AINES and Glucocorticoids

• Here are study notes about AINES and Glucocorticoids

AINES (Non-Steroidal Anti-Inflammatory Drugs)

• AINES are categorized by their derivative, such as Salicylate or Acetic Acid.

Salicylates

• Aspirin (acetylsalicylic acid) uses:
  • Treatment for acute myocardial infarction
  • Antiplatelet at 300mg/day
  • Analgesic for mild to moderate pain ranging from 300-2400 mg/day
  • Antipyretic for patients with fever at 300-2400 mg/day
  • Anti-inflammatory at 2400-4000 mg/day
• Adverse effects of Aspirin include:
  • Gastric intolerance
  • Reye's Syndrome (fulminant hepatitis and cerebral edema)
  • Salicylate Intoxication: hyperventilation, respiratory alkalosis followed by metabolic acidosis, vertigo, hyperpyrexia, coma, renal insufficiency

Propionic Acid Derivatives

• Ibuprofen is an analgesic used for Rheumatoid Arthritis and Osteoarthritis and closes PDA in premature infants
• Flurbiprofen is an analgesic used for Rheumatoid Arthritis and Osteoarthritis and Spondyloarthritis; also used for perioperative analgesia in minor ear, neck, and nose surgery
• Common adverse effects of Propionic Acid Derivatives:
  • Gastrointestinal disorders
  • Increased risk of heart attack and stroke

Oxicums

• Piroxicam used for Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis, and acute gout
• Exel (meloxicam) used for Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis, and acute gout
• Oxicums have a lesser gastrointestinal effect, resulting in a lower risk of developing ulcers.
• Oxicums are NOT cardioprotective

Pyrazolons

• Metamizole is an analgesic for moderate pain and fever, that doesn't respond to antipyretics. Should not be administered to patients with allergies to sulfa drugs or sulfur components
• Adverse effects of Metamizole:
  • Hematologic reactions (agranulocytosis and aplastic anemia)
  • Can cause heat, facial flushing, palpitations, hypotension, and nausea

Acetic Acid Derivatives

• Indomethacin treats Gout, Ankylosing Spondylitis, and Bartter's Syndrome and Rheumatoid Arthritis
• Sulindaco treats rheumatic diseases, suppresses familial intestinal polyposis, and inhibits the appearance of colon, breast and prostate cancer.
• Tolmetina treats acute gout
• Ketorolac provides analgesia for moderate pain
• Adverse effects of Acetic Acid Derivatives:
  • Diarrhea, abdominal pain, headache, pancreatitis, dizziness, confusion, depression, nausea, dyspepsia, and pain at the injection site
  • High toxicity which includes diarrhea, abdominal pain, headache, dizziness, confusion, depression, nephrotoxicity, nausea, dyspepsia, and thrombocytopenic purpura

COX-2 Inhibitors

• Celecoxib analgesic, antipyretic, and anti-inflammatory for patients with rheumatic arthrosis
• Etoricoxib the most selective inhibitor, used for pain and inflammation in osteoarthritis and rheumatoid arthritis and treats acute gout
• Parecoxib (prodrug of valdecoxib) used for short-term postoperative pain relief
• Common adverse effects of COX-2 Inhibitors:
  • Edema, rash, diarrhea, headaches, diarrhea, respiratory infections and nausea
  • Do not administer if patient is allergic to sulfa drugs or sulfur components

Para-aminophenols

• Paracetamol is an antipyretic and analgesic.
• Side effect is Skin rash
  • Overdose can cause nausea, vomiting, anorexia, abdominal pain, and ultimately fatal liver necrosis
  • The antidote for overdose is N-acetylcysteine

Glucocorticoids

• Potent anti-inflammatories and immunosuppressants that enhance B2 agonists, promote bronchodilation, and diminish bronchoconstriction response. Also reduces synthesis of leukotrienes and redistributes immune cells.
• Elevated glucose levels in the blood is due to gluconeogenesis, increased muscle catabolism, and lipolysis.

Effects and mechanisms

• Excessive doses of glucocorticoids (GC) increase muscle protein catabolism, leading to weakness and fatigue and have catabolic effects on muscle, resulting in weakness and fatigue
• GC effects on bone tissue reduce intestinal calcium absorption and increase renal calcium excretion, resulting in a negative calcium balance.
• GC increase the catabolism of muscle proteins
• GC cause skin disorders like thinning, stretch marks (striae), and bruising (ecchymosis) by suppressing fibroblast function and collagen synthesis.
• GC usage alters blood composition by increases erythrocytes and neutrophils, and decreasing lymphocytes and eosinophils counts.
• GC can cause ulceration in the gastrointestinal tract by increasing gastric acid secretion and decreasing gastric mucosa production.
• GC promote central obesity, increase appetite, creating a moon face, buffalo hump. They trigger hyperglycemia, increasing insulin release, leading to fat deposition, and can elevate plasma triglycerides

Therapeutic Indications and Medications

• Skin diseases like atopic dermatitis use Hydrocortisone, Dexamethasone, or Betamethasone
• Eye disorders: acute uveitis or allergic conjunctivitis use Prednisone, Prednisolone, Dexamethasone, or Betamethasone.
• Pulmonary diseases like aspiration pneumonia: Beclomethasone, Fluticasone, Budesonide, Prednisone, or Methylprednisolone
• Thyroid diseases like malignant exophthalmos or subacute thyroiditis uses Dexamethasone
• Odontological uses include extractions of third molars or osteoarthritis of the temporomandibular joint use Prednisone, Prednisolone, Dexamethasone, or Betamethasone
• Infections for gram (-) septicemia Hydrocortisone or Dexamethasone is used
• To treat Medication reactions or anaphylaxis or contact dermatitis use Hydrocortisone or Dexamethasone

Other glucocorticoid uses

• Inflammatory bone and joint conditions like: arthritis, bursitis, or osteoarthritis is treated by Prednisone, Prednisolone, Dexamethasone, or Betamethasone
• Neurological disorders like postoperative cerebral edema from Methylprednisolone.
• Organ transplant rejection use Hydrocortisone or Dexamethasone

Glucocorticoid Groups

• Inhibitors like Metirapone are used to cortisol synthesis and in Cushing's syndrome.
• Inhibitors (Ketoconazol and Fluconazol) inhibit cytochrome P-450 enzymes and are used in steroid biosynthesis and Cushing's syndrome
• Antagonists like Spirolactone, compete with cortisol receptors, used adrenal hypocortisolism and hyperglycemia in Cushing's syndrome