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Non- Steroidal anti-inflammatory drugs


  • All drugs grouped in this class have analgesic, antipyretic and anti-inflammatory actions in different measures.
  • In contrast to morphine they do not depress CNS, do not produce physical dependence, have no abuse liability and are weaker analgesics (except for inflammatory pain). They are also called non-narcotic, non-opioid aspirin like analgesics.
  • They act primarily on peripheral pain mechanisms, but also in the CNS to raise pain threshold. They are more commonly employed and many are over-the-counter drugs.





Inducible, but Constitutive In Brain, Kidney
Inflammation, Carcinogenic
(Chemotaxis, Cytokines Production)

Pain Perception In CNS
Paracetamol Inhibits
?? Anti-Inflammatory


  1. MC used analgesics
  2. Heterogeneous drugs
  3. All are equally effective
  4. One may work, when other does not
  5. All have common mechanisms & toxicities


Inhibit prostaglandin synthesis by inhibiting cyclooxygenase enzyme (COX).



  • Analgesic
  • Antipyretics
  • Anti-inflammatory
  • Antithrombotic
  • Closure of ductus arteriosus in newborn


  • Gastric mucosal damage
  • Bleeding: inhibition of platelet function
  • Limitation of renal blood flow: Na+ and water retention
  • Delay/prolongation of Labour
  • Asthma and Anaphylactoid reactions in susceptible individuals




Non-Selective COX inhibitors

  1. Salicylates: Aspirin.
  2. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen

  3. AnthraniIic acid derivatives: Mephenamic acid
  4. Aryl-acetic acid derivatives: Diclofenac, Aceclofenac.
  5. Oxicam derivatives: Piroxicam, Tenoxicam
  6. Pyrrolo-pyrrole derivatives: Ketorolac
  7. lndole derivatives: Indomethacin.
  8. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone

Preferential COX-2 inhibitors: Nimesulide, Meloxicam, Nabumetone

Selective COX-2 inhibitors: Celecoxib, Etoricoxib, Parecoxib

Analgesic-Antipyretics with poor Anti-inflammatory action:

  1. Paraaminophenol derivatives: Paracetamol (Acetaminophen)
  2. Pyrazolone derivatives: Metamizol, Propiphenazone.
  3. Benzoxazine derivatives: Nefopan


1.       Aspirin 

  1. Oldest NSAID                   
  2. Obtained from bark of Willow plant                 
  3. Synthesized by Hoffman’1999




  • Covalently acetylates COX (all isoforms), resulting SUICIDE INHIBITION.
  • In addition to COX inhibition, quenching of free radicals may contribute to its anti-inflammatory act









  1. Well absorbed
    1. Weak acid with low pKa (3.5)
    2. Absorbed from stomach (being an acidic drug; remains unionized)
  2. Short half life
  3. Undergoes glycine conjugation
  4. Eliminated in urine



  1. Rhematoid arthritis          
  2. Acute rheumatic fever                  
  3. Still’s disease


Side effects

  1. MC-Dyspepsia Peptic ulcer                               
  2. Perforation                      
  3. Ulceration
  4. Hemorrhage                                            
  5. Obstruction                     
  6. Bleeding tendencies (high dose)
  7. Edema                                                       
  8. Bronchospasm
  9. Increased risk of hypertension                             
  10. Worsening of CHF and nephritic syndrome

Aspirin Induced Asthma
Aspirin block the COX-1 enzyme, production of thromboxane and some prostaglandins is decreased, and in patients with aspirin-induced asthma this results in the overproduction of leukotrienes (LTC-4, LTD-4) and produces the severe asthma and allergy-like effects. (SAMPTAR TRIAD- asthma, ethmoidal polyp, aspirin).


  1. Contraindications
    1. Peptic ulcer                                             
    2. Asthma             
    3. Nasal polyp
    4. Bleeding disorders                                 
    5. Hey fever         
    6. Children with viral fever- Reye’s Syndrome (A type of metabolic encephalopathy) 
      *Wherever aspirin is contraindicated; paracetamol can be used.
  2. Paracetamol
    1. Para-aminophenol derivative
    2. Short acting drug
    3. Well absorbed
    4. Undergoes glutathione conjugation
    5. Produces a hepatotoxic metabolite NABQI
      Detoxified by hepatic glutathione  


  1. DOC
    All conditions where aspirin is C/I


  1. Hepatotoxicity is major problem
  2. Accounts for hepatic transplant in many countries
  3. 4 gram can produce hepatotoxicity in CHF, cirrhosis/nephrotic syndrome patients
  4. N acetyl benzoquinimine (NABQI) produces centrilobular necrosis of liver

Paracetamol induced hepatotoxicity:

  1. May be asymptomatic for upto 48 hours
  2. Vomiting & jaundice occur; liver enlargement follows
  3. Activated charcol given
    1. Given i.v.
    2. Given with in 24 hours for best results    
    3. Liver transplant may have to be done
  1. Ibuprofen 
    1. Safest oldest NSAID                         
    2. Rare s/e-retrobulbar neuritis
  2. Flurbiprofen 
    1. Propionic acid                                  
    2. Optical isomer
    3. Prevents intraoperative meiosis during cataract surgery
  3. Diclofenac 
    1. Topical NSAID
    2. DOC
      1. Preemptive analgesia                             
      2. Postoperative nausea              
      3. Postoperative and posttraumatic pain
    3. Most hepatotoxic NSAID
  4. COX-2 Nsaids
    1. Highly selective
    2. Safer than older NSAID’s
      Acute complications are same, however risk of symptomatic s/e is low
    3. Safety concerns now a days  


COX-2 inhibitors

-   COX-2 enzyme is inducible and is over expressed in case of inflammation

-Synthesized with notion of reducing risk of side effects while maintaining the efficacy. Relatively selective COX-2 inhibitor

  • Nabumetone (only non acid NSAID)              
  • Nimusulide         
  • Aceclofenac

COX-2 selective inhibitors

(Banned due to their adverse CARDIO-VASCULAR EFFECTS  (rofecoxib) and allergic reactions)

  1. Lumaricoxib
  2. Celecoxib (least selective COX-2 inhibitor)
  3. Valdecoxib
  4. Rofecoxb
  5. Etoricoxib (Monitor liver function, most selective COX-2 inhibitor)


Safety issues

  1. Block COX-2, 1000 times more than COX-1
  2. Increases platelet activation
  3. Clotting occurs
  4. Risk of cerebro-vascular episodes (rofecoxib)
  5. Valdecoxib- allergic reactions


Safety issue - Nimesulide

  1. Alleged hepatotoxic, STEVEN JHONSON
  2. Banned drug  
  1. Indomethacin 
    1. Potent NSAID                                                           
    2. Long acting                     
    3. Anti-chemotactic            
    4. Well absorbed
    5. Undergo entero-hepatic circulation                   
    6. Protein bound                  
    7. Eliminated by bile
    8. Uses
      1. Acute gout                                        
      2. Closure of PDA                            
      3. Ankylosing spondylitis     
      4. Sex-related headaches                
      5. Barter’s syndrome  
  • Side Effects
  1. Frontal headache                             
  2. Confusion                       
  3. GI upset           
  4. Hyperkalemia                                
  5. Agranulocytosis             
  6. Renal papillary necrosis
  1. ​C/I
    1. Epilepsy             
    2. Psychiatry patients     
    3. Highway drivers       
    4. Hematological diseases
  2. Drug interactions
    1. Indomethacin + triamterene---renal failure
  1. Oxyphenbutazone 
    1. Most potent NSAID
  2. Phenylbutazone 
    1. Most toxic NSAID
      1. Aplastic anemia---serious s/e
  3. Ketorolac 
    1. Efficacy equals to that of morphine
      Long term administration---nephrotoxic
    1. Pro-drug
    2. Long acting NSAID (AIIMS’ May 2003)
    3. Anti-chemotactic
    4. Toxic on systemic administration
    5. Undergoes entero-hepatic circulation
    6. S/E
      1. GI upset, CNS s/e
      2. Peptic ulcer
  5.  Tramadol 
    1. Has both characters (opioid + non opioid)
    2. Serotonergic mechanism
    3. Avoided with SSRIs or MAO inhibitors: serotonin syndrome can occur
    4. Use:
      1. Postoperative
        Posttraumatic pain
  6. Sulindac 
    1. Sulfoxide prodrug
    2. Eliminated in bile
    3. Related structurally to diclofenac

d.       Does not inhibit renal prostaglandin synthesis



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