Nonselective COX inhibitors

Question 1

Phenylacetic acid derivative
Half life of 1.1 h ; <1% excreted unchanged in urine

Adverse effect : GI disturbance, occult GI bleeding, gastric ulceration
>150mg/dl = impaired renal blood flow and dec. GFR
Elevated serum AST/ALT

Answer 1

Diclofenac

Question 2

Phenylpropionic acid
Dose of 2400mg daily and half life of 2h
*effective in closing PDA in preterm infants

Use with aspirin dec. its anti inflamm effect

Contraindicated in px with nasal polyps, angioedema, and bronchospastic reactivity

Antagonize the irreversible platelet inhibition caused by aspirin

Rare hematologic effect : agranulocytosis and aplastic anemia

Answer 2

Ibuprofen

Question 3

Inhibit phospholipase A and C
Reduce neutrophil migration
Decrease T and B cell proliferation

Half life of 4-5h

*Probenecid prolongs the half life by inhibiting both renal and biliary clearance

Indicated for GOUT and ANKYLOSING SPONDYLITIS

Also for treatment of PDA and gingival inflamm

Adverse effects 
    Headache
    Thrombocytopenia and aplastic anemia
    Hyperkalemia (due to dec. PG in kidneys)
    Renal papillary necrosis

Answer 3

Indomethacin

Question 4

Propionic acid that inhibits BOTH COX(nonselectively) AND LOX

Half life of 1.8 h

*Probenecid prolongs its half life

Adverse effect on GIT and CNS

Answer 4

Ketoprofen

Question 5

Mainly used as analgesic not as anti iflamm
Effective analgesic if given thru IM, IV, or oral
*may decrease opiod requirement by 25-50%
Used for opthalmic preparation for ocular imflamm conditions

Answer 5

Ketorolac

Question 6

Inhibit both COX and phospholipase A2

Half life of 3h

Answer 6

Meclofemate and Mefenamic

Question 7

*only NSAID that is marketed as a single enantiomer

Half life of 14h

Free fraction higher in women

Albumin binding very high in both sexes

Rare cases of allergic pneumonitis

Answer 7

Naproxen

Question 8

Oxicam

High conc. inhibits PMN migration, decrease oxygen radical formation, and innibits lymphocyte function

Long half life : 57h

Adverse : GI disturbance, dizziness, tinnitus
*>20mg/dl = inc. risk for peptic ulcers

Risk 9.5 times higher than other NSAIDS

Answer 8

Piroxicam

Question 9

Sulfoxide prodrug

Excreted in bile and reabsorbed in intestine

Half life of 8h

Enterohepatic cycling prolongs the duration of action to 12-16h

Suppress intestinal familial polyposis

Inhibit devt of colon, breast, prostate cancer

Answer 9

Sulindac

Question 10

*only nonacid NSAID in current use

Half life of 26h (OD dose)

Do not enter enterohepatic circulation

Renal impairment doubles its half life and 30% inc. area under the curve

Adverse : pseudoporphyria and photosensitivity

Answer 10

Nabumetone

Question 11

Propionic acid derivative

Very long half life (50-60h)

Do not enter enterohepatic circulation

Mildly uricosuric

Answer 11

Oxaprozin

Question 12

Similar to oxicam

Long half life (72h)

Answer 12

Tenoxicam

Question 13

Nonselective

Short half life (1-2h)

*ineffective for treating gout

May cause thrombocytopenic purpura

Answer 13

Tolmetin

Question 14

From salicylic acid

Half life of 13h

500-1000mg daily (divided to 2 doses)

*effective for cancer pain from bone metastases

Limited to px with renal impairment

Answer 14

Diflunisal

Question 15

Racemic acetic acid derivative

Half life of 6.5h

COX2:COX1 activity ratio of about 10

200-400 TID

Transient impairment of renal function

Answer 15

Etodolac

Question 16

Propionic acid derivative

Half life of 2.5h

*associated with interstitial nephritis

Answer 16

Fenoprofen

Question 17

Propionic acid dereivative

Affect TNF-A and NO synthesis

Extensive hepatic metabolism

Associated with cogwheel rigidity, ataxia, tremor, myoclonus

Answer 17

Flurbiprofen

Question 18

Racemic propionic acid rerivative
Does not undergo stereoconversion

Short half life (1-2h) but inc. of 2-4 h in elderly

Inhibits renal uric acid reabsorption

Answer 18

Tiaprofen

Question 19

Pyrazolone derivative

Very toxic, rarely used

Answer 19

Phenylbutazone