Rheumatologic therapies Flashcards
What are some risks/disadvantages of disease modifying antirheumatic drugs?
dose creep- you may have to raise doses over time
lymphoma risk of treatment
infection risk
risk of progressive multifocal leukoencephalopathy
biologics can’t be combined safely
avoid live vaccines
Methotrexate: dosing considerations, mechanism
weekly dosing safer than daily
works by inhbiting DHFR (dihydrofolate reductase): inhibits purine synthesis
inhibits AICART: incr. relase of anti-inflammatory adenosine (but can be bad for asthma- adenosine is a bronchoconstrictor)
Risks of methotrexate
cirrhosis (very rare) pneumonitis (rare) oral sores and scalp hair loss lymphoma psoriasis (does not interact with NSAIDs)
limitations of methotrexate, onset of action
takes 4-6 wks to see effect
does not control nodules in RA
does not control central arthritis, so less useful for pts with seronegative spondylarthropathies
requires monitoring of CBC, creatinine, and liver function tests
Advantages of methotrexate
reduces mortality in RA
good for SLE
good for maintenance for vasculitis but not for induction treatment
hydroxychlorquine: usage considerations (what monitoring is required, interactions, onset of action)
weak, but safe
often used in combo with other drugs
requires annual eye exam to look for retinal damage- mostly medico-legal
4-6 months for onset of action
hydroxychloroquine MOA
interferes with antigen progcessing (TLR9)
uses of hydroxychloroquine
malaria, RA, SLE (helps keep a lid on the disease- first line)
sulfasalazine MOA
AICART inhib leads to release of adenosine (anti-inflammatory)
sulfasalazine: usage considerations (what monitoring, interactions, onset of action)
must do G6PD screen before use
then monitor CBC every quarter
6-8 wks before you see a good effect
risks of sulfasalazine
rashes, pancytopenia, bloating
uses of sulfasalazine
RA, colitis in IBD, peripheral arthritis of seronegative spondies
Azathioprine: MOA
prodrug for 6-mercaptopurine that is a purine analog that inhibits purine metab
Azathioprine usage considerations (what monitoring, interactions, onset of action)
several weeks to take effect
requires monthly CBC
metabolism inhibited by allopurinol
azathiprine risks
allergic hepatitis (rare, more likely with nausea/vomiting and/or dehydration), lymphomas, autoimmunity/allergy
uses of azathioprine
transplant recipients, RA, SLE, myositis, vasculitis maintenance,
cyclosporine MOA
calcineurin inhbitor. prevents NFKB activity in nucleus
MOSTLY anti-Tcell effects
side effects of cyclosporine
dose related
may cause HTN, then renal insuffiency- must stop once renal insufficiency develops (only useful for a few yrs)
cyclosporine usage considerations: interactions, onset, uses
6-8 wks
usually used with methotrexate
RA, SLE, chronic urticaria
TNF alpha inhibitors: uses and onset of benefit
takes a few weeks
used for RA and seronegative spondies (single best treatments)
reduces RA mortality
not useful for CT disease or vasculitides
most effective in combo with methotrexate
TNF-alpha inhibitors: monitoring and risks
incr. TB risk- check PPD
histoplasmosis risk increased
TNF-alpha inhibitors contraindications
CHF, MS, active infection
TNF-alpha inhibitor types
enbrel: fixed dose and can up-regulate T cell cytokine response
infliximab. remicade: indicated for use with methotrexate
rituximab: MOA, monitoring/considerations, time to response, risks
anti-CD20. ppl usually ok with low b cells
plasma cells survive
response seen within days
must premedicate with steroids and acetaminophen to prevent severe infusion reactions
risk of PML (progressive multifocal leukoecephalopathy
rituximab uses
RA, Wegener’s, possibly SLE/sjogrens
