Rheumatoid Arthritis Flashcards
(31 cards)
NSAIDs
- Effect
Anti-inflammatory Action
- Decrease Prostaglandin E2
- Prostacyclin reduces vasodilation
- Reduction of mediators, number of inflammatory cells are not reduced
Analgesic Effect
- Decrease Prostaglandin generation
–> Less inflammatory mediators to activate nociceptive nerve ending
- Decreased Prostaglandin mediated vasodilation
–> Headache relief
Antipyretic Effect
- Prevent interleukin-1 from releasing prostaglandins in the CNS
–> Prevent elevation of hypothalamic set point for temperature control
–> Prevent fever
NSAIDs
- MOA
Inhibit Cyclooxygenase Enzyme (COX-1/COX2)
- Inhibiting conversion of arachidonic acid to prostaglandin
NSAIDs
- COX-1 vs COX-2
COX-1: Constitutive Enzyme
- Protective role
–> Responsible for producing cytoprotective mucus in stomach
–> Responsible for platelet aggregation
COX-1: Inducible Enzyme
- Have to be stimulated by inflammatory mediators
–> Associated with inflammation
(COX-2 has no effect on stomach)
NSAIDs
- Indication
- Pain
- Inflammation
-Fever
NSAIDs
- Adverse Effects
Contraindicated with Active Peptic Ulcer
Aspirin must be taken with food
NSAIDs
- Nonselective Adverse Effects
Gastrointestinal Effects
- Inhibition of COX-1 affects production of cytoprotective mucus)
Edema
- PG inhibits Water and Salt retention
Acute Renal Failure
- Renal PGs protect high-risk patients by countering the effect of angiotensin 2 and vasopressin
NSAIDs
- COX-2 Adverse Effects
Cardiovascular
- Caused by the disruption in the balance between platelet-activating effects of COX-1 and platelet inhibiting effects of COX-2
NSAIDs
- All Adverse Effects
CNS (Confusion, Dizziness, Depression, Hallucination)
- Likely caused by COX-2 which is abundant in the CNS
- Could also be caused by COX-3
Methotrexate
- Indication
Rheumatoid Arthritis
- Anti-inflammatory Action in small doses
Cancer
- Cytotoxic in large doses
Psoriasis Arthritis
Ankylosing Spndylitis
Polymyositis and Vaculitis
Methotrexate
- MOA
Disease-Modifying Antirheumatoid Drug (DMARD)
Folate Antagonist (Oral)
- Interferes with thymidylate synthesis (Essential in DNA synthesis)
–> Suppresses immune system
Methotrexate
- Adverse Effects
Gastrointestinal Disturbance
Dose-related Liver Toxicity
Bone Marrow Depression
Sulfasalazine
- Indication
- Rheumatoid Arthritis
- Juvenile Arthritis
- Inflammatory Bowel Disease
Sulfasalazine
- MOA
Disease-Modifying Antirheumatoid Drug (DMARD)
- Acts in the colon to release salicylic acid
–> Anti-inflammatory action
Leflunomide
- Indication
Rheumatoid Arthritis
Leflunomide
- MOA
Disease-Modifying Antirheumatoid Drug (DMARD) - (Oral)
- Increases amount of metabolite that inhibits dihydroorotate dehydrogenase
–> Inhibition of T-Cell Proliferation
–> Decreased production of autoantibodies by B cells
Leflunomide
- Adverse Effects
- 25% of patients get diarrhoea
- Increased BP
- Weight Gain
Targeted Synthetic DMARD
- MOA
Tofacitinib
- Inhibits Janus Kinase (JAK)
–> Reduces inflammation
Biological DMARD
- MOA
Infliximab (IV)
- Monoclonal antibody against TNF-alpha that prevents it from interacting with receptors on inflammatory cells
Biological DMARD
- Indication
Active Rheumatoid Arthritis
- Combined with methotrexate if DMARDs have yet to work
Ankylosing Spondylitis (If other therapy has not worked)
Psoriatic Arthritis (If other therapy has not worked)
Biological DMARd
- Adverse Effects
- Nausea
- Vomiting
- Headache
- Upper Respiratory Tract Infections with Cough
Colchicine
- MOA
Crystal Associated Arthritis (Gout)
- Inhibits microtubule polymerization
–> Binds protein and tubulin needed for mitosis
- Inhibits Neutrophil
–> Prevents activation and migration - Blocks inflammasome complex in neutrophils and monocyte
–> Prevent inflammation - Inhibits superoxide anion production in response to Urate Crystals
- Interrupts mast cell degranulation
Result: Inhibits Inflammation
Colchicine
- Indications
- Gout
- Acute Attack (Joint pain caused by gout)
- Prevent recurrent attacks (Uric Acid Lowering Therapy)
Colchicine
- Adverse Effects
Contraindicated in Renal Failure
- Increased Risk of Toxicity
Narrow Therapeutic Index
Gastrointestinal
- Diarrhea (Very Common)
Bone Marrow Suppression
- Antimitotic target rapidly dividing cells such as bone marrow
Myopathy may occur
Neuropathy may occur
Uricosurics
- MOA
Treats Gout
- Enhance Uric acid excretion
- Prevent Uric acid reabsorption (Probenecid)
–> Lower Uric Acid level
