Nsaids

Front 1

Three major components of acute responses

Back 1

1) Change in vascular caliber
2) Change in microvasculature (gaps allow plasma proteins/leukocytes to leave circulation)
3) Emigration of leukocytes out of microcirculation and accumulation at focus of injury

Front 2

Inflammatory Mediators

Back 2

1) Arachidonic acid metabolites (COX products, lipoxygenase products)
2) Cytokines
3) Vasoactive amines
4) Others (bradykinin, plasma proteases, clotting factors, PAF, nitric oxide)

Front 3

Points of Intervention

Back 3

1) Production of mediators
2) Action of mediators
3) Adhesion molecules

Front 4

Arachadonic acid metabolism

Back 4

1) Leukotrienes
2) Prostaglandins and thromboxane
3) These lipid mediators are:
a) synthesized de novo
b) released rapidly
c) labile

Front 5

PGH synthase

Back 5

An enzyme comprising both COX and peroxidase activity

Front 6

Compare and contrast COX-1 and COX-2

Back 6

1) COX-1 is constitutively expressed
2) COX-2 is inducible and is considered to be more important than COX-1 in inflam responses and assoc fever and pain.
3) Both convert AA to PGG2
4) Different aa sequence, products of different genes
5) Different functions

Front 7

NSAID: Mechanism of Action

Back 7

1) Inhibition of COX w/ consequent reduction in synthesis of PGs
2) direct effects on inflam cells
3) changes in gene expression (inhibition of transcription factor, NF-kappa B)

Front 8

Therapeutic uses: Fever

Back 8

1) Affect body temp incr due to inflam, tissue damage or dz
2) Mech of antipyresis
fever results from resetting the temp reg. center in the hypothalamic region of the brain

Front 9

Therapeutic uses: Pain

Back 9

1) mild to moderate pain
2) Mech of analgesia
a) physiological concentrations of PGs do not produce pain
b) PGs at site of inflam increase sensitivity of peripheral sensory nerve endings to algesic stimuli
c) Inhibition of PG synthesis returns nociceptors to normal sensitivity

Front 10

NSAIDS vs. opioids

Back 10

NSAIDS do not cause respiratory depression or tolerance or physical dependence, no sedation.

Front 11

Therapeutic uses: Inflammation

Back 11

1) Arthritis
2) Pain from inflammation

Front 12

Pharmacokinetics

Back 12

1) Absorption, distribution
a) well absorbed in GI
b) highly bound to plasma protein
2) Metabolism, Excretion
a) species differences in clearance rates
b) largely cleared via hepatic metabolism and urinary excretion of conjugates
c) some undergo enterohepatic circulation

Front 13

Potential adverse side effects

Back 13

1) Gastric or intestinal irritation
2) Increased bleeding time
3) Prolonged gestation
4) Renal injury/failure

Front 14

Mechanism of Gastric/Intestinal Irritation

Back 14

a) Decreased synthesis of cytoprotective PGs

Prevent by:
1) coadministration of a PGE analog (misoprostol)
2) selective blockade of COX-2

Front 15

Treatment of NSAID poisoning

Back 15

1) removal of drug from stomach w/ emetic or gastric lavage
2) correction of dehydration
3) correction of acid-base balance
4) forced diuresis