1. Gout
1.1. • Metabolic Disorder • Characterized by presence of excess uric acid in tissues and blood • Diagnosis: Synovial fluid analysis; Presence of needle shaped crystals (MSU=Monosodium urate)
1.1.1. Clinical Presentations of Gout 1. Acute Gout or Acute gouty arthritis • (+) Acute monoarticular arthritis (Common) • Most commonly affected joint - 1st metatarsophalangeal joint (base of the toe) 2. Chronic gout with chronic hyperuricemia
1.2. ACUTE Management of Gout
1.2.1. NSAIDS
1.2.1.1. All are useful except ASA (worsens gout) and Tolemetin
1.2.1.2. Preferred are those with short half-life
1.2.1.2.1. • Indomethacin • Diclofenac • Ibuprofen • Naproxen
1.2.2. Colchicine
1.2.2.1. MOA: Inhibits microtubule function and synthesis; prevents chemotaxis and inflammation activation
1.2.2.2. Dose
1.2.2.2.1. **Oral** - 0.06 mg tablet q6-8 until symptoms resolve then continue as BID or TID
1.2.2.2.2. Alternative: **IV** if patient cannot take PO (Max dose < 4 mg)
1.2.2.3. **DOC** for **ACUTE GOUT** and **initial treatment for Chronic gout**
1.2.2.4. Adverse effects
1.2.2.4.1. • Hematologic: Aplastic anemia, Thrombocytopenia, Agranulocytosis • GIT disturbance: Nausea and Vomiting; Diarrhea • Paresthesia (Needle prick sensation)
1.2.2.5. Toxicities
1.2.2.5.1. • Bloody diarrhea • Vasomotor collapse • Coma and Death
1.2.3. Glucocorticoids
1.2.3.1. **Oral**
1.2.3.1.1. Prednisone
1.2.3.2. **Intra-articular (Intrasynovial)**
1.2.3.2.1. Triamcinolone or methylprednisolone
1.2.4. Adrenocorticotropin Hormone ACTH
1.2.4.1. • 40-80 units IM q12-24 hrs for 1-2 days • use for patients who cannot be given colchicine
1.3. CHRONIC Management of Gout
1.3.1. **Hypouricemic drugs:** Lowers uric acid in blood to <300-360 mmol/L or 5 mg/dL
1.3.1.1. Indication for Hypouricemic Drugs - • > 2 attacks of acute gout • (+) Signs and symptoms of chronic gout (Tophi/uric acid stones) • Commitment to lifelong treatment
1.3.1.1.1. Hypouricemic Drugs
1.3.2. Colchicine therapy overlapping with **HYPOURICEMIC** therapy
2. RHEUMATIC DISORDER
2.1. Autoimmune and inflammatory disease that attacks the joints, muscles, bones and organs
2.2. Treated with NSAIDS and DMARDS (Disease-modifying antirheumatic drugs)
2.2.1. Non-biologic drugs
2.2.1.1. 1st-Line Drugs or Drugs of Choice
2.2.1.1.1. Methotrexate (MT)
2.2.1.1.2. Sulfasalazine (SSa)
2.2.1.1.3. Hydroxychloroquine (HCQ)
2.2.1.2. 2nd-Line drugs
2.2.1.2.1. Leflunomide
2.2.1.3. 3rd-Line drugs
2.2.1.3.1. Gold Preparations
2.2.1.3.2. Penicillamine
2.2.2. Biologic drugs
2.2.2.1. TNF-Blockers
2.2.2.1.1. Etanercept
2.2.2.1.2. Infliximab - Antibody to TNF (Chimeric)
2.2.2.1.3. Adalimumab - Antibody to TNF (Human)
2.2.2.1.4. Use: For patients with failed DMARD treatment and untolerated DMARD treatment
2.2.2.1.5. Adverse effects: - Increased risk of infection - Increased risk of reactivating TB - Increased risk of Lymphoma - Pain at injection site
2.2.2.2. Anakinra
2.2.2.2.1. Recombinant IL-1 receptor antagonist
2.2.2.2.2. • AE: Major reaction at injection site • NOTE: Rarely effective in those with failed TNF-blocker treatment
2.2.2.3. Rituximab
2.2.2.3.1. Chimeric antibody directed CD20 that depletes mature B-cells
2.2.2.3.2. **Alternative to failed TNF blocker treatment**
2.2.2.3.3. **Combined with Methotrexate to stop progression of bone damage**
2.2.2.4. Abatacept
2.2.2.4.1. - Inhibits T-Cell activation - Can be combined with **Methotrexate**
2.2.3. Glucocorticoids
2.2.3.1. **Low dose** - Suppress inflammation and stops progression of bone erosion
2.2.3.1.1. Given at **low doses** with DMARDs
2.2.3.2. Increases bone sparing effects of Methotrexate
2.2.3.3. Pulse Therapy - Give high dose of methylprednisolone (0.5 mg/kg/day orally or 1000 mg methylprednisolone)
2.2.3.4. AE: • Inc. risk of infection • Hyperglycemia • Hypertension • Osteoporosis
2.2.4. Cytotoxic drugs
2.2.4.1. • “Toxic to Cells” and used as antineoplastics or anticancer drugs • Prevents replication or growth of cells • Always given with glucocorticoids
2.2.4.2. - Cyclophosphamide (alkylating agent) - Azathioprine - Mycophenolate mofetil
2.2.4.2.1. Adverse effects: Irreversible testicular/ovarian failure; N&V; Alopecia; Inc. risk of infection
3. Non-opioid Analgesics
3.1. Para-aminophenol
3.1.1. MOA: Weak inhibitor of Prostaglandins
3.1.2. • Historical: **Phenacetin** a **Prodrug** of **APAP** • Clinical: **Acetaminophen/Paracetamol**
3.1.2.1. Initial treatment for Osteoarthritis
3.1.2.2. Mild pain states
3.1.2.3. Antipyretic
3.1.3. Adverse event: Relatively safe in children, pregnant, lactating mothers
3.1.4. Toxicity: **Hepatotoxicity** up to **5-6g/day**
3.1.5. Hepatotoxicity develops at lower doses in cases of: • Polypharmacy • Pre-existing Liver disease •Chronic alcoholism • Presence of Viral Hepatitis
3.1.5.1. Treatment:
3.1.5.1.1. NAC
3.1.5.1.2. Glutathione
3.1.5.1.3. Captopril
3.1.6. Other adverse effects of APAP • **Transaminitis** - Elevation of liver enzymes (AST/SGOT and ALT/SGPT) • Stevens-Johnsons Syndrome-Toxic Epidermal Necrolysis **(SJS-TEN)** • **<10 %** skin involvement - **SJS** •10-30 % skin involvement - SJS-TEN • >30 % skin involvement - TEN
3.2. Non-steroidal Anti-inflammatory Drugs - **weakly acidic in it's active form**
3.2.1. COX 2 Forms: **COX-1 and COX-2**
3.2.1.1. Selective Cox-2 Inhibitor
3.2.1.1.1. Meloxicam and - Coxibs (Celecoxib, Etoricoxib, Rofecoxib, Valdecoxib)
3.2.1.1.2. Adverse effect: Less incidence of GI bleeding
3.2.1.1.3. Increased risk for cardiovascular and thrombotic events
3.2.1.1.4. Reversible Decrease in Glomerular Filtration Rate
3.2.1.1.5. Elevation of Uric Acid levels
3.2.1.1.6. Reye’s Syndrome
3.2.1.2. Non-selective Cox inhibitor
3.2.1.2.1. Acetylsalicylic acid/Aspirin/ASA - Prodrugs
3.2.1.2.2. NSAID Drugs
3.2.2. Only basic NSAID - **Nabumetone**
3.2.3. Mechanism of action: Inhibition of Cyclooxygenase (leads to dec. of prostaglandins) = Decreased INFLAMMATION