NSAID's Flashcards
Molecular Inflammatory Mediators (3 Major groups)
Kinins (bradykinin) Neuropeptides (Substance P) and Vasoactive amines (histamine, 5HT)
Arachidonic acid metabolites - Cyclooxygenase, Prostaglandin, Thromboxanes
Prostacyclin
Lipoxins and leukotrienes
Cytokines (e.g., TNF-alpha), oxygen free radicals, and proteases
Two areas of relief of pain
site of injury
spinal cord
3 main functions of NSAID’s
Targets
Analgesia
Anti-pyretic
Anti-inflammatory
Primary target –> COX-1, COX-2
COX 1
constitutively active
widely distributed
HOUSEKEEPING FUNCTIONS
i.e. synthesis of PG in stomach mucosa
COX 2
INDUCIBLE
production of INFLAMMATORY molecules
vascular endothelium - PGI-2
Renal COX-2 - essential for normal function
What two prostaglandins are most prominent?
PGE-2
PGI-2
Two major pathways from arachidonic acid
Lipoxygenase - leukotrienes
Cyclooxygenase - prostaglandins, prostacyclins, thromboxanes
Two types of NSAID’s
COX-2 Specific
Non-specific
Aspirin and other PG synthesis inhibitors should be avoided in what clinical scenarios?
Viral illness
Children - Reye’s Syndrome
Aspirin dose dependent actions
kinetics for each
low dose - analgesic, anti-pyretic (first order kinetics)
high dose - anti-inflammatory (zero order kinetics)
Aspirin has potential for drug interactions due to what characteristic?
bound to plasma proteins
Acetylation of COX is _______
irreversible
Anti-inflammatory and analgesic effects due to inhibition of _____
COX-2
Anti-pyretic effects due to?
blockage of prostaglandin production in the CNS
resets temperature control at hypothalamus
fall in temp leads to dilation of superficial blood vessels
Anti-coagulant effects due to
IRREVERSIBLE INHIBITION OF COX-1
decreased thromboxane A-2
Main Adverse Effects of Aspirin
GI upset
GI Irritation - inhibition of protective PG’s synthesis
Platelet inhibition - prolonged bleeding time
Kidney function Hepatitis Hypersensitivity TINNITUS Reye's syndrome
Non-selective COX inhibitors
Aspirin Ibuprofen Indomethacin Ketorolac Naproxen Oxaprozin Piroxicam Sulindac
COX-2 Inhibitors have ______ adverse effects
Increased incidence of _______
less GI adverse effects
cardiovascular thrombotic events
COX-2 INhibitors (3)
Celecoxib
Etoricoxib
Meloxicam
Acetaminophen has ______
NO ANTI-INFLAMMATORY PROPERTIES
Acetaminophen safety
HEPATOTOXICITY at high doses
150 mg/kg liver necrosis
350 mg/kg liver failure
interactions with CYTOCHROME P450 2E1 substances
Capsaicin MOA
BINDS TO VANILLOID RECEPTOR (heat activated channels on nociceptor neurons
release of substance P
PROLONGED ACTIVATION DEPLETES SUBSTANCE P
NSAID Interactions
Displacement of protein binding - warfarin, phenytoin, steroids
Diuretics
Anticoagulatns
GI Effects
Gout due to
associated with?
deposits of uric acid crysals in joints and cartilage
hyperuricemia
First line treatment for acute gout
Indomethacin (has largely replaced colchicine)
other NSAID’s can be used
Aspirin NOT USED due to renal retention of uric acid at low dose
Colchicine MOA
INHIBITS LEUKOCYTE MIGRATION AND PHAGOCYTOSIS
through inhibition of microtubule aggregation
Xanthine Oxidase INhibitors (2)
Allopurinol
Febuxostat
Uricosuric Drugs
Probenicid
Sulfinpyrazone
