Chapter 75 Cyclooxygenase Inhibitors: Non-steroidal Anti-Inflammatory Drugs and Acetaminophen

COX

• Found in all tissues and helps regulate multiple processes

• At sites of tissue injury, COX catalyzes the synthesis of prostaglandin E₂ (PGE₂) and prostaglandin I₂ (PGI₂ also known as prostacyclin), which promote inflammation and sensitize receptors to painful stimuli

• In the stomach COX promotes synthesis of PGE₂ and PGI₂ which help protect the gastric mucosa

• Three mechanisms are involved: reduced secretion of gastric acid, increased secretion of bicarbonate and cytoprotective mucus, and maintenance of submucosal blood flow

• In platelets, COX promotes synthesis of TXA₂ which stimulates platelet aggregation

• In blood vessels, COX promotes synthesis of prostacyclin, which causes vasodilation

• In the kidney, COX catalyzes synthesis of PGE₂ and PGI₂, which promotes vasodilation and thereby maintain renal blood flow

• In the brain, COX-derived prostaglandins mediate fever and contribute to perception of pain

• In the uterus, COS-derived prostaglandins help promote contractions at term

Cyclooxygenase (COX-1)

• Found practically in all tissues

• Mediates “housekeeping” chores

  • Protecting the gastric mucosa

  • Supporting renal function

  • Promoting platelet aggregation

Cyclooxygenase (COX-2)

• Produced mainly at sites of tissue injury where it mediates inflammation and sensitizes receptors to painful stimuli

• Also present in the brain (where it mediates fever and contributes to perception of pain)

• Present in the kidney where it supports renal function

• Present in the blood vessels where it promotes vasodilation

• Present in the colon where it contributes to colon cancer

Inhibition of COX-1

• Gastric erosion and ulceration

• Bleeding tendencies

• Renal impairment

• One Beneficial Effect:

  • Protection against MI and stroke (secondary to reduced platelet aggregation)

Inhibition of COX-2

• Suppression of inflammation

• Alleviation of pain

• Reduction of fever

• Protection against colorectal cancer

• Two Adverse Effects:

  • Renal Impairment

  • Promotion of MI and Stroke (Secondary to Suppressing Vasodilation)

Classification of Cyclooxygenase (COX) Inhibitors

• Two Major Categories:

  • Drugs that have anti-inflammatory properties

    • Nonsteroidal Anti-inflammatory Drugs (NSAIDS)

    • Aspirin, Ibuprofen (Advil, Motrin, others), Naproxen (Aleve, others)

    • Celecoxib (Celebrex)

  • Drugs that lack anti-inflammatory properties

    • Acetaminophen (Tylenol, others)

      • Reduces pain and fever but does not suppress inflammation

Subdivision of NSAIDS

• Two Groups:

  • First-Generation NSAIDS

    • Conventional NSAIDS, Traditional NSAIDs

    • Inhibits both COX-1 and COX-2

      • Unable to suppress pain and inflammation without posing a risk for serious side effects (gastric ulceration, bleeding, renal impairment)

  • Second-Generation NSAIDS

    • Selective COX-2 Inhibitors

    • Inhibits only COX-2

      • Can suppress pain and inflammation and also (possibly) cause fewer adverse effects than the first-generation NSAIDS

      • In reality, they appear even less safe than the first generation NSAIDs because of their increased risk for MI and stroke

    • Celecoxib (Celebrex)

Prototype Drugs for First Generation NSAIDs

• Aspirin

• Ibuprofen

Prototype Drug for Second Generation NSAIDS

Celecoxib

Aspirin

• Provides excellent relief of mild to moderate pain, reduces fever, suppresses inflammation and protects against thrombotic disorders

• Available over the counter (OTC)

• Suppression of platelet aggregation

• Cancer prevention

• Can cause GI effects

• Too much aspirin can cause tinnitus (salicylism)

  • Stop dose if occurs

• Watch for signs of acute poisoning (overdose/toxicity)

Aspirin Toxicity

• Progresses from mild findings in salicylism to sweating, high fever, acidosis, dehydration, electrolyte imbalances, coma, and respiratory depression

• Nursing Actions:

  • Aspirin toxicity should be managed as a medical emergency in the hospital

  • Activated charcoal can be given to decrease absorption

  • Hemodialysis can be indicated

  • Cool the client with tepid water

  • Correct dehydration and electrolyte imbalance with IV fluids

  • Reverse acidosis and promote salicylate excretion with bicarbonate

  • Perform gastric lavage

Aspirin Interactions

• Anticoagulants (Heparin and Warfarin)

  • Increase the Risk of Bleeding

• Glucocorticoids

  • Increase the Risk of Gastric Bleeding

  • Client Education: Take Anti-ulcer Prophylaxis (Misoprostol) to Decrease the Risk for Gastric Ulcer

• Alcohol

  • Increases the Risk of Bleeding and Gastric Ulceration

• Ibuprofen (Other Concurrent NSAIDS)

  • Decreases the anti-platelet effects of low-dose aspirin used to prevent MI

• ACE Inhibitors and ARBs

  • Increases the risk for acute renal failure

• Over the Counter Medications

  • Supplements (Feverfew, Garlic, Ginger) can increase the risk for bleeding in clients who are taking NSAIDs

  • The supplement ginkgo biloba can suppress coagulation and is used with caution in clients who are taking NSAIDS

• Vaccines

  • Blunt the immune response

Nursing Actions for Gastrointestinal Discomfort (Aspirin)

• Damage to gastric mucosa can lead to gastrointestinal (GI) bleeding and perforation, especially with long-term use

• Risk is increased in older adults, clients who smoke or have alcohol use disorder, and those who have a history of peptic ulcers or previous inability to tolerate NSAIDS

• Observe for indications of GI bleeding (passage of black or dark-colored stools, severe abdominal pain, nausea, vomiting)

• Administer a proton pump inhibitor (omeprazole) or an H₂ receptor antagonist (cimetidine) to decrease the risk of ulcer formation

• Client Education:

  • Take medication with food or with an 8 oz glass of water or milk

  • Avoid alcohol

Nursing Actions for Impaired Kidney Function

• Signs/Symptoms:

  • Decreased urine output

  • Weight gain from fluid retention

  • Increased BUN and creatinine levels

• Nursing Actions:

  • Use cautiously with older adults and clients who have heart failure

  • Monitor I&O and kidney function (BUN, creatinine)

Reye Syndrome

• This occurs when aspirin is used for fever reduction in children and adolescents who have a viral illness (chickenpox or influenza)

• Characteristic Symptoms:

  • Encephalopathy

  • Fatty liver degeneration

Things to Remember About First Generation NSAIDS

• All of the non-aspirin first generation NSAIDS are much alike aspirin itself

• Some therapeutic use include anti-inflammatory, antipyretic, and analgesic actions (mild to moderate pain)

• Although these drugs can suppress platelet aggregation, these drugs are not used to prevent MI and stroke.

  • In fact, these medications can increase the risk of heart attack and stroke due to secondary suppression of vasodilation when inhibiting COX-2 (except Aspirin, it is a platelet aggregator)

  • Labs: Hemoglobin, Hematocrit

• All are associated with GI bleeding

• Take with food or water or milk to avoid GI disturbances

• Avoid alcohol

• Renal impairment with prolonged use (dialysis)

  • Labs: BUN and Creatinine

• Contraindications:

  • Pregnancy

  • Peptic Ulcer Disease

  • Bleeding Disorders (Hemophilia, Vitamin K deficiency)

  • Hypersensitivity to aspirin and other NSAIDS

Second Generation NSAID (Celecoxib)

• A last choice medication for chronic pain due to the increased risk of myocardial infarction (MI) and stroke due to secondary suppression of vasodilation

• Contraindicated in clients who have an allergy to sulfonamides

• Low risk for gastroduodenal ulceration (GI bleeding)

• Can impair renal function

• Does not inhibit COX-1

• No cardiovascular benefit

Acetaminophen

• Can result in liver damage, assess liver studies

  • AST and ALT studies

• Does not exceed more than 3 grams per day

• Does not reduce inflammation

• Does not cause gastric ulceration

• Does not suppress platelet aggregation

• Does not impair renal function

• Take one product containing acetaminophen at a time

• Treat acetaminophen overdose with PO or IV acetylcysteine