NSAIDs 1 - Overview - Slides 1-13

Question 1

What actions do NSAIDs have?

Answer 1

Anti-inflammatory
Analgesic
Antipyretic
Decrease prostaglandin synthesis by inhibition of cyclooxygenase

Question 2

What are the steps of inflammation?

Answer 2

Tissue insult occurs whether by trauma, chemical irritant, foreign protein, or infection

Histamine, serotonin, eicosanoid, and bradykinin are released locally

Prostaglandins and histamine cause capillary vasodilation

PG, LT, and histamine cause increased endothelial permeability

LT’s cause leukocyte migration into the inflamed tissue

PG’s and lysozymes are released from the leukocytes, cause tissue damage

Pain fibers are stimulated by PG’s, substance P, and bradykinin

PG’s and LT’s cause decreased firing threshold of pain fibers (increasing pain sensitization)

Question 3

How do NSAIDs work to block inflammation?

Answer 3

They inhibit PG and LT mediated vasomotor activity
Block permeability changes
Inhibit leukocyte migration
Inhibit lysozyme release from leukocytes

Question 4

How do NSAIDs work to reduce pain?

Answer 4

PG’s sensitize pain fibers (NSAIDs inhibit PG’s)
Pain from inflammation and tissue damage
Mild to moderate pain only

Question 5

How do NSAIDs work to reduce fever?

Answer 5

Fever is caused by endogenous and exogenous pyrogens
Endotoxins include lipopolysaccharides from gram - bacteria
IL-1, IL-6, interferon alpha, and TNF alpha are produced during inflammation

PGE2 formation in the hypothalamus causes the temperature point to reset (to a higher temp so body keeps self at a higher temp)
Blocking PG formation will prevent the temp point from resetting

Question 6

What determines duration of effect of an NSAID? Speed of effect?

Answer 6

Duration - whether it’s irreversible or reversible

Speed - competitive vs non-competitive

Question 7

Describe COX-1 vs COX-2. What about COX-3?

Answer 7

COX-1 is constitutive, meaning it is always expressed (in the blood vessels, stomach, and kidneys)

COX-2 is inducible for inflammation, but is also always found in blood vessels

COX-3 is a COX-1 variant found in the CNS, thought to be the target of APAP (bc APAP treats fever and pain but not inflammation)

Question 8

What are the therapeutic uses of NSAIDs?

Answer 8

Anticoagulant
Antipyretic
Analgesia
Anti-inflammatory
Colon cancer
Alzheimers
Close ductus arteriosus
Rheumatoid arthritis
Gout

Question 9

What are the common side effects of NSAIDs?

Answer 9

Gastric or intestinal ulceration (bc decreased mucus due to decreased PG synthesis)

Decreased platelet aggregation (bleeding due to decreased thromboxane)

Hypersensitivity reactions (rashes, anaphylaxis)

Prolonged gestation (delays spontaneous labor, can have adverse fetal effects by closing the ductus arteriosus)

ASTHMA, bronchospasm bc of increased Lipoxygenase activity (increasing leukotrienes/increasing bronchospasm)

Impaired hepatic function - increase in serum liver enzymes

Decreased renal function - PG’s involved in normal renal control mechanisms (PG’s control vasodilation of afferent arteriole)

Uncouples oxidative phosphorylation, respiratory alkalosis