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HSS 3106 C - Pharmacology: Mechanisms and Compliance - Autoimmune Diseases

Autoimmune Diseases

  • Definition: Conditions where the immune system mistakenly attacks the body’s own tissues, viewing them as foreign invaders.
  • Difference from Autoinflammatory Diseases:
    • Autoimmune diseases involve the adaptive immune system.
    • Autoinflammatory diseases stem from malfunctions in the innate immune system, leading to inflammation.
  • Causes: Likely multifactorial, involving genetic and environmental influences.

Classification of Autoimmune Diseases

  1. Systemic autoimmune diseases: Affect multiple organs/tissues (e.g., Rheumatoid arthritis, Multiple sclerosis).
  2. Organ-specific autoimmune diseases: Affect specific organs (e.g., Inflammatory bowel disease (IBD), Type 1 diabetes).
  3. Skin-related autoimmune diseases: Affect the skin (e.g., Psoriasis, Vitiligo).

Treatment Approaches

  • Cure: No cure available for autoimmune diseases; treatments focus on symptom management and progression control.
  • Medications:
    • NSAIDs: Reduce pain, swelling, and stiffness.
    • Corticosteroids: Reduce inflammation and suppress the immune system.
    • Immunosuppressive drugs: Inhibit the immune activity.

Rheumatoid Arthritis (RA)

  • Definition: A chronic autoimmune disease characterized by joint inflammation, pain, and stiffness.
  • Genetics: Associated with environmental factors (e.g., infections, smoking) and genetic predispositions (HLA-DRB1, HLA-DR4).
  • Pathogenesis:
    • T-cells and macrophages release inflammatory cytokines (e.g., TNF-α, IL-1, IL-6).
    • Leads to cartilage breakdown and formation of pannus, causing joint damage.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

  • Function: Modify or slow the progression of rheumatoid arthritis.
  • Types:
    1. Biologic DMARDs: Derived from biological materials.
    2. Non-biologic DMARDs: Chemically synthesized.
  • Common DMARDs: Methotrexate, Leflunomide, Hydroxychloroquine, Sulfasalazine.
Methotrexate
  • Role: First-line treatment for moderate to severe RA.
  • Mechanism:
    • Folic acid analog that inhibits nucleotide synthesis.
    • Suppresses T and B cell proliferation, reducing inflammation and joint damage.
  • Side Effects:
    • Bone marrow suppression (leukopenia, anemia, thrombocytopenia).
    • Hepatic and renal toxicity, pulmonary toxicity.
    • Teratogenic effects during pregnancy.
Leflunomide
  • Mechanism: Inhibits DHODH, affecting T-cell proliferation and reducing joint damage.
  • Side Effects: Bone marrow suppression, hepatotoxicity, gastrointestinal disturbances.
  • Contraindicated: In pregnancy and severe immunodeficiency.
Hydroxychloroquine
  • Use: Originally an anti-malarial, also effective in RA.
  • Mechanism: Inhibits release of TNF-α and IL-1.
  • Side Effects: Retinal damage, skin hyperpigmentation, muscle weakness.
  • Safe during pregnancy.

Inflammatory Bowel Disease (IBD)

  • Definition: Chronic gastrointestinal inflammation, divided into Crohn's Disease (CD) and Ulcerative Colitis (UC).
  • Symptoms: Include abdominal pain, diarrhea, urgency, rectal bleeding, weight loss, fatigue.
  • Treatment Goals: Reduce inflammation, address symptoms, and stop future flare-ups.
  • Medications: Aminosalicylates, corticosteroids, immunomodulators, biologics, antibiotics.

Corticosteroids in IBD

  • Uses: Effective for IBD flare-ups but not recommended for long-term use due to side effects.
  • Examples: Prednisone, hydrocortisone, budesonide.
  • Mechanisms: Anti-inflammatory effects via genomic and non-genomic pathways.
  • Side Effects: Increased infection risk, osteoporosis, mood changes, weight gain.

Multiple Sclerosis (MS)

  • Definition: Chronic disease affecting the central nervous system (CNS), leading to myelin damage and disrupted communication.
  • Symptoms: Vary widely but can include vision problems, muscle weakness, numbness, cognitive issues.
  • Types:
    1. Relapsing-remitting MS: Fluctuating symptoms with periods of remission.
    2. Secondary progressive MS: Initially similar to RRMS but with constant progression.
    3. Primary progressive MS: Steady worsening of symptoms from the start.

Disease-Modifying Therapies (DMTs) for MS

  • Types: Biologic and non-biologic DMTs.
  • Examples:
    1. Fingolimod: Prevents immune cell entry to CNS.
    2. Dimethyl fumarate: Activates Nrf2 for neuroprotection and anti-inflammatory effects.
    3. Teriflunomide: Inhibits DHODH, decreases MS relapse frequency.
  • Side Effects: Risk for serious infections, gastrointestinal issues, contraindicated in pregnancy.

Conclusion

  • Understanding autoimmune diseases, their classifications, treatments, and management strategies is critical for effective patient care in pharmacology.