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Obat anti inflamasi non

steroid
Nurina H, dr
Inflammation
injurious stimulus inflammatory process
Calor Dolor
noxious agents : Rubor Tumor
Infection Functiolesa
Antibodies Phase : acute subacute
Physical injuries chronic proliferative

Essential for survival in inflammatory may be exaggerated & sustained


the face of environmental response without apparent benefit & w/
pathogens and injury 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 Varied pharmacokinetic


chemical classes characteristics

But NSAIDs have some


general properties in common
NSAIDS: NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
Chemistry & Pharmacokinetics
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


NSAIDS: NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
PHARMACODYNAMICS
antiinflammatory
analgesic antipyretic
Except paracetamol w/ very
low anti inflammatory effect

Inhibition of Prostaglandin Biosynthesis


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
Origin
& Effects
of Prostaglandin
Classification of NSAIDs
I. 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
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 INHIBITOR


1. DIARYL – SUBTITUTED FURANONES
- ROFECOXIB
2. DIARYL – SUBTITUTED PYRAZOLES
- CELECOXIB
3. INDOLE ACETIC ACIDS
- ETODOLAC
4. 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)
NSAIDs: group-specific
adverse effects
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 enzymes
larger doses→dizziness, excitement,
disorientation
15 g→ severe hepatotoxicity; acute renal
tubular necrosis
DIPIRON

 analgesic +, antipyretic +, anti


inflammatory – (weak)
 Administered orally; parenteral
 Adverse Effects : agranulositosis, anemia
aplastik, trombositopeni, hemolisis