Pharmacology of Non-Steroidal Anti-Inflammatory Drugs NSAIDs

Introduction:-

         Non-steroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-pyretic, anti-inflammatory (in higher doses) and anti-platelet effects. The NSAIDs are one of the most frequently prescribed groups of drugs, and include a variety of drugs.

Analgesic effect:-

Anti-Pyretic  effect:-

     Antipyretics cause the hypothalamus to override an interleukin-induced increase in temperature. The body then works to lower the temperature, resulting in a reduction in fever.The most common antipyretics in the United States are ibuprofen and aspirin, which are used primarily as pain relievers

Anti-Inflammatory effect:-

Anti-Platelet  effect:-

                 Usually all NSAIDs are not referred for anti-platelet effect, however, Aspirin in low doses produces anti-platelet effect by preventing the synthesis of Thromboxane A2.

Mechanism of Action:-

   By blocking prostaglandins, undesirable effects such as pain and inflammation are relieved. NSAIDs act on the hypothalamus to inhibit prostaglandin E2 to produce an anti-pyretic effect.Aspirin has anti-platelet effect for the life span of platelets, because it binds irreversibly with cyclooxygenase and permanently block thromboxane  A2 rather than other drugs of this class.

 

 

 

 

 

Classification:-

Drug Classifications	Prototype Drug	Related Drugs
Salicylates	Acetylsalicylic acid (aspirin, ASA, several drug names)	Choline magnesium Choline salicylate Balsalazide Diflunisal Mesalamine Magnesium salicylate Olsalazine Salsalate Sodium Salicylate Sodium thiosalicylate
Propionic acids	Ibuprofen (Motrin, Advil, others)	Fenoprofen Flurbiprofen Ketoprofen Naproxen Oxaprozin
Acetic acids	Indomethacin (Indocin)	Diclofenac Potassium Diclofenac Sodium Etodolac Ketorolac Sulindac Tolmetin

Enolic acids	There is no prototype for this classification.	Piroxicam Meloxicam Lornoxicam Tenoxicam
Cyclooxygenase-2 enzyme inhibitors(COX-2 inhibitors)	Celecoxib	Etoricoxib Paracoxib
Fenamic acids	There is no prototype for this classification.	Diflunisal Meclofenamate Mefenamic acid
Anilides	Paracetamol	There are no related drugs at this time.
Non-acidic NSAIDs	There is no prototype for this classification.	Nabumetone
Butylpyrazolidines	Phenylbutazone	There are no related drugs at this time.
Pyrazolones	Metamizol	There are no related drugs at this time.

Uses:-

Common acute (short-term) conditions that can be treated with NSAIDs include:

qHeadaches

qPainful periods

qToothache

qSoft tissue injuries such as sprains and strains

qInfections, such as the common cold or the flu (NSAIDs do not treat the underlying   infections, but can help to relieve symptoms; especially fever

Common chronic (long-term) conditions that can be treated with NSAIDs include:

qMost types of arthritis, including rheumatoid arthritis and osteoarthritis

qBack pain

qNeck pain

Side Effects and Adverse Effects:-

       Some of the common side effects are:

      qNausea

      qVomiting

      qRash

      qDiarrhea

      qLiver  and kidney  failure

      qEdema

      qReye’s Syndrome in children

      qStomach and intestinal  adverse effects

      qMay increase the risk of  heart attack and stroke in elderly patients

     

      Interactions:-

      qNSAIDs reduce blood flow to the kidneys and therefore reduce the action of diuretics.

      qIt cause severe bleeding when taking with drugs that cause bleeding.

      q NSAIDs antagonize the action of drugs that are used to treat hypertension.

      qNSAIDs increase the negative effect of cyclosporine on kidney function.

      qNSAIDs cause stomach ulcers in patients taking alcoholic beverages.

      Contraindications:-

 NSAIDs should usually be avoided by people with the following conditions:

     qPeptic ulcer

     qA past transient ischemic attack

     qCoronary artery disease

     qUncontrolled hypertension

     qA past stroke

     qUndergoing Coronary artery bypass surgery

     qKidney disease

     qA past Myocardial infarction

     qTaking aspirin for heart

     qIn third trimester of pregnancy

    Examples:Indomethacin (Indocin)

     qIndomethacin works by reducing the production of prostaglandins.

     qTreat patent ductus arteriosus (PDA) in certain premature infants.

     qSide effects are headache, dizziness, vomiting, diarrhea, constipation etc.

     qSome products that may interact: aliskiren, ACE Inhibitors, angiotensin II receptor  blockers, cidofovir, corticosteroids, cyclosporine, lithium, methotrexate, pemetrexed, water pills.

     qShould not be prescribed to patients with any type of allergy.

      Diclofenac sodium (Volteran):-

      qDiclofenac is used to relieve pain, swelling, and joint stiffness caused by arthritis.

      qIts side effects include upset stomach, nausea, diarrhea, constipation etc.

      qDrug interactions are same as that of all NSAIDs.

      qPrecautionary measures should be as prescribed by the doctor.

     Piroxicam (Feldene):-

      qThis medication is used in the treatment of osteoarthritis; temporo mandibular  joint  disorder; pain; frozen shoulder; rheumatoid arthritis.

      qIts side effects are hives, difficulty breathing; swelling of body parts, chest pain, shortness of  breath, slurred speech, problems with vision.

     qDrug interactions are same as that of all NSAIDs.

     qPrecautionary measures should be as prescribed by the doctor.

     Meloxicam (Mobic) :-

     qIt is used in the treatment of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid  arthritis,tendonitis.

     qStomach upset, nausea, dizziness, or diarrhea may occur.

     qDrug interactions are same as that of all NSAIDs.

     qPrecautionary measures should be as prescribed by the doctor.

      Paracetamol:-

     qIt works as both an analgesic and antipyretic to treat aches, pains and reduce fevers.

     qIts side effect can be nausea, loss of appetite, stomach pain, discolored urine or stool, jaundice etc.

     qSome products that may interact : blood thinners,  isoniazid and ketoconzole.

     qBefore taking it, consult your doctor if you have a history of any of the following medical conditions: liver disease, alcohol abuse.

     Celecoxib (Celebrex):-

     qIt is used in the treatment of pain, inflammation, and stiffness of arthritis.

     qStomach upset or gas may occur.

     qSome products that may interact : aliskiren, ACE Inhibitors angiotensin II receptor blockers.

     qShould not be prescribed to patients with any type of allergy.

    

 

 

 

 

 

 

    

 

 

 

      Aspirin (Acetylsalicylic Acid):-

      Pharmacokinetics:-

      qOrally Administered

      qRapidly absorbed

      q70% is metabolized in the liver

      qSlowly enters the brain but freely crosses the placenta

      qPoor solubility is the limiting factor

      qSolubility is more at higher pH

       qHalf life with low dose is 4h

       qHalf life with high dose is over 15h

       Adverse effects:-

       Epigestric distress, nausea, vomiting, gastric mucosal damage, peptic ulcer,        hypersensitivity

      Aspirin contraindications:-

       qPeptic ulcer

       qUlcerative colitis

       qGout

       qRenal failure

       qHemophilias

        Aspirin Doses (Oral):-

       q As analgesic and anti pyretic: 0.3­0.6 gm, 6­8 hours.

       qAcute rheumatic fever: 75­100mg/kg/day in divided doses/4­ days

       qRheumatoid arthritis: 3­5mg/day

  

 

 

 

      

       Ibuprofen (Propionic Acid):-

   Pharmacokinetics:-

         qOrally Administered

         qRapidly absorbed

         qIt is supplied as a tablet potency of 200 to 800mg

         qUsual dose is 400 to 800mg thrice a day

         qMostly insoluble in water having pKa of 5.3

         qRapidly biotransformed with a serum half life of 1.8 to 2 hours.

        qIbuprofen tablets either under fasting conditions or immediately    before meals yield

        qQuiet similar serum concentrations time profile.

        

        Drug Interaction:-

       qIbuprofen has established drug interactions: lithium, warfarin, oral hypoglycemic, high dose, methotrexate, anti-hypersensitiveness, angiotensin converting enzyme inhibitors, B blockers and diuretics.

      Ibuprofen contraindications:-

      qHeart problem

      qKidney disease

      qLiver disease