MSK - Drugs for Arthritic Disorders (including gout) Flashcards

1
Q

What does SYSADOA stand for?

A

Symptomatic Slow-acting Drug for Osteoarthritis

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2
Q

Name an evidence-based SYS ADOA for osteoarthritis

A

Intra-articular hyaluronic acid

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3
Q

Briefly explain the mechanisms of action of intra-articular hyaluronic acid

A

● Hyaluronic acid (HA) is a large glycosaminglycan (naturally in synovial fluid)
● Shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain & stiffness
● Induces biosynthesis of endogenous HA & extracellular matrix

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4
Q

List TWO supplements commonly used for osteoarthritis for which there is limited medical evidence

A

Chondroitin sulphate and glucosamine

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5
Q

Name the 4 compartments and 3 things of immune cell reponses

A

Compartments:
Innate immunity:
(1) Complement
(2) Phagocytes

Adaptive immunity:
(3) B cells
(4) T cells

3 things immune cells do when activated:
(1) Proliferate
(2) Cytokine production
(3) Trafficking and adhesion

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6
Q

List anti-inflammatory drugs used to control acute gouty attacks

A
  1. Nonselective NSAIDs (e.g., naproxen, indometacin)
  2. COX‐2 selective NSAIDs (e.g., celecoxib)
  3. Glucocorticoids (e.g., prednisolone)
  4. Colchicine
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7
Q

List TWO classes of drug used to reduce uric acid levels

A

(1) Uric acid synthesis inhibitors
(xanthine oxidase inhibitors)
(A) Purine analogue e.g., allopurinol
(B) non-purine e.g., febuxostat

(2) Uricosuric agents (solute carrier family 2 & 22 inhibitor) e.g, probenecid

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8
Q

Briefly explain the mechanisms of action of colchicine

A
  1. Binds tubulin
  2. Prevent tubulin polymerization into microtubules
  3. Inhibits leukocyte migration and phagocytosis
  4. Inhibits leukotriene B4 (LTB4) and prostaglandin (PG) production
  5. Relieves pain and inflammation of acute gouty attack within 24-36 hours
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9
Q

What is the dose-limiting adverse effect of colchicine?

A

Diarrhoea and GIT disturbance.

At higher doses, binding tubulin and preventing microtubule polymerization prevents cell proliferation. As cells of the GIT walls are rapidly proliferating, diarrhoea and GIT disturbance is usually the first adverse effect seen. The colchicine dose must be titrated to control the acute gouty attack without causing intolerable diarrhoea.

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10
Q

List adverse effects of colchicine

A

diarrhoea, nausea & vomiting, abdominal pain, muscle weakness, unusual bleeding, pale lips, and change in urine amount

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11
Q

List THREE risk factors for allopurinol causing severe cutaneous adverse reaction

A
  1. Renal impairment
  2. HLA‐B*58:01 genotype
  3. Thiazide therapy
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12
Q

What measures can be taken to reduce the risk of kidney stones when probenicid is prescribed

A

Precautions:
● Take plenty of fluid to minimize renal stone formation
● Keep urine pH >6.0 by administration of alkaline (e.g., potassium citrate)

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13
Q

Which drugs should not be started during an acute gouty attack?

A
  1. Uricosuric agents
  2. Uric acid synthesis inhibitors
    ● Reduction of plasma urate levels can increase mobilisation ftom joints and hence recognition and attack by immjne cells
  3. Uricosuric agents
    ● Use during acute attack when increased urate is mobilised to plasma and excreted pushes more urate out into urine and increases risk of kidney stones
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14
Q

What can be done to reduce the risk of precipitating acute gouty attack when starting uric acid synthesis inhibitors or uricosuric agents?

A

Combine with low dose NSAID or colchicine

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15
Q

What is the first-line csDMARD?

A

Methotrexate

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16
Q

List FOUR examples of csDMARDs

A

Methotrexate (first-line)
Sulfasalazine Leflunomide Hydroxychloroquine (best tolerated) Ciclosporin

17
Q

Name a tsDMARD

A

Tofacitinib or any other jakinib DMARD

18
Q

List THREE examples of bDMARDs

A

Anti‐TNF mAb (e.g., infliximab, adalimumab, etanercept)
IL‐1R antagonist (e.g., anakinra)
Anti-IL‐6 receptor mAb (e.g., tocilizumab)
Anti‐CTLA4Ig (e.g., abatacept)
Anti‐CD20 (e.g., rituximab)

19
Q

Briefly explain the mechanisms of action of methotrexate

A

● Major Action: Increased adenosine levels due to ATIC inhibition
● Minor Action: Inhibits dihydrofolate reductase and thymidylate synthetase
● 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

20
Q

How can methotrexate-induced nausea/vomiting, mouth and GI uclers, and hair-thinning be reduced?

A

Concomitant folic acid (high dose) or folinic acid given 12‐24hr after methotrexate decreases toxicity

21
Q

List adverse effects and cautions for jakinibs in the treatment of rheumatoid arthritis

A

● Cytopenia including neutrophils, lymphocytes, platelets and natural killer cells
● Immunosuppression resulting opportunistic infections [increased risk of herpes zoster infection (especially in Asian population)]
● Anaemia (affects JAK2 activitation by erythropoietin)
● Hyperlipidaemia: increases in total, LDL and HDL cholesterol and trigylcerides
● Do NOT combine with biological DMARDs

22
Q

Name an example of a TNF signalling blocking bDMARD

A

● Mabs against TNF:
Infliximab, adalimumab, golimumab
● Decoy TNFR2 receptor‐IgG1 fusion protein intercepts TNF:
etanercept

23
Q

Name an example of a bDMARD blocking IL-1 signalling

A

Anakinra - Modified version of human interleukin-1 receptor antagonist protein.

24
Q

Name an example of a bDMARD blocking IL-6 signalling

A

Tocilizumab - mab against IL-6 receptor

25
Q

Explain why toc ilizumab has drug-drug interactions with drugs undergoing hepatic metabolism

A

Like most mabs, tocilizumab is cleared by proteolytic metabolism.

But interacts with CYP450 34A, 1A2 or 2C9 substrates

IL-6 decreases expression of these CYP450 enzymes, so tocilizumab blocking IL-6 signalling increases expression