Disease Modifying Anti-rheumatics (DMARD) (+ 25qs) Flashcards
OA - fill in about colexcicb
State the treatment pyramid for RA:
Pain management: [2]
First line disease treament (Mild RA): [2]
Second line disease treatment (moderate RA) [2]
Second line disease management: (severe RA) [2]
Pain management: NSAID & Opioids
First line: Methotrexate & 2nd line DMARD
Second line disease treatment (moderate RA) Methotrexate & TNF-inhibitor
Second line disease management: (severe RA) Methotrexate & Rituximab
If have a flair of RA which drug might be used as adjunct therapy? [1]
Oral corticosteroid pulse (e.g. prednisilone)
How may you start DMARD treatment if have severe RA? [2]
Start with high dose and taper down once under control
OR
Add prednisilone
State 3 reasons why may not prescribe methotrexate [3]
Liver damage (methotrexate metabolised in liver)
Pregnant
Co-morbidities
State two factors that DMARDs improve [2]
What does DMARD not improve? [1]
Improves:
* early improves number of swollen
* improves radiographic progression
No effect:
* the patients fatigue severity
Explain MoA of methotrexate [4]
How is it administered? [1]
Oral dose (can change to subcut. or IM)
MoA:
* Folic acid antagonist which will limits DNA and RNA synthesis by inhibiting dihydrofolate reductase and thymidylate synthetase
* Causes a reduction in purine synthesis
* Induce ROS
* Causes activation of apoptosis
* Inhibits pro-inflam cytokines IL-1 & NF-kB
State three side effects of methotrexate [2]
Can cause liver problems
Can affect blood count
Hair
Describe MoA of Sulfasalazine [5]
Mode of action in RA not well understood:
* Metabolised in the colon by gut bacteria to 5-ASA
* 5-ASA stays in large intestine lamina propria and has local anti-inflammatory actions
* Supresses generation of superoxide radicals and cytokine production by inflammatory cells
* IL8 decreased in synovial fluid and decreased production of IgM and IgG, and decreased angiogenesis
* Inhibits IL-1 and TNF-a
Describe the MoA of Hydroxychloroquine [2]
- Accumulates in lysosomes increasing the pH decreasing protein modifications
- Blocks Toll-like receptor 9 which recognises DNA containing immune complexes decreases activation of dendritic cells: less autoantobodies produced
Describe MoA of Leflunomide [3]
Pro-drug: gets metabolised in liver
Inhibits dihydroorotate dehydrogenase (DHODH) and therefore stops pyrimidine biosynthesis
Reduces pro-inflammatory cytokines: IL-1, TNF-A and IL-6
Blocks T cell proliferation
leflunomide has a similar mechanism of action to
Etanercept
Infliximab
Methotrexate
Sulfasalazine
Hydroxychloroquine
Methotrexate
Both block block on RNA and DNA synthesis via different, synergestic pathways
State which of the following blocks pyrimidine or purine synthesis:
Methotrexate
Leflunomide
Methotrexate: stops purine synthesis
Leflunomide: stops pyrimidine synthesis
Name two TNF-a blockers for RA [2]
Etanercept
Infliximab
Explain MoA of Etanercept:
What is etanercept a fusion protein for? [1]
What is etanercept Fc for? [1]
When TNF-a is released: finds receptors on cells, activates and causes signal transduction
Etanercept is a fusion protein human TNF receptor 2 and Fc human IgG.
Etanercept binds to TNF-a before TNF-a can get to cell and cause inflammatory, signalling
Describe MoA of Infliximab [1]
Monoclonal antibody against TNFα
Which of the following acts quicker:
Infliximab
Etanercept
Infliximab
Etanercept
Infliximab often prescribed alongside which drug? [1]
Infliximab and methotrexate
Name another TNF-inhibitor used in RA [1]
Adalimumab
Name a Human recombinant IL-1 receptor antagonist to treat RA
Anakinra
Describe efficacy of IL-1 antagonists c.f TNF-alpha blockers
IL-1 receptors antagonists are not as effective in RA as TNF-alpha blockers
Despite good efficacy, why is Anakina not as commonly prescribed for RA? [1]
Requires subcut daily injections
Describe MoA of Anakinra [1]
Monoclonal antibody that is a IL-1 antagonist
Describe MoA of Rituximab
Monoclonal antibody that targets CD20 on B cells
Means B cell can’t become activated
Destroys normal and malignant B cells
AEs of Rituximab?
Risk of infection as B cells destroyed
How long does Rituximab take before positive effect? [1]
3 months after infusions
Describe MoA of Abatacept
Blocks T cell activation which thus means macrophages and B cells cannot be activated.
Competes with CD28 binding to CD80/86 by upregulating CTLA-4, which switches T cell off
Reduces production of TH17 cells
Thus reducing inflammation
Tocilizumab targets which IL? [1]
Describe MoA [2]
Interleukin 6
Monoclonal antibody that binds to IL-6 cytokine before it reaches target receptor
What drug class is the first oral biological? [1]
JAK inhibitors
State three JAK inhibitors used to treat RA [3]
Tofacitinib, baricitinib and upadacitinib
Describe the MoA of JAK inhibitors
Targets Janus kinase (JAK) pathways: means that multipe cytokines are blocked
Describe the MoA of JAK inhibitors
Targets Janus kinase (JAK) pathways: means that multipe cytokines are blocked
State why biologicals, despire their efficacy are not used straight away for RA treatment? [2]
Due to the develop of anti-drug antibodies that will develop no matter what - decrease efficacy
Explain the mechanism of neutralising ADAs [2] & non-neutralising ADAs [2]
Because they are chimeric / humanised antigens you get anti-drug antibodies:
Neutralising ADA
* Directly interferes with the biological drugs ability to work
* Bind to the antibody/biological directly and stop it being able to bind to TNF-alpha, IL-1, etc
Non-neutralising ADA
* May form immune complexes around injection site reducing drug concentration and pharmacokinetics
Increased clearance
RA
Methotrexate and Rituximab would be
First line treatment
Second line treatment
Third line treatment
Fourth line treatment
Third line treatment
RA
Methotrexate and a 2nd line DMARD would be
First line treatment
Second line treatment
Third line treatment
Fourth line treatment
First line treatment
RA
Methotrexate & a TNF-inhibitor would be
First line treatment
Second line treatment
Third line treatment
Fourth line treatment
Second line treatment
Methotrexate inhibits which enzyme? [1]
dihydrofolate reductase
RA
Sulfasalazine is a prodrug for [1]
5-ASA
Hydroxychloroquine blocks:
TLR7
TLR8
TLR9
TLR10
TLR11
TLR9
RA
Leflunomide inhibits which enzyme? [1]
What is the effect of this? [2]
Dihydroorotate dehydrogenase (DHODH): stops pyrimidine synthesis & therefore reduces pro-inflammatory cytokines: IL-1, TNF-A and IL-6; Blocks T cell proliferation
Which is the staple treatment for RA?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which is the staple treatment for RA?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which treatment for RA inhibits dihydrofolate reductase?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which treatment for RA inhibits dihydrofolate reductase?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which treatment for RA reduces purine synthesis?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Methotrexate
Which treatment for RA reduces pyrimidine synthesis?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Leflunomide
Which treatment for RA is safe for pregnant people?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Sulfasalazine
Which treatment for RA is prodrug that operates in large intestine?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which treatment for RA is prodrug that operates in large intestine?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Which treatment for RA that targets TLR-9?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Hydroxychloroquine
Which treatment for RA that reduces dendritic cell activation?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Hydroxychloroquine
Which is a treatment for RA that inhibits dihydro-orotate dehydrogenase?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Hydroxychloroquine
Which treatment for RA requires folate to be given alongside?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Methotrexate
Which treatment for RA is a tumor necrosis factor-alpha (TNF-alpha) inhibitor?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Infliximab
Which treatment for RA is a monoclonal antibody?
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Infliximab
Infliximab
Which treatment for RA is an anti-CD20 monoclonal antibody?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Rituximab
Which treatment for RA causes B cell depletion?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Rituximab
Which treatment for RA leads to decreased T-cell proliferation and cytokine production?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Abatacept
Which treatment for RA is an IL-1 antagonist?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Anakinra
Which treatment for RA targets IL-6?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Tolizumab
Which treatment for RA targets upregulates CTLA-4, which switches T cell off?
Etanercept
Adalimumab
Anakinra
Rituximab
Abatacept
Tolizumab
Tolizumab
