Treatment of rheumatoid athritis Flashcards
As well as the joints, what does RA affect
Tendon sheaths
Is it symmetrical or asymmetrical
Symmetrical
What criteria is used to diagnose rheumatoid athritis
ACR/EULAR criteria
3 types of drugs used to manage rheumatoid athritis
- Pain relief drugs
- Drugs to modify disease progression
- Adjunct therapy
What drug type can be used to manage rheumatoid athritis
Disease modifying anti-rheumatics (DMARDS)
What adjunct therapy can be used for RA
Oral corticosteroid pulse
When are DMARDS usually prescribed
In newly diagnosed rheumatoid athritis
What drugs specifically should be prescribed if DMARDs are being given in a combination
Methotrexate
+ one other DMARD
+ short term glucocorticoid
When may combination therapy not be appropriate
Comorbities or pregnancies
What should be done if recent onset RA is being treated with combination DMARD and things seem to be ok
Cautiously reduce dosage
What drug is first choice in rheumatoid athritis
Methotrexate
How is methotrexate administered normally
Orally once a week on the same day
2.5mg tablets.
Dosage from 5-10mg a week
How should methotrexate be adminstered if oral form doesn’t work
Subcutaneous or IM injection
How many weeks pass before benefit of using methotrexate is seen
3-12 weeks
What side effects may be experienced with methotrexate (5)
Liver problems
Can affect blood count
Folic acid antagonist so limits DNA/ RNA synthesis
Inhibits dihydrofolate reductase and thymidylate synthethase
How does methotrexate enter the cell
Reduced folate carrier using endocytic pathway activated by a folat ereceptor
What happens to methotrexate once it enters the cell (5)
- Polyglutamated
- Inhibits dihydrofolate reductase
- Conversion of dihydrofolate to tetrahydrofolate is blocked
- Tetrahydrofolate stores depleted reducing thymidylate synthesis
- DNA and RNA synthesis blocked
What is sulfasalazine
Antibiotic that combines sulfapyridine and salicylate with azo bond
How is sulfasalazine administered
500mg daily orally, gradually increased over 4 weeks to 1g twice a day
How long must you take sulfasalazine before benefit is noticed
12 weeks
What are the disadvantages of sulfasalazine
Not well absorbed across the gut
Where in sulfasalazine concentrated
In connective tissue and serous fluid
What metabolises sulfasalazine
Gut bacteria
What does sulfasalazine break down into
5-aminosalicylic acid
Sulfapyridine
Describe how sulfapyridine interacts with each part of the body
Absorbed rapidly in colon
Aceylated in the liver
Excreted in the urine
Does sulfapyridine have therapeutic action in ulcerative colitis
Nah
What is the effect of 5-ASA on ulcerative colitis and how does this work
Induces remission
Inhibits COX, LOX PAF, cytokines, IL-1 and TNF-alpha
What was hydroxychloroquine originally used to treat
Malaria
How is hydroxychloroquine administered
- oral with or after food
- start 400mg daily
- reduced to 2-3 times a week
Briefly describe the mechanism of action of hydroxychloroquine
- Accumulates in lysosomes increasing the pH decreasing protein modifications
- Blocks T cell receptor 9 which recogises DNA containing immune complexes
- Decreases dendritic cell activation
What drug is Leflunomide’s efficacy most similar to
Methotrexate
What is the dosage of Leflunomide
10-20mg a day
1st 3 days 100mg a day
What is the mechanism of action of leflunomide
Inhibits pyrimidine biosynthesis through inhibiting dihydroorotate dehydrogenase
How are gold salts administered
IM injections once a week-50mg
How long must you be taking gold salts before a change is noticed
4-6 months
How are biologicals generated
Genetic engineering
What do biologicals inhibit
- TNF-alpha
- Interleukin 1
- B cells
- T cell stimulation
- IL-6
- IL-17 and 23
Give an example of a drug that blocks TNF-alpha (2)
Etanercept
Infliximab
What 2 molecules is etanercept a fusion of
human TNF receptor 2
Fc human IgG1
How is etanercept administered
50mg once a week
Subcutaneous injection
Describe the time scale of etanercept
1-4 weeks for effect
Progressive improvement 3-6 months
What is infliximab
Monoclonal antibody against TNF-alpha
Antibody designed against mouse binding site of TNF-alpha with remaining 75% human IgG1
How is infliximab administered
3mg/kg influsions
2-3 hours in duration
2-6 weeks apart
Whata is adalimumab and what does it bind
Human TNF alpha monoclonal antibody
Binds TNF-alpha both soluble and bound
How is adalimumab administered
40mg subcutaneously every other week
Name 3 drugs that work against IL-1
Anakinra
Canakinumab
Rilonacept
What is anakinra
Human recombinant IL-1 receptor antagonist
Why is anakinra different from normal IL-1
Addition of n terminal methionine
At what dosage is anakinra prescribed
100mg per day
Subcutaneous
What is canakinumab
A human monoclonal antibody that target IL1B
What is rilonacept
Dimeric fusion protein extracellular domain of IL1R1 and human IgG1
Used for gout
Name a drug that works against B cells
Rituximab
What is rituximab
Chimeric monoclonal antibody against CD20 which is primarily found on B cells
What drug is rituximab given in combo with
Methotrexate
When is rituximab presribed
If patients fail to respond to one or more anti-TNFa agents
Name a drug that works against T cells
Abatacept
How does abatacept work
Prevents second signal from being delivered to T cell
Pros/ cons of abatacept
Similar clinical symptom improvement as TNFa inhib
Slower onset
Fewer adverse effects
What does Tocilizumab act again
IL-6
What drug should Tocilizumab be given in combo with
Methotrexate
Name 2 drugs that can be used in psoriasis. What antibodies do they go again
Secukinumab for IL 17
Ustekinumab for IL 23
what is a neutralising anti drug antibody
Directly interferes with biological drugs ability to work
What is a non neutralising anti drug antibody
May form immune complexes around injection site reducing drug concentration and pharmacokinetics
