Anti-inflammatory agents and nsaids

Copyright © 2002, 1998, Elsevier Science (USA). All rights reserved.

Antiinflammatory Agents Antiinflammatory Agents and Nonsteroidal and Nonsteroidal

Antiinflammatory Drugs Antiinflammatory Drugs (NSAIDs)(NSAIDs)


NSAIDsNSAIDs

• Large and chemically diverse group of drugs Large and chemically diverse group of drugs with the following properties:with the following properties:

– AnalgesicAnalgesic

– AntiinflammatoryAntiinflammatory

– AntipyreticAntipyretic


NSAIDs: Mechanism of ActionNSAIDs: Mechanism of Action

• Activation of the arachidonic acid Activation of the arachidonic acid pathway causes:pathway causes:

• painpain

• headacheheadache

• feverfever

• inflammationinflammation


Instructors may wish to use Instructors may wish to use EIC Image #107: EIC Image #107:

Arachidonic Acid PathwayArachidonic Acid Pathway



Analgesia—treatment of headaches and painAnalgesia—treatment of headaches and pain

• Block the undesirable effects of prostaglandins, Block the undesirable effects of prostaglandins, which cause headacheswhich cause headaches



Antipyretic: reduce feverAntipyretic: reduce fever

• Inhibit prostaglandin EInhibit prostaglandin E22 within the area of the brain within the area of the brain that controls temperaturethat controls temperature



Relief of inflammationRelief of inflammation

• Inhibit the leukotriene pathway, the prostaglandin Inhibit the leukotriene pathway, the prostaglandin pathway, or bothpathway, or both


NSAIDsNSAIDs

Six structurally related groups:Six structurally related groups:

• Acetic acidsAcetic acids

• Carboxylic acidsCarboxylic acids

• Propionic acidsPropionic acids

• Enolic acidsEnolic acids

• Fenamic acidsFenamic acids

• Nonacidic compoundsNonacidic compounds


NSAIDs: Acetic AcidNSAIDs: Acetic Acid

• diclofenac sodium (Voltaren)diclofenac sodium (Voltaren)

• diclofenac potassium (Cataflam)diclofenac potassium (Cataflam)

• etodolac (Lodine)etodolac (Lodine)

• indomethacin (Indocin)indomethacin (Indocin)

• sulindac (Clinoril)sulindac (Clinoril)

• tolmetin (Tolectin)tolmetin (Tolectin)


NSAIDs: Carboxylic AcidsNSAIDs: Carboxylic Acids

AcetylatedAcetylated• aspirin (ASA)aspirin (ASA)• choline magnesium salicylate (Trilisate)choline magnesium salicylate (Trilisate)• diflunisal (Dolobid)diflunisal (Dolobid)

NonacetylatedNonacetylated• salicylamide salicylamide • salsalate (Disalcid)salsalate (Disalcid)• sodium salicylatesodium salicylate


NSAIDs: Propionic AcidsNSAIDs: Propionic Acids

• fenoprofen (Nalfon)fenoprofen (Nalfon)

• flurbiprofen (Ansaid)flurbiprofen (Ansaid)

• ibuprofen (Motrin, others)ibuprofen (Motrin, others)

• ketoprofen (Orudis)ketoprofen (Orudis)

• ketorolac (Toradol)ketorolac (Toradol)

• naproxen (Naprosyn)naproxen (Naprosyn)

• oxaprozin (Daypro)oxaprozin (Daypro)


NSAIDs: Other AgentsNSAIDs: Other Agents

Enolic acidsEnolic acids• phenylbutazone (Butazolidin)phenylbutazone (Butazolidin)• piroxicam (Feldene)piroxicam (Feldene)

Fenamic acidsFenamic acids• meclofenamic acid (Meclomen)meclofenamic acid (Meclomen)• mefenamic acid (Ponstel)mefenamic acid (Ponstel)

Nonacidic compoundsNonacidic compounds• nabumetone (Relafen)nabumetone (Relafen)


NSAIDs: Other AgentsNSAIDs: Other Agents

COX-2 InhibitorsCOX-2 Inhibitors

• celecoxib (Celebrex)celecoxib (Celebrex)

• rofecoxib (Vioxx)rofecoxib (Vioxx)


NSAIDs: Drug EffectsNSAIDs: Drug Effects

• Analgesic (mild to moderate)Analgesic (mild to moderate)

• AntigoutAntigout

• AntiinflammatoryAntiinflammatory

• AntipyreticAntipyretic

• Relief of vascular headachesRelief of vascular headaches

• Platelet inhibition (ASA)Platelet inhibition (ASA)


NSAIDs: Therapeutic UsesNSAIDs: Therapeutic Uses• Relief of mild to moderate painRelief of mild to moderate pain• Acute goutAcute gout• Various bone, joint, and muscle painVarious bone, joint, and muscle pain• OsteoarthritisOsteoarthritis• Rheumatoid arthritisRheumatoid arthritis• Juvenile rheumatoid arthritisJuvenile rheumatoid arthritis• DysmenorrheaDysmenorrhea• FeverFever


NSAIDs: Specific AgentsNSAIDs: Specific Agents

salicylates (aspirin)salicylates (aspirin)

• More potent effect on platelet aggregation and More potent effect on platelet aggregation and thermal regulatory center in the brainthermal regulatory center in the brain

– analgesicanalgesic

– antipyreticantipyretic

– antiinflammatoryantiinflammatory

• Antithrombotic effect: used in the treatment of MI Antithrombotic effect: used in the treatment of MI and other thromboembolic disordersand other thromboembolic disorders


NSAIDs: Specific AgentsNSAIDs: Specific Agents

phenylbutazone (Butazolidin)phenylbutazone (Butazolidin)

• Greater effects on uric acid production and Greater effects on uric acid production and excretion, in addition to antiinflammatory effectsexcretion, in addition to antiinflammatory effects

• More commonly used for treatment of goutMore commonly used for treatment of gout


NSAIDs: Side EffectsNSAIDs: Side Effects

GastrointestinalGastrointestinal

• dyspepsia, heartburn, epigastric distress, nauseadyspepsia, heartburn, epigastric distress, nausea

**GI bleeding**GI bleeding

**mucosal lesions (erosions or ulcerations)**mucosal lesions (erosions or ulcerations)

• Misoprostol (Cytotec) can be used to reduce these Misoprostol (Cytotec) can be used to reduce these dangerous effects.dangerous effects.



RenalRenal

• reductions in creatinine clearancereductions in creatinine clearance

• acute tubular necrosis with renal failureacute tubular necrosis with renal failure



CardiovascularCardiovascular

• noncardiogenic pulmonary edemanoncardiogenic pulmonary edema


NSAIDs: Salicylate ToxicityNSAIDs: Salicylate Toxicity

• Adults: tinnitus and hearing lossAdults: tinnitus and hearing loss

• Children: hyperventilation and CNS effectsChildren: hyperventilation and CNS effects

• Effects arise when serum levels exceed Effects arise when serum levels exceed 300300g/mL.g/mL.

• Metabolic acidosis and respiratory alkalosis Metabolic acidosis and respiratory alkalosis may be present.may be present.


NSAIDs: Nursing ImplicationsNSAIDs: Nursing Implications

• Before beginning therapy, assess for Before beginning therapy, assess for conditions that may be contraindications to conditions that may be contraindications to therapy, especially:therapy, especially:

– GI lesions or peptic ulcer diseaseGI lesions or peptic ulcer disease

– Bleeding disordersBleeding disorders

• Assess also for conditions that require Assess also for conditions that require cautious use.cautious use.

• Perform lab studies as indicated (cardiac, Perform lab studies as indicated (cardiac, renal, liver studies, CDC, platelet count).renal, liver studies, CDC, platelet count).



• Perform a medication history to assess for Perform a medication history to assess for potential drug interactions.potential drug interactions.

• Several serious drug interactions exist:Several serious drug interactions exist:– alcoholalcohol– heparinheparin– phenytoinphenytoin– oral anticoagulantsoral anticoagulants– steroidssteroids– sulfonamidessulfonamides



• Salicylates are NOT to be given to children Salicylates are NOT to be given to children under age 12 because of the risk of Reye’s under age 12 because of the risk of Reye’s syndrome.syndrome.

• Because these agents generally cause GI Because these agents generally cause GI distress, they are often better tolerated if distress, they are often better tolerated if taken with food, milk or an antacid to avoid taken with food, milk or an antacid to avoid GI irritation.GI irritation.

• Explain to patients that therapeutic effects Explain to patients that therapeutic effects may not be seen for 3 to 4 weeks.may not be seen for 3 to 4 weeks.



• Educate patients about the various side Educate patients about the various side effects of NSAIDs, and to notify their effects of NSAIDs, and to notify their physician if these effects become severe physician if these effects become severe or if bleeding or GI pain occur.or if bleeding or GI pain occur.

• Patients should watch closely for the Patients should watch closely for the occurrence of any unusual bleeding, occurrence of any unusual bleeding, such as in the stool.such as in the stool.

• Enteric-coated tablets should not be Enteric-coated tablets should not be crushed or chewed.crushed or chewed.



• Monitor for therapeutic effects, which vary Monitor for therapeutic effects, which vary according to the condition being treated:according to the condition being treated:

decrease in swelling, pain, stiffness, decrease in swelling, pain, stiffness, and tenderness of a joint or muscle areaand tenderness of a joint or muscle area

Education

Anti-inflammatory agents and nsaids