Pharmacology

1. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):

• Inhibition of Cyclooxygenase (COX) Enzymes:

  NSAIDs primarily inhibit cyclooxygenase (COX) enzymes, namely COX-1 and COX-2. These enzymes are responsible for the synthesis of prostaglandins, thromboxanes, and prostacyclins from arachidonic acid. Prostaglandins mediate inflammation, pain, and fever.

  • COX-1: Involved in maintaining normal physiological functions such as gastric mucosal protection, platelet aggregation, and renal blood flow.
  • COX-2: Primarily induced during inflammation and responsible for producing prostaglandins that promote inflammation, pain, and fever.

  By inhibiting COX enzymes, NSAIDs reduce the production of these inflammatory mediators, thereby alleviating pain, fever, and inflammation. Selective COX-2 inhibitors (e.g., celecoxib) were developed to reduce gastrointestinal side effects associated with non-selective COX inhibition but have been linked to cardiovascular risks.

• Other Mechanisms:

  Some NSAIDs might also influence other inflammatory mediators or pathways, contributing to their anti-inflammatory effects, but the primary mechanism remains COX inhibition.

2. Steroidal Anti-Inflammatory Drugs (Corticosteroids):

• Genomic Effects:

  Corticosteroids (e.g., prednisone, dexamethasone) enter cells and bind to glucocorticoid receptors in the cytoplasm. This complex translocates to the nucleus and affects gene transcription.

  • Increased Production of Anti-Inflammatory Proteins: Corticosteroids increase the synthesis of anti-inflammatory proteins such as lipocortin-1 (annexin A1), which inhibits phospholipase A2, reducing the availability of arachidonic acid, a precursor for prostaglandins and leukotrienes.
  • Decreased Production of Pro-Inflammatory Proteins: They suppress the expression of genes encoding pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-α), chemokines, adhesion molecules, and inflammatory enzymes (e.g., COX-2, iNOS).
• Non-Genomic Effects:

  Corticosteroids can also have rapid, non-genomic effects by interacting directly with cell membrane receptors or affecting intracellular signaling pathways. These effects contribute to their immediate anti-inflammatory actions.

• Overall Effects:

  Corticosteroids have broad anti-inflammatory and immunosuppressive effects, reducing inflammation, edema, pain, and immune cell activity.

Summary:

Anti-inflammatory agents act by targeting different components of the inflammatory cascade. NSAIDs primarily inhibit COX enzymes to reduce prostaglandin synthesis, while corticosteroids modulate gene transcription to decrease pro-inflammatory mediators and increase anti-inflammatory proteins. Both classes of drugs effectively reduce inflammation but differ in their mechanisms, side effects, and clinical applications.