NSAIDs and DMARDs Flashcards
NSAIDs? DMARDs?
nonsteroidal anti inflammatory drugs
disease modifying antiherumatic drugs
NSAIDs use?
analgesic, antipyretic, anti-inflammatory
risk reduction for reinarction and stroke
closure of patent DA in neonates
treat biochemical degredation of Bartter’s syndrome
Chemoprevention of certain cancers such as colon cancer
NSAIDs all inhibit?
COX
inhibit prostaglandin synthesis largely responsible for therapeutic effect
no affect course of disease, just symptomatic relief
General side effect?
GI, Renal, CV, CNS
Cyclooxygenase forms?
COX1 COX2
COX-1?
constitutively expressed in most cells/tissues
important for normal homeostasis
COX-2?
mostly inducible
proinflammatory and mitogenic function
PGs in inflammatory sites (synociocytes, macrophages)
prevent proinflammatory cascade
Do you get platelet effect with COX-2?
no only COX-1
Joint inflammation from?
COX-2
Kidney damage?
both COX-1 and 2
inhibitors of both cause kidney damage
Nonselective inhibitors?
drugs tend to cause GI toxic, COX-1 inhibition
COX 2 selective?
better GI safety profile
Inhibition of PG synthesis impt in those?
who have stimulated PG synthesis
- renal disease
- Effective volume depletion
NSAIDs and renal function?
Acute renal failure -PGs normally oppose vasoconstriction, without goes unopposed Hyperkalemia Edema and Hyponatremia Increase BP
Acetylsalicylic acid?
ASA, aspirin
nonselective, irrverisble COX inhibitor
Non-acetlyated salicylates?
all else (but aspirin) non selective COX inhibitors reversible
Low dose aspirin?
cause antithromotic effects (anitplatelet)
High dose aspirin?
cause antiinflammatory effects
limited by toxicity
(interfere with uric acid elim and aggravate control of gout)
Salicylates Adverse effects?
GI toxic
increased bleeding time
renal toxic
liver toxic
Acute mild toxicity?
tinnitus (common)
headache, dizziness, drowsiness, mental confusion, sweating, nausea/vomit
Acid base abnormalities?
direct stim respiratory center
cause fall in CO2, respiratory alkalosis
componsated renal alkalosis
anion gap metabolic acidosis can follow
Acid/base in severe intox?
decrease respiration
respiratory acidosis
Aspirin toxicity treatment?
Decontaminate (activated charcoal, gastic levage) volume resuscitation suplemental glucose alkalization hemodialysis
Reyes syndrome?
high incidence with aspirin use in children with viral illness
avoid aspirin, use acetaminophen instead
Non-salicylate nsaids?
nonselective cox blockers
reversible inhibit
reversible inhibit of platelet aggegation
Antiinflammtory effects?
not immediate (after steady state, 5 half lives)
decrease capillary permeable, decrease lysosomal enzyme release, decrease release of mediators from PMN
Adverse effects Non-salicylate nsaids?
GI toxic- ulcers, bleeding
Misoprostol and NSAIDs?
in combo for patients at high risk for GI toxicity
M- PGE analog, decrease gastric acid, stim bicarb and mucus production
Also decrease GI toxic with NSAIDs?
proton pump inhibitors
need acid and pepsin to develop ulcer/lesion, decreased acid is protective
Nephrotoxicity with Non-salicylate nsaids?
some degree of
acute renal failure
analgesic nephropathy
Indomethacin?
most toxic NSAIDs
not treat fever
gout, RA, other inflammation
DA in newborns
similar AE and Contra as others
Ibuprofen (motrin)?
low cost, low tox
use in RA (limited, 4x day dosing)
AEs less than aspirin
may negate aspirins cardioprotective effects by antagonizing aspirins irreversible platelet inhibition
Naproxen?
most frequent prescribed
half life allow 2x day dosing
Ketorolac?
analgesic not antiinflam
mod to severe pain, short term (ulcers, silent bleed)
COX 2 inhibitors?
induced in peripheral tissues by noxious simuli that cause inflammation and pain
have better GI safety profile
no safer to GI than nonselective
Celecoxib?
celebrex
increased incidence of MIs
may be useful in treatment of certain tumors that express COX-2
Acetaminophen?
not an nsaid
inhibits COX-2
no significant antiinflammatory effects
analgesic, antipyretic effects
Use acetaminophen?
pain and fever relief
when aspirin cant be used
-children, patients on anticoagulants, gouty patients on uricosurics
Adverse reactions acetaminophen?
dose dependent hepatic necrosis
usually in acute overdose
Prevent severe hepatic necrosis with aceta?
NAC (N-acteylcystine) given within 24 hrs can protect the liver too
Predict toxicity with acteminophen?
Rumack-Matthew Nomogram
DMARDs?
more toxic than NSAIDs
slow progress of RA
MOA not well defined
DMARD use for RA?
can slow progress if introduced early
Methotrexate?
gold standard for RA treatment
initial drug for RA
anti-RA effects begin within 6 wks
lower dose than chemo treatment, still get some side effects
Hydroxychloroquine?
antimalarial drug
MOA unclear
early, mild RA without poor prognostic features
can take 2-3 months to see improvement
Hydroxychloroquine side effects?
GI upset
skin changes
-hyperpigmentation
Sulfasalazine?
antiinflammtory agetn
MOA unclear
prefer over hydrox in pts with more symptoms and signs of actuve synovitis
clin improvement with 1-2 months
Leflunomide?
option for nonresponsive or who cannot tolerate MTX
inhibit de novo synthesis pyrimidine synthesis
adverse effects-
-hypertension, hepatotoxicity
Gold Salts?
MOA unclear
effective in early rapid stages of RA, short term
Gold salts adverse?
toxic
less with oral but not as effective
-dermatitis, hematological abnormalities, nephrotoxicity
Penicillamine?
if gold doesnt work chelating agent (copper poison, Wilson's disease) MOA unclear decrease bone destruction in RA
Adverse Penicillamine?
more frequent than gold
severe side effects limit use
-GI, agranulocytosis, nephrotoxicity, allergy
Biological DMARDs?
generally alter TNFalpha activity
Etanercept?
form of recombinant TNFalpha receptor fake receptor response may occur in a couple of wks como with methotrexate, no increase in tox less frequent occur SE rash at injection site
Infliximab?
monoclonal antibody to TNFalpha bind and neutralize free TNFalpha adverse effects risk of infection hypersentivity SLE like syndrome
Bio modifiers adverse?
Heart failure and TNF inhibitors
Cancer risk-lymphoma and others
TB, invasive infection
Anakinra?
IL-1 receptor antagonist
block inflammatory and immunologic rxn of IL-1 in RA
adverse effects
-pain,inflammation, erythema at injection
increased risk of infection
Use combo of biological modifiers?
no increase risk of infection
