Nonsteroidal Anti inflammatory drugs (NSAID)

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Nonsteroidal Anti inflammatory drugs (NSAIDs)

Nonsteroidal Anti inflammatory drugs (NSAID) are Non narcotic analgesics (pain killers) which used for skeletal analgesia. NSAIDs also known by Aspirin-like drug name. these widely use in practice. in some country NSAIDs are over the counter drugs.

Mechanism of action of NSAIDs

Anti Inflammatory action is produced by inhibition of prostaglandin  synthesis at the site of injury. Many other mediators may also play a role in inflammation Eg: Leukotrienes, Platelet  Activating Factor (PAF) etc. But the NSAIDs inhibit only Prostaglandins. Analgesic action is brought about  by affecting the transduction of pain in nerve endings. Prostaglandins (analgesic agents) sensitize nerve endings to long lasting dull pain.

Antipyretic action by counteracting  infection generation of pyrogens, interleukins, Tumor necrosis factor (TNFα). Prostaglandins  production in hypothalamus plays an important in thermoregulation. Thus, NSAIDs block the action of pyrogens , reset the thermostat, promote sweating and cutaneous vasodilatation heat loss. NSAIDs do not cause hypothermia in normal patients.

Classification of NSAIDs

Classifications of Nonsteroidal Anti inflammatory drugs (NSAID)
Classifications of Nonsteroidal Anti inflammatory drugs (NSAID)

Pharmacokinetics of NSAIDs

  • NSAIDs are weak acids
  • Well absorbed after oral administration
  • Highly protein bound and have poor Volume of distribution
  • Displacement from albumin binding by other substrates is possible
  • Metabolized in liver
  • Conjugates excreted in urine
  • Age and species variation plays an important role in pharmacokinetics

Commonly used NSAIDs Drug list

Aspirin

  • Use in dog, cat, cattle. Available as enteric coated, film coated, buffered, time release tablets.
  • Mostly preferred in cats
  • Undergoes glucuronidation
  • Use as analgesic, antipyretic.
  • Inhibits platelet aggregation – In humans, low dose aspirin is used for prevention of thrombus in arteries to prevent heart attacks

Paracetamol 

  • Acts mainly as antipyretic
  • Most popular drug in humans.
  • Action not through COX inhibition
  • Contraindicated in cats
  • No anti-inflammatory effect
  • Glucuronidation is the major pathway

Phenylbutazone

Analgesic, antipyretic and antiinflammatory and also uricosuric action. Popular in horses and dogs. Irritating if given i/m or s/c.

Flunixin meglumine

Drug of widespread use in veterinary practice. For musculoskeletal pain and also in colic in horses. Low dose (1.1mg / kg).

Ketoprofen

Powerful anti-inflammatory . major use in horses @ 2.2 mg / kg in horses. Overdose may cause laminitis.

Ibuprofen

More anti-inflammatory and less analgesic. Low tendency to produce gastrointestinal ulcers.

Meclofenamic acid

Used in horses for osteoarthritis and soft tissue inflammation. May cause gastrointestinal irritation and colic in horses.

Meloxicam

Meloxicam is a another popular drug in veterinary medicine, recently introduced into the Indian market. Low potency to induce gastrointestinal side effects, so it’s more safe to use.

Nimesulide 

Selective COX2 inhibitor. Injectable form introduced into market. Low tendency to cause gastric side effect.

Diclofenac

Popular drug but cause GI ulcers. However, drug residues in food animal tissues created havoc by wiping out vultures in North West India and Pakistan. Prohibited for veterinary use in Indian subcontinent.

COX2 selective Inhibitors

COX2 (Inducible) isoform involved in inflammation while COX1 (constitutive) plays a role in homeostasis– gastrointestinal protection, renal flow etc. Selective Inhibitors of COX2 have less chances of side effects related to gastrointestinal ulcers.

Examples of COX2 selective inhibitors are Nimesulide, valdecoxib, rofecoxib.

Beneficial effects of NSAIDs

  1. Analgesic 
  2. Antipyretic
  3. Anti-inflammatory
  4. Anti thrombotic– NSAIDs inhibit both Proaggregatory Thromboxanes (TXA2) and Antiaggregatory Prostacyclin (PGI2) but effect on Thromboxanes predominate. Thus, increase bleeding time
  5. Closure of ductus arteriosus– Patency of Ductus in foetal life is maintained by local prostaglandins, and closes after birth. In case of a failure of closure of ductus, NSAIDs will help to close the ductus by inhibiting prostaglandins.

Clinical applications of NSAIDs

  1. Fever
  2. Analgesia
  3. Peripheral pain
  4. Musculoskeletal pain
  5. Endotoxemia
  6. Anticoagulant (platelet) activity
  7. Patent ductus arteriosus closure
  8. As an adjunct therapy in mastitis with antibiotics in veterinary practice

Toxicity of Nonsteroidal Anti inflammatory drugs (NSAID)

  1. Gastric Ulceration– Major toxicity of NSAIDs. prostaglandins exert cytoprotective effect by protecting the mucous membrane against attack by acid. NSAIDs, by inhibiting prostaglandins lead to exposure of Mucosa to acid causing erosion, ulcers and bleeding. Typical ulcers are reported in dogs and horses.
  2. Renal toxicity– Prostaglandins regulate local blood flow in kidney. With other nephrotoxic agents or conditions like shock, dehydration leading to  edema, Na+ retention, nephrosis
  3. Delay in labour process owing to inhibition of prostaglandins which have a role in parturition
  4. Hepatotoxicity – possible with all NSAIDs. Paracetamol forms a hepatotoxic metabolite by an alternate pathway (glucuronidation – poor in cats)
  5. Blood dyscriasis – phenylbutazone – causes blood dyscrasias
  6. Asthma and anaphylactic reactions in many individuals – due to overproduction of leukotrienes

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