Rheumatological Therapies Flashcards
Describe examples of NSAIDs
- ibuprofen, usual dosage 200-400mg
- naproxen (has good CVS profile)
- diclofenac
- indomethacin
- piroxicam
- celecoxib
- etoricoxib
- -coxib (celexocib, etorixocib)→ COX2 inhibitors; these are predominantly prescribed for people who have lower risk of CVS conditions
What are the side effects of NSAIDs?
Dide effects:
- headaches
- dizziness
- abdominal pain
- diorrhea
- nausea + indigestion
- bleeding
- swollen ankles (salt and water retention)
- chest pains
- difficulty breathing
- rash/sunlight sensitivity
- high BP
- effects on kidney
Describe steroids
Next in line from NSAIDs - like a bridging med for rheumatological conditions
Corticosteroids/steroids are synthetic hormones, reduce inflammation, act FAST
Prednisolone/dexamethasone (oral)
I/m and intra-articular methylprednisolone injections
Topicals e.g. eumovate
I/v methylprednisolone
What are steroids used for in rheumatology?
- inflammatory, rheumatoid, crystal arthritis
- vasculitis - e.g. giant cell arteritis
- small or medium vessel vasculitis
- connective tissue diseases - e.g. SLE
- inflammatory myositis
Dosing=dependent on the severity of the condition, side effects are proportional to the dosing amount
What are the side effects associated with steroids?
Systemic-increased appetite, GIT upset, weight gain, increased infection risks, raised glucose levels, sleep disturbance inc vivid dreams, mood disorders, psychosis, glaucoma, salt and water retention, cushingoid effects, osteoporosis.
If administering locally, you can get side effects of: intra-articular/intramuscular-fat atrophy, depigmentation, infection, tendon rupture, nerve damage.
A patient comes in with acute swollen knee joint. How would you go about diagnosing this?
Differential diagnosis: septic, reactive, mono, crystal or new presentation of inflammatory arthritis
Go into history: recent infection, as a consequence of that→ septic arthritis?
Aspiration of fluid from joint effusion tells you the diagnosis (mc and s/crystal analysis)
If sure that it isn’t an infective joint, then offer relief: intra-articular injection of methylprednisolone (40-80mg)
disease modifying drugs (DMARDs) work long term to prevent certain conditions from worsening. When are these drugs used?
Class of drugs used in treatment of inflammatory arthritis/other autoimmune conditions:
RA, psoriatic arthritis, spondyloarthritis
Connective tissue disease - systemic sclerosis, SLE, Sjogren syndrome
Inflammatory myositis, vasculitis, IBD, psoriasis
- conventional DMARDs
- biological DMARDs
Describe common DMARDs and the dose, route and side effects
Specifically talk about Methotrexate, Sulfasalazine and Hydroxychloroquine
Hydroxychloroquine - anti-malarial as well. Used in management of lupus.
Sulfasalazine and Hydroxychloroquine are second line to methotrexate
Describe common DMARDs and the dose, route and side effects not already mentioned
if you cannot tolerate methotrexate, then give lefluonomide (BUT has hepatotoxicity + acute hepatic failure)
Azafioprine and cyclosporine are used as alternative and not really mainline drugs
Describe methotrexate
Prodrug - active AFTER polyglutamation in cells
Takes up to 27.5 weeks to achieve a steady state
Therapeutic effect ~12 weeks
30mg is the highest dose for this drug in oncology
Mostly eliminated by kidneys hence renal impairment may cause toxicity on bone marrow
Oral, SC or IM routes, dose range from 7.5mg-25mg weekly typically used
NSAIDs can reduce excretion of methotrexate, can be used at lower doses
What is the mechanism of action of methotrexate?
FIX THIS IN WEB BS TO.MAKE SURE BOTH DIAGRAMS ARE IN THE IMAGE
MTX inhibits dihydrofolate reductase, so no dihydrofolic acid (FH2) and FH4 is produced
MTX reduces amount of FH4 available to puridine and pyrimidine metabolism; amino acid and polyamine synthesis (basc stops it from going to other cellular pathways)
MTX may bind to other folate-dependent enzymes: purine biosynthesis
What are other modes of action due to methotrexate?
MTX leads to increased extracellular concs of anti inflammatory adenosine
-extracellular dephosphorylation of adenine nucleotides via ecto-5’-nucleotidase.
Other mechanisms:
- Decreased production of proinflammatory activated T cells
- Inhibition of methylation
- Suppression of IL-1β production by mononuclear cells.
What additional prescription do we give to patients taking methotrexate?
MTX inhibits the enzyme dihydrofolate reductase - that can lead to folic acid deficiency (so we prescribe additional folic acid)
Used not on the same day that the MTX is administered, but either day before or day after
This is because it can cancel out effects of MTX
Describe the mechanisms of action of other DMARDs
hydroxychloroquine: mild agent which inhibits intracellular toll-like receptor TLR9.
Leflunomide inhibits dihydroorotate dehydrogenase with inhibition of pyrimidine synthesis and preventing lymphocyte proliferation.
Sulfasalazine has anti-inflammatory effects by reducing oxidative, nitrative, and nitrosative damage. Patient with sulphonamide allergy would not be able to take something like sulfasalazine
What is TNF? What are the diverse effects that it has?
TNF(alpha or beta)=produced by macrophages. It activates macrophages, T and B cells, as well as signalling pathways:
- transcription factor activation (nuclear factor kB)
- proteases (caspases)
- protein kinases (c-Jun N-terminal kinase, MAP kinase)
leads to inflammation
Also produces IL1, IL6 and chemokines IL-8, RANTES
Expresses adhesion molecules (ICAM-1, E-selectin)
Inhibits Tregs, upregulates RANK-ligand expression, makes matrix metalloproteinase and induces apoptosis
Biologic DMARDs include Anti TNF, IL17 inhibitors, JAK inhibitors and Apremilast.
Describe Anti TNF drug therapies Etanercept, infliximab and adalimumab
Infliximab is an infusion, which has been used for 20 yrs in NHS
Administered every 8 weeks as an infusion over an hour - done in hospital
However it can be time consuming, so instead you can take etanercept, which is self injecting
Very effective and very potent drugs
Biologic DMARDs include Anti TNF, IL17 inhibitors, JAK inhibitors and Apremilast.
Describe Anti TNF drug therapies Golimumab and Certolizumab-pegol
