Senin, 02 April 2012

NSAID’s (Non Steroidal Anti Inflammatory Drugs)

Actions of NSAID’s

Anti-inflammatory effects of NSAIDs
This effect of NSAIDs is due to the inhibition of the enzyme COX, which converts arachidonic acid to prostaglandins, TXA2 and prostacyclin.
Acetylsalicylic acid irreversibly inactivates COX-1 and COX-2 by acetylation of a specific serine residue.
Other NSAIDs reversibly inhibit COX-1 and COX-2

Additional anti-inflammatory mechanism may include:
  • Interference with the potentiative action of other mediators of inflammation – bradykinin, histamine, serotonin
  • Modulation of T-cell function
  • Stabilization of lysosomal membranes
  • Inhibition of chemotaxis

Analgesic effect of NSAID s
This effect of NSAIDs is thought to be related to the peripheral inhibition of prostaglandin production, but it may also be due to the inhibition of pain stimuli at a subcortical site.
NDAIDs prevent the potentiating action of prostaglandins on endogenous mediators
of peripheral nerve stimulation ( e.g. bradykinin )

Antipyretic effect of NSAIDs
This effect is believed to be related to inhibition of the interleukin-1 and interleukin-6 induced production of prostaglandins in the hypothalmus and the “resetting” of the termoregulatory system, leading to vasodilation and increased heat loss

Clinical uses of NSAIDs
1) Analgesia
2) Inflammation
3) Antipyresis
4) Antiplatelet effect
5) Cancer preventive agents

Adverse effects of NSAIDs
  • Gastrointestinal effects: abdominal pain, gastric and duodenal ulcer, diarrhea, pancreatis
  • Gastrointestinal hemorrhage, hepatotoxicity
  • Renal effect
- Disturbances of renal function with water and sodium retention
  • Inhibition of platelet aggregation
  • central symptoms: headache, decreased hearing, tinnitus, dizziness, confusion, depression
  • Allergic reactions: asthma, rashes, photosensitivity

Pharmacodynamic  interaction NSAIDs with other drugs

  • NSAIDs  + hypotensive drugs ( β-blockers, ACE-inhhibitors, diuretics ) = ↓ hypotensive effect
  • NSAIDs + ehanol = ↑risk of bleeding from gastrointestinal tract
  • NSAIDs  + ticlopidine or clopidogrel = ↑risk of bleeding
  • NSAIDs  + lithium = ↑lithium toxicity  
  • NSAIDs  + cylosporine or ACE-inhibitors or takrolimus= ↑nephrotoxicity of drugs
  • NSAIDs  + fluoroquinolons = ↑ toxic action of fluoroquinolons on CNS
  • NSAIDs  +oral antidiabetic drugs  =↑ risk of hypoglycemia
  • NSAIDs  + cumarines = ↑risk of bleeding from gastrointestinal tract

Pharmacokinetic interaction NSAIDs with other drugs
  • NSAIDs + oral antidiabetic drugs = ↑ risk of hypoglycemia
  • NSAIDs  + cumarines =↑risk of bleeding
  • NSAIDs  + corticosteroids = risk gastropathy and bleeding from gastrointestinal tract
  • NSAIDs  + aminogycosides = ↑ ototoxicity and  nephrotoxicity of aminogycosides
  • NSAIDs  + fenytoine or valproinic acid  = ↑action of fenytoine or valproinic acid 
  • NSAIDs   + metotrexat or digoxin = ↑action and ↑ toxicity metotrexat or digoxin
  • NSAIDs   + tricycles antidepressive drugs  neuroleptics or antiarrhytmic drugs or
  • selective serotonin reuptake inhibitors ( SSRI ) = ↑ action of drugs
Classification of NSAIDs According to mechanism of action

1) COX-1 selective inhibitors
    - Acetylsalicylic acid at low dosage
2) Non selective  COX  inhibitors
    - Acetylsalicylic acid at high  dosage
    - Diclofenac
    - Ibuprofen
    - Ketoprofen
    - Flurbiprofen
    - Indomethacin
    - Piroxicam
    - Naproxen
3) More COX-2 selective inhibitors
   - Etodolak
   - Meloxicam
   - Nabumeton
4) COX-2 selective inhibitors
    - Celecoxib
    - Etorcoxib
    - Valdecoxib

Chemical classification of Non-steroidal anti-inflammatory Drugs (NSAIDs)

A: Salicylates
Acetyl salicylic acid (aspirin), sodium salicylate, Mg salicylate, choline salicylate,
Na thio salicylate, salicyl salicylate

B: Propionic acid derivatives
Ibuprofen, ketoprofen, naproxen, oxaprozin, flurbiprofen

C:Indole acetic acid
Indomethacin, sulindac,

D: Substituted anthranilic acids (Rarely used)
Mefenamic acid, meclofenamate Na

E: Pyrrole alkanoic acid (Rarely used)

F: Oxicams
Piroxicam, meloxicam

G: Difluorophenyl derivatives

H: Phenyl acetic acid

I:Acetic acid derivatives

J: Naphthyl acetic acid prodrugs

K: Para-amino phenol derivatives

Theraputic classification of NSAID s

A: Analgesics
Aspirin, paracetamol

B: Anti-inflammatory
Indomethacin, naproxen, ibuorofen

C: Anti-coagulants

D: Anti-pyretics
Aspirin, paracetamol, indomethacin, celecoxicv, ibuprofen

E: Inflammatory bowel disease
Sulfasalazine, infiximab

F: Anti-cancer drugs

G: Anti-malarial
Chloroquine, hydroxychloroquine

H: Tissue transplantation

I: Chelating agents in wilson’s disease

J: Anti-gout drugs
Indomethacin, ibuprofen

W.H.O Classification

A: Drugs with weak anti-inflammatory effect

B: Drugs with mild to moderate anti-inflammatory effect
Propionic acid derivatives, anthranilic acid derivatives

C: Drugs with marked anti-inflammatory effects
Salicylates, acetic acid derivatives, oxicams, diclofenac, etodolac