NSAIDS

  • Aspirin
  • Salicylic Acid
  • Indomethacin
  • Diclofenac
  • Sulindac
  • Tolmetin
  • Ibuprofen
  • Naproxen
  • Ketoprofen
  • Pranoprofen
  • Miroprofen
  • Phenylbutazone
  • Apazone
  • Piroxicam
  • Celecoxib
  • Acetaminophen
  • Chloroquine
  • Gold salts
  • Colchicine
  • Probenecid
  • Sulfinpyrazone
  • Allopurinol

Common Feature of All NSAIDS

1)     anti-inflammatory

2)     analgesic – effective against pain of low to moderate intensity

3)     anti-pyretic

4)     GI/intestinal ulceration: local irritation and inhibition of PGs

5)     Prolonged bleeding due to inhibition of thromboxane synthetase – TXA2

6)     Intolerance crosses over all NSAIDS

7)     Can be used in pregnancy but discontinue prior to partuition

Salicylates – Aspirin (ASA) and salicylic acid

  • used for analgesia, anitpyresis
  • uncouples oxidative phosphorylation which leads to increased O2 consumption
  • GI effects: ulceration, N&V at high doses
  • Hepatic and Renal: hepatotoxicity is dose dependent; Nephrotoxicity with acetaminophen + ASA
  • Reye’s syndrome
  • Prolongs bleeding time
  • See blood levels and correlating data on p. 103

Acetic Acids – Indomethacin, sulindac, tolmetin

  • Indomethacin is the most potent inhibitor of COX
  • Variable t1/2 because of enterohepatic cycling
  • Used to close ductus arteriosus
  • Drug interactions

Ø  Probenecid will raise the plasma concentration of indomethacin

Ø  Furosemide is antagonized by indomethacin

Ø  Thiazide diuretics effects on controlling HTN decreased

  • Toxic effects: GI ulcers of entire upper GI tract, headaches, dizziness, confusion, neutropenia, thrombocytopenia
  • Uses: Acute gout, pericarditis, acute flare up of RA, ankylosing spondylitis

Sulindac is prodrug converted to active form in the liver

Tolmetin is bound to p.p but has no interference with warfarin or oral hypoglycemic drugs

Propionic Acids – Ibuprofen, Naproxen, Ketoprofen, Pranoprofen, Miroprofen

  • better tolerated
  • used in RA and analgesia
  • Ibuprofen: high pp binding, rapid urine excretion
  • Naproxen – longer t1/2 than Ibuprofen (2x daily dosing possible)

Pyrazoles – phenylbutazone, apazone

  • not used as an analgesic or antipyretic due to toxicity (GI ulceration)
  • penetrates into synovial fluid
  • displaces other drugs from pp
  • use: Reiter’s syndrome, ankylosing spondylosis

Oxicams – piroxicam

  • absorption not affected by food
  • long t1/2: 45 h: due to enterohepatic cycling
  • single daily dose possible
  • Toxic effects: 11-45% of patients; low incidence of peptic ulcer

Celecoxib

  • Celecoxib is a selective COX-2 inhibitor
  • Analgesic, antipyretic, and antiinflammatory activity
  • No gastroduodenal ulcers
  • Uses: OA, RA patients with a history of ulcers
  • Contraindications: asthma, severe hepatic insufficiency, severe renal insufficiency, late pregnancy
  • Interactions: Lithium, ACE inhibitors, fluconazole, furosemide
  • Side effects: edema, not too much data yet

Non-opiate Analgesics – Acetaminophen

  • No anti-inflammatory activity
  • Unsure of mechanism of action
  • Indications: ASA poorly tolerated, blood abnormalities, HX of peptic ulcer

Slow acting anti-inflammatory agents – Chloroquine, hydroxychloroquine, Gold (auro)

Chloroquine

  • uses: RA and lupus, mild disease in patients not responding to NSAIDS

Gold Compounds

  • 2nd line drugs for RA
  • unknown mechanism
  • concentrates in synovium
  • Toxicity: toxic in 33% of patients, dermatitis, blood abnormalities, GI disturbances
  • CI: impaired liver or kidney; pregnancy

Drugs used in Gout – Colchicine, Probenecid, Sulfinpyrazone, Allopurinol

Colchicine

  • relieves the pain and inflammation; no change in urate metabolism
  • MOA: prevents migration of leukocytes and phagocytosis by inhibiting tubulin
  • Side effects: diarrhea, N&V

Uricosuric Agents: Probenecid and Sulfinpyrazone

  • MOA: decreased the body pool of urates

Ø  acts at anionic transport site of tubules and thus decreases resorption of uric acid at proximal convuluted tubule (site C)

  • requires functioning kidney
  • Side effects: GI irritation, allergic dermatitis
  • Maintain large urine volume to minimize stone formation

Allopurinol

  • MOA: reduces uric acid synthesis – inhibits xanthine oxidase
  • NOT TO BE USED IN ACUTE GOUT ATTACK
  • Indications:

1)     patients with lots of uric acid

2)     patients with allergy to uricosuric agents

3)     renal impariment

4)     recurrent renal stones

  • Side effects: GI disturbances, severe hepatic and renal toxicity, severe allergic skin reactions