Cyclooxygenase Inhibitors

COX-1

Protecting the gastric mucosa

Supporting renal function

Promoting platelet aggregation

COX -2

Produced at sites of tissue injury

Mediates inflammation

Sensitizes receptors to painful stimuli

Mediates fever

Kidneys: Supports renal function

vasodilation of renal blood vessels

Colon: can contributes to colon cancer

COX-1 INHIBITORS

Gastric Erosion

Bleeding tendencies

Renal impairment

Protection against MI and CVA (reduces PLT aggregation

COX-2 Inhibitors

Suppresses inflammation

Alleviates pain

Reduces fever

Protects against colorectal cancer

Renal impairment

Promotes MI and CVA (suppresses vasodilation)

Inhibiting COX-1

Beneficial Effects

Protection against MI and stroke secondary due to platelet aggregation

Inhibiting COX-1

Harmful Effects

Gastric erosion/ulceration & bleeding

Bleeding tendencies

Renal impairment

Inhibiting COX-2 Beneficial Effects

Suppression of inflammation

Alleviation of pain

Reduction of fever

Protects against colon cancer

Inhibiting COX-2 (bad) Harmful Effects

Renal Impairment

Promotes MI and Stroke (secondary to suppressing vasodilation)

Acetaminophen,

Inhibits cyclooxygenase in the CNS only

Antipyretic effects and Analgesic effects

Does not have anti-inflammatory properties

Does not suppress platelet aggregation

Does not cause gastric ulcers

Does not impair renal blood flow

No renal impairment

Acetaminophen (Tylenol)

Excreted in urine but Metabolized by liver

Contraindications – ETOH abuse, hepatic disease, & viral hepatitis

Drug Interactions: Warfarin, Vaccines, Alcohol

Acetaminophen (Tylenol):Adverse Effects and Drug Interactions

Liver injury

Hypertension risk?? (lots of conflicting data)

Monitor BP!

Possible relationship with development of Asthma??

Anaphylaxis or rash (SJS, TEN, AGEP)

Tylenol overdose

Hepatic necrosis

Early symptoms – N,V, D, sweating, abdominal discomfort

Treatment – acetylcysteine (mucomyst) ASAP

Tylenol

Nursing Alerts

Max dosing: 4000mg/day (FDA)

Aspirin,

#Irreversible Nonselective inhibitor of COX

Reduction of fever, pain, inflammation (d/t COX 2 inhibition)

Protects against MI and CVA (d/t COX 1 inhibition)

Low doses selectively inhibit COX 1 so can be used as selective antiplatelet drug

Aspirin Pharmacokinetics

Administered PO or suppository

Metabolism – rapidly converted in liver to salicylic acid

Excreted by the kidneys

Dependent on urinary pH

Raising the pH from 6 to 8 will increase excretion fourfold

High salicylate levels can lead to toxicity (Salicylism)

Aspirin Therapeutic Uses

Suppresses inflammation

Analgesia

Reduces fever

Dysmenorrhea – Why?

Suppression of platelet aggregation

MI, stroke, TIA, previous MI, unstable angina, angioplasty

Cancer prevention

With regular low dose use?

Aspirin Adverse Effects

Gastrointestinal

GI distress

Heartburn

Nausea

Bleeding

Renal Impairment

Salicylism

Headache, tinnitus, sweating, dizziness

Reyes Syndrome (risk for those < 18 years old)

Hypersensitivity Reaction (rare)

Aspirin Contraindications

Peptic ulcer disease

Bleeding disorders

Hypersensitivity to ASA or other NSAIDs

Aspirin Precautions

Children

Elderly

Pregnant women

Hepatic cirrhosis

Renal dysfunction

Asthma

Alcohol abuse

Aspirin Interactions

Anticoagulants

Heparin

Warfarin

Glucocorticoids

Promote gastric ulceration

Alcohol

Increased risk of gastric bleeding

Ibuprofen

Decreases the antiplatelet effects of aspirin hour beforenor after

ACE inhibitors and ARBs

Impair renal function

NSAIDS Acute Poisoning with Aspirin

Lethal in children

Signs and Symptoms

Initially respiratory alkalosis with respiratory depression

Acidosis

Hyperthermia

Sweating

Dehydration, electrolyte imbalances

Stupor  Coma

Treatment  Supportive

Fluids, Gastric lavage and activated charcoal

Aspirin What about ASA prior to surgery?

Inhibition last lifetime of platelet—approx. 8 days…

Do not take 7 days before surgery

NSAIDS

first gen Nonselective COX inhibitors

second cox 2 cele

Reversible inhibition

Anti-inflammatory, analgesic, and antipyretic

Adverse effects generally the same

Hypersensitivity to ASA will likely have cross sensitivity

REVERSIBLE

non aspirin NSAIDS Indications

inflammation (itis)

Mild to moderate pain

Dysmenorrhea

DOES NOT PROTECT AGAINST MI

Ibuprofen,

Fever, Mild to moderate pain, dysmenorrhea

promotes closure of ductus arteriosus in preterm infants (clinical trials)

Less gastric bleeding, less inhibition of platelet aggregation

Available PO or IV

Ketorolac

Powerful analgesic with minimal anti-inflammatory properties

Kidney Stone Pain, Orthopedic pain, Post-op pain

Short term use only!!

Gi bleeding

Mi and stroke

Naproxen

Prolonged half-life therefore can be administered less frequently

Celecoxib

Does not inhibit COX-1

Therapeutic Uses-osteoarthritis, RA, dysmenorrhea acute pain, & Ankylosing spondylitis

Contraindications - similar to Ibuprofen

Adverse effects - similar to Ibuprofen

Adverse Effects of Celebrex

GI Ulcerations (lower incidence than with NSAIDS

Renal impairment

Increased risk for MI and Stroke (suppresses vasodilation)

Other CV effects

Avoid in those with CV disease/ risk factors

Risk for allergic reaction

Premature closure of ductus arteriosus

Don’t use during 3rd trimester

Celebrex Drug Interaction

Increases the anticoagulant effects of warfarin remember this drug does not affect platelet aggregation (that is COX-1)

Has sulfa component  do not use if a patient has a sulfa allergy!!!!

Remember does not protect against MI/Stroke d/t not inhibiting COX -1 which suppressess PLT aggregation