NSAID's Flashcards
(28 cards)
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
