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pipi&pi2 > (FE) Drugs for Gout and Osteoarthritis > Flashcards

(FE) Drugs for Gout and Osteoarthritis Flashcards

1
Q

What drugs are used to treat acute gout attacks?

A

1) NSAIDS
- Non-selective COX inhibitors (Naproxen, Indometacin)
- COX-2 inhibitors (CELECOXIB, ETORICOXIB)

2) Corticosteroids (PREDNISOLONE)

3) Leucocyte mobility inhibitors (COCHICINE)

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2
Q

What drugs are used to treat hyperuricemia / prevent gouty arthritis?

A

1) Uric acid synthesis inhibitors / Xanthase oxidase inhibitors (ALLOPURINOL, Febuxostat)

2) Uricosuric agents (PROBENECID)

Note: Never use at the start of acute attacks
- Crystal gradient will be too much -> ^ movement of crystal into the joint

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3
Q

What is the MOA of NSAIDs in treating gout?

A

1) Inhibit production of prostaglandins (reduces inflammation)

2) Inhibits urate crystal phagocytosis

Indometacin, Naproxen (non-selective), CELECOXIB , ETORICOXIB (COX-2)

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4
Q

What are the contraindications for NSAIDs in treating gout?

A
  • Use of low-dose aspirin or salicylates
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5
Q

What is the MOA of leucocyte mobility inhibitors in treating gout?

A

1) Binds to tubulin to prevent polymerization into microtubules

2) Inhibits leucocyte migration and phagocytosis

3) Inhibits leukotriene B and phagocyte production

4) Relieves pain and inflammation from gouty attack within 24 - 36 hours

COLCHICINE

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6
Q

What are the side effects of colchicine/leucocyte mobility inhibitors?

A
  • Diarrhea, N&V, abdominal pain
  • Muscle weakness
  • Unusual bleeding
  • Pale lips
  • Change in urine amount
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7
Q

What are the indications for uric acid synthesis inhibitors / XOI?

A
  • Debilitating gout attacks
  • Chronic erosive arthritis
  • Urate nephrolithiasis (kidney stones)

ALLOPURINOL (1st-line), Febuxostat (2nd-line)

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8
Q

What are the adverse effects of XOI / Allopurinol?

A
  • Skin rash
  • N&V, diarrhea, stomach
  • Fever
  • Sore throat
  • Dark urine
  • Jaundice
  • Allopurinol hypersensitivity reaction (AHS)
  • Severe cutaneous adverse reaction (SCAR)
    ~ Common in HLA-B 58:01 genotype
    ~ Higher risk in px with renal impairment (w/ creatinine clearance of <60ml/min)
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9
Q

What is the MOA of uricosuric agents?

A
  • Prevents gout attacks
  • Inhibits uric acid re-absorption from kidneys
  • Increases uric acid excretion

PROBENECID

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10
Q

What are the indications for uricosuric agents?

A
  • When allopurinol is contraindicated for tophaceous gout
  • Increasingly frequent gouty attacks
  • Only start 2-3 weeks after attacks start
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11
Q

What are the precautions and side effects of uricosuric agents?

A
  • Requires frequent hydration to prevent formation of renal stones
  • Requires sodium citrate to keep pH of body >6.0
  • N&V
  • Painful urination
  • Lower back pain
  • Allergic reactions, rash
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12
Q

What drugs can be used to treat osteoarthritis?

A

1) Analgesics
- PARACETAMOL
- NSAIDs (Diclofenac, celecoxib)

2) Anti-inflammatory
- Corticosteroids (Prednisolone)

3) Symptomatic slow-acting drugs
- Intra-articular (HYALURONIC ACID)
~ Helps in shock absorption, traumatic energy dissipation, protective coating of cartilage, lubrication, reduces pain & stiffness

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13
Q

What drugs can be used to treat rheumatoid arthritis?

A

1) NSAIDS
~ For short-term relief of joint pain and stiffness
2) CORTICOSTEROIDS
~ For anti-inflammatory therapy

3) Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDS)
- METHOTREXATE

4) Targeted Synthetic DMARDS (tsDMARDS)
- TOFACITINIB

5) Biologic DMARDS (bMARDS)
- INFLIXIMAB

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14
Q

What is the difference between csDMARDs, tDMARDs and bDMARDs?

A

1) csDMARD
- Traditional first-line treatments for RA
- Used in combination with other DMARDs

2) tsDMARD
- Target specific molecules in the inflammatory process
~ eg Janus kinases (JAK) inhibitors
- Typically used in px w/ inadequate response to csDMARDs

3) bDMARD
- Derived from living organisms, such as proteins, antibodies, or cytokines
- For px with moderate - severe RA who have not responded adequately to csDMARDs or tDMARDs

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15
Q

What is the MOA of csDMARDs?

A
  • Increases adenosine levels (reduces inflammatory effects of cells and cytokines - major effect)
  • Anti-proliferative effects on T cells and inhibition of macrophage functions
  • Decrease in pro-inflammatory cytokines, adhesion molecules, chemotaxis and phagocytosis

METHOTREXATE (1st line) FEVER

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16
Q

What are the side effects of csDMARDs?

A
  • N&V
  • Mouth & GI ulcers
  • Hair thinning
  • Leukopenia
  • Hepatic fibrosis
  • Pneumonitis

Note: Giving folic/folinic acid 12-24 hrs after Methotrexate decreases toxicity

17
Q

How does folinic acid help to treat methotrexate toxicity?

A
  • Usually, dihydrofolate reductase is involved in the conversion of N5/N10-Methylene-FH4 into purines which make up DNA
    ~ Since methroxate inhibits enzyme action, DNA cannot be formed properly in toxicity
  • However, folinic acid is rapidly converted to N5, N10-MethyleneFH4, without the need of dihydrofolate reductase
    ~ Since enzyme activity is
    bypassed, it is more efficient at rescuing
    methotrexate toxicity
18
Q

What are the MOA of the less common csDMARDs?

A

1) Sulfasalazine
- Decreases IgA and IgM rheumatoid factors
- Suppresses T and B cells and macrophages-
- Decrease in inflammatory cytokines (e.g., IL-1E, TNF and IL-6)

2) Leflunomide
- Inhibits T cell proliferation and B cell autoantibody production
- Inhibits NF-NB activation pro-inflammatory pathway

  • Warning:
    ~ Very long half-life (detectable even years after last dosing)
    ~ Colestyramine (bile salt binding resin) wash-out (e.g., before pregnancy)

3) Chloroquine and Hydroxychloroquine
- Effective anti-inflammatory agents in RA (least potent DMARD)
- Reduced MHC Class II expression and antigen-presentation
- Reduced TNF and IL-1, and cartilage resorption

19
Q

What are the side effects of the less common csDMARDs?

A

1) Sulfasalazine
- N&V
- Headache
- Rash
- Hemolytic anemia , neutropenia
- Reversible infertility in men

2) Leflunomide
- Diarrhoea
- Alopecia
- Increased liver enzymes
- Weight gain
- Teratogenic

3) Hydroxychloroquine
- N&V
- Stomach pain
- Dizziness
- Hair loss
- Ocular toxicity

20
Q

What is the MOA of tsDMARDs?

A
  • Combined with methotrexate for moderate - severe RA
  • Janus-Kinase (JAK) pathway inhibitor
    ~ Blocks cytokine production by blocking JAK activation of gene transcription

TOFACITINIB

21
Q

What are the side effects of tsMARDS?

A
  • Cytopenia including neutrophils, lymphocytes,
    platelets and natural killer cells
  • Anaemia (affects JAK2 activitation by erythropoietin)
  • Immunosuppression

Note: Do not combine with biological DMARDs

22
Q

What are the types of bDMARDS?

A

1) TNF blockers (INFLIXIMAB)
- Refer to screenshot

2) IL-1 blockers (ANAKINRA)
- Differs from the sequence of the protein by one
methionine

3) IL-6 blockers (TOCILIZUMAB)
- For px who do not respond well to sDMARD
- Used in combination with other Methatroxine

23
Q

What are the side effects and contraindications for bDMARDS?

A
  • Respiratory and skin infection
  • Increased risk of lymphoma, optic
    neuritis, exacerbation of multiple sclerosis, leukopenia, aplastic anemia
  • Contraindicated in live vaccines and hep B
  • Need to screen for active TB

pipi&pi2 (16 decks)

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