Analgesic Anti Pyre Tic Agents Piatos

ANALGESIC-ANTIPYRETIC AGENTS; PHARMACOTHERAPY OF by: GOUT

Edgar Allan A. Piatos, M.D.

NSAIDS Non Steroidal Anti-Inflammatory Drugs Mechanism of Action: Inhibit cyclooxygenase enzyme COX-1 COX-2

Therapeutic Effects: b. Pain - effective in pain of low to moderate intensity - do not change perception of sensory modalities other than pain b. Fever

Other Clinical Uses: Systemic Mastocytosis Bartter’s Syndrome Cancer Chemoprevention Niacin Tolerability

Adverse Effects of NSAID Therapy: Gastrointestinal - Ulcers Cardiovascular - Myocardial Infarction; Stroke Blood Pressure, Renal, Renovascular Adverse Events - Retention of salt and water Analgesic Nephropathy

Pregnancy and lactation - Prolongation of gestation - Increase risk of postpartum hemorrhage Hypersensitivity Aspirin Resistance

Drug Interactions  Concomitant NSAIDS and Low Dose Aspirin - increase likelihood of gastrointestinal adverse events  ACE Inhibitors - attenuate effectiveness of ACE inhibitors  Corticosteroids/Warfarin - increase incidence of bleeding

SALICYLATES Pharmacological Properties  Analgesia  Antipyresis  Respiration  Acid-Base and Electrolyte Balance and Renal Effects  Cardiovascular Effects  Gastrointestinal Effects

Hepatic Effects Uricosuric Effects Effects on the Blood Metabolic Effects * Oxidative phosphorylation * Carbohydrate metabolism  Endocrine Effects  Salicylates and Pregnancy  Local Irritant Effects    

Therapeutic Effects: Antipyresis Analgesia Rheumatoid Arthritis Inflammatory Bowel Disease Salicylate Intoxication Coma; Convulsions Cardiovascular Collapse

Salicylism: Headache; dizziness; tinnitus; difficulty of hearing

Treatment of Salicylate Poisoning: Airway Breathing Circulation Decontamination

DIFLUNISAL Difluorophenyl derivative of salicylic acid Devoid of antipyretic effects Osteoarthritis, musculoskeletal strains or sprains No auditory side effects Less gastrointestinal and platelet effects

PARAAMINOPHENOL DERIVATIVES: ACETAMINOPHEN Active metabolite of phenacetin Weak anti-inflammatory effects No effect on CVS, respiratory systems, on platelets and coagulation No acid-base changes or uricosuric effects Does not produce gastric irritation Associated with hepatic necrosis

ACETIC ACID DERIVATIVES b. INDOMETHACIN * more potent inhibitor of COX than aspirin * does not interfere with uricosuric effects of probenecid * platelet inhibition; gastric irritation * antagonizes the natriuretic and antihypertensive effects of diuretics, betablockers, ACE inhibitors, AT1 receptor antagonists

* ankylosing spondylitis, osteoarthritis, acute agout * closusre of persistent PDA Adverse Effects Gastrointestinal Frontal headache

b. SULINDAC - related to indomethacin

- prodrug: sulfide metabolite - rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute gout - prevent colon cancer in patients with FAP

c. ETODOLAC - COX-2 selective

- uricosuric - osteoarthritis -rheumatoid arthritis

FENAMATES (Mefenamic, Meclofenamic, Flufenamic Acid)

Pain in soft tissue injuries Dysmenorrhea Rheumatoid arthritis osteoarthritis

TOLMETIN Osteoarthritis; Rheumatoid Arthritis Juvenile Rheumatoid Arthritis Ankylosing Spondylitis KETOROLAC Parenteral administration Greater analgesic than antiinflammatory activity Short-term alternative to opoiods Used widely in post-operative patients

DICLOFENAC Most commonly used NSAID in Europe Potent against COX-2 Rheumatoid Arthritis; Osteoarthritis; Ankylosing Spondylitis Acute musculoskeletal pain Post-operative pain Dysmenorrhea

PROPIONIC ACID DERIVATIVES IBUPROFEN NAPROXEN FENOPROFEN KETOPROFEN FLURBIPROFEN OXAPROZIN - Rheumatoid Arthritis; Osteoarthritis - Ankylosing Spondylitis; Bursitis - Acute Tendinitis - Acute Gouty Arthritis - Primary Dysmenorrhea

ENOLIC ACIDS (OXICAMS) PIROXICAM MELOXICAM NABUMETONE

PYRAZOLON DERIVATIVES PHENYBUTAZONE OXYPHENBUTAZONE ANTIPYRINE AMINOPYRINE DIPYRONE - associated

with agranulocytosis

CYCLOOXYGENASE 2 SELECTIVE NSAIDS CELECOXIB VALDECOXIB ROFECOXIB PARECOXIB LUMIRACOXIB ETORICOXIB OTHER NSAIDS APARAZONE

NIMESULIDE

PHARMACOTHERAPY OF GOUT COLCHICINE Acute Gout Familial Mediterranean Fever ALLOPURINOL Most commonly used antihyperuricemic agent Primary hyperuricemia of gout Hyperuricemia secondary to Polycythemia Vera, Myeloid Metaplasia, Blood Dyscrasias

RASBURICASE Recombinant urate-oxidase Lowers urate levels more effectively than allopurinol Pediatric patients with leukemia, lymphoma, solid tumor malignancies

URICOSURIC AGENTS PROBENECID SULFINPYRAZONE BENXBROMAZONE