Hikmawan Wahyu S

DRUG IN
MUSKULOSKELETAL

Sign of inflammation

AUTACOIDS THAT PLAY A ROLE IN

INFLAMMATION
1. Histamine
2. Bradykinin
3. Serotonin (5-Hydroxytryptamine, 5HT)
4. Lipid derived Autacoids (Eicosanoid
and Platelet Activating Factors/PAF)
5. Cytokines

Non
selective
NSAID/
tNSAID

COX-2
SELECTIV
E
INHIBITO
R NSAID

Physiologic function

Inflammation

Classification of NSAID
by chemical similarity
GROUPS

EXAMPLES

Salicylic acid

Aspirin, sodium salicylate, diflunisal

Acetic acids

Ketorolac, indomethacin, tolmetin,

nabumethone, sulindac, etodolac,
diclofenac, lumiracoxib

Propionic acid

Flurbiprofen, ketoprofen, fenoprofen,

naproxen, ibuprofen

Fenamic acid

Meclofenamate

Diarylheterocyclics

Celecoxib, valdecoxib, rofecoxib,

etoricoxib

Enolic acids

Piroxicam, meloxicam

Other

Acetaminophen (paracetamol)

Black : non selective/ tNSAID

Red : COX-2 selective inhibitor

PHARMACOKINETICS
ABSORPTION:
Most of NSAIDs are rapidly absorbed
following oral ingestion, and peak
plasma concentration usually are reach
within 2-3 hours
Food intake may delay absorption and
sometimes decreases systemic
availability (i.e. fenoprofen, sulindac)

PHARMACOKINETICS
DISTRIBUTION:
95-99% NSAIDs bound to plasma protein, usually
albumin
Most NSAIDs are distributed widely throughout the
body and readily penetrate arthritic joints, yielding
synovial fluid concentration in various range of plasma
concentration
Direct transport of topically applied NSAIDs into
inflamed tissues and joints appears to be minimal, and
detectable concentrations in synovial fluid of some
agent (i.e diclofenac) following topical use are
primarily attained via dermal absorption and systemic
circulation

PHARMACOKINETICS
METABOLISM:
Acetaminophen, at therapeutic dose, is oxidized
only to small fraction to form highly reactive
metabolites, N-acetyl-p-benzoquinone imine (NAPQI)
When overdosed (usually >10 g of acetaminophen)
the principal metabolic pathway are saturated and
hepatotoxic NAPQI concentration can be formed

EXCRETION:
Hepatic biotransformation and renal excretion is the
principal route of elimination of the majority of
NSAIDs

THERAPEUTIC USES
1. Antipyretic (all NSAIDs)
2. Analgesic (all NSAIDs)
3. Anti inflammatory (all NSAIDs
except acetaminophen)
4. Fetal circulatory system/ to close
inappropriate patent ductus
arteriosus in neonates (tNSAID)
5. Cardio protection (aspirin)

ADVERSE EFFECT OF NSAID

THERAPY
SYSTEM

MANIFESTATION

1 GIT

Abdominal pain, nausea, diarrhea, anorexia, GI

hemorrhage , gastric erosion/ ulcer (15-30%), anemia,
perforation

2 Platelet

Inhibited platelet activation, increased risk of

hemorrhage

3 Renal

Salt and water retention, edema, decreased

effectiveness of antihypertensive and diuretic
medication

4 CVS

Closure of ductus arteriosus, stroke, trombosis

5 CNS

Headache, vertigo, dizziness

6 Uterus

Prolongation of gestation, inhibition of labor

7 Hypersensiti
Urticaria, asthma,
shock
Red:
side effect decreased
with COX-2
selective NSAIDs
vity : with exception of low dose aspirin
Green