Anti-inflammatory Pharmacology Notes

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

  • Drugs:
    • Ibuprofen (Advil, Motrin)
    • Ketorolac (Toradol)
    • Meloxicam (Mobic)
    • Naproxen (Aleve)
    • Indomethacin
    • Aspirin
  • Mechanism of Action (MOA): Inhibits cyclooxygenase (COX) one and two, which inhibits prostaglandin production, leading to reduced inflammation. Also reduces the protective lining of the stomach.
    • COX Effects Breakdown:
      • COX 1: Supports the stomach lining, kidneys, platelet aggregation, and promotes vasodilation.
      • COX 2: Pro-inflammatory.
  • Indications:
    • Anti-inflammatory (e.g., rheumatoid arthritis, gout).
    • Analgesia (pain relief).
    • Antipyretic (fever reduction).
    • Aspirin: Specifically used for suppression of platelet aggregation; used for prevention of cardiovascular events.
      • Aspirin should be stopped before major surgery and childbirth due to its effects on platelet aggregation.
  • Black Box Warning:
    • GI bleeding.
    • Adverse cardiac events.
  • Prescription Requirements: Meloxicam, indomethacin, and ketorolac are available by prescription only.
  • Side Effects/Adverse Effects (SE/AE):
    • GI bleeding.
    • Nephrotoxicity (kidney damage).
    • Hepatotoxicity (liver damage).
    • Tinnitus (ringing in the ears) - specifically associated with aspirin.
  • Aspirin and Children: Aspirin is not to be used in children under 18 years old due to the risk of Reye’s Syndrome.
  • Routes of Administration: NSAIDs are available through multiple different routes with varying onsets of action.

NSAIDs – COX 2 Inhibitors

  • Drug:
    • Celecoxib (Celebrex)
  • MOA: Inhibits COX 2, reducing prostaglandin production and inflammation.
  • Indication: Anti-inflammatory, particularly in conditions like rheumatoid arthritis (RA).
  • Alternative: Considered as an alternative anti-inflammatory due to increased risk of adverse cardiovascular events with non-selective NSAIDs.
  • GI Effects: Lower risk of adverse GI effects compared to non-selective NSAIDs.

Glucocorticoids / Corticosteroids

  • Drugs:
    • Hydrocortisone
    • Prednisone
    • Methylprednisolone
    • Dexamethasone
    • Betamethasone
  • MOA:
    • Suppresses inflammation by inhibiting multiple inflammatory cytokines.
    • Suppresses immune response: reduces leukocyte function.
    • Suppresses adrenal function via negative feedback.
  • Indications:
    • Adrenocortical insufficiency.
    • Addison's disease.
    • Inflammation.
    • Immune suppression.
    • Nausea.
    • Specific conditions: gout, asthma, COVID-19, inflammatory bowel disease (IBD), allergies, cancers.
  • Side Effects/Adverse Effects (SE/AE):
    • Immunosuppression.
    • Hyperglycemia (high blood sugar).
    • Hypertension (high blood pressure).
    • Osteoporosis (bone thinning).
    • Mood swings.
    • Weight gain.
    • Sodium and fluid retention.
    • Peptic ulcer disease (PUD).
    • Abnormal fat deposits (Cushing’s syndrome).
  • Administration: Preferential use of select steroids with a local effect versus a systemic effect (e.g., intranasal vs. oral).
    • Available topically, intranasally, via inhalation, orally, and via injection.
  • Tapering: Steroids must always be tapered when discontinued to avoid adrenal insufficiency.
  • Drug Interactions: Increased risk of adverse effects if given with NSAIDs.
  • Monitoring: Monitor bone density with long-term use; encourage calcium and vitamin D supplementation.
  • Contraindications: Avoided in patients with an active infection due to immunosuppressive effects.

Serotonin 5-HT Agonists (Triptans)

  • Drugs:
    • Sumatriptan (Imitrex)
    • Zolmitriptan
    • Rizatriptan
  • MOA: Cerebral vasoconstriction and decreases perivascular inflammation.
  • Indications: Acute cluster headache and acute migraines.
  • Side Effects/Adverse Effects (SE/AE): Common complaint is a vague feeling of chest pressure or heaviness.
  • Administration: Taken upon the onset of migraine (aura).
  • Use: First-line agent for acute migraines.
  • Rebound Headaches: Can cause rebound headaches if taken in excess of twice per week or nine times per month.
  • Pregnancy: Unknown safety in pregnancy – not recommended as first line in pregnancy.
  • Serotonin Syndrome: Can cause serotonin syndrome if taken with other serotonin medications.
    • Symptoms include agitation, confusion, fever, tachycardia, hypertension, hyperreflexia, tremors.
  • Contraindications: Contraindicated in those with cardiac disease or uncontrolled hypertension.
  • Overdose Treatment: Overdose treated with a beta-adrenergic antagonist.

Migraine Treatment

  • Acute Treatment:
    • Ergot alkaloids (e.g., ergotamine).
    • CGRP receptor antagonists (e.g., rimegepant, ubrogepant).
  • Prevention (Prophylaxis):
    • Beta-blockers (e.g., propranolol).
    • SNRIs (e.g., venlafaxine).
    • TCAs (e.g., amitriptyline).
    • Anti-epileptics (e.g., topiramate, valproic acid).
    • CGRP monoclonal antibodies (e.g., erenumab, fremanezumab).