Anti-Inflammatory Agents ESAT 4001 Pharmacology in Athletic Training

Effects of NSAIDS Analgesia Analgesia Antipyresis Antipyresis Anticoagulation Anticoagulation Control inflammation Control inflammation

Action of NSAIDs Hinder cyclooxygenase pathway Hinder cyclooxygenase pathway Block synthesis of prostaglandins and thromboxanes Block synthesis of prostaglandins and thromboxanes prostaglandins and thromboxanes involved in production of pain, inflammation, fever and excessive blood clotting prostaglandins and thromboxanes involved in production of pain, inflammation, fever and excessive blood clotting NSAIDs inhibit platelet formation = decreased thrombus formation NSAIDs inhibit platelet formation = decreased thrombus formation 2 reasons this may be counterproductive 2 reasons this may be counterproductive Tissue trauma while taking for tendinitis Tissue trauma while taking for tendinitis If started immediately following trauma platelet aggregation may be affected If started immediately following trauma platelet aggregation may be affected

Side Effects of NSAIDs GI irritation/damage GI irritation/damage Irritation of gastric mucosa Irritation of gastric mucosa Inhibition of prostaglandins Inhibition of prostaglandins Hepatic and renal disorders Hepatic and renal disorders Some studies indicate aspirin and other NSAIDs inhibit synthesis of some components of connective tissue Some studies indicate aspirin and other NSAIDs inhibit synthesis of some components of connective tissue

Side Effects Specific to Aspirin Overdose Overdose S&S – headache, tinnitus, hearing difficulties, confusion, & GI irritation S&S – headache, tinnitus, hearing difficulties, confusion, & GI irritation Reye’s syndrome Reye’s syndrome S&S – high fever, vomiting, liver dysfunction, & decreasing level of alertness S&S – high fever, vomiting, liver dysfunction, & decreasing level of alertness Hypersensitivity Hypersensitivity Allergic reactions – bronchospasms, hives, sever rhinitis Allergic reactions – bronchospasms, hives, sever rhinitis Possibility of CV shock in these people Possibility of CV shock in these people

Classes of NSAIDs

Acetic Acids Products Indomethacin Indomethacin Indocine Indocine One of the strongest cyclooxygenase inhibitors One of the strongest cyclooxygenase inhibitors Typically fully excreted w/in 48 hours Typically fully excreted w/in 48 hours Diclofenac Diclofenac Voltaren & cataflam Voltaren & cataflam Absorbed rapidly, short half-life Absorbed rapidly, short half-life

Acetic Acids Products Sulindac Sulindac Clinoril Clinoril Structurally/pharmacologically related to indomethacin Structurally/pharmacologically related to indomethacin Prodrug Prodrug Converted to active sulfide metabolite Converted to active sulfide metabolite Sulfide metabolite is 500 times more potent as a cyclooxygenase inhibitors than parent drug Sulfide metabolite is 500 times more potent as a cyclooxygenase inhibitors than parent drug

Acetic Acids Products Tolmetin Tolmetin Tolectin Tolectin Arthritis Arthritis Rapid absorption and elimination Rapid absorption and elimination Complete excretion w/in 24 hours Complete excretion w/in 24 hours Common side effects – nausea and vomiting Common side effects – nausea and vomiting

Acetic Acids Products Ketorolac Ketorolac Toradol Toradol Excellent analgesic effects w/o side affects of morphine Excellent analgesic effects w/o side affects of morphine Loading dose (IM or IV) Loading dose (IM or IV) Rapid absorption Rapid absorption Common side effects associated with acetic acid products Common side effects associated with acetic acid products Abdominal pain, headache, dizziness, and tinnitus Abdominal pain, headache, dizziness, and tinnitus

Enolic Acids Phenylbutazone Phenylbutazone Butazolidin Butazolidin Originally, was first NSAID alternative to aspirin Originally, was first NSAID alternative to aspirin Has been found to be potentially fatal Has been found to be potentially fatal Used only in short-term treatment (gout) Used only in short-term treatment (gout) Side effects – bone marrow depression, decreased production of platelets and RBCs Side effects – bone marrow depression, decreased production of platelets and RBCs Not often used in athletic medicine Not often used in athletic medicine

Enolic Acids Piroxicam Piroxicam Feldene Feldene Long half-life ~ one-a-day dosage Long half-life ~ one-a-day dosage Rapid absorption, long action Rapid absorption, long action Side effects – GI symptoms, dizziness, tinnitus, and headache most commonly reported Side effects – GI symptoms, dizziness, tinnitus, and headache most commonly reported Taking w/ food does not effect absorption, but does decrease gastric symptoms Taking w/ food does not effect absorption, but does decrease gastric symptoms

Fenamic Acid Derivatives Meclofenamate Meclofenamate Meclomen Meclomen Rapid absorption Rapid absorption Peak effect of drug w/in.5-2 hours Peak effect of drug w/in.5-2 hours Common side effects of all NSAIDs Common side effects of all NSAIDs Side effects tend to be more common Side effects tend to be more common

Propionic Acids Ibuprofen Ibuprofen Advil, Motrin, Nuprin Advil, Motrin, Nuprin Used more often for analgesic effect than for anti- inflammatory effect Used more often for analgesic effect than for anti- inflammatory effect Analgesic effects in 2-4 hours Analgesic effects in 2-4 hours Anti-inflammatory effects require days to weeks Anti-inflammatory effects require days to weeks Absorption slowed when taking w/ food, however total absorption is unaffected Absorption slowed when taking w/ food, however total absorption is unaffected Maximum dose = 3200 mg/day Maximum dose = 3200 mg/day Self-medication is common Self-medication is common

Propionic Acids Ketoprofen Ketoprofen Orudis Orudis Absorbed rapidly and completely Absorbed rapidly and completely Analgesia w/in 1 hr ~ last 3-4 hrs Analgesia w/in 1 hr ~ last 3-4 hrs Upset stomach (dyspepsia) most common side effect Upset stomach (dyspepsia) most common side effect

Propionic Acids Naproxen Naproxen Aleve, Naprosyn, Anaprox Aleve, Naprosyn, Anaprox Better patient tolerance than aspirin and indomethacin Better patient tolerance than aspirin and indomethacin Aleve – loading dose of 440 mg followed by 220 mg 12 hr later Aleve – loading dose of 440 mg followed by 220 mg 12 hr later 660 mg daily max or 10 days of treatment 660 mg daily max or 10 days of treatment Half-life of hr. Half-life of hr.

Propionic Acids Fenoprofen Fenoprofen Nalfon Nalfon GI irritation is common GI irritation is common Taken w/ food decreases GI side effect Taken w/ food decreases GI side effect Delays absorption, decreased peak plasma concentration Delays absorption, decreased peak plasma concentration Analgesic effects w/in m., lasts 4-6 hr. Analgesic effects w/in m., lasts 4-6 hr. Half-life = hr, q 4-6 hr. Half-life = hr, q 4-6 hr.

Carboxylic Acids Aspirin Aspirin 1 st NSAID introduced 1 st NSAID introduced Prodrug – inactive until metabolized into constituent parts Prodrug – inactive until metabolized into constituent parts Liver Liver Permanently binds to platelets ~ producing anticoagulant effect up to 10 days Permanently binds to platelets ~ producing anticoagulant effect up to 10 days Each tablet = 325 mg Each tablet = 325 mg

Carboxylic Acids Diflunisal Diflunisal Dolobid Dolobid Good anti-inflammatory and analgesic effects Good anti-inflammatory and analgesic effects Poor antipyretic Poor antipyretic Loading does of 1 g, followed by 500 mg every 8-12 hours as needed Loading does of 1 g, followed by 500 mg every 8-12 hours as needed

Adrenal Steroid Compounds Glucocorticoids Glucocorticoids Most frequently used in athletics Most frequently used in athletics Excellent anti- inflammatory response Excellent anti- inflammatory response Effects include: reduction of tissue heat, reduction of erythema, control of swelling, & decreased local temperature Effects include: reduction of tissue heat, reduction of erythema, control of swelling, & decreased local temperature

Glucocorticoid Action Action Works by inhibiting prostaglandin and leukotriene production Works by inhibiting prostaglandin and leukotriene production Also impair function of macrophages and leukocytes Also impair function of macrophages and leukocytes Side effects/precautions Side effects/precautions Catabolic effect not limited to target structures Catabolic effect not limited to target structures Injection directly into ligament or tendon will weaken structure for 2-6 weeks Injection directly into ligament or tendon will weaken structure for 2-6 weeks Repeated injections into a joint can lead to intra-articular degeneration and arthritis. Repeated injections into a joint can lead to intra-articular degeneration and arthritis.

Types of Glucocorticoids Cortisone Cortisone Short-acting (8-12 hr) Short-acting (8-12 hr) Often provided in pill form in a dose pack Often provided in pill form in a dose pack Long term use can be harmful Long term use can be harmful Can be used to prevent/suppress inflammation, and suppress immune reactions Can be used to prevent/suppress inflammation, and suppress immune reactions

Types of Glucocorticoids Hydrocortisone Hydrocortisone Administered orally, topically, or by injection Administered orally, topically, or by injection Peak effect w/in 1-2 hr Peak effect w/in 1-2 hr Duration dependant on injection site Duration dependant on injection site Average duration is 8-12 hr Average duration is 8-12 hr

Types of Glucocorticoids Prednisone Prednisone Most commonly prescribed oral corticosteroid Most commonly prescribed oral corticosteroid 4x more potent than Hydrocortisone 4x more potent than Hydrocortisone Intermediate acting Intermediate acting Duration of action is hr. Duration of action is hr. Metabolized in liver to active form prednisolone Metabolized in liver to active form prednisolone

Types of Glucocorticoids Dexamethasone Dexamethasone Decadron Decadron Anti-inflammatory and immunosuppressive uses Anti-inflammatory and immunosuppressive uses Administered enterally and parenterally Administered enterally and parenterally Injection or iontophoresis Injection or iontophoresis Longest acting glucocorticoid Longest acting glucocorticoid Duration of action from 1-3 days Duration of action from 1-3 days