Salicyclic Acid Derivative

MOA: Irreversible inhibition of COX-1 & COX-2

Aspirin is widely distributed to most tissues and can cross both placental and blood brain barrier

Uses: (1) Anti-inflammatory by irreversibly inactivating COX-1 (2) Prolongs bleeding time by inhibiting COX enzyme in platelets, which blocks formation of thomboxane A₂ and thus platelet aggregation

Dosage required for tinnitus is also dosage required for anti-inflammatory effect, indicated adequate serum levels

Toxicity: GI, Hepatic, Hypersensitivity, Reye's Syndrome, Salicylism (chronic salicylate intoxication), tinnitus

Reye's Syndrome associated with Varicella or Influenza and administration of aspirin

Aspirin Triad = Aspirin senstivity, asthma, and nasal polyps

ASA during pregnancy is contraindicated; low doses can treat preeclampsia; nursing mothers can affect platelet function in child

Salicuclic Acid Derivative

Difluorophenyl derivative of salicylic acid

Not a true salicylate

Use: Analgesic and Antiinflammatory effects, little antipyretic effect

MOA: REVERSIBLE inhibition of COX-1 and COX-2

Toxicity: (1) Mild GI (less than ASA) (2) Headache (3) Renal (4) Hypersensitivity

T1/2 is 8-12 hours (much longer than ASA!)

Acetic Acid Derivative

Methylated indol derivative

Use: Rheumatoid Arthritis (NOT JUVENILE!), Osetoarthritis, tocolytic agent

MOA: REVERSIBLE inhibition of COX-1 and COX-2

Toxicity: (1) Severe GI (2) Gestation prolongation (3) Renal (4) CNS - Headache and aggrevate depression

DO NOT GIVE TO CHILDREN

Acetic Acid Derivative

Use: Rheumatoid arthritis, Osteoarthritis, postoperative analgesia

MOA: REVERSIBLE inhibition of COX-1 and COX-2, BUT

MORE COX-2 SELECTIVITY

Toxicity: GI, less severe than indomethacin

Acetic Acid Derivative

Use: Rheumatoid arthritis, Osteoarthritis, analgesia/dysmenorrhea

MOA: REVERSIBLE inhibition of COX-1 and COX-2

Toxicity: GI, CNS (dizziness and headache)

Acetic Acid Derivative

Use: Juvenile Rheumatoid Arthritis (and regular RA), osteoarthritis

MOA: REVERSIBLE inhibition of COX-1 and COX-2

Toxicity: GI, CNS (headache), Anaphylactoid reactions concerning

Short t1/2 (1.5 hrs)

Can cause autoimmune hemolytic anemia

Acetic Acid Derivative

Use: Moderately severe, acute pain (notice not used for RA)

MOA: REVERSIBLE inhibition of COX-1 and COX-2

Toxicity: GI, CNS (headache)

Propionic Acid Derivatives

Use: RA & Osteoarthritis, Analgesia, Dysmenorrhea, Fever

MOA: Reversible inhibition of COX-1 and COX-2

Toxicity: (1) Less GI than aspirin or indomethacin (2) Ocular disturbances (3) Hypersensitivity (rash/dermatitis) (4) Avoid during pregnancy or breastfeeding

Propionic Acid Derivatives

Use: Juvenile RA, RA, Osteoarthritis, Analgesia, Dysmenorhea

MOA: Reversible inhibition of COX-1 and COX-2

Toxicity: (1) GI greater than indomethacin (2) CNS: headache greater than indomethacin (3) Hypersensitivity

Propionic Acid Derivatives

 Use: RA, Osteoarthritis, Analgesia, Dysmenorrhea

Toxicity

MOA: Reversible inhibition of COX-1 and COX-2

Toxicity: (1) GI: 30% of patients (2) CNS: headache

Propionic Acid Derivative

Use: RA & osteoarthritis

MOA: Reversible inhibition of COX-1 and COX-2 (taken as once-daily)

Toxicity: GI

Oxicam

LONG T1/2 (30-86 hrs)

Oxicam

NOT used for rheumatoid arthritis

COX-2 Inhibitor

Use: RA, Osteoarthritis, Dysmenorrhea, Acute Pain, Familial Adenomatous Polyposis

MOA: Inhibition of COX-2 (emphasize does NOT inhibit COX-1 - reduced risk for GI ulcers)

Toxicity: Minor disturbances in GI, CNS, respiratory, rash, and sulfonamide allergy (don't give to pts who are also allergic to sulfonamides)

Use: Antipyretic and analgesic, osteoarthritis for relief of pain

MOA: Analgesia by elevation of pain threshold by weak inhibition of COX-1 and COX-2; Antipyresis by action on hypothalamic heat-regulating center

Inhibits prostaglandins mainly in CNS (not periphery)

Metabolized in liver by CYP450 to produce NAPBQ (highly toxic) which is normally inactivated by glutathione, however high amounts can saturate this system and cause hepatotoxicity

N-Acetylcystein (Mucomyst) is the antidote for acetaminophen toxicity