NSAIDS ( Non Steroidal Anti Inflammatory Drugs)

                      

 INTRODUCTION

•       Bacteria are the essential etiologic agents in periodontal disease. The role which the host's immunoinflammatory responses play in the destruction of the periodontal attachment structures. Several mediators of inflammation have been identified as principal factors in disease progression.

•        These include short peptides such as bradykinin, long peptides such as interleukin-1 (IL-1) and complement, amines such as histamine and 5-hydroxytryptamine, and products from cells such as prostaglandins, leukotrienes..

                    

PAIN 

• An unpleasant emotional experience usually initiated by noxious stimulus and transmitted over a specialized neural network to the CNS where it is interpreted as such.  (C Richard  Monheim’s)

•               An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.

 

     Types of pain

Nociceptive- Nociceptive pain is caused by stimulation of sensory nerve fibres  that respond to stimuli approaching or exceeding harmful intensity.  Nociceptive pain may also be divided into "visceral", "deep somatic" and "superficial somatic" pain. 

Visceral  is diffuse, difficult to locate and often referred  to a distant, usually superficial, structure. It may be accompanied by nausea and vomiting and may be described as sickening, deep, squeezing, and dull.

 Deep somatic pain is initiated by stimulation of nociceptors in ligaments, tendons, bones, blood vessels, fascia and muscles, and is dull, aching, poorly-localized pain

 Neuropathic- Neuropathic pain is caused by damage or disease affecting any part of the nervous system involved in bodily feelings.

      Phantom pain  -- pain felt in a part of the body that has been lost or from which the brain no longer receives signals. It is a type of neuropathic pain

       Acute pain-- starts suddenly and is short-term Acute pain was once defined simply in terms of duration.

       Chronic pain -- lasts for a longer period of time Chronic pain is now recognized as pain that extends beyond the period of healing,

Definition of NSAIDs

 The anti-inflammatory ,analgesic ,antipyretic ,drugs are a heterogenous group of compound  often chemically unrelated ,which nevertheless share certain therapeutic action and side effect.  They also are frequently called NSAIDs  . (According to Goodman Glliman).  

History 

•       Sodium salicylate, discovered in 1763, was the first nonsteroidal antiinflammatory drug (NSAIDs). In the early 1950s; this was the first nonsalicylate NSAIDs developed for use in patients with inflammatory conditions.

•        Phenylbutazone is a weak prostaglandin synthetase inhibitor that also induces uricosuria. Indomethacin, another indoleacetic acid derivative, was developed in the 1960s as a substitute for phenylbutazone.

CLASSIFICATION (KD Tripathi 1^st ed)

OPIOID ANALGESICS

•        Natural Opium alkaloids . Morphine & Codeine.

•         Semi synthetic opiates---Diacetylmorphine, oxymorphone ,Pholcodeine .

•        Synthetic opioids--  Pethidine ,  Fentanyl ,  Methadone , Dextropropoxyphene , Ethoheptazine,  Tramadol.

   NSAIDs

A) Nonselective Cox inhibitors (Traditional NSAIDs) 

1.Salicylates-                                     Aspirin

2.Pyrazolone derivatives-            Phenylbutazone, oxyphenbutazone 

3.Indole derivatives-                     Indomethacin, Sulindac 

4.Propionic acid derivatives-      Ibuprofen, Naproxen, Ketoprofen 

5.Anthranilic acid derivatives-   Mephenaimic acid

6.Aryl-acetic acid derivatives-   Diclofenac , Aceclofenac 

7.Oxicam derivatives-                   Piroxicam, Tenoxicam 

8.Pyrrole derivatives-                    Ketorolac

B) Preferential cox-2 inhibitors 

•       Nimesulide, Meloxicam,Nabumetone.

C) Selective cox- 2 inhibitors 

•       Celecoxib, Rofecoxib,Valdecoxib,Parecoxib.

D) Analgesics- Antipyretics with poor  anti inflammatory action

•       Para amino phenol derivatives : Paracetamol (Acetaminophen). 

•       Pyrazolone derivatives : Metamizol (Dypirone), Propifenazone. 

•       Benzoxazocine derivative : Nefopam. 

  

ASPIRIN  

•        Aspirin is acetylsalicylic acid .It is rapidly converted in the body to salicyclic acid . 

•       Pharmacological action ---- Inhibits prostaglandin synthesis, resulting in analgesia, anti-inflammatory activity, and platelet aggregation inhibition; reduces fever by acting on the brain's heat-regulating center to promote vasodilation and sweating.

•       Pharmacokinetics ---  Absorption Rapidly and completely absorbed . 

•         Distribution--Widely distributed to all tissues and fluids, including CNS,  breast milk, and fetal tissues.

•       Metabolism---- Rapidly hydrolyzed to salicylic acid (active). Salicylic acid is conjugated in the liver to the metabolites 

•       Elimination = Salicylic acid plasma half—life is approximately 6 h. The half life-- is approximately 15 to 20 min for aspirin. 

•       Dose ----             300---500 mg/4-6 hr        

INDOMETHACIN

•       Indole derivative Potent inhibitor of PG synthesis & suppresses neutrophil motility. Well absorbed orally.

•        Adverse effects: Gastric irritation, nausea, anorexia, gastric bleeding & diarrhoea, frontal headache, dizziness, ataxia, mental confusion, depression, psychosis, leukopenia, rashes, increased risk of bleeding. 

•       Contraindicated in machinery operators, drivers, psychiatric patients, epileptics, kidney disease, pregnant women & children

•       Dose: 25-50mg BD-QID

IBUPROFEN

•       Propionic acid derivative

•       Adverse effects: Gastric discomfort, nausea & vomiting ,Headache, dizziness, blurring of vision, tinnitus & depression.Avoided in pregnancy, peptic ulcer patient & asthmatic patients

•         USES: Analgesic & Antipyretic ,Rheumatoid arthritis, osteoarthritis, musculoskeletal disorders ,Soft tissue injuries, fractures, vasectomy, tooth extraction ,Postpartum & postoperatively : suppress swelling & inflammation

•       Dose: 400-800 mg TDS

     DICLOFENAC SODIUM

•       Aryl-acetic acid derivative

•       Well absorbed orally, Plasma t ½ - 2 hrs 

•       Adverse effects: Epigastric pain, nausea, headache, dizziness, rashes 

•       Uses: Rheumatoid arthritis, ankylosing spondylitis, dysmenorrhea, post traumatic & post inflammatory conditions.

•        Dose: 50mg TDS

 KETOROLAC

•       Pyrrolo-pyrrole derivative

•       Potent analgesic & modest anti inflammatory . Rapidly absorbed after oral & i.m administration

•       Plasma half life  is 5-7 hrs 

•       Adverse effects: Nausea, abdominal pain, dyspepsia, ulceration, loose stools, drowsiness, headache, dizziness, nervousness, pruritis, pain & fluid retention

•       Orally in a dose of 10-20 mg 6 hrly.

   PARACETAMOL

•       The deethylated active metabolite of phenacetin.Paracetamol is a good and promptly acting antipyretic. Paracetamol  is a poor inhibitor of PG synthesis in   peripheral tissues, but more active on COX in brain (poor ability to inhibit COX in presence of peroxides generated at site of inflammation). 

•       PHARMACOKINETICS --Well absorbed orally;only 1/4^th is plasma bound ; uniform distribution in body  2-3hrs;effect of an oral dose lasts for 3-5hrs

•       ADVERSE EFFECTS: Nausea and rashes are occasional , Leukopenia is rare  Acetaminophen overdose can cause hepatotoxicity,

•          Dose    ---- 325-650 mg/4-6 h

SIDE EFFECTS of NSAIDs

Cardiovascular system – an increased risk of infarction associated with NSAIDs do so in patients who consume or have consumed such medication for long periods of time. The studies evaluating only occasional NSAIDs consumption have revealed no rise in relative risk . Naproxen was even associated with a significant reduction in the risk of acute myocardial infarction

Gastrointestinal system – In patients who use these drugs on a routine basis, nausea or dyspepsia  and  endoscopically manifest ulcerations  who consume NSAIDs during a period of three months . The greatest consumption of NSAIDs corresponds to arthrosis-arthritis, typically in elderly patients .

•       NSAIDs are prescribed for short periods of time in patients of all age groups, and in relation to acute infectious-inflammatory processes, or as prophylaxis against such processes. When used in this way, the most frequent side effects are dyspepsia, diarrhea and abdominal pain .

•       Henry et al.  evaluate the risk of serious gastrointestinal complications abdominal  bleeding or perforation associated with commonly used NSAIDs,

•        Ibuprofen was seen to pose the least risk of gastrointestinal toxicity

Liver toxicity – Long-term use of NSAIDs, especially at high doses, can rarely harm the liver. Monitoring the liver function with blood tests may be recommended in some cases.

Kidney toxicity – inhibition of prostaglandin synthesis by NSAIDs can trigger renal hypoperfusion, nephrotic syndrome or interstitial nephritis. The risk is high for indomethacin and phenylbutazone . The most commonly observed side effect is peripheral edema secondary to inhibition of prostaglandin E2 synthesis. 

•       The edema and sodium retention are usually moderate, and the result is a 1-2 kg increase in body weight in the first weeks of treatment. In some rare cases the condition may be severe, with marked edema, important weight gain, blood pressure increments and heart failure.

NSAIDS IN PREGNANCY : NSAIDs in the third trimester of pregnancy with premature closure of the ductus arteriosus, found the risk of such premature closure to increase as much as 15-fold in the offspring of women who had used indomethacin for short periods of time. Paracetamol is adequate during pregnancy. 

                     

                                                                                                                              DR. ANJUSHA SHARDA