Anti-Inflammatory Drugs

(NSAIDs & Corticosteroids)

 Outline
Inflammation:
– Definition
– Etiology
– Signs
– Classification
– Patofisiologi
Anti-inflammatory drugs
– Corticosteroid
– NSAID
 DEFINITION

 Inflammation  “Inflame” – to set fire.

 Inflammation is a dynamic response of
vascularised tissue to injury.
 It is a protective response.
It serves to bring defense & healing mechanisms
to the site of injury.
Inflammation may ends with either :

Complete healing Permanent destruction

of tissues of tissues
 CLASSIFICATION

Acute • < 48 hours

Inflammation • Cell type: Neutrofil (PMN)

• > 48 hours (weeks, months, years)

Chronic • Cell type: Mononuclear cell
Inflammation (macrophages, lymphocytes, plasma
cell)
 ETIOLOGY

Microbial infections: bacterial, viral, fungal, etc.

Physical agents: burns, trauma, radiation
Chemicals: drugs, toxins, etc.
Immunologic reactions: rheumatoid arthritis.
 SIGNS
Rubor (redness)
Calor (heat)
Dolor (pain)
Tumor (swelling)
Fuctio laesa
(loss of function)
 PATOPHYSIOLOGY
Three main processes occur at the site of inflammation,
due to the release of chemical mediators :
1. Increased blood flow
2. Increased vascular permeability
3. Leukocytic Infiltration
Mechanism of Inflammation

The major local manifestations of

acute inflammation, compared
to normal:

(1) Vascular dilation and increased

blood flow (causing erythema and
warmth).

(2) Extravasation and deposition of

plasma fluid and proteins (edema).

(3) Leukocyte emigration and

accumulation in the site of injury.
 Leukocyte emigration

 Divided into 4 steps

1. Margination, rolling, and adhesion to endothelium

2. Diapedesis (trans-migration across the endothelium)

3. Migration toward a chemotactic stimuli from the

source of tissue injury.

4. Phagocytosis
 Chemical Mediators
Chemical substances synthesised or released and
mediate the changes in inflammation.
 histamine
 5-HT (serotonin)
 Bradykinin Main
 Prostaglandins (eg PGE2 ) inflammatory
 Interleukines mediator
 Substance P
 Nitrous oxide
PROSTAGLANDIN
PROSTAGLANDIN & INFLAMMATION
ANTI-INFLAMMATORY DRUGS
 Classification

Corticosteroids

NSAIDs

5-LOX Inhibitors

Leukotriene receptor antagonists

 Corticosteroids
Naturally-occurring hormones produced by the adrenal glands

1. Glucocorticoid
• Hydrocortisone (cortisol),
prednisonprednisolone, methylprednisolone,
betamethasone, dexamethasone, triamcinolone
2. Mineralocorticoid
• Aldosterone, fludocortisone
Remember this..!!
Actions of Corticosteroids
 CORTICOSTEROID
Hidrokortison
– Oral sbg terapi pengganti
– I.V pada shock & asma
– Topikal, misal untuk eksim
Prednison
– Oral sbg antiinflamasi &
antialergi
Betametason, deksametason
– Sangat poten
– Tidak menyebabkan retensi
cairan
Beklometason dipropionat &
Budesonid
– Absorbsi p.o kecil, topikal lbh
aktif (utk eksim)
– Aerosol  digunakan untuk
asma
Triamsinolon
– Asma berat
– Injeksi inta artikular 
inflamasi sendi
 Comparison of systemic
corticosteroids

Triamsinolon 5 0 12-36

Betametason 25 0 36-72

Fludokortison 10 125 12-36

 Corticosteroid Side Effects
“Cushing’s Syndrome”
Increased gastric acidity
Sodium retention
– Fluid retention
– Potassium loss and metabolic
alkalosis
Gluconeogenesis Decreased resistance to
Osteoporosis infection/immunossuppresion
– MDI may cause candidiasis 
Physical changes
rinse mouth after MDI
– Increased fat production and
redistribution Dependency
– Acne – Both physical and
– Hirsutism psychological
– Fragile skin • Patients may need to be
weaned from steroid therapy
 NSAIDs

 Non Steroid Anti-Inflammatory Drugs

 Mechanism of action :
Inhibit Cyclooxygenase (COX)
COX-1 vs COX-2
COX-1 vs COX-2 Inhibition
 NON SELECTIVE COX

CARBOXYLIC ACID ENOLIC ACID

Phenylbutasone
Mefenamic acid
(Pirazolone)
Ibuprofen, ketoprofen, Piroxicam, meloxicam*
naproksen (propionic acid) (oxicam)
Aspirin, diflusinal (salicylic
acid)
Diklofenac, indomethasine
(asetic acid)
SELECTIVE COX-2
 NSAIDs: Classification by COX selection
Non-specific inhibition of COX-1 results in gastrointestinal and platelet side effects

In vitro assessment
of COX-1 – COX-2 activity

Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed., Copyright © 2006 Saunders,
An Imprint of Elsevier
 NSAIDs Selectivity and Effects

Rofecoxib, valdecoxib
NSAIDs and GI
NSAIDs and Platelet (CVD risk)
NSAIDs and Renal
NSAIDs

ASETOSAL(ASPIRIN)
 Asetosal
Golongan..??
Merupakan prototype dari obat anti inflamasi
Mkx scra umum: hambat siklo-oksigenase (COX) sebagai
antagonis kompetitif dengan acara asetilasi enzim COX
Indikasi :
– inflamasi (anti-inflamasi)
– pain (analgesik)
– demam (antipiretik)
 Efek Asetosal
Anti-inflamasi  menurunkan sistesis prostaglandin melalui
penghambatan COX
Antipiretik  penghambatan sistesis PGE2 di pusat pengatur
panas hipotalamus
Analgesik  mencegah sensitisasi reseptor rasa sakit terhadap
rangsangan mekanik dan kimiawi & menurunkan sintesis PGE2
(sbg mediator nyeri)
Efek terhadap pernapasan : merangsang pernapasan dg pe↑
ventilasi alveoli  dosis terapi : mempertinggi konsumsi O2 dan
produksi CO2
Efek urikosorik : dosis kecil (1,0-2,0 g/hari) menghambat ekskresi
asam urat  kadar asam urat dalam darah ↑
 Efek Asetosal
Efek terhadap darah :
memperpanjang masa
pendarahan karena
mengasetilasi COX-1
trombosit sehingga
pembentukan
tromboksan A2 terhambat
 Efek Asetosal
Efek terhadap saluran cerna : penghambatan sintesis
prostasiklin (PGI2), PGE2, PGF2α  efek iritasi terhadap
lambung
– PGI2  menghambat sekresi asam lambung
– PGE2 & PGF2α  merangsang sekresi mukus protektif dalam
lambung dan usus kecil
Efek terhadap ginjal : pe ↓ sisntesis prostaglandin  retensi
Na dan air, edema dan hiperkalemia
– PGE2 & PGI2  memelihara aliran darah ke ginjal, terutama pada
vasokonstriktor yang bersirkulasi
 Farmakokinetika Asetosal

Pada pemberian per oral  salisilat diabsorbsi dg cepat dalam

bentuk utuh di lambung dan di sebagian usus halus bagian atas
Metil salisilat diabsorpsi dengan cepat melalui kulit
Absorbsi rektal salisilat lambat dan tidak sempurna
Salisilat (kecuali diflusinal) mudah menembus sawar darah otak dan
plasenta
Biotransformasi salisilat terjadi di banyak jaringan, terutama di
mikrosom dan mitokondria hati
Salisilat diekskresi dalam bentuk metabolitnya terutama melalui
ginjal, sebagian mell keringat dan empedu
 DOSIS
Dosis :
– Antipiretik :
• Dewasa :325-650 mg p.o tiap 3-4 jam
• Anak2 : 15-20 mg/kgBB tiap 4-6 jam
– Analgesik :u/ nyeri tidak spesifik, msl : sakit kepala, nyeri
haid, neuralgia & mialgia (dosis sama dg antipiretik)
– Demam rematik akut :
• Dewasa : 5-8 g/hari, diberikan 1,0 g/kali
• Anak : 100-125 mg/Kg BB tiap 4-6 jam selama seminggu,
stlh itu tiap minggu diturunkan sd 60 mg/KgBB
– Reumatoid Artritis :3,6-5,4 g/hari pd 3-4 dosis terbagi
Penggunaan lain : mencegah thrombus koroner
dan thrombus vena (50-100 mg)
Asetosal Efek samping
– Saluran pencernaan : iritasi GI,
mual, muntah
– Darah : perpanjangan wkt
pendarahan
– Pernapasan : depresi pernapasan
pd dosis toksik
– Proses metabolik : melepaskan
fosforilasi oksidatif
– Hipersensitivitas : urtikaria,
bronkokonstriksi, angioedema
– Sindrom Reye
 Interaksi Obat
Asetosal (90-95% terikat pd protein
plasma)  mengganti obat terikat
protein lain spt warfarin, phenytoin, or
valproic acid  peningkatan
konsetrasi obat lain
Asetosal vs Probenecid atau
sulfinpyrazone  penurunan
ekskresi asam urat melalui ginjal
Asetosal dan ketorolak
dikontraindikasikan  risiko
pendarahan GI dan inhibisi agregasi
platelet
 LOX & Leukotriene Inhibitors

 Used to prevent airway inflammation

Zileuton (Zyflo)
– Taken as a pill Q.I.D.
Zafirlukast (Accolate)
– Taken as a pill B.I.D.
Montelukast (Singulair)
– Taken as a pill just once
a day
Any Question..??