Drugs for Systemic Autoimmune disease Flashcards
what’s the point of being COX-2 selective
there are two cyclooxyrgenase enzymes
COX-1: physiological function in the gut and kidney
COX-2: induced in inflammation and repair
by being selective for COX-2 you avoid GI side effects
NSAIDs that are not COX-2 selective
ibuprofen, diclofenac, naproxen, ketoprofen
NSAIDs that are COX-2 selective
meloxicam, celecoxib, etoricoxib
cardiovascular toxicity of NSAIDs
increases rates of vascular events, hypertension and heart failure
do non-selective or selective NSAIDs increase cardiovascular risk
both
how corticosteroids are used
usually prednisolone or prednisone
used for things like RA, SLE, cranial arteritis, polymyalgia rheumatica etc.
how corticosteroids are used
usually prednisolone or prednisone
used for things like RA, SLE, cranial arteritis, polymyalgia rheumatica etc.
problems with corticosteroids
obesity, muscle wasting
osteoporosis, bone loss, minimal trauma fractures
increased risk fo sepsis (immunosuppressive)
raised BSL
hypertension
increased rate of vascular events - myocardial infarction and stroke
mechanism of action of antimalarials
antilysosomal
interferes with antigen processing, decreased stimulation of T cells, decreased cytokine release
what are antimalarials used for to treat systemic autoimmune disease
used as single agent in RA and Lupus
mechanism of action of sulphasalazine
binding of sulphapyridine molecule with acetylsalicylic acid via an azo bond
inti inflammatory, action on folate metabolising enzymes, action on inhibiting neutrophils
toxicity of sulphasalazine
GIT, rash (may be severe), headache, pancytopenia, hepatitis,
pharmacology of methotrexate
forms monoglutamates and poly glutamates
higher blood levels in renal impairment
can be used in combination with NSAIDs, probenecid imparts its clearance
immunomodulatory effects in RA
toxicity of methotrexate
nausea, vomiting, diarrhoea
general fatigue and higher function problems, concentration and memory
bone marrow suppression, hepatic toxicity (particularly with alcohol) and mouth ulceration, hair loss
pneumonitis
can reduce folic acid
monitoring for sulphasalazine
FBC, LFTs
monitoring for methotrexate
FBCs, LFTs, AST, U&Es monthly
reduce 2-3 monthly
leflunomide is a
prodrug
pharmacology of leflunamide
blocks pyrimidine synthesis and interferes with T cell function
blocks dihydroorotate dehydrogenase
toxicity for leflunomide
GIT, hypertension, peripheral neuropathy, rash, hepatic, bone marrow, pneumonitis
monitoring for leflunomide
FBS, LFTs
pharmacology of azathioprine
purine analogue
blocks HGPRT synthase
reduces purine synthesis
lymphocytes can’t proliferate (B and T cells)
problem with Azathioprine
some people have functional genetic polymorphisms affecting the TPMT enzymes responsible for metabolism.
low activity of the TPMT enzyme causes metabolites of 6-MP (6TGN) to accumulate.
this causes bone marrow toxicity
azathioprine is metabolised into
6-MP
low TPMT causes what to accumulate
6TGN
6TGN causes
bone marrow toxicity
toxicity of azathioprine
GIT
increased rate of infection and malignancies
bone marrow and hepatic toxicity
cyclosporin A pharmacology
fungal metabolite
lipophilic cyclic peptide
inhibits T cell proliferation
mycophenylate mofetil
calcineurin inhibitor
used for lupus, polymyositis, vasculitis
tacrolimus is used for
used in SLE
cyclophosphamide
alkylating agent
severe lupus, scleroderma lung
list some Anti-TNF inhibitors
etanercept, alalimumab, infliximab, certolizumab, pegol, golimumab
toxicity of anti-TNF inhibitors
usual and atypical infections
(also very expensive)
anti-TNF inhibitors are contraindicated in
TB, skin cancers, heart failure contraindicated and in demyelinating conditions
can produce autoimmune conditions
anti-T cell inhibitor - abatacept
blocks interaction with CD28
blocks T cell costimulation and activation
combine with methotrexate
anti L6 inhibitor: tocilizumab
use without methotrexate
blocks IL-6, suppresses synovitis and joint damage and the acute phase response
what to monitor for anti L6 inhibitor tocilizumab
monitor FBC, increased rate of common and atypical infections
anti B cell inhibitor: rituximab
significantly reduces B cell numbers and immunoglobulin levels
combine with methotrexate
can be repeated every 6-12 months
new biologics and small molecules
anti IL17 and anti IL22 molecules - can be combined
JAK kinase inhibitor
apremilast
phosphodiesterase inhibitor for psoriatic arthritis
