Anti-Rheumatic Drugs - Drugs used for arthritic disorders Flashcards Preview

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Flashcards in Anti-Rheumatic Drugs - Drugs used for arthritic disorders Deck (31):
1

Treatment of osteoarthritis (3)

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

2

Classes of drugs used in gouty arthritis & examples

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)

3

NSAIDs & COX-2 inhibitors in gouty arthritis

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

4

Mechanism of action of colchicine

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

5

Uses of colchicine

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

6

Toxicity of colchicine (3)

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

7

Mechanism of allopurinol

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

8

Uses of allopurinol (3)

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

9

Toxicity of allopurinol (5)

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

10

Mechanism of action of uricosuric agents

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

11

Uses of uricosuric agents (3)

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

12

Toxicity of uricosuric agents (4)

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

13

Classes of drugs used in rheumatoid arthritis & examples

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)

14

Mechanism of action of methotrexate

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

15

Toxicity of methotrexate (5)

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

16

Mechanism of action & uses of hydroxychloroquine

- 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

Toxicity of hydroxychloroquine (3)

1. Ocular toxicity
2. Dyspepsia
3. Nausea, vomiting

18

Mechanism of action of sulfasalazine

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

Toxicity of sulfasalazine (5)

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

20

Mechanism of action of leflunomide

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

Toxicity of leflunomide (5)

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

22

Uses of anti-TNF-α

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

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

1. Respiratory infection
2. Skin infection
3. Increased risk of lymphoma
4. Optic neuritis
5. Exacerbation of multiple sclerosis
6. Leukopenia
7. Aplastic anemia

1. Live vaccination
2. Hepatitis B

24

Mechanism of action of anakinra

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

25

Toxicity of anakinra (2)

1. Infections
2. Injection site reactions

26

Mechanism of action of rituximab

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

27

Toxicity of rituximab (2)

1. Rash in first dose
2. Respiratory infection in COPD

28

Mechanism of action & uses of abatacept

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

1. T cell therapy, IV

29

Toxicity of abatacept (2)

1. Respiratory infection in COPD
2. Increased lymphoma incidence

30

Mechanism of action of tocilizumab

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

31

Toxicity of tocilizumab (7)

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