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Pharmacology > Arthritic Disorders > Flashcards

Arthritic Disorders Flashcards

1
Q

Drug treatment for osteoarthritis is…

A

mostly symptomatic.

Relieve pain or inflammation.

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2
Q

List examples of pain relief/anti-inflammatory drugs used for osteoarthritis.

A

Pain relief/anti-inflammatory

  1. Paracetamol
  2. Non-selective NSAIDs (e.g. meloxicam)
  3. COX-2 inhibitor (e.g. celecoxib)
  4. Corticosteroids

If the above drugs do not work, move to symptomatic slow-acting drugs for OA (SYSADOA).

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3
Q

List examples of SYSADOA drugs used for osteoarthritis.

A
  1. Intra-articular hyaluronic acid: hyaluronic acid naturally exists in synovial fluid. It is a large glycosaminoglycan that works for shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication & reducing of pain and stiffness. Ultimately, it induces body’s biosynthesis of hyaluronic acid and extracellular matrix
  2. Chrondroitin sulphate (oral/intra-articular injection)
  3. Glucosamine
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4
Q

What are the goals of gouty arthritis drug treatment?

A
  1. Relieve acute gouty attack

2. Prevent recurrent gouty episodes

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5
Q

What are examples of drugs used to relieve acute gouty attacks?

A
  1. NSAIDs (e.g. naproxen)
  2. COX-2 inhibitors (e.g. celecoxib)
  3. Glucocorticoids (e.g. prednisolone)
  4. Colchicine
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6
Q

What are examples of drugs used to relieve prevent gouty episodes?

A

Intention is to lower uric acid in body!

  1. Xanthine oxidase inhibitors (e.g. allopurinol)
  2. Uricosuric agents (e.g. probenecid)
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7
Q

MOA of colchicine?

A

Used for gout treatment - relieves pain and inflammation in an acute gouty attack within 24-36h.

  1. Binds to tubulin
  2. Prevents tubulin polymerisation into microtubules
  3. Inhibits leukocute migration and phagocytosis
  4. Inhibits leukotriene B4 and PG production
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8
Q

Side effects of colchicine?

A

Diarrhoea
Nausea/vomiting
Abdominal pain

Unusual bleeding
Pale lips

Muscle weakness

Change in urine amount

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9
Q

MOA of xanthine oxidase inhibitors?

A

e.g. allopurinol

  1. Allopurinol is a purine analog
  2. Binds to XO and inhibits it
  3. Decrease metabolism of hypoxanthine to xanthine to uric acid
  4. Acts as a anti-hyperuricemic agent
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10
Q

Xanthine oxidase inhibitors can be used for…

A
  1. Debilitating gout attacks
  2. Chronic erosive arthritis
  3. Urate nephrolithiasis
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11
Q

Contraindications for xanthine oxidase inhibitors?

A

Allopurinol hypersensitivity syndrome (AHS), manifesting as SJS (common in Asians).

Risk factors:

  1. Renally impaired (increased risk of AHS)
  2. Thiazide therapy (induces hyperuricemia)
  3. HLA-B58 antigen (causes SJS/TEN with allopurinol)
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12
Q

Side effects of xanthine oxidase inhibitors?

A

Jaundice
Dark urine

Skin rash

Nausea, vomiting
Diarrhoea
Stomach pain

Fever
Sore throat

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13
Q

MOA of uricosuric agents?

A

e.g. probenecid

  1. They are organic acids
  2. Will inhibit anion transport sites at the proximal tubule, which inhibits uric acid reabsorption (and increases its excretion)
  3. Use it when XO inhibitors are contraindicated
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14
Q

Precautions for use of uricosuric agents (probenecid)?

A
  1. Take a lot of fluid to minimise renal stone formation

2. Keep urine at pH >6 by administering alkaline substances e.g. potassium citrate

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15
Q

Side effects of uricosuric agents (probenecid)?

A

Nausea, vomiting

Painful urination

Lower back pain

Allergic reactions
Rash

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16
Q

What are the goals of rheumatoid arthritis drug treatment?

A
  1. Remission of symptoms involving the joints
  2. Return to fill function
  3. Maintenance of remission with DMARD therapy (sDMARD alone or combi; add bDMARD for targeted therapy)

RA is hard to treat

17
Q

What are the anti-inflammatory agents used to treat RA?

A
  1. NSAIDs
    For short-term relief of pain and stiffness
    Give with PPI to reduce GI side effects
  2. Corticosteroid
    Only a bridging therapy for first 2-3 months
    Move to DMARD soon
18
Q

What are the DMARDs used to treat RA?

A

DMARD=Disease Modifying Anti-Rheumatic Drug

Conventional Synthetic DMARDs (csDMARD):

  1. Methotrexate (standard of care)
  2. Hydroxychloroquine (usually give + methotrexate, well tolerated)
  3. Cyclosporine A (can also +methotrexate)

Targeted Synthetic DMARD (tsDMARD):
1. Tofacitinib (JAK inhibitor)

Biologic DMARD (bDMARD, give with methotrexate):

  1. Anti TNF-a mAb
  2. Recombinant IL-1R antagonist
  3. Anti-IL-6 receptor mAb
19
Q

MOA of methotrexate?

A

Methotrexate is used to treat RA. It is a folic acid analog, and is the first choice for DMARD therapy.

  1. Major action:
    Inhibits AICAR transformylase
    Inhibits thymidylate synthetase (reduce T cell proliferation, more relevant when used as anti-cancer drug)
  2. Minor action:
    Inhibits dihydroxyfolate reductase (reduce T cell proliferation, more relevant when used as anti-cancer drug)

Effect:

  1. Increase extracellular adenosine level
  2. Adenosine is an endogenous anti-inflammatory mediator
  3. Bind to and activate adenosine A2a G-coupled receptor
  4. Anti-proliferative effect on T cells, inhibit macrophage functions
  5. Decrease pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis
20
Q

Side effects of methotrexate?

A 
Nausea, vomiting
Mouth and GI ulcers
Leukopenia
Hepatic fibrosis
Pneumonitis

To reduce side effects:

  • Give low dose.
  • Give folic acid/folinic acid 12-24h after methotrexate intake to minimise toxicity.
21
Q

MOA of hydroxychloroquine?

A
  1. Reduce MHC class II expression and antigen presentation to T cell
  2. Reduced TNF-a and IL-1
  3. Inhibit cartilage resorption
  4. Antioxidant activity
22
Q

MOA of tofacitinib?

A

A Targeted Synthetic DMARD (tsDMARD).

Inhibits JAK (1 and 3), blocking downstream signalling, reducing inflammatory response.

23
Q

Efficacy of tofacitinib?

A
  1. Superior to methotrexate
  2. Effective in methotrexate-refractory active RA (aka methotrexate resistant RA)
  3. MTX + biologic DMARD/Tofacitinib = both equally effective, so can use it as replacement if bDMARD is not working
  4. Tofacitinib is also approved for psoriatic arthritis (PsA)
24
Q

Side effects of tofacitinib?

A
  1. Increased risk of herpes zoster infection (esp in Asian population, due to immunosuppression)
  2. Anemia (because it affects JAK2 activity in EPO pathway)
  3. Cytopenia
  4. Hyperlipidemia
25
Q

bDMARD targets which cytokines?

A

IL-1
IL-6
TNF-a

26
Q

When should anti-TNFa bDMARD be used?

A

Use with methotrexate if no good response to sDMARD therapy.

27
Q

Side effects of anti-TNFa bDMARD?

A

Leukopenia
Aplastic anemia

Respiratory infection
Skin infection

Increased risk of lymphoma

Exacerbation of multiple sclerosis

Optic neuritis

28
Q

Contraindications for bDMARD?

A

Live vaccination and hep. B patients

Monitor and screen for TB

Pharmacology (7 decks)

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