Antiinflammatory Drugs

Front 1

clinical uses of glucocorticoids (4)

Back 1

-replacement therapy in adrenal insufficiency
-tx of chronic inflammatory dz(RA)
-tx of allergic rxn
-immunosuppression: prevention of graft rejection

Front 2

ADR of glucocorticoids:
1. muscoloskeletal
2. GI
3. eye
4. endocrine

Back 2

1.osteoporosis
2.peptic ulceration, gastric bleeding
3.cataracts
4. suppression of the hypothalamic-pituitary-adrenal axis

Front 3

two isozyme forms of cyclooxygenase

Back 3

COX1 and COX2

Front 4

major PG involved and sythesized by both COX1 and COX2

Back 4

PGE2

Front 5

cyclooxygenase activity during acute and chronic inflammation

Back 5

PGE2 produced by COX2 produces pain and vasodialtion

Front 6

cyclooxygenase activity in the gastric mucosa

Back 6

PGE2 produced by COX1

Front 7

cyclooxygenase activity in platelets

Back 7

COX1 stimulates TXA2-induced platelet aggregation

Front 8

cyclooxygenase activity in the renal cortex

Back 8

COX1 and COX2 present, but COX1 predominates/
COX2 activity also needed for normal renal fx

Front 9

PGE2 and PGI2 produced in kidney do what?

Back 9

-cause renal vasodialtion
-maintain renal perfusion

Front 10

effects of nonselective NSAIDS

Back 10

-antiinflammatory, analgesia,antipyretic, decrease gastric mucosal protection/increase risk of ulceration
-decrease renal perfusion
-decrease platelet aggregation and increase bleeding tendency

Front 11

MOA of nonselective NSAIDs

Back 11

-inhibit COX1,COX2, and thromboxane synthesis

Front 12

advantage of COX2 over COX1 inhibitors?

Back 12

-decreased GI toxicity
-others have not been proven such as decreased risk of GI ulceration, renal toxicity,and bleeding
-idea that COX2 only produced during tissue injury and inflammation too simplistic

Front 13

COX inhibitors and risk of heart disease or stroke

Back 13

-not as decreased as it is with ASA
-COX1 can induce platelet aggregation since TXA2 is formed only through COX1 and PGI2 formed only through COX2

Front 14

therapeutic effects of NSAIDs

Back 14

antiinflammatory, analgesic, antipyretic, antiplatelet, relife of dysmenorhea

Front 15

NSAID GI ADR

Back 15

-loss of cytoprotective function of PGs results in irritation, gastritis, PUD, and bleeding

Front 16

NSAID hematologic ADR

Back 16

-inhibit cyclooxygenase to decrease thromboxane production, decrease platelet aggregation, and increase bleeding time
-ASA causes IRREVERSIBLE inactivation of platelet cyclooxygenase

Front 17

NSAID renal ADR

Back 17

-cause decreased PG synthesis, decreased GFR, ischemia, acute renal failure, and salt/H2O retention
-renal insufficiency, sodium/water retension, and hyperkalemia

Front 18

NSAID ADR in elderly

Back 18

-CHF risk increases with increased dose
-use of selective COX2 inhibitor won't solve problem b/c COX2 is required for normal renal function

Front 19

ASA selectivity

Back 19

-nonselective
-irreversible inhibition of COX1 and COX2

Front 20

clinical uses of ASA

Back 20

-antiplatelet effect
-analgesic for mild/moderate pain
-antiinflammatory

Front 21

ADR/toxicity of ASA at arthritic doses

Back 21

-GI ulcers/bleeding
-salicylism
-direct action on respiratory center (resp. alkalosis and hyperventilation)

Front 22

ASA Exacerbated Respiratory Disease (AERD)
(AKA ASA sensitivity and ASA-induced asthma)

Back 22

triad of asthma, rhinitis with nasal polyps, and ASA insensitivity

Front 23

salicylism

Back 23

tinnitus, deafness, HA, confusion, increased pulse and respiratory rate

Front 24

ASA cross-reactivity

Back 24

NSAIDs which inhibit COX1 are cross reactive

Front 25

ASA-warfarin DI

Back 25

increased anticoagulant effect

Front 26

ASA-Ibuprofen DI

Back 26

-decreases or negates cardioprotective effects of ASA(not all nonselective NSAIDs do this)
-ASA and COX2 selective NSAIDs don't interact

Front 27

ASA-ETOH DI

Back 27

avoid ETOH (exacerbates bleeding)

Front 28

selectivity of nonacetyl salicylates

Back 28

nonselective/reversible COX1 and COX2

Front 29

there is lower incidence of ________with nonacetyl salicylates than with ASA

Back 29

GI toxicity and bleeding

Front 30

Diflunisal:
1. potency
2. antipyretic activity?
3.duration of action

Back 30

1.3-4x more potent than ASA as analgesic and antiinflammatory
2. none-does not cross BBB
3. longer acting than ASA

Front 31

Diflunisal

Back 31

nonacetyl salicylate

Front 32

1st generation NSAIDs are used mainly for?

Back 32

antiinflammatory effects as 1st line agents for relief of symptoms in chronic inflammatory disease states (RA, acute gout, acute ankylosing spondylitis)

Front 33

dosing considerations for 1st generation NSAIDs

Back 33

-avoid ETOH (exacerbates GI irritation and bleeding)
-cross sensitivity with ASA

Front 34

OTC Ibuprofen indicated for?

Back 34

-nonselective 1st gen. NSAID
-mild pain, fever, and dysmenorrhea

Front 35

Naproxen Dosing

Back 35

-BID dosing due to longer halflife

Front 36

OTC Naproxen indicated for?

Back 36

-nonselective 1st gen. NSAID
-mild to moderate pain/fever

Front 37

Indomethacin ADR
(nonselective 1st gen. NSAID)

Back 37

-GI bleeding/ulceration
-CNS:HA, vertigo, confusion
-blood dyscrasias: neutropenia, thrombocytopenia

Front 38

Piroxicam

Back 38

-nonselective 1st gen. NSAID
-"COX2 preferrential"
-taken once daily
-decreasedincidence of GI toxicity

Front 39

phenylbutazone:
potency and ADR (nonselective 1st gen. NSAID)

Back 39

-most potent and dangerous
-long term tx has caused fatal aplastic anemia

Front 40

Ketorlac(Toradol)

Back 40

-2nd generation NSAID
-approved for parenteral admin

Front 41

Acetaminophen

Back 41

-nonopioid, nonsteroidalanalgesic and antipyretic

Front 42

Acetaminophen vs ASA

Back 42

-effective alternative for analgesic/antipyretic effects, but much weaker antiinflammatory
-lacks antiinflammatory and antiplatelet effects

Front 43

In an effort to decrease liver toxicity associtated with acetaminophen, it is now considered a ____?

Back 43

narrow therapeutic index drug

Front 44

Acetaminophen ADR
-hepatic

Back 44

-depletion of glutathione allows toxic metabolites to accumulate resulting in hepatic necrosis, jaundice, bleeding, and encephalopathy

Front 45

Conditions that deplete glutathione

Back 45

-chronic high acetaminophen doses
-chronic ETOH consumption
-AIDS
-poor nutrition

Front 46

Acetaminophen ADR
-GI/Hematological

Back 46

much lower incidence than ASA of both

Front 47

Acetaminophen ADR
-hypersensitivity/anaphylaxis

Back 47

-4-6%pts with ASA hypersensitivity are also intolerant to acetaminophen
-anaphylaxis is very rare

Front 48

Acetaminophen DI

Back 48

-chronic ethanol ingestion can cause hepatic toxicity even with normal acetaminophen doses
-involves ETOH-induced induction of CYP2EI which is major isoenzyme involved in production of the toxic metabolite

Front 49

Labeling of OTC Acetaminophen must have warning about?

Back 49

possibility of liver damage when large amount of ethanol are consumed regularly

Front 50

Taking NSAIDs with food decreases direct GI irritation, but does not___?

Back 50

lessen risk of NSAID induced ulcer

Front 51

NSAIDs given parenterally do not decrease the risk of____?

Back 51

GI toxicity

Front 52

COX1 vs COX2 structure

Back 52

-both have long narrow tunnel with hairpin bend @end
-both are membrane associatedso arachidonic acidreleased adjacent to channel drawn in and converted to PG
-NSAIDs block channel halfway leaving pocket in COX2

Front 53

celecoxib (Celebrex)
-CV risk

Back 53

-increased risk of CV thrombotic events, MI, & stroke
-all NSAIDs have similar risk
-contraindicated for tx of perioperative pain in CABG

Front 54

celecoxib (Celebrex)
-GI risk

Back 54

-increased risk of serious GI adverse events
-elderly pts at greater risk for serious GI effects

Front 55

celecoxib (Celebrex)
-contraindications

Back 55

-pts with allergy to sulfonamides
-hx of asthma, uticaria, or allergic rxns after taking ASA or NSAIDs