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OA/RA Drugs Flashcards

This deck tests your knowledge of osteoarthritis / rheumatoid arthritis drugs.

1
Q

What anti-inflammatory drugs can be used to treat OA/RA?

A
  1. NSAIDs (diclofenac, eterocoxib, paracetamol)
  2. Corticosteroids (hydrocortisone)
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2
Q

What do anti-inflammatory drugs do for OA/RA?

A

They provide symptomatic relief of inflammatory symptoms

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3
Q

What is polysaccharide SYSADOA?

A

Systematic, slow-acting drugs for OA
(intra-articular hyaluronic acid)

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4
Q

What is intra-articular hyaluronic acid?

A
  • GAG, naturally found in the synovial fluid
  • Plays a role in cartilage health and protection, shock absorption / energy dissipation, and lubrication
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5
Q

How does intra-articular hyaluronic acid work?

A
  1. Anti-inflammatory
  2. Replenishes HA
  3. Reduces chondrocyte cell death and damage
  4. Raw material for biosynthesis of cartilage
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6
Q

What are the major adverse effects of intra-articular hyaluronic acid?

A

Only minor allergic reactions

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7
Q

What are DMARDs?

A
  • Disease-modifying anti-rheumatic drugs
  • Classified as cs (conventional synthetic), ts (targeted synthetic), and b (biologic)
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8
Q

What are the csDMARDs?

A

MS LeeCH
Methotrexate, Sulfasalazine, Leflunomide, Chloroquine, Hydroxychloroquine

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9
Q

What is the only tsDMARD?

A

Tofacitinib

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10
Q

What are the bDMARDs?

A

AATARi
Anti-TNF mABs, Anakinra, Tocilizumab, Abatacept, Rituximab

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11
Q

What is methotrexate?

A

Folic acid analog; firstline DMARD

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12
Q

What three things does methotrexate inhibit?

A
  1. Inhibits AICAR transformylase
  2. Inhibits dihydrofolate reductase (DHFR)
  3. Inhibits thymidylate synthesis
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13
Q

How does methotrexate inhibiting AICAR transformylase work?

A
  • Inhibiting AICAR transformylase leads to adenosine accumulation
  • Adenosine binds to adenosine receptors, which exert anti-inflammatory effects like (a) inhibiting inflammatory cytokine production (IL-1, IL-6, TNF), (b) inhibiting activation and function of immune cells, (c) inhibiting cell apoptosis and chemotaxis
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14
Q

How does methotrexate inhibiting DHFR work?

A
  • DHFR produces tetrahydrofolate, which is necessary for the production of purines and thymidylate
  • Without these, DNA replication and repair in rapidly-dividing immune cells is inhibited
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15
Q

How does methotrexate inhibiting thymidylate synthesis work?

A
  • Thymidylate is needed for pyrimidine synthesis
  • Without this, DNA replication and repair in rapidly-dividing immune cells is inhibited
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16
Q

How can you increase the efficacy of methotrexate?

A

Polyglutamate it, so it is retained for longer in immune / liver cells

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17
Q

How is methotrexate cleared?

A

Hepatic metabolism > Renal excretion

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18
Q

What are the six adverse effects of methotrexate?

A
  1. nausea / vomiting
  2. oral / GI ulcers
  3. immunosuppression
  4. bone marrow suppression
  5. hepatorenal toxicity
  6. pneumonitis (HS)
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19
Q

How do you prevent methotrexate toxicity?

A
  • Concomitant folic acid OR folinic acid 12-24h later
  • Folinic acid is more effective as it does not rely on DHFR function
  • Folic acid is cheaper
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20
Q

What is sulfasalazine?

A

It is a prodrug, which is converted by gut microflora into sulfapyridine and 5-aminosalicylic acid

21
Q

What do sulfapyridine and 5-ASA do?

A
  • Sulfapyridine inhibits production of inflammatory cytokines (e.g. IL-6, TNF)
  • 5-ASA inhibits production and function of inflammatory mediators (e.g. leukotrienes, prostaglandins)
22
Q

What are the five adverse effects of sulfasalazine?

A
  1. Nausea / Vomiting
  2. Headache
  3. Sulfa allergy skin rash
  4. Haemolytic anaemia and neutropenia
  5. Reversible male infertility (sulfapyridine)
23
Q

What is leflunomide?

A

Prodrug, converted to active metabolite teriflunomide

24
Q

What does teriflunomide do?

A
  1. Inhibits DHODH, which synthesises pyrimidines
  2. Inhibits NF-kB pathway, which helps lymphocytes activate/survive + produces inflammatory cytokines
25
What are the five adverse effects of leflunomide?
1. Diarrhoea 2. Elevated liver enzymes 3. Weight gain 4. Teratogen (perform colestyramine washout before pregnancy) 5. Alopecia
26
What is unique about leflunomide's half-life?
Very long
27
How is leflunomide cleared?
Hepatic metabolism + biliary excretion
28
What is chloroquine/hydroxychloroquine?
Anti-malarial agent, which is also anti-inflammatory
29
What does chloroquine/hydroxychloroquine do?
1. Antioxidant activity 2. Inhibits production of inflammatory cytokines 3. Increases lysosome pH, thus decreasing antigen presentation
30
Is chloroquine/hydroxychloroquine a good DMARD?
No, least potent
31
What are the five adverse effects of chloroquine/hydroxychloroquine?
1. Nausea/Vomiting 2. Stomach pain 3. Dizziness 4. Ocular toxicity with chronic use 5. Alopecia
32
What is tofacitinib?
A Jakinib, which is a non-selective Janus kinase inhibitor
33
Is tofacitinib effective?
Yes, best used with methotrexate / other csDMARDs, but not bMARDS
34
What does tofacitinib do?
- Inhibits JAK-STAT cell signalling pathway (by inhibiting JAKs, especially 1/3) - Disrupts almost all immune cell processes, esp. lymphocyte differentiation and function
35
What are the five adverse effects of tofacitinib?
1. Immunosuppression (can cause opportunistic herpes zoster infection in Asians) 2. Anaemia (erythropoietin and thrombopoietin rely on JAKs) 3. Cytopenia 4. Risk of malignancies (anti-cancer effects of JAK inhibited, e.g. NK activation) 5. Hyperlipidemia (due to lack of chronic inflammation)
36
What are the four anti-TNF mAbs?
I AGE Infliximab, adalimumab, golimumab, Etanercept
37
What do the anti-TNF mAbs do?
1. "-mAbs" bind to and inhibit TNF-a 2. Etanercept is a recombinant fusion protein, which binds to and inhibits TNF-a and LT-a
38
What are the five adverse effects of anti-TNF mAbs?
1. Immunosuppression 2. Aplastic anaemia 3. Malignancies, esp. lymphoma 4. Optic neuritis 5. Exacerbated multiple sclerosis (TNF-a has protective effects on myelin; without it, further demyelination occurs)
39
What are the two contraindications of anti-TNF mAbs, due to immunosuppression?
1. Live vaccine patients 2. Hep B patients
40
What is anakinra?
It is a modified IL-1R antagonist protein
41
What does anakinra do?
It competitively inhibits with IL-1 to bind to its receptor
42
What are the three adverse effects of anakinra?
1. Immunosuppression 2. Malignancies 3. Injection site reaction
43
What is tocilizumab?
Anti-IL-6R mAb, prevents Il-6 from binding to its receptor by binding to receptor first
44
What are the adverse effects of tocilizumab?
1. Immunosuppression 2. Neutropenia 3. Hyperlipidemia 4. Increased liver enzymes 5. CYP enzyme interaction (IL-6 normally downregulates these enzymes) 6. Skin eruptions (autoimmune)
45
What is abatacept?
Recombinant fusion protein which binds to CD80 / 86, and prevents CD28 activation = blocks T-cell activation and proliferation
46
What are the two adverse effects of abatacept?
1. Respiratory reaction, esp. in COPD patients 2. Malignancies
47
What is rituximab?
Chimeric mAb which binds to CD20 = blocks B-cell activation and proliferation
48
What are the two adverse effects of rituximab?
1. Respiratory reaction, esp. in COPD patients 2. Rash with first dose

MSK (6 decks)

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