lecture 3 - anti-inflammatory

Cyclooxygenase (COX) Inhibitors​ Inhibit enzyme (COX) that converts __________ into ________

arachidonic acid into prostanoids

COX - 1 inhibitors

beneficial effects and adverse effects

decreased platelet aggregation - protection against MI and stroke

AE - gastric erosion & ulceration

bleeding tendencies

renal impairment

COX - 2 inhibitors

beneficial effects and adverse effects

suppresses 

• inflammation 

• pain 

• fever 

• colorectal cancer 

AE - renal impairment 

suppresses vasodilation - promote MI and stroke

COX inhibitors with anti-inflammatory effects

Aspirin

Ibuprofen

Celecoxib

Ketorolac

COX inhibitors without anti-inflammatory effects

acetaminophen

1st generation NSAIDS

• used to treat what 

• inhibits what

• side effects

inflammatory disorders 

inhibits COX 1 and COX 2 

gastric erosion and ulceration 

renal impairment 

bleeding tendencies 

2nd generation NSAIDS 

inhibits what 

selectivity? 

risks? 

COX-2 only 

selectivity suppresses pain and inflammation 

fewer side effects than NSAIDS 2 

LESS safe due to increased risk of MI and stroke 

renal impairment  

Ibuprofen

NSAID – reversible non-selective cyclooxyrgenase inhibitor-propionic acid derivative​

inhibits COX-1 and COX-2

mild to moderate pain

• GI effects - ulcers → bleedings

• renal impairment

• increased risk for MI, stroke - thrombotic events 

• SJS 

• affects fetus in pregnancy 

take with food, milk, or antacid

educate pt. on bleeding and concurrent use with blood thinners

lowest dose for shortest amount of time

NO protection against MI or stroke

caution with renal impairment

Ketorolac (Toradol)

NSAID – reversible non-selective cyclooxygenase inhibitor​

inhibits COX 1 and 2

moderate to severe pain 

• similar to ibuprofen 

for patients who cannot take opioids - similar to morphine 

• only take for 5 days 

• monitor renal function 

no protection against MI or stroke 

**** contraindicated in any brain dysfunction or resp. issues 

Celecoxib (Celebrex)

2nd generation selective cyclooxygenase inhibitor​

inhibits COX-2 - decreases inflammation and pain

• common - dyspepsia and abdominal pain 

• increased MI risk - vasoconstriction

• renal impairment 

• affects fetus in pregnancy 

possible cross allergies with sulfas

selectivity - decreased GI risk

no protection of CVA or MI risk  

monitor for renal function  

Acetaminophen

reduces prostaglandin synthesis in CNS

for fever and pain

• increased blood pressure

• hepatotoxicity

• anaphylaxis, SJS, TEN (toxic epidermal necrosis)

assess alcohol consumption - equal to or less than 3 drinks

safe 24 hour dosing

• 3,000 mg for healthy individuals

• 4,000 for those at low risk for liver failure

OVERDOSE - acetylcysteine (Acetadote)

Symmetric joint stiffness & pain​

• Most pain in the AM, then lessens​

Systemic manifestations​

• Fever, weakness, fatigue​

• Weight loss​

• Skin thinning​

• Nodules under skin & periosteum​

RA 

caused by autoimmune response that results in synovial inflammation → pannus → damage to the cartilage leading to bone-on-bone contact & eventual bone fusion ​

RA

Drugs for RA​

• NSAIDs – 

• Glucocorticoids – 

• Disease-modifying anti-rheumatic drugs (DMARDs) - 

rapid relief, rapid relief and slow progression, slow disease progression and joint destruction 

adverse effects of glucocorticoids 

increased blood glucose → glycosuria 

infection 

weight gain - increased appetite 

osteoporosis, adrenal insufficiency, moon face 

Sulfasalazine (Azulfidine)​

non-biologic DMARD - modulate local chemical mediators 

IBS and RA

• H/N/D, anorexia, abdominal pain

• dermatologic - rash, pruritis, uriticaria

• SJS and TENS

• hepatitis and bone marrow suppression

take after meals - enteric release

assess for bone marrow suppression and hepatitis

look for sulfa allergies and derm. effects