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systemic pharmaco > Anti-Rheumatic Drugs - Drugs used for arthritic disorders > Flashcards

Anti-Rheumatic Drugs - Drugs used for arthritic disorders Flashcards

1
Q

Treatment of osteoarthritis (3)

A
  1. Pain Relief & Anti-inflammatory
    - Acetaminophen, non-selective NSAIDs, COX-2 inhibitors, glucocorticoids
  2. Viscosupplementation
    - Intra-articular hyaluronic acid - shock absorption, protective coating of cartilage, lubrication, reduce pain, induce biosynthesis of hyaluronic acid & ECM
  3. Symptomatic slow-acting drugs for OA
    - Chondroitin sulphate, glucosamine
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2
Q

Classes of drugs used in gouty arthritis & examples

A

Anti-Inflammatory: relieve acute gouty attack

  1. NSAIDs & COX-2 inhibitors (indomethacin, naproxen, celecoxib)
  2. Glucocorticoids (prednisolone - oral/intra-articular injection)
  3. Colchicine

Urate-Lowering Therapy: prevent recurrent gouty episodes

  1. Xanthine oxidase inhibitors (Allopurinol, Febuxostat)
  2. Uricosuric agents (Probenecid, sulfinpyrazone)
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3
Q

NSAIDs & COX-2 inhibitors in gouty arthritis

A
  • Inhibit production of prostaglandins & urate crystal phagocytosis
  • Contraindications: low dose of aspirin/salicylates - anti-uricosuric actions
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4
Q

Mechanism of action of colchicine

A
  1. Binds to tubulin - prevents tubulin polymerization into microtubules
  2. Inhibits leukocyte migration & phagocytosis, inhibits leukotriene B4 production
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5
Q

Uses of colchicine

A
  1. Relieve pain & inflammation in acute gouty attack in 12-24h (fast action)
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6
Q

Toxicity of colchicine (3)

A
  1. Diarrhea, nausea, vomiting, abdominal pain
  2. Muscle weakness
  3. Allergic reactions `
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7
Q

Mechanism of allopurinol

A

Decreases uric acid production by inhibiting xanthine oxidase enzyme (oxidation of xanthine to uric acid)

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8
Q

Uses of allopurinol (3)

A
  1. Debilitating gout attacks (target uric acid<6.0mg/dL)
  2. Chronic erosive arthritis
  3. Urate nephrolithiasis
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9
Q

Toxicity of allopurinol (5)

A
  1. Allopurinol Hypersensitivity Syndrome eg Stevens-Johnson syndrome - risk factors - renal impairment with creatinine clearance <60ml/min, thiazide therapy, HLA-B58 antigen
  2. Skin rash
  3. Vasculitis
  4. Diarrhea
  5. Hepatitis
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10
Q

Mechanism of action of uricosuric agents

A

Inhibits anion transport sites at proximal tubule - inhibits uric acid reabsorption + increases uric acid excretion

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11
Q

Uses of uricosuric agents (3)

A
  1. When allopurinol is contraindicated
  2. Tophaceous gout
  3. Increasingly frequent gouty attack
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12
Q

Toxicity of uricosuric agents (4)

A
  1. Allergic reactions, rash, swelling
  2. Nephrotic syndrome
  3. Severe lower back pain
  4. Maintain large urine volume to prevent urolithiasis, increase urine pH by alkali eg potassium citrate
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13
Q

Classes of drugs used in rheumatoid arthritis & examples

A

Anti-Inflammatory

  1. NSAIDs - short term relief of pain & stiffness + PPI to reduce GI side effects
  2. Glucocorticoids

Synthetic/Non-biologic DMARDs

  1. Methotrexate +
  2. Hydroxychloroquine (best tolerated) or sulfasalazine, leflunomide, immunosuppressants

Biological DMARDs

  1. Anti-TNF-α (Infliximab, adalimumab, etanercept)
  2. Anti-IL-1 receptor (anakinra)
  3. Anti-CD20 (rituximab)
  4. Anti-CTLA41g (abatacept)
  5. Anti-IL-6 receptor (tocilizumab)
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14
Q

Mechanism of action of methotrexate

A
  1. Folic acid analog, inhibits AICAR transformylase
  2. Inhibits thymidylate synthetase
  3. Inhibits dihydrofolate reductase (minor)
  4. Increases extracellular adenosine levels & activates adenosine A2a receptor
    - anti-proliferative effects on T cells & inhibition of macrophage function
    - decrease in pro-inflamm cytokines, adhesion molecules, chemotaxis, phagocytosis
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15
Q

Toxicity of methotrexate (5)

A
  1. Myelosuppression
  2. Mouth & GI ulcers
  3. Hepatic fibrosis
  4. Pneumonitis
  5. Teratogenic effects
  • Concomitant folic/folinic acid given 12-24h after methotrexate decreases toxicity
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16
Q

Mechanism of action & uses of hydroxychloroquine

A
  • Mechanism unclear, involves suppression of T cell response, decreased chemotaxis & inhibition of DNA & RNA synthesis
  1. Used with methotrexate in RA
  2. Anti-malarial agent
17
Q

Toxicity of hydroxychloroquine (3)

A
  1. Ocular toxicity
  2. Dyspepsia
  3. Nausea, vomiting
18
Q

Mechanism of action of sulfasalazine

A
  1. Decreased IgA & IgM rheumatoid factors
  2. Suppression of T & B cells, and macrophages
  3. Decrease in inflammatory cytokines eg IL-1β, TNF-α, IL-6
19
Q

Toxicity of sulfasalazine (5)

A
  1. Nausea, vomiting
  2. Headache
  3. Rash
  4. Hemolytic anemia, neutropenia
  5. Reversible infertility in men
20
Q

Mechanism of action of leflunomide

A
  1. Inhibits dihydroorotate dehydrogenase
  2. Decrease in pyrimidine synthesis & growth arrest at GI phase
  3. Inhibits T cell proliferation & B cell autoantibody production
  4. Inhibits NF-kB activation pro-inflammatory pathway
21
Q

Toxicity of leflunomide (5)

A
  1. Diarrhea
  2. Elevation of liver enzymes
  3. Alopecia
  4. Weight gain
  5. Teratogenic
22
Q

Uses of anti-TNF-α

A
  1. RA patients who do not respond well with DMARD therapy

2. Used with methotrexate for optimal effects (and prevents human anti-chimeric Ab prod)

23
Q

Toxicity of anti-TNF-α & Contraindications (7+2)

A
  1. Respiratory infection
  2. Skin infection
  3. Increased risk of lymphoma
  4. Optic neuritis
  5. Exacerbation of multiple sclerosis
  6. Leukopenia
  7. Aplastic anemia
  8. Live vaccination
  9. Hepatitis B
24
Q

Mechanism of action of anakinra

A
  1. Recombinant IL-1R antagonist, binds to IL-1 receptor - bloocks signalling
    - less effective than anti-TNF
25
Q

Toxicity of anakinra (2)

A
  1. Infections

2. Injection site reactions

26
Q

Mechanism of action of rituximab

A
  1. Chimeric mAb IgG directed at CD20 on B cells - depletes CD20+ B cells
  2. Blocks Ag presentation, autoantibody & cytokine level
27
Q

Toxicity of rituximab (2)

A
  1. Rash in first dose

2. Respiratory infection in COPD

28
Q

Mechanism of action & uses of abatacept

A

Recombinant fusion protein with CTLA4-FcIgG1 (IV), binds to CD80 & CD86 & prevents CD28 activation

  1. T cell therapy, IV
29
Q

Toxicity of abatacept (2)

A
  1. Respiratory infection in COPD

2. Increased lymphoma incidence

30
Q

Mechanism of action of tocilizumab

A

Humanized mAb IgG1 directed at IL-6Rα chain - prevents binding of IL-6 to IL-6Rα and homodimerization of IL-6Rβ signalling

31
Q

Toxicity of tocilizumab (7)

A
  1. Infections
  2. Skin eruptions
  3. Stomatitis
  4. Fever
  5. Neutropenia
  6. Increase in ALT/AST
  7. Hyperlipidemia

systemic pharmaco (18 decks)

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