Chapter 57: Cyclooxygenase Inhibitors: Nonsteroidal Anti-inflammatory Drugs and Acetaminophen Flashcards
Cyclooxygenase Inhibitors: uses
Suppress inflammation
Relieve pain
Reduce fever
2 Types of cox receptors
2 types: cox 1 and cox 2
Cox 1 is found I practically all tissues where it mediates “housekeeping chores” protects gastric mucosa, supports renal function, platelet aggregation “good cox”
Cox 2 is produced mainly at sites of tissue injury, mediates inflammation and sensitizes receptors to painful stimuli. Also present in brain, it mediates fever and contributes to the perception of pain. Supports renal function. Supports vasodilation. Can contribute to colon cancer. “Bad cox”
Cyclooxygenase Inhibitors: ADR
Gastric ulceration
Bleeding
Renal impairment
Cyclooxygenase Inhibitors: MOA
Inhibit cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostanoids (prostaglandins and related compounds)
Inhibition of COX-1 (“good COX”)
Gastric ulceration
Bleeding
Renal impairment
Inhibition of COX-1: Beneficial effects
Protection against myocardial infarction (MI) and stroke
Secondary to reducing platelet aggregation
Inhibition of COX-2 (“bad COX”): Largely beneficial effects:
Suppression of inflammation
Alleviation of pain and reduction of fever
Protection against colorectal cancer
2 bad effects of inhibiting cox 2
renal impairment and promote of MI and stroke.
Classification of Cyclooxygenase Inhibitors
Drugs with antiinflammatory properties
Nonsteroidal antiinflammatory drugs (NSAIDs)
Aspirin, celecoxib, ibuprofen, and naproxen
Drugs without antiinflammatory properties
Acetaminophen
First-Generation NSAIDs
Inhibit COX-1 and COX-2
Used to treat inflammatory disorders (rheumatoid arthritis, osteoarthritis, and bursitis)
Alleviate mild to moderate pain
Suppress fever
Relieve dysmenorrhea
Suppress inflammation but pose risk of serious harm
ASA
Nonselective inhibitor of cyclooxygenase
ASA therapeutics ses
Analgesic, antipyretic, and antiinflammatory
Suppression of platelet aggregation
Protects in thrombotic disorders
Dysmenorrhea
Cancer prevention
Prevention of Alzheimer disease
ASA ADR
Gastrointestinal (GI) effects
Heartburn, nausea
Can reduce by taking ASA with full glass of water
Long-term can cause gastric ulceration, perforation, and bleeding
At risk pt: adv age, PUD hx, prev. Intolerance to ASA or other nzoids, hx of alcohol abuse (alcohol intensified irritant effects of ASA)
Bleeding
Taking 2 325 mg of ASA can double bleeding time for about 1 week
Concerning for surgery and childbirth. D/c high ASA doses a week before procedure. No need to stop low doses of ASA or if there is a low risk for bleeding like dental, derm, cataract sx
Renal impairment
Acute, reversible impairment of renal function
Reduce UO, weight gain
Salicylism: Tinnitus (ringing in the ears), sweating, headache, and dizziness
Develops when ASA climbs slightly above therapeutic levels
Withhold ASA until those s/sx subside
Reye syndrome
ASA use in kids under 18 years old with influenza or chicken pox
Pretty much avoid in children <18
Mortality rate of ~20-30%
Encephalopathy and fatty liver degeneration
Pregnancy
Anemia, postpartum hemorrhage; may prolong labor
Risk to pt and baby
Inhibits prostaglandin synthesis, so suppress spontaneous uterine contractions and thereby prolong labor
Hypersensitivity reaction
If pt develops rash or any other kind of sx, mark as allergy to ASA
ASA drug interactions
Anticoagulants: Warfarin and heparin
Prolong bleeding, even in low dose
Glucocorticoids
Promote gastric alteration
Alcohol
Increased r/o gastric bleeding
Ibuprofen
NSAIDs
Reduce anti plt of ASA by blocking access to cox 1 receptors
Prevent interference by giving ASA 2 hr before other NSAIDs
ACE inhibitors and ARBs
Can impair renal function
Do not want these patients on high dose ASA
Vaccines
Can blunt immune response
ASA acute poisoning
Remove ASA from system
Immediate threats to life: Respiratory depression, hyperthermia, dehydration, and acidosis. Treatment is largely supportive
Nonaspirin First-Generation NSAIDs
Aspirin-like drugs with 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: Rheumatoid arthritis and osteoarthritis
Do not protect against MI and stroke
Ibuprofen [Advil, Motrin]
Inhibits cyclooxygenase and has antiinflammatory, analgesic, and antipyretic actions
Indications: Fever, mild to moderate pain, arthritis
Generally well tolerated
Low incidence of adverse effects
SAFETY ALERT: All first-generation NSAIDs are associated with an increased risk of GI bleeding that can lead to hospitalization or death
Second-Generation NSAIDs
Just as effective as traditional NSAIDs in suppressing inflammation and pain
Somewhat lower risk for GI side effects
Can impair renal function and cause hypertension and edema
Increased risk of MI and stroke
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
Does not inhibit cox 1
Celebrex uses
Osteoarthritis
Rheumatoid arthritis
Acute pain
Dysmenorrhea
Familial adenomatous polyposis
Celebrex ADRs
Dyspepsia
Abdominal pain
Renal impairment
Use cautious in pt with HTN, HF, CKD, edema
Inhibition of cox 2
Sulfonamide allergy
Contraindication in pt with sulfa allergy
Contains sulfa molecule, can cause allergic reaction
Cardiovascular impact (stroke, MI, and other serious events)
Use in pregnancy
This med along with other NSAIDs can cause premature closure of ducts arteriosus in fetus
contraindicated in 3rd trimester
Research shown after 12 months, this medication shows no difference in this and other NSAIDs for GI side effects
Celebrex drug interactions
Warfarin
Increase risk of bleeding
May decrease diuretic effect of furosemide
May decrease antihypertensive effect of ACE inhibitors
May increase levels of lithium
Celecoxib levels may be increased by fluconazole
Acetaminophen [Tylenol] uses
Analgesic, antipyretic
Does not have any antiinflammatory or antirheumatic actions
Not associated with Reye syndrome
Does not suppress plt aggregation
Does not cause GI alteration
Does not decrease renal BF or cause renal impairment
Big concern is hepatic injury
Tyl MOA
Inhibits prostaglandin synthesis in central nervous system
Tyl ADR
Very few at normal doses
S
tevens-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), and toxic epidermal necrolysis (TEN)
Painful rashes, blistering of the skin and mucous membranes, Medical emergencies, Can result in death, Can occur at any time, even if pt has taken drug before
Recovery takes weeks to months, If rash occurs –stop drug immediately an seek medical attention
Hepatotoxicity
With overdose or in patients with liver failure
Tyl OD
Signs and symptoms of hepatic failure, coma, death
Early symptoms: Nausea and vomiting, diarrhea, sweating, abdominal pain
Treatment for overdose: Acetylcysteine (Mucomyst)
Tyl drug interactions
Alcohol
Increases risk of liver injury with excessive tyl doses
Increases risk for both liver and kidney damage
Warfarin
Tyl can increase risk off bleeding by influencing metabolism of warfarin
Vaccines
Blunt immune responses to vaccines
Do not use tyl before vaccinations
Tyl max dose
Maximum adult dose: 40000 mg/day
30000 if using alcohol
Tylenol is in many preparations
AHA Statement on COX Inhibitors
Most COX inhibitors, especially COX-2 inhibitors, increase the risk for MI and stroke
American Heart Association (AHA) recommends a stepped-care approach:
1: PT, exercise, weight loss, ice/heat
2: tyl, ASA -> tramadol, opioid (only short term)
3: non-selective NSAIDs
Naproxen, ibuprofen
4: selective COX 2 inhibitors
Last resort –greatest risk for CV harm
Celecoxib is last-choice drug for chronic pain
Lowest dose for the shortest time
