ANTIINFLAMMATORY DRUGS

TOYA ARIAWAN
 INFECTION
TOXIN EXPOSURE
CELL INJURY

INFLAMMATION

NONSTEROIDAL
ANTIINFLAMMATORY
DRUGS
(NSAIDs)
ANTIINFLAMMATORY
DRUGS STEROIDAL
ANTIINFLAMMATORY
DRUGS
(CORTICOSTEROIDS)
 NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
(NSAIDs)
 ANALGESIC
CNS and peripheral effect, may involve non-PG
related effects. At peripher they PG that sensitize
E receptors to inflammatory mediators
F ANTIPYRETIC
CNS effect. Inhibition PGE production in
F the hypothalamus (center for normal body
E temperature regulation).
C ANTINFLAMMATORY
due mainly to inhibition of PG production
T Some shown to inhibit activation, aggregation,
S adhesion of neutrophils & release of lysosomal
enzymes
ANTITHROMBOTIC
Aspirin reducing platelet aggregation
ASPIRIN

Low dose range (< 300mg/day)

effective in reducing platelet aggregation

Intermediate doses (300 - 2400 mg/day)

analgesic & antipyretic effects

High doses ( 2400 – 4000 mg/day)

antinflammatory effects
 NSAIDs

Gastric mucosa
Kidney
Platelets
Vascular endothelium
 NSAID CLASSIFICATION
NONSELECTIVE COX INHIBITORS
Ibuprofen Indomethacin
Diclofenac Phenylbutazone
Piroxicam Aspirin
Naproxen Mefenamic acid
Ketorolac
SELECTIVE COX-2 INHIBITORS
Celecoxib
Rofecoxib
------ Have been withdrawn
Valdecoxib
 Clinical uses
1. Analgesic
mild to moderate pain
ketorolac promoted mainly as analgesic (given i.m.)

2. Antipyretics
any kind of fever
Ibuprofen, aspirin
3. Anti-inflammatory
Rheumatoid arthritis
Osteoarthritis
Gout (except tolmetin)
 Clinical uses
4. Antithrombotic
Aspirin uses for this purpose, because it
irreversibly inhibit platelet COX 1, so that its
antiplatelet effect last 8-10 days (the life of
platelet)
Transient Ischemic Attack (TIA)
Unstable angina, myocardial infarction,
After coronary bypass

5. Closing patent ductus arteriosus in preterm infants

Indomethacin, ibuprofen
 Risk of GI Complications Related
to NSAID Used than for Non-users
DRUGS RELATIVE RISK
Indomethacin 2.25

Naproxen 1.83

Diclofenac 1.73

Piroxicam 1.66

Tenoxicam 1.43

Meloxicam 1.24

Ibuprofen 1.19

Ann Rheum Dis 2004;63:759-76

 PARACETAMOL
(ACETAMINOPHEN)

 Antipyretic
 Analgesic
 no significant anti-inflammatory effect, but used for
its mild analgesic effect

Well-absorbed and without GIT irritation.

At high doses, severe hepatotoxicity results.
Antidote : acetylcystein
CORTICOSTEROID
CORTICOSTEROID

GLUCOCORTICOID
Cortisol
Natural
(Hydrocortisone)

Prednisone
Synthetic Prednisolone
Triamcinolone
Dexamethasone
MINERALOCORTICOID Betamethasone
Natural Aldosterone
Synthetic Fludrocortisone
ANTI-INFLAMMATORY EFFECTS

Mechanism of action

synthesis of prostaglandine and leukotrene

(by induce synthesis of lipocortin that inhibit phospolipase 2
and mRNA for cyclooxygenase 2)

interleukin2, interleukin3
platelet activating factor (PAF, an inflammmatory
cytokine)
 LEUKOTRINE PROSTAGLANDINE

LTB4 THROMBOXANE A2

Phagocyte Leukocyte
attraction, modulation
activation

Inflammation Inflammation
OTHER EFFECTS

1. METABOLIC EFFECT
Stimulate gluconeogenesis hyperglycemia
Stimulate lipolysis & lipogenesis fat
deposition in the face (moon face), shoulder
& upper part of back (buffalo hump)
2. CATABOLIC EFFECT
Muscle protein catabolism
Bone ---- osteoporosis
Growth is inhibited (children)

3. IMMUNOSUPPRESSIVE EFFECT
Inhibit cell mediated immunologic function
(especially dependent on lymphocyte)
Lympholytic ---- hematologic cancer
OTHER EFFECTS

4. RENAL SODIUM RETENTION

5. STIMULATE GASTRIC SECRETION & DECREASE

RESISTANCE TO ULCER FORTMATION

6. CNS EFFECT (behaviour changes in large dose)

 PROPERTIES OF CORTICOSTEROIDS

Drugs Anti-inflammatory. Salt retaining Topical activity

potency Potency
PRIMARILY GLUCOCORTICOID
S Short acting
Cortisol 1 1.0 1
(hydrocortisone)
Cortisone 0.8 0.8 0

Prednisone 4 0.8 0

Prednisolone 5 0.3 4

Methylprednisolone 5 0 5

Intermediate acting

Triamcinolone 5 0 5

Long acting

Dexamethasone 30 0 10

Betamethasone 25-40 0 10

PRIMARILY
MINERALOCORTICOID
Fludrocortisone 10 250 0
CLINICAL USES

1. ADRENAL DISORDERS
Adrenal insufficiency (Addison’s disease)

2. NONADRENAL DISORDERS

Inflammatory or immune in nature

Asthma, rheumatic disorder,
collagen disease, organ transplant rejection
Others: hematopoietic cancer
chemotherapy- induced vomiting
given to pregnant woman in premature labor
to hasten maturation of fetal lung
S
I
D
E

E
F
F
E
C
T
S

Growth inhibition
(in children)