Chapter 57: Cyclooxygenase Inhibitors: Nonsteroidal Anti-inflammatory Drugs and Acetaminophen

Question 1

Cyclooxygenase Inhibitors: uses

Answer 1

Suppress inflammation

Relieve pain

Reduce fever

Question 2

2 Types of cox receptors

Answer 2

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”

Question 3

Cyclooxygenase Inhibitors: ADR

Answer 3

Gastric ulceration

Bleeding

Renal impairment

Question 4

Cyclooxygenase Inhibitors: MOA

Answer 4

Inhibit cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostanoids (prostaglandins and related compounds)

Question 5

Inhibition of COX-1 (“good COX”)

Answer 5

Gastric ulceration

Bleeding

Renal impairment

Question 6

Inhibition of COX-1: Beneficial effects

Answer 6

Protection against myocardial infarction (MI) and stroke
Secondary to reducing platelet aggregation

Question 7

Inhibition of COX-2 (“bad COX”): Largely beneficial effects:

Answer 7

Suppression of inflammation

Alleviation of pain and reduction of fever

Protection against colorectal cancer

Question 8

2 bad effects of inhibiting cox 2

Answer 8

renal impairment and promote of MI and stroke.

Question 9

Classification of Cyclooxygenase Inhibitors

Answer 9

Drugs with antiinflammatory properties
Nonsteroidal antiinflammatory drugs (NSAIDs)
Aspirin, celecoxib, ibuprofen, and naproxen

Drugs without antiinflammatory properties
Acetaminophen

Question 10

First-Generation NSAIDs

Answer 10

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

Question 11

ASA

Answer 11

Nonselective inhibitor of cyclooxygenase

Question 12

ASA therapeutics ses

Answer 12

Analgesic, antipyretic, and antiinflammatory

Suppression of platelet aggregation
Protects in thrombotic disorders

Dysmenorrhea

Cancer prevention

Prevention of Alzheimer disease

Question 13

ASA ADR

Answer 13

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

Question 14

ASA drug interactions

Answer 14

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

Question 15

ASA acute poisoning

Answer 15

Remove ASA from system
Immediate threats to life: Respiratory depression, hyperthermia, dehydration, and acidosis. Treatment is largely supportive

Question 16

Nonaspirin First-Generation NSAIDs

Answer 16

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

Question 17

Ibuprofen [Advil, Motrin]

Answer 17

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

Question 18

Second-Generation NSAIDs

Answer 18

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

Question 19

Celecoxib [Celebrex]

Answer 19

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

Question 20

Celebrex uses

Answer 20

Osteoarthritis

Rheumatoid arthritis

Acute pain

Dysmenorrhea

Familial adenomatous polyposis

Question 21

Celebrex ADRs

Answer 21

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

Question 22

Celebrex drug interactions

Answer 22

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

Question 23

Acetaminophen [Tylenol] uses

Answer 23

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

Question 24

Tyl MOA

Answer 24

Inhibits prostaglandin synthesis in central nervous system

Question 25

Tyl ADR

Answer 25

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

Question 26

Tyl OD

Answer 26

Signs and symptoms of hepatic failure, coma, death

Early symptoms: Nausea and vomiting, diarrhea, sweating, abdominal pain

Treatment for overdose: Acetylcysteine (Mucomyst)

Question 27

Tyl drug interactions

Answer 27

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

Question 28

Tyl max dose

Answer 28

Maximum adult dose: 40000 mg/day

30000 if using alcohol

Tylenol is in many preparations

Question 29

AHA Statement on COX Inhibitors

Answer 29

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