharmacokinetics
NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS
Weak organic acids except nabumetone
Most are well absorbed
Food doesn’t 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
PHARMACODYNAMICS
NSAIDS: NONSTEROIDAL ANTIINFLAMMATORY DRUGS
antiinflammatory
analgesic antipyretic
Inhibition of Prostaglandin Biosynthesis
Except paracetamol w/ very low anti inflammatory effect
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
Classification of NSAIDs
I. NON SELECTIVE COX INHIBITORS1. SALICYLIC ACID DERIVATIVES
- ASPIRIN, SODIUM SALICYLATE, SALSALATE, 2. PARA – AMINOPHENOL DERIVATIVES
- ACETAMINOPHEN ( PARACETAMOL )3. INDOLE & INDENE ACETIC ACIDS
- INDOMETHACIN, SULINDAC4. HETEROARYL ACETIC ACIDS
- TOL METIN, DICLOFENAC, KETOROLAC
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
Classification of NSAIDs - cont
II SELECTIVE COX – 2 INHIBITOR1. DIARYL – SUBTITUTED FURANONES
- ROFECOXIB2. DIARYL – SUBTITUTED PYRAZOLES
- CELECOXIB3. INDOLE ACETIC ACIDS
- ETODOLAC4. SULFONANILIDES
- NIMESULIDE
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)
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
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
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
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
Paracetamol/Acetaminophen
Adverse Effects therapeutic doses→a mild increase in
hepatic enzymeslarger doses→dizziness, excitement,
disorientation15 g→ severe hepatotoxicity; acute
renal tubular necrosis
DIPIRON
analgesic +, antipyretic +, anti inflammatory – (weak)
Administered orally; parenteral Adverse Effects : agranulositosis,
anemia aplastik, trombositopeni, hemolisis
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