Pharmacology of Arthritis Flashcards
what is the 3 steps of the pain ladder
non-opiod (aspirin, paracetamol or NSAID) +/- adjuvant
weak opioid for mild to moderate pain (e.g. codeine) +/- non opioid +/- adjuvant
strong opiod for moderate to severe pain (e.g. morphine) +/- non-opioid +/- adjuvant
what are examples of adjuvant therapies in the pain ladder
muscle relaxants, anticonvulsants, antipsychotics, antidepressants, corticosteroids, anxiolytics and psychostimulants
what is the actions of NSAIDs
non steroidal anti-inflammatory
analgesic
name 4 NSAIDs
ibuprofen, naproxen, diclofenac, celecoxib (cox 2 inhibitor)
what are the indicators for NSAIDs
inflammatory arthritis, mechanical MSK pain, pleuritic/ pericardial pain (CTD)
what are the adverse affects of NSAIDs
dyspepsia, oesophagus, gastritis, peptic ulcer, small/large bowel ulceration, renal impairment, increased cardiovascular events (cox 2 inhibitors + all anti-inflammatory), fluid retention, wheeze, rash
what does DMARD stand for
disease modifying anti-rheumatic drug
what is the treatment for inflammatory arthritis
early, aggressive DMARD therapy within three months of symptom onset
what do DMARDs do
pure anti inflammatory with no analgesic effect
reduce rate of joint damage and inflammatory markers
what are the DMARDs of choice
methotrexate and sulfasalazine
name two other DMARDs
leflunomide
hydroxychloroquine
how long do DMARDS take to work
6 weeks- can use steroids as a bridge to reduce inflammation
how does methotrexate work
folate antagonist
how can methotrexate be administered
orally or subcutaneously
what is methotrexate used in
RA, psoriatic arthritis, CTD and vasculitis
can you gain normal joint function after the window of oppurtunity
no
what are the adverse effects of methotrexate
leucopenia/ thrombocytopenia hepatitis, cirrhosis (alcohol intake must be limited) pneumonitis rash, mouth ulcers nausea, diarrhoea
what do you need to monitor in methotrexate
FBC and LFTs
is methotrexate safe in pregnancy
no is teratogenic- must be stopped in males and females at least 3 months before conception
describe leflunomide
DMARD
similar efficacy and side effects to methotrexate
also teratogenic
what is an additional requirement of leflunomide
requires a wash out due to its very long half life
when and with what is sulfasalazine used
often used in early inflammatory arthritis in combo with methotrexate
what are the adverse effects of sulfasalazine
nausea rash/mouth ulcers neutropenia hepatitis reversible oligozoospermia (reduced sperm count)
what do you need to monitor in sulfasalazine
FBC and LFT
does hydroxychloroquine affect joint damage
no effect on joint damage
when is hydroxychloroquine used
CTD: SLE, sjogrens and RA
what do biologics do
target specific aspects of the immune system found to be implicated in inflammatory arthritis
what do biologics target
TNF
CD 20 B cells
interleuken 6, 17, 12 and 23
what is anti TNF used for
RA, psoriatic arthritis, ankylosing spondylitis
is sulfasalazine safe in pregnancy
yes- when also taking folic acid supplement
can anti TNF be used in combo with DMARDs
yes- makes it more effective
is anti TNF safe in pregnancy and breast feeding
yes
give examples of anti TNF drugs
etanercept, the ‘-mab’s’
how are most anti tnfs delivered
sub cutaneously
why is TNF targeted
as is an intergral cytokine in sad conditions (RA, psoriatic arthritis, AS)
what is the criteria for anti TNF use
high disease activity score
use of previous standard DMARDs
what are the adverse effects of anti TNF
risk of infection (especially TB), possible risk of malignancy
contraindicated in certain situations (pulmonary fibrosis, heart failure)
what does rituximab target
monoclonal antibody against B (CD20) lymphocytes
what does tocilizumab do
inhibits IL-6
what does abatacept do
CTLA-4 Ig- blocks full activation of T lymphocytes
what does ustekinumab do
inhibits IL 12 and 23
what does secukinimab do
inhibtis IL 17
what does tofacitinib/ baricitinib do
janus kinase inhibitors
what is used to treat an acute episode of gout
colchicine (diarrhoea common)
NSAIDs (naproxen)
steroids (either oral/IM)
what is used as gout prophykaxis- how does it work
urate lowering drugs:
allopurinol (increased gradually whilst checkin urate levels)
febuxostat
uricosurics
what is the threshold for urate
360 micromoles
in an acute episode of gout would you stop previously prescribes allopurinol
no
what is allopurinol
xanthine oxidase inhibitor
is febuxostat safe to give patients who have renal failure
yes
what are the adverse effects of allopurinol
rash (vasculitis- commonly in elderly and in renal impairment- use lower doses)
azathioprine interaction
rarely marrow aplasia
how does febuxostat work
xanthine oxase inhibitor
when would you give febuxostat instead of allopurinol
if patients cannot tolerate allopurinol (e.g. renal impairment)
what should you be cautious of in febucostat
if patients have ischaemic heart disease
name some uricosurics
probenecid
sulphinpyrazone
azapropazone
benzbromarone
what rheumatological problems are corticosteroids used in
CTD, polymyalgia rheumatica/giant cell arteritis, vasculitis, RA
how can you administer corticosteroids
oral, IA, soft tissue injections, IM, IV
what are the adverse effects of corticosteroids
weight gain (centripetal obesity) muscle wasting skin atrophy osteoporosis diabetes hypertension cataracts glaucoma fluid retention adrenal suppression immunosuppression avascular necrosis of the femoral head
how do you reduce the toxicity of corticosteroids
lowest dose for shortest time possible
steroid sparing agents
osteoporosis prophylaxis
watch cardio risk factors
what usually happens to RA in pregnancy
gets better
how often do you take nwthotrexate
weekly
