Pharm: DMARDS and NSAIDS Flashcards
NSAIDs
non-steroidal anti-inflammatory drugs: anti-inflammatory, analgesic, antipyretic
COX inhibitors
hepatic metabolism
effects: reduce urinary metabolites of PGI2 and TXA2, inhibit platelets
AE: GI, RENAL, increase bleeding time, increase BP, increase CV risk in those on aspirin regimen, liver (low risk in most)
CI: decrease clearance of lithium and methotrexate
monitor: LFTs, serum creatinine/BUN, stool guaiac
*does not slow progression of RA
DMARDs (non-biological)
disease modifying anti rheumatic drugs
AE: BLOOD DYSCRASIA
monitor: CBC
biological DMARDs
DMARDs with specific epitopes
AE: immunosuppression, infection
other: blood dyscrasia and malignancy
CI: vaccine
acetaminophen
NSAID
NO anti-inflammatory effect
NOT used for arthritis
AE: GI in IV use, renal rarely, HEPATIC
aspirin
NSAID
irreversibly acetylates COX
platelet does not have a nucleus and cannot regenerate COX-1
MI prophylaxis
AE: hepatic (Reye’s: flu), salicylate poisoning
monitor: serum salicylate
diclofenac
NSAID
short acting
low GI risk
AE: high dose: vascular event
ibuprofen
NSAID
COX inhibitor
AE: high risk GI, high dose: vascular event
indomethacin
NSAID
AE: most adverse effects of all NSAIDs
ketoprofen
NSAID
short acting
ketorolac
NSAID
COX-1 inhibitor
naproxen
NSAID
AE: high risk GI
*NO CV risk increase even with high dose
piroxicam
NSAID
LONG ACTING
sulindac
NSAID
AE: HEPATIC (hypersensitive)
celecoxib
NSAID
selective COX-2 inhibitor
low GI risk
AE: vascular event
methotrexate
DMARD (non-biological)
DHFR inhibitor, adenosine inhibition
polyglutamation to remain intracellular
AE: bleeding, opportunistic infections, malignant lymphoma, GI, fatal dermatologic rxns, PULMONARY, TERATOGEN
CI: liver problems, alcoholic, renal failure, vaccinations (suboptimal), pregnancy, breast feeding
monitor: LFT, serum uric acid, serum creatinine/BUN
hydroxychloroquine
DMARD (non-biological) intracellular vacuole alkalization (need acidic for assembly of MHC) AE: blood dycrasias, CNS, EYE CI: liver, alcoholism, EYE Tx: malaria, RA, SLE monitor: OPHTHALMOLOGIC exam
leflunomide
DMARD (non-biological)
inhibits dihydroorotate dehydrogenase: inhibits pyrimidine synthesis
urocosic effect
AE: LFT, TERATOGEN
CI: immune suppression, infection
monitor: LFT, pregnancy test, electrolytes
sulfasalazine
DMARD (non-biological)
metabolized by colon bacteria to mesalamine that inhibits PG and LT produciton
acetylated
CI: renal, hypersensitivity to salicylate or sulfonamide
monitor: LFT, serum creatinine/BUN, urinalysis
betamethasone
DMARD
POTENT
long T1/2: poor solubility
corticosteroid
cortisone
DMARD
corticosteroid
dexamethasone
DMARD
POTENT
long t1/2: poor solubility
corticosteroid
hydrocortisone
DMARD
low potency
SHORT t1/2
corticosteroid
methylprednisolone
DMARD
corticosteroid
prednisolone
DMARD
corticosteroid
prednisone
DMARD
corticosteroid
triamcinolone
DMARD
corticosteroid
abatacept
CTLA4
binds CD80/86 to prevent T-cell co-stimulatory signal engaging with CD28
AE: maltose complicates blood glucose test
adalimumab
TNFa mAb
anakinra
IL-1 antagonist
AE: blood dycrasias
certolizumab
TNFa mAb
AE lacking?: CV
AE: blood dycrasias
etanercept
TNFa inhibitor: false TNF receptor
AE lacking?: CV
Postlewaite uses this TNFa inhibitor before others: variable suppression so less infection
golimumab
TNFa mAb
AE lacking?: lupus like syndrome
AE: LFT
infliximab
TNFa mAb
CI: HEART FAILURE
AE: LFT
apremilast
oral
PDE4 inhibitor
CYP substrate
Pgp
Tx: psoriatic arthritis and plaque psoriasis
AE: WEIGHT LOSS, depression, suicide ideation
rituximab
CD20 mAb (B cell)
need CONTRACEPTION (up to 4-6 mo. after ending)
AE: Steven-Johnson syndrome, epidermal necrolysis, CV, blood dycrasias
CI: PREGNANCY
tocilizumab
IL-6 mAb
AE: blood dycrasias
monitor: LFT, serum lipids
PGE2
activation of inflammatory cells
cytoprotective
mucus secretion, bicarb release, initiation of repair
How do COX-2 selective inhibitors differ from traditional NSAIDs?
inhibit prostacyclin without thromboxane inhibition: pro-thrombotic state
NO: GI toxicity, platelet inhibition, increase bleeding time, normal urinary TXA2 metabolites
How do NSAIDs damage the gastric mucosa?
direct chemical irritation and inhibition of PGE2
causes: ulceration and gastric bleeds
risk factors for adverse GI events with NSAIDs
- prolonged use, max dose
- age, male
- GI Hx
- comorbidity: CV, HTN, diabetes, hepatic, renal
- alcohol, smoking
- use of aspirin, warfarin, oral corticosteroids, SSRIs, venlafaxine, duloxetine
ways to reduce GI toxicity of NSAIDs
- enteric coating
- FDA says: milk/ food
Sweatman says: empty stomach to reduce doses - PG analog (misoprostol)
- H2 antagonist
- PPI (BEST)
COX-1
platelet
TXA2 production
prothrombotic
COX-2
endothelial
PGI2 (prostacyclin) production
antithrombotic
How can NSAIDs cause RENAL toxicity?
PGI2 and E2 are released in abnormal conditions and maintain renal blood flow and GFR
inhibition of PGs can damage kidney
Sx: hematuria, pyuria, white cell casts, proteinuria, etc.
salicylate poisoning
ASPIRIN overdose
stimulate medullary respiratory system: hyperventilation
RESPIRATORY ALKALOSIS
uncoupling of oxidative phosphorylation: METABOLIC ACIDOSIS
cerebral and pulmonary edema, CV collapse
sign: RINGING of EARS
prolonged prothrombin time
Tx for RA
What if this Tx fails?
early aggressive therapy
- DMARD: methotrexate (or hydroxychoroquine: less AE)
- addition: NSAID and corticosteroid
- failure with traditional approach: biological as mono therapy or with methotrexate
How does adenosine inhibition help in RA?
METHOTREXATE
inhibits lymphocyte proliferation and suppresses IL-1, IFN-y and TNF
increase IL-4
corticosteroids
inhibit: Nf-kb, AP-1, NF-AT: reduced TNFa, IL-1, IL-6
upregulate: RANKL, M-CSF
Src inhibition; intercalate plasma and mitochondrial membrane
Tx: RA
AE: osteoporosis, cushingoid, diabetes, obesity, lipid profile
(reduce with localized injection depot), hyperglycemia, weight gain
monitor: osteoporosis, fasting blood sugar levels, glaucoma risk, ankle edema
TNFa inhibitors AE
malignancy
lupus-like syndrome
CV: CHF, hypotension, angina, dysrhythmia
Drugs with AE of blood dyscrasias
anakinra certolizumab rituximab tocilimumab non-biologic DMARDs
Drugs need to monitor LFT
golimumab
infliximab
tocilimumab
Drugs self-administered SC
injection site rotation abatacept adalimumab anakinra certolizumab etanercept golimumab
