NSAIDs

Nota:

• Non-steroidal anti Inflammatory drugs.

1. Effects

   Nota:

   •  3 primary effects: Anti-inflammatory effect: Modification of the inflammatory reaction. Analgesic effect: Reduction of pain, Antipyretic effect: Lowering of raised temperatures.
   1. Anti Inflammatory

      Nota:

      • Release of prostaglandins produce increased vasodilation and vascular permeability Inhibition reduces inflammatory reaction.
   2. Anti-pyretic

      Nota:

      • Inhibition of E type prostaglandins in response to IL-1 Prostaglandins E responsible for elevating hypothalamic set point.
   3. Analgesic

      Nota:

      • Decreased prostaglandins, Hence no sensitization of nociceptive nerve endings to other inflammatory mediators such as bradykinin and histamine
2. Classes of NSAIDs

   Nota:

   • Note that the paracetamol has no anti-inflammatory effect.
   1. Aspirin

      Nota:

      • Acetylsalicyclic acid. Non-selective inhibitor. Irreversibly inhibited COX and inhibit the platelet aggregation. However there are adverse effects such bleeding into the gut (COX1 housekeeping effects lowered). Not given to people under age of 16 due to possible brain inflammation and liver damage.
   2. Iboprofens and non selective NSAIDS

      Nota:

      • Reversible COX inhibitors Treatment for mild to moderate pain and inflammation Side effects include GIT potential renal problems due to retained sodium and potassium.
   3. COX-2 Inhibitor

      Nota:

      • Selectivive, inhibitors have the antipyretic, analgesic and anti-inflammatory. ---Coxibs.
      1. Paracetamol (acetaminophen)
   4. Topical Opthalmic NSAIDS

      Nota:

      • Applied in the eye, but may be absorbed in the systemic circulation. Used for treatment of corneal abration, decrease postoperative ocular inflammation or allergic inflammations, photophobia (abnormal sensitivity to light)
   5. Exercise

      Nota:

      • Affect platelet aggregation May induce GIT bleeding Delayed onset of muscle soreness and may enhance performance
3. Effect
   1. Cyclooxygenases
      1. COX1

         Nota:

         • It is for constituitive function. It produces housekeeping functions for stomach, intestines lungs... Such as endothelial integrity, vascular patency, gastric mucosal integrity, bronchodilation Kidney is to maintain renal function Platelets, platelet function. If it was inhibited. it may provide unwanted side effects.
      2. COX2

         Nota:

         • Inducible inflammatory responses Blocking it provides therapeutic anti-inflammatory effects.
      3. Synthesis

         Nota:

         • Phospholipid turns to Arachidonic acid via Phospholipase A2 Then arachidonic acid can branch into 2 paths, One was catalysed by cyclooxygenase to PGG2 and subsequently all the way to Prostaglandins and thromboxanes and prostacyclin The other was catalysed by 5-lipoxygenase into cysteinyl and LTs.
   2. Inhibition

      Nota:

      • Irreversible inhibiton: Aspirin Competitive Inhibition : most NSAIDS Reversible Non-competitive inhibition: Paracetamol.
4. Side effects
5. Glucocorticoids

   Nota:

   • Anti-inflammatory and immunosuppressant Used in certain treatments such as Rhematoid arthritis. inflammatory bowel condition, bronchial asthma, inflammatory skin conditions.
   1. Anti-inflammatory

      Nota:

      • Reduced production of eicosanoids, reduced and inhibit formation of arachidonic acid. It also inhibits phospholiopase A2 and formation of prostaglandins and leukotrienes
   2. Immunosuppresant

      Nota:

      • Inhibit accumulation of neutrophils and monocytes Decreased antigen processing by macrophage Decreased T-helper cell function, phagocytosis, antibody production, and decreased production of IL-2
   3. Side Effects

      Nota:

      • Suppression of the immune system  Altered bone metabolism (may lead to osteoporosis) Impaired wound healing Development of diabetes and peptic ulcers. Growth suppression in children like asthma, (minimised side effects by inhalation) Cushing's Syndrome.
6. DMARDS

   Nota:

   • Combination of drugs.
7. Anti-cytokine

   Nota:

   • Biological preparations that target action of cytokines such as TNF-alpha. Monoclonal antibodies against the a chain of the IL-2 receptors
8. Anti-histamines

   Nota:

   • H1 receptor antagonists Uses for allergic reactions Antiemetics for motion sickness Sedation