Non-opioids, gout, rheum arthritis Flashcards
what are non-pharm approaches to gout & RA?
dietary modifications: reduce purine-rich foods, weight
PT: for RA, to improve joint mobility
acute pain management = cold/hot compresses
non opioid analgesic types
NSAIDs, acetaminophen, DMARDs, colchicine
fatty acid in cell membrane phospholipids
released w/ cell activation or damage by phospholipase A2 enzyme
PGs and LTs derived from this
arachidonic acid
pathway = leukotrienes, prostanoids
what drug inhibits COX enzymes that produce prostaglandins and mediate pain and inflammation
NSAIDs
non-selective NSAIDs
salicyclates = aspirin, topical salicyclic acid, bismuth-subsalicylate (pepto bismol)
cox-2 selective NSAID
celecoxib (celebrex)
other nsaids
classes: heteroaryl acetic acids, propionic acid derivatives, oxicam derivatives, acetic acid derivatives
ibuprofen, naproxen, diclofenac, ketoprofen, indomethacin, meloxicam, ketorolac
what drug is analgesic, anti-inflamm, antipyretic for RA, osteoarthritis, gout, acute pain, or closure of PDA?
NSAIDs
What are propionic acid derivative NSAIDs?
OTC: ibuprofen, naproxen
rx: ketoprofen, oxaprozin
What are propionic acid derivative NSAIDs indicated for?
chronic treatment of RA and OA, mild-mod acute pain and fever, closure of PDA (ibuprofen)
What are acetic acid derivatives NSAIDs?
Rx: indomethacin, sulindac
what are indications for acetic acid derivatives NSAIDs?
acute gout attack, closure of PDA
acetic acid derivatives NSAIDs have high toxicity with adverse effects in –
1/3 of patients
pancreatitis, headache, dizziness, confusion, hallucinations, thormbocytopenia and aplastic anemia
what are oxicam derivatives
RX: piroxicam, meloxicam
long half lives, meloxicam preferentially inhibiting COX-2, less GI
heteroaryl acetic acid NSAIDs
RX: diclofenac, keterolac (great for renal calculi)
strongest NSAIDs are
heteroaryl acetic acid NSAIDs
indications for heteroaryl acetic acid NSAIDs
moderate to severe pain, only can use short-term up to 5 days with risk of nephrotoxicity
- Cr baseline, monitor w/ severe renal disease
—– may increase LFTs, check at baseline and monitor with heteroaryl acetic acid NSAIDs
diclofenac
selective, reversible inhibition of COX-2 with no antiplatelet effect
celecoxib = increased CV risks
celecoxib is used for
long term treatment of RA and OA, mild/mod acute pain
celecoxib ADRs
same black box warnings as NSAIDs, increased risk of MI/stroke (avoid in high risk), may interfere with aspirin’s antiplatelet effects
C in 1st/2nd trimester, D for DEATH in 3rd trimester
toxicities of NSAIDs
GI Toxicities - protect w/ PPI or H2 blockers, metabolized by 2C9
renal toxicities – dose adjustments needed wit kidney injuries, nephrotic syndrome, hyperkalemia
cardiovascular risk: increased risk of MI and stroke
hepatic toxicity: varying degrees of enterohepatic circulation, liver damage possible
non-selective, irreversible inhibition of COX
acetylsalicyclic acid –> alicylate
aspirin
use in antiplatelet effects, decreased strokes, reduced mortality w/ MI and recurrence, reduce risk with stable angina
aspirin
aspirin ADRs
GI= discomfort, bleeding, PUD, take with food
** pregnancy category X **
hematologic
allergic
reye’s syndrome (nausea, lethargy, confusion)
gout = lowers renal uric acid clearance
C in 1st and 2nd, D in third
aspirin DDIs
can displace warfarin, phenytoin, valproic acid
mild salicylism (ASA overdose)
N/V, dizziness, tinnitus –> hospitalize –> activated charcoal
moderate-severe salicyclism
restlessness, hallucination, seizures, coma, death
admit, activated charcoal
other salicylates like
bismuth-subsalicylate (pepto bismol), anti-inflamm, antacid, part of h pylori eradication, dark stools
topical salicylic acid
WHat are ADRs of NSAIDs
HTN due to fluid retention, edema, headaches, tinnitus, dizziness, hypersensitivity
ADRs of non selective NSAIDs
black box = increased CV risk, GI bleed. PUD, separate w/ ASA at least 2 hours
most pregnancy B in 1st and 2nd trimesters (oxaprozin and keterolac are C) and D in 3rd trimester – avoid!
highest NSAID GI risk
keterolac
(ibuprofen is lowest)
highest NSAID CV risk
naproxen
(celecoxib is lowest)
inhibition of COX enzymes in brain without anti-inflammatory
acetaminophen (also doesn’t have antiplatelet effect)
acetaminophen is metabolized in the
liver, with renal excretion
use acetaminophen for
mild-moderate pain relief, fever reduction, DOC with viral illness, pregnancy category B
acetaminophen is better because of
less GI irritation, no anti-inflammatory effects
acetaminophen can cause
liver toxicity from toxic metabolite production (NAPQI conversion from CYP2E1)
overdose of acetaminophen can occur with
long term supratherapeutic doses, 4gm/day MAX – monitor LFTs with high dose therapy
the bad metabolite is
NAPQI
treat acetaminophen toxicity with
n=acetylcysteine
RF: chronic alcohol use, malnutrition, use of other drugs
What are the different types of RA meds?
DMARDs = methotrexate, sulfasalazine, leflunomide, hydroxychloroquine
biologics = TNF-alpha inhibitors, T cell inhibitor
glucocorticoids
NSAIDs
DMARDs
disease modifying antirheumatic drugs
** prevent and slow disease progression and destruction **
takes 2 weeks - 6 months
most have serious effects and cannot be used in pregnancy
safest RA drug in pregnancy
steroids, sulfasalazine, hydroxychloroquine
primary choice for RA
methotrexate
3-6 week onset
folic acid antagonist
methotrexate
methotrexate is never
dosed daily – weekly dose, 7.5mg-22.5mg
ADRs of methotrexate
lots of black box warnings – must wait 3 months after finishing drug to concieve or donate blood
category X
hepatotoxicity – must test for hep B and C before therapy, monitor
bone marrow suppression
immunosuppression cannot administer live vaccines
can cause lung inflammation
methotrexate montioring
liver function, CBC, renal function
folate supplementation to reduce side effects
DMARD aminosalicyclate anti-inflamm COX inhibitor (5-ASA)
sulfasalazine
onset 1-3 months
1st line for mild, mod, severe RA
sulfasalazine
What are ADRs of sulfasalazine
N/V, ab pain, skin rash, dyspepsia, arthralgias, myalgia, bone marrow suppression
sulfasalazine is CI in
ASA and sulfa allergies
pregnancy category B (only if benefits outweigh risks)
interferes with folate absorption, so give patient a supplement
DMARD: inhibiting pyrmidine synthesis with inhibiting T and B cell production
leflunomide
1st line for mild, mod, severe RA, onset in 4-6 weeks
leflunomide
ADRs of leflunomide
diarrhea, nausea, headache, alopecia, HTN, hepatotoxiity (get hep B and C tested, elevated LFTs, monitor at baseline and monthly x 6 months)
rash, pruritus, allergic reaction
teratogenic!!!!!!!!!!!!!!! pregnancy category X = must have negative test before starting med, and use 2 forms of BC, must have undetectable drug levels on TWO occasions before trying to get pregnant
cytotec causes
medical abortion
induce leflunomide elimination by
cholestyramine
less effective DMARD
hydroxychloroquine – unclear MOA, for mild RA, effect in 3-6 months
ADRs: ocular toxicity, N/V, dyspepsia, abdominal pain, dizziness, ataxia, headache
category C = only if benefits outweigh risk
biologic RA first line
TNF inhibitors
etanercept
infliximab
adalimumab
biologic RA 2nd
rituximab (CD20+ B cells)
anakinra (Il-1)
abatacept (T lymph inhib)
tocilizumab (IL-6)
can give biologics with
methotrexate when severe disease w/ poor prognosis, 2ndary for resistant disease (combo of 2+ DMARDs failing to achieve low disease activity after 3 months)
ADRs of biologics
black box for serious infections and malignancy – immunosuppression –> evaluate TB risk, test for latent disease at baseline and annually
increased risk of malignancy, infusino reaction, HF, hepatotoxicity
monitor for RA meds
methotrexate: monitor LFTs, CBC, Cr
biologics: infections, CBC, LFTs, renal
hydroxychloroquine: retinal toxicity, eye exams
gout tx
NSAIDs, colchicine, steroids, urate lowering therapy (allopurinol, febuxostat, probenecid)
acute gout attack tx
NSAIDs = indoemthacin * , ibuprofen, naproxen, diclofenac, meloxicam
colchicine
steroids
reduce inflammation with NSAIDs DOC
chronic gout tx
allopurinol, febuxostat, probenecid, lower uric acid levels
DOC for acute gout with no CIs (PUD, renal insufficiency, CHF)
NSAIDs = indomethacin!
do not use – in gout
aspirin
inhibits leukocyte migration and phagoytosis, relieving pain and inflammation by reducing inflammation in joint
3A4 and PGP substrate – strong inhibitors can lead to serious and fatal toxicity (amiodarone, clarithormycin)
reduce dose!
colchicine = can take at first signs of an attack
use – if NSAIDs are CI in gout
colchicine
initial dose 1.2mg + additional .6mg one hour later is just as effective!
narrow therapeautic index
ADRs of colchicine
N/V, diarrhea, caution in hepatic and renal impairment
monitor gout with
serum uric acid levels, joint aspiration, renal function
steroids in gout are
3rd line, if both previous are CId
intra-articular methylprednisonlone or triamcinolone for monoarticular disease
oral prednisone for polyarticular disease
avoid if you have not ruled out septic joint!
blocks xanthine oxidase enzyme
allpurinol
what to use to prevent acute attacks in chronic gout?
allopurinol with 2-3+ attacks/year with continued elevation of uric acid levels
not anti-inflammatory
ADRs of allopurinol
titrate slowly, use NSAID or colchicine in flare, cataracts
allergic skin reaction
GI, hepatic
nonpurine xanthine oxidase inhibitor and can be administered to renal insufficiency without dose adjustments
febuxostat
decreases uric acid reabsortion, inhibits excretion of penicillins, aspirin can decrease effectiveness
probenecid (uricosuric drugs)
ADRs: titrate and use NSAID/colchicine in flares
uric acid stones, must drink 2L of fluid/day during therapy
what are pregnancy category B drugs of this lecture
NSAIDs (1st/2nd trimester)
biologics
acetaminophen
what are category C drugs of this lecture
celebrex NSAID
biologics
colchicine
what are category X drugs of this lecture
methotrexate
