Pharmacology for the Athletic Trainer Over The Counter Medications (OTCs) NSAIDs

1. Pharmacology for the Athletic TrainerOver The Counter Medications (OTCs)NSAIDs David S. Knitter, MD, FCCP February 7, 2000

2. In 1997, the Nonprescription Drug Manufacturers Association (NDMA) published the report of a study conducted by Kline & Co. and subtitled "Economic Benefits of Self-Medication." “The economic analysis resulted in an estimate that OTC availability for the categories studied resulted in savings to the consumer of $20.6 billion annually when compared with the costs of treating the ailments using physicians and prescription medications. The researchers estimated that nearly two-thirds of the calculated savings could be traced to Rx-to-OTC switched products.”

3. Time Limits on OTC Use Because nonprescription products may be used without any medical advice, making patients aware of time limits can be critical in ensuring their safety.

4. Time Limits on OTC Use • Sustained use of nonprescription products could mask a serious underlying condition that should be diagnosed. • If there is no noticeable response by that time, the risk of an adverse reaction outweighs any possible benefit to further use. • Prevent patients from using them as alternatives to healthier interventions • The problem should have resolved if the product was used properly and the patient actually had the problem for which the product was indicated. • Some products may result in addiction if overused

5. Time Limits for OTC Usage

6. No Time Limits of OTC Use • the condition they treat is not easily confused with any other; • the condition requires lifelong therapy; • the medications used to treat the condition are fairly safe; • the medication prevents a problem. • Examples • fluorides for dental care, • antihistamines for motion sickness or allergic rhinitis, • simethicone for intestinal gas, • sunscreens to prevent sunburn, • acne medications

8. Rise In OTC Sales

11. NSAID Classes

12. Current OTC NSAIDs • Aspirin • 325mg not to exceed 4 grams in 24 hours • Ibuprofen • 200mg not to exceed 1200 mg in 24 hours • Advil • Nuprin • Mortin AB • Naprosyn • 200mg not to exceed 600mg in 24 hours • Aleve • Ketoprofen • 12.5mg not to exceed 75mg in 24 hours • Orudis KT

13. Prostaglandin (PG) Synthesis • Prostaglandins have been implicated in pathogenesis of inflammation and fever • Aspirin-like drugs inhibit the biosynthesis and release of PGs • Inhibition of the synthesizing enzyme (cyclo-oxygenase) is fairly well correlated with anti-inflammatory action • Inhibition of COX2 (inducible) may be responsible for therapeutic effects of NSAIDs • Inhibition of COX1 (constituitive) may be responsible for many adverse effects of NSAIDs

14. Prostaglandin (PG) Synthesis • Pain • Direct administration of PGs causes local pain evidence suggests that PGs (PGE2?)sensitizes pain receptors to bradykinin, a local mediator of pain released during inflammation • Aspirin is less effective against sharp pain (direct stimulation of nerve endings - no PGs, opioids more effective) than against the dull, throbbing pain of inflammation (involves PGs)

15. Prostaglandin (PG) Synthesis • Fever • Infection bacterial endotoxins cause release of endogenous pyrogens from neutrophils • Tissue damage or inflammation interleukin 1 released by macrophages (principal role is to activate lymphocytes) affects hypothalamus • Aspirin-like drugs work by increasing heat loss (vasodilatation of peripheral blood vessels) not by reducing heat production

16. Prostaglandin (PG) Synthesis • Inflammation • Signs of inflammation - erythema, edema, tenderness and pain • Damage to microvasculature - leakage of blood components • Infiltration of leukocytes • Release of chemical mediators including PGs • Aspirin-like drugs relieve symptoms not pathology

17. Possible Future Switches of NSAIDS • Diclofenac potassium and sodium • Diflunisal • Etodolac • Naproxen sodium (controlled-release) • Piroxicam • Sulindac • Tolmetin

18. Adverse Effects • Gastrointestinal Effects • nausea and vomiting stimulation of CTZ in medulla • gastric bleeding 3-8 ml/day blood loss with 4-5 g aspirin/day vs 0.6 ml in untreated subjects • Blood Clotting • aspirin irreversibly inhibits platelet synthesis of thromboxane A2 (TXA2) which is required for aggregation • other NSAIDs - reversible effect on clotting • non-acetylated salicylates - no effect on clotting • terminate chronic use of aspirin 1 week prior to elective surgery (most other NSAIDs 24-48 hr)

19. Adverse Effects • Salicylism • characterized by tinnitus (may be related to increased labyrinthine pressure or effect on cochlear hair cells, pehaps secondary to vasoconstriction of auditory microvasculature), headache, nausea and vomiting, dizziness and dimness of vision • Aspirin Hypersensitivity or ”Aspirin Intolerance" • 1/4 million in USA • symptoms include rhinitis, profuse watery secretions, bronchial asthma, bronchconstriction, hypotension, vasomotor collapse, coma • non-acetylated salicylates may be used cautiously

20. Adverse Effects • Reye's syndrome • rare but often fatal consequence of infection with varicella and various other viruses • salicylates are contraindicated in children and adolescents with chicken pox or influenza

21. Acetaminophen • Little or no anti-inflammatory activity • Mechanism of action is unknown • Very weak inhibitor of cyclo-oxygenase • Greater effect in the CNS ?? • Minimal gastrointestinal irritation • No effect on bleeding time

23. Acetaminophen Toxicity • Hepatic necrosis (acute - 10-15 g; >25 g usually fatal) • Increased incidence of hepatotoxicity in the presence of ethanol and/or fasting (with as little as 4 g/day) • Ethanol induces hepatic MFO metabolism (pathway 3) shifting reaction toward toxic metabolite (limited glutathione available)

24. Renal Tubular Necrosis • Increased risk with lifetime intake • Associated greater than 1000 tablets of acetaminophen • Associated greater than 5000 tablets of NSAIDs • ? effect of aspirin