Exam 2: Lecture 2, NSAIDs Flashcards
What is inflammation?
Protective response of the body to tissue injury
What can cause tissue injury?
Trauma, chemicals or microbiologic agents
inflammation may cause progressive tissue injury
Inflammation is the first step in….
a big number of pathophysiological processes
and
in a variety of immunological disorders
NSAID’s are…
Analgesic = mild/moderate pain
Antipyretic (fever reducer) in fever pt, little effect on normal people
Anti-inflammatory = arthritis, osteoarthritis, musculoskeletal disorders
NSAId’s used for self treatment for….
Headaches, Dental Pain, and Muscle Pain
NSAID common properties
weak organic acids (except nabumetone = keto prodrug)
Well absorbed
Highly metabolized phase I and II
Biliary excretion and reabsorption through the enterohepatic circulation
GI irritation correlate with the amount in enterohepatic circulation
After repeated doses, NSAIDs found in synovial fluid
NSAID’s primary mech of action
COX inhibition
act indirectly, don’t block PG receptors, no effect on previously formed PG’s
Cox-1
Found in many tissues, important under normal conditions
Cox-2
Found in inflammatory tissue, expressed during inflammation
Renal tissue - exception, found in normal tissue
Cox-1 vs Cox-2
Channel in Cox 2 wider than in Cox 1
some drugs can get into Cox 2, not Cox 1
How do NSAID’s block Cox?
Enter channel, and block it. (Except aspirin)
Bind to arginine via H-bonds
Cause reversible inhibition of Cox
How does aspirin work?
Acetylates the enzyme (Cox) at serine and causes irreversible inhibition of Cox
Which prostaglandins do NSAID’s suppress?
PGE2
PGD2
PGF2a
PGI
TXA2
Aspirin Clinical I
inhibit platelet aggregation
produces anticoagulant effect + prevent thrombosis
reduce inflammation
reduce pain via reduce PGE2 synthesis
Peripherally inhibit PGs in inflamed tissue
Aspirin Clinical II
Antipyretic effect mediated though the hypothalamus (CNS)
No effect on temp in healthy individuals, but effect with those that have fever (by reducing PGE2 synthesis)
Aspirin Absorption
Oral + stomach absorption = rapid
Upper portion of Small intestine = major site of absorption
Rectal = slow and unpredictable absorption
Aspirin Excretion
Alkalization of urine increases salicylates excretion
via increase ionization and decreased reabsorption in the renal tube.
Aspirin Effect on Blood I
decrease platelet aggregation
recommended in individual with 1 or more MIs
prevents incidence of first MI and Transient ischemic attacks
Aspirin Effect on Blood II
TXA2 synthesis in platelets reduced, recovers only when new platelets formed
takes 7 days to recover from single dose
increase bleeding time, shouldn’t be taken 1 week before surgery
Aspirin effect on Cardiovascular system
therapeutic dose = no effect
High dose = effect smooth muscle
Toxic dose = cause central vasomotor paralysis
Aspirin effect on Respiratory System
directly effects respiratory center
Toxic doses can depress respiratory center, cause metabolic acidosis
indirectly increases O2 consumption in skeletal muscle
Indirectly increases CO2 production in skeletal muscles
Aspirin effect on GI system
decrease PGE2/PGE2a = decrease mucus protection
Dose related gastric ulceration, bleeding, erosive gastritis
worsening of peptic ulcer, gastric bleeding leading to iron-deficiency
Epigrastic distress, nausea and vomiting by irritating mucosa lining
Stimulate CTZ in CNS
Should be taken with food + significant act water
Aspirin effects on Urinary System
determine effect on urinary system
Decreased PGI2 production = decrease kidney blood flow = increase Na/H20 retention = edema and hyperkalimia
may increase circulating plasma volume by 20%
Aspirin decrease inflammation by…
decreasing PGs, PGI2, and TXA2
