Bones and Joints - Arthritis Flashcards
3 groups of arthritic disorders
- osteoarthritis
- gouty arthritis
- rheumatoid arthritis
osteoarthritis drugs
- 2 groups + drugs
- pain relief and anti-inflammatory
- paracetamol
- NSAIDs (meloxicam)
- Glucocorticoids - symptomatic slow-acting drugs
- intra-articular hyaluronic acid (injection)
- chondroitin sulphate
- glucosamine
intra-articular hyaluronic acid MOA
shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain and stiffness, induces biosysnthesis of hyaluronic acid and extracellular matrix
gouty arthritis drugs
- relieve acute gouty attack inflammatory symptoms
- NSAIDs (naproxen)
- COX2 inhibitors (celecoxib)
- Glucocorticoids (prednisolone)
- Colchicine* specific for GA - prevention of recurrence - urate lowering therapy (ULT)
- Xanthine Oxidase Inhibitors (XOI): allopurinol
- Uricosuric Agents: probenecid
Colchicine MOA
- binds to tubulin
- prevent tubulin polymerization into microtubules
- inhibits leukocyte migration and phagocytosis
- inhibits leukotriene B4 and prostaglandin productions
Relieves pain and inflammation in acute gouty attack within 24‐36 hours
Colchicine ADR
DIARRHEA
Nausea/Vomitting, abdominal pain, muscle weakness, unusual bleeding, pale lips, and change in urine amount
Xanthine oxidase inhibitor (XOI) MOA
anti-hyperuricemic agents - decrease uric acid production used for: ‐ debilitating gout attacks ‐ chronic erosive arthritis ‐ urate nephrolithiasis (kidney stone)
XOI ADR
Allopurinol: allopurinol hypersensitivity syndrome (AHS) - SJS (skin peeling + blistering)
may cause renal impairment
skin rash, N/V, diarrhea, fever, sore throat, stomach pain, dark urine, jaundice
Uricosuric agents drug
probenecid
Probenecid MOA
‐ inhibits anion transport sites at the proximal tubule,
‐ inhibits uric acid reabsorption -> all excreted (so increase conc in urine -> chance of renal stones formation)
‐ increases uric acid excretion
used when:
‐ when allopurinol is contraindicated in tophaceous gout,
‐ in increasingly frequent gouty attack,
‐ start at 2‐3 weeks after an acute attack
Uricosuric agents ADR
possible formation of renal stones -> drink a lot of water so uric acid conc is decreased
N/V, painful urination (high uric acid conc in urine), lower back pain, allergic reactions, rash
Groups of RA drugs (4)
- anti-inflammatory agents
- NSAIDs
- corticosteroids
DMARD: disease-modifying anti-rheumatic drugs
conventional, targeted, biologic
- conventional synthetic DMARD - old gen
- Methotrexate
- Hydroxychloroquine (best tolerated) - targeted DMARD
- Tofacitinib (tyrosine kinase inhibitor) - Biologic DMARD
- Anti-TNF-a/ anti IL-1/ anti IL-6 mAb (monochromal antibody)
Methotrexate (csDMARD) MOA**
folic acid analog
often combined with other sDMARDs for optimal effects
- Inhibits AICAR transformylase,
- Inhibits thymidylate synthetase - less thymine available for DNA replication of leukocytes
- Inhibits dihydrofolate reductase
Overall Effects:
Increase in extracellular adenosine level and activation of Adenosine A2a receptor,
- Anti‐proliferative effects on T cells and inhibition of macrophage functions,
- Decrease in pro‐inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis
Methotrexate ADR**
N&V, mouth and GI ulcers, leukopenia, hepatic fibrosis, pneumonitis
to reduce side effects: - Concomitant folic acid or folinic acid given 12‐24 hr after methotrexate decreases toxicity
Hydroxychloroquine (csDMARD) MOA
anti-malarial
anti-oxidant
effective in reducing inflammation:
- Reduced MHC Class II expression and antigen‐presentation
- Reduced TNF‐a and IL‐1, and cartilage resorption