NSAIDs (8-26-15)

Question 1

Aspirin (Bayer)

Answer 1

• Indication: simple fever, anti-inflammatory, analgesic, Rheumatoid Arthritis…
• MOA: IRREVERSIBLE COX-1 inhibitor; acetylates COX-2 but active site is very large
• PK: can be zero-order kinetics at increasing doses! (highest doses used for anti-inflammation)
• Toxicity/side-effects: in pregnancy–delayed onset of labor, early closing of ductus arteriosus in fetus!
• Contraindications: Pt hx of: GI ulcers, bleeding disorders or on anti-coagulants, renal disorders, hypersensitivity to any NSAIDs, pregnant patients, elderly patients; NO aspirin for children due to RISK of REYE’S SYNDROME. Note that in 20% of people aspirin can cause serious airway hypersensitivity and an asthma attack!! No salicylates for gout patients.
• Comparisons: “baby aspirin” dose (81 mg) given for prophylaxis
• Aspirin/salicyclate OD: metabolic acidosis, dehydration, hyperthermia, seizures, cerebral edema, coma and death.

Question 2

Salicylates (Oil of wintergreen, salsalate, diflunisal)

Answer 2

• Indication: better than aspirin for pts w/GI complications or bleeding (hemophiliacs)
• MOA: COX1/COX2 inhibitor (not irreversible, only aspirin is–everyone else=reversible!)
• Toxicity/side-effects: WORSENS GOUT PATIENTS due to decreased uric acid elimination
• Contraindications: Pt hx of: GI ulcers, bleeding disorders or on anti-coagulants, renal disorders, hypersensitivity to any NSAIDs, pregnant patients, elderly patients; NO aspirin for children due to RISK of REYE’S SYNDROME. Note that in 20% of people aspirin can cause serious airway hypersensitivity and an asthma attack!! No salicylates for gout patients.
• Comparisons: DIFLUSINAL cannot be used for FEVER (doesn’t cross BBB!)
• Note: not acetylated, do not irreversibly inhibit COX-1 like aspirin, all salicylates except diflusinal cross BBB & placenta!

Question 3

Ibuprofen

Answer 3

• Indication: fever/acute pain
• MOA: traditional NSAID (-COX)
• PK: rapid onset of action 15-30 min
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)
• Comparisons: equipotent w/aspirin
• Note: traditionals all have liver metabolism & kidney excretion

Question 4

Naproxen

Answer 4

• Indication: fever
• MOA: traditional NSAID (-COX)
• PK: THIRD longest 1/2 life 14 hrs, rapid onset 60 min
• Toxicity/side-effects: one of the safest NSAIDs, see LESS GI bleeding
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)
• Comparisons: 20x more potent than aspirin
• Note: Long t 1/2 allow for 2x daily dose!

Question 5

Celecoxib (‘Coxibs)

Answer 5

• Indication: RA & Osteoarthritis; inflammation in pts w/GI bleeding
• MOA: selective COX-2 inhibitor
• Toxicity/side-effects: note COX-2 is constitutively expressed in endothelium, may explain CV effects
• Contraindications: PATIENTS w/ CVD risk; renal patients (COX-2 constitutive in kidney)
• Comparisons: do not present w/ COX-1 associated side effects like GI bleeds or platelet effects
• Note: celecoxib does NOT screw up the good effects of low-dose aspirin!

Question 6

Acetominophen (Tylenol, Paracetamol)

Answer 6

• Indication: mild to moderate pain NOT from inflammation; analgesia/anti-pyretic in kids or in those with GI bleeds or hemophilia
• MOA: non-NSAID analgesic/anti-pyretic; does not inhibit COX 1 or COX 2 in the periphery
• PK: Well absorbed orally, metabolized in the liver
• Toxicity/side-effects: FATAL (over 15g ingested) as result of HEPATOTOXICITY b/c of metabolite NAPQI; slow death in 4-7 days
• Contraindications: DO NOT TAKE WITH ALCOHOL–>risk of serious liver damage
• Comparisons: Not an NSAID; no anti-inflammatory actions; no anti-platelet actions; works mainly in the CNS
• Note: treat overdose with n-acetyl cysteine (replaces glutathione levels, which stops NAPQI formation)

Question 7

Indomethacin

Answer 7

• Indication: anti-inflammatory (10-40x better than aspirin); also used to close PDA in babies and slow labor
• MOA: traditional NSAID (-COX)
• Toxicity/side-effects: not tolerated as well as ibuprofen–toxicity limits use
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)

*Note: 50% of users have side effects (CNS-dizziness, anxiety, confuse)

Question 8

Diclofenac*

Answer 8

• Indication: more potent anti-inflammatory than indomethacin or naproxen
• MOA: traditional NSAID (-COX)
• Toxicity/side-effects: increased heart/stroke risk similar to vioxx (rofecoxib)
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)
• Comparisons: relatively COX-2 selective
• Note: *Traditional NSAID problem children….yikes!!

Question 9

Ketorolac

Answer 9

• Indication: IV for post-surgical pain; weak anti-inflammatory, is mainly for pain
• MOA: traditional NSAID (-COX)
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)

*Comparisons: can be used to replace opioids, like morphine

Question 10

Oxaprozin

Answer 10

• Indication: Gout
• MOA: traditional NSAID (-COX)
• PK: slow onset (6 hrs); LONGEST t 1/2 50-60 hrs
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)
• Comparisons: increases uric acid excretion!
• Note: HUGE t 1/2 allows for 1x daily dose or even less

Question 11

Meloxicam*

Answer 11

• Indication: osteoarthritis (OA) and rheumatoid arthritis (RA)
• MOA: traditional NSAID (-COX)
• Toxicity/side-effects: increased heart/stroke risk
• Contraindications: all traditionals share general contraindications–pt history of GI ulcers, bleeding disorders, on anti-coagulants, taking other protein-binding drugs, renal disorders (normal patients should not have renal problems!), hypersensitivity (watch asthmatics too); elderly patients (susceptible to GI bleeds and already have decreased renal function)
• Comparisons: relatively COX-2 selective
• Note: *Traditional NSAID problem children….yikes!!