Bones and Joints - Arthritis Flashcards

1
Q

3 groups of arthritic disorders

A
  • osteoarthritis
  • gouty arthritis
  • rheumatoid arthritis
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2
Q

osteoarthritis drugs

- 2 groups + drugs

A
  1. pain relief and anti-inflammatory
    - paracetamol
    - NSAIDs (meloxicam)
    - Glucocorticoids
  2. symptomatic slow-acting drugs
    - intra-articular hyaluronic acid (injection)
    - chondroitin sulphate
    - glucosamine
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3
Q

intra-articular hyaluronic acid MOA

A

shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain and stiffness, induces biosysnthesis of hyaluronic acid and extracellular matrix

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4
Q

gouty arthritis drugs

A
  1. relieve acute gouty attack inflammatory symptoms
    - NSAIDs (naproxen)
    - COX2 inhibitors (celecoxib)
    - Glucocorticoids (prednisolone)
    - Colchicine* specific for GA
  2. prevention of recurrence - urate lowering therapy (ULT)
    - Xanthine Oxidase Inhibitors (XOI): allopurinol
    - Uricosuric Agents: probenecid
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5
Q

Colchicine MOA

A
  1. binds to tubulin
  2. prevent tubulin polymerization into microtubules
  3. inhibits leukocyte migration and phagocytosis
  4. inhibits leukotriene B4 and prostaglandin productions

Relieves pain and inflammation in acute gouty attack within 24‐36 hours

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6
Q

Colchicine ADR

A

DIARRHEA

Nausea/Vomitting, abdominal pain, muscle weakness, unusual bleeding, pale lips, and change in urine amount

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7
Q

Xanthine oxidase inhibitor (XOI) MOA

A
anti-hyperuricemic agents
- decrease uric acid production 
used for:
‐ debilitating gout attacks 
‐ chronic erosive arthritis
‐ urate nephrolithiasis (kidney stone)
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8
Q

XOI ADR

A

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

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9
Q

Uricosuric agents drug

A

probenecid

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10
Q

Probenecid MOA

A

‐ 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

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11
Q

Uricosuric agents ADR

A

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

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12
Q

Groups of RA drugs (4)

A
  1. anti-inflammatory agents
    - NSAIDs
    - corticosteroids

DMARD: disease-modifying anti-rheumatic drugs
conventional, targeted, biologic

  1. conventional synthetic DMARD - old gen
    - Methotrexate
    - Hydroxychloroquine (best tolerated)
  2. targeted DMARD
    - Tofacitinib (tyrosine kinase inhibitor)
  3. Biologic DMARD
    - Anti-TNF-a/ anti IL-1/ anti IL-6 mAb (monochromal antibody)
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13
Q

Methotrexate (csDMARD) MOA**

A

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

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14
Q

Methotrexate ADR**

A

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

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15
Q

Hydroxychloroquine (csDMARD) MOA

A

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

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16
Q

Hydroxychloroquine ADR

A

N/V, stomach pain, dizziness, hair loss, ocular toxicity

17
Q

Tofacitinib MOA (tDMARD)

A

Oral
JAK tyrosine kinase inhibitor (JAK/STAT pathway)
- prevents STAT phosphorylation
-> prevents STAT translocation into the nucleus and activation of gene transcription

higher efficacy than methotrexate
used if pt failed to respond to other bDMARD

18
Q

Tofacitinib ADR

A
  • Increased risk of herpes zoster infection (especially in Asian population)
  • Anemia (affects JAK2 activity by erythropoietin)
  • Cytopenia including neutrophils, lymphocytes, platelets and natural killer cells (from immunosuppression)
  • Hyperlipidemia: increases in total, LDL and HDL cholesterol and trigylcerides
19
Q

biologic DMARD drugs

A

anti TNF-a

  • Adalimumab
  • Infliximab
  • Etanercept
20
Q

bDMARD ADR and contraindications

A
  • Respiratory infection and skin infection
  • increased risk of lymphoma, optic neuritis, exacerbation of multiple sclerosis, leukopenia, aplastic anemia,
    CI: Live vaccination, hepatitis B
21
Q

bDMARD - purpose and combination

A

RA pts that dont respond to sDMARD

combination with methotrexate

22
Q

naproxen (NSAID) vs celecoxib (COX2 inhibitor)

A

naproxen inhibits both COX1 and COX2, while celecoxib specifically inhibits only COX2

COX1 inhibition inhibits thromboxane A2 and prostaglandin formation
selective COX2 inhibition does not inhibit thromboxane A2

23
Q

naproxen side effects

A

GI bleeding
Renal toxicity (vasoconstrict afferent arterioles due to decrease prostaglandin)
Fluid retention due to increase NaCl reabsorption
Delayed wound healing, pseudo-allergic reaction (rash)

24
Q

celecoxib side effects

A

Increase risk of thrombosis (cause of lack of inhibition of TXA2)
Premature closure of ductus arteriosus in pregnancy
Delayed wound healing
Renal toxicity

25
Q

celecoxib (selective COX-2 inhibitor MOA)

A

inhibit prostaglandin production
inhibits vasodilation -> decrease vascular permeability -> decrease swelling
sensitises nociceptors against stimulation by inflammatory mediators