Obat anti inflamasi non steroid

Nurina H, dr

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

Origin & Effects of

Prostaglandin

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)

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 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