NSAIDs

Cyclooxygenase Inhibitors:Nonsteroidal Anti-inflammatory Drugs and Acetaminophen

Cyclooxygenase Inhibitors

• Aspirin and related drugs

  • Aspirin protects against MI and stroke

• Inhibit__prostaglandin synthesis_________; mediator of the inflammatory reactions ___

Cyclooxygenase Inhibitors USE

• Suppress inflammation

• relieve pain_______

• Reduce fever

Cyclooxygenase Inhibitors AE

• Gastric ulceration ________

• Bleeding_______________

• Renal impairment

Four adverse effects of cyclooxygenase inhibitors

• Gastric Ulceration

• Bleeding___________

• Renal Impairment

• May cause _MI and Stroke

COX 1 COX 2

COX 1 (Housekeeper)

• Protects gastric mucosa

• Supports renal fxn

• Promotes platelet aggregation __________

COX 2

• Produced at tissue injury sites.

• Mediates inflammation________________

• Receptors sensitized to painful stimuli

• Mediates fever and pain perception _____

• Vasodilitation

COX I

• Protects Gastric Mucosa

• Supports renal fxn__

• Promotes platelet aggregation________

COX I Inhibited

• Gastric erosion and ulceration________

• Bleeding tendencies_

• Renal __impairment

COX II

• Produced at tissue injury sites.

• Mediates inflammation__

• Receptors sensitized to painful stimuli

• Mediates fever and pain perception__________

• Vasodilitation

COX II Inhibited

• Inflammation is suppressed.

• Pain is alleviated _____

• Fever is ____reduced_____

• Protection against colorectal cancer

• Vasoconstriction

Drugs with anti-inflammatory properties

• NSAIDs: nonsteroidal anti-inflammatory drugs

  • Aspirin

  • Ibuprofen___________________

  • Naproxen

  • Celecoxib__________________

NSAIDs: nonsteroidal anti-inflammatory drugs

Aspirin

NSAIDs: nonsteroidal anti-inflammatory drugs

Ibuprofen

NSAIDs: nonsteroidal anti-inflammatory drugs

Naproxen

NSAIDs: nonsteroidal anti-inflammatory drugs

Celecoxib

Drugs without anti-inflammatory properties

• Acetaminophen

  • Para-aminophenol derivative_____

1st gen NSAIDS

Aspirin (P)

Aspirin (P)

• Inhibits COX I and COX II

• Suppresses pain & inflammation; promotes gastric ulceration, bleeding and renal imp___

2nd gen NSAIDS

coxibs

coxibs

• Inhibits COX2 only. Suppresses pain and inflammation with increased Stroke and MI risks.

Effects of NSAIDS

First-Generation NSAIDs

Inhibit COX-1 and COX-2

First-Generation NSAIDs: Tx inflammatory disorders

• RA_________________________

• OA________________________

• Bursitis______________________

• Alleviate mild to moderate pain

• Suppress fever

• Relieve dysmenorrhea

First-Generation NSAIDs: Risk

• Suppress inflammation but have risk of serious harm

  • NSAID-induced ulcers

Aspirin (Salicylates)

• Nonselective inhibitor of cyclooxygenase

• Irreversible inhibitor of COX

• Aka Acetylsalicylic acid (ASA)

Aspirin Therapeutics:

• Analgesic

  • Small doses_____________

• Antipyretic

  • Small doses

• Anti-inflammatory

  • Large doses___________________

• Suppression of platelet aggregation

  • Protects in thrombotic disorders

• Dysmenorrhea

Aspirin AE

• GI

  • Distress__________________

  • Heartburn

  • Nausea___________________

• NI: Food of full glass of water

  • Bleeding_________________

• Renal impairment

• Salicylism (aspirin overdose)__________

  • HOLD the ASA

• Reye’s syndrome____________________

  • Encephalopathy

• Pregnancy

  • Postpartum ___hemorrhage_______

  • May prolong labor

• Hypersensitivity reaction

• Patient teaching: Box 16-3

• Contraindications – use aspirin (overdose), acholol

Aspirin Drug interactions

• Anticoagulants

  • warfarin and heparin _______

• Glucocorticoids

  • Promote gastric ulceration

    • Omeprazole reduces GI risk__

• Alcohol

  • Increases the risk of GI bleeds___

• Ibuprofen

  • Reduces aspirin’s antiplatelet fxn

• ACE inhibitors and ARBS_______

• Acute poisonings

  • Salicylism

Nonaspirin First-Generation NSAIDs

• Aspirin-like drugs

  • fewer GI, renal, and hemorrhagic effects than aspirin __________

• 20+ nonaspirin NSAIDs available

  • (all similar, but for unknown reasons, patients tend to do better on one drug or another)

• Inhibit COX-1 and COX-2

• inhibition is reversible (unlike with aspirin)

• Principal indications

  • RA_____________________

  • OA_____________________

• Do not protect against ____MI and stroke___

  • Increase the risk of thrombotic events.

  • Minimize CV risk: Lowest dose for the shortest time.

  • ex: indomethacin (Indocin)

First-Generation NSAIDs (Propionic Derivatives)

Drugs that inhibit prostaglandin synthesis in the CNS and PNS systems.

Ibuprofen (Advil, Motrin) (P)

• Inhibits cyclooxygenase_______________

• Anti-inflammatory, analgesic, antipyretic props _______

• Tx: Fever, ___mild to mod, arthritis _________

• Risk for MI and Stroke

Naproxen (Aleve, Naprosyn)

• Inhibits cyclooxygenase

• Selective for COX I

• Long half life

• Tx: arthritis, dysmenorrhea, mild to moderate pain _______.

• A/E: GI disturbances, increase MI and Stroke

  • Selective: Lower risk

First-Generation NSAIDs (Propionic Derivatives)

• Ibuprofen (Advil, Motrin) (P)

• Naproxen (Aleve, Naprosyn)

First-Generation NSAIDs (Propionic Derivatives): Uses

• Mild to moderate pain

• Dysmenorrhea

• OA and RA

• Initial gout attacks

• Fever in children > than age 6

First-Generation NSAIDs (Propionic Derivatives): AE

• Dyspepsia________

• Dry mouth

• Heartburn

• Nausea

• Constipation______

• Epigastric pain

• GI ulceration_______

• Gingerval hyperplasia

• Nephrotoxicity

  • Elevated BUN__and creatinine

First-Generation NSAIDs (Propionic Derivatives): Contraindications

Sensitivities to ibuprofen and salicylates

Drugs that increase the effects of Ibuprofen:

Anticoagulants

Drugs that have an additive analgesic effects

• Codeine

• Oxycodone

Additive gastric irritant:

Corticosteroids

Patient Teaching:

• Take the drug with food or fluid

• Drink fluid daily when taking the drug regularly

• Report any signs of bleeding to the practitioner

Alcohol, Ginger, Garlic, Ginkgo and Feverfew

• increase bleeding risk

Oxicam Derivatives Drugs

• meloxicam (Mobic) (P)

• Piroxicam (Feldene)

Oxicam Derivatives

• COX I and COX 2 Inhibitor

• Anti-inflammatory, Analgesic, and Antipyretic effects___

• Uses: ___OA and RA______

  • Onset: 1 hour

  • Peak: 5 to 6 hours

• -Contraindications

  • Allergies_________

  • Creatinine clearance less than 20ml/min is not recommended.

Oxicam Derivatives AE

• SOB

• Bronchospasm______

• Hemoptysis

• Hematuria

• Bleeding_________

• Decreased platelets

• Decreased H & H

• Bone marrow depression_

• Edema

• N/V

• Diarrhea__

• Black Box:

  • CV Events/GI Bleed

Acetic Acid Derivatives Drug

indomethacin (Indocin) (P)

Acetic Acid Derivatives Uses

• RA_________________________

• OA_________________________

• Bursitis

• Tendonitis

• Gout

ketorolac (Toradol)

• Anti-inflammatory effects; more severe adverse effects that propionic acid derivatives.

• Powerful analgesic______________

• No respiratory depression or physical depression

• A/E: Peptic ulcers, GI bleeds, Prolonged bleeding time

Acetic Acid Derivatives AE

• H/A

• Dizziness

• Insomnia

• Gi Bleeds_______

• Abdominal pain

• Distention

• Transient ileus _____

• Renal impairment

• Decreased clotting time

Acetic Acid Derivatives Contraindications

• Hypersensitivity

• Hx of GI bleeds

• Status post CABG_

Acetic Acid Derivatives: Parenteral Formulations are contraindicated

• Bleeding

• Thrombocytopenia

• Coagulation defects

Drugs that increase indomethacin effects:

• Phenytoin___

• Salicylates

• Sulfonamides_

• Sulfonyureas

Drugs used with indomethacin that increase the risk of bleeding:

• Salicylates

• Anticoagulants

• Lithium

Second-Generation NSAIDs (COX-2 Inhibitors)

• Just as effective as traditional NSAIDs at suppressing inflammation and pain

• Somewhat lower risk for GI side effects

  • May have bleeding_____________

  • Gastroduodenal ulcers

  • Can impair renal fxn

  • Cause HTN and Edema

  • Increase the risk for MI and stroke__, two coxibs withdrawn from use:

    • rofecoxib____ (Vioxx) and valdecoxib______ (Bextra)

      • Use of celecoxib has sharply declined

Celecoxib (Celebrex)

• Second-generation COX-2 inhibitor

• Fewer adverse effects than first-generation drugs

• Because of cardiovascular risks, last-choice drug for long-term management of pain.

Celecoxib (Celebrex) Use

• Osteoarthritis _________

• Rheumatoid arthritis (RA)

• Acute pain_____________

• Dysmenorrhea

Celecoxib (Celebrex) AE

• Gastroduodenal Ulcer____________

• Cardiovascular Effects

  • Does not inhibit COX-1

  • Aggregation-----Not suppressed

  • Inhibits COX 2---promoting vasoconstriction

• Renal toxicity_______________________

  • Impairs renal fxn

  • COX 2 inhibited

• Sulfonamide allergy

• Use in pregnancy

  • May close may cause premature closure of ductus arteriosus____

Celecoxib (Celebrex): Drug interactions

• Warfarin

  • May decrease diuretic effects of furosemide_______

  • May decrease ___antihypertensive effect of ACE inhibitors___

  • May increase ___levels of lithium ____

    • Narrow therapeutic range

  • Levels of celecoxib may be increased by fluconazole

Acetaminophen (Tylenol) Therapeutic uses:

• Analgesic, antipyretic

• Does not have any anti-inflammatory or antirheumatic actions

• Not associated with Reye’s syndrome __

Acetaminophen (Tylenol) MOA

• Inhibits prostaglandin synthesis _____ in central nervous system

• -> reduce fever and pain

Acetaminophen (Tylenol) AE

• Very few at normal doses

• Hepatotoxicity____________________

  • With overdose or in patients with liver failure

Acetaminophen (Tylenol) Overdose

• Hepatic necrosis

  • S/S of hepatic failure, coma, death

• Early symptoms: N/V, diarrhea, sweating, abdominal pain

• The effect of ----__harmful, poisonous__------ or toxic substances on the liver resulting in liver damage.

Acetaminophen (Tylenol) Treatment for overdose:

• N-acetylcysteine (Mucomyst) ______

Acetaminophen (Tylenol) Drug interactions

• Alcohol

  • increase the risk of liver injury from acetaminophen____

• Warfarin

  • Increases bleeding ___warfarin metabolism is inhibited _________

AHA Statement on COX Inhibitors

• Most COX inhibitors

  • Especially COX-2 inhibitors, increase the risk for MI and stroke.

• AHA___recommends a stepped-care approach_____

• Four basic steps

  • Nondrug measures

  • Acetaminophen/Aspirin

  • Ibuprofen/Naproxen

  • Last resort----COX 2 Inhibitor