E3: NSAIDS Flashcards
Glucocorticoids inhibit (COX1 &/or COX2)
COX2 inhibits (COX1 &/or COX2)
Inflammation inducer: (COX1 &/or COX2)
Constitutive homeostatic functions: (COX1 &/or COX2)
Glucocorticoids inhibit: COX1 & COX2
COX2 inhibits: COX2
Inflammation inducer: COX2
Constitutive homeostatic functions: COX1
COX1 or COX2
Give examples
Salicylates (1):
NSAIDS (4) (rank from most nonselective to Most COX1:
COX-2 Selective Inhibitors (1):
Salicylates (1):COX-1 inhib > COX 2 inhib
acetylsalicylic acid (Aspirin)
NSAIDS (4): COX-1,COX-2 inhibition non-selective
1. ibuprofen-Motrin®
2. Naproxen-Naprosyn®
3. Diclofenac-Voltaren®
4. Ketoralac-Toradol
COX-2 Selective Inhibitors (1):
1. celecoxib-Celebrex®
NSAID Pharmacology
MOA
3 main activities
block cyclooxygenase (cox-1 and cox-2) and formation of prostaglandins and thromboxanes
- anti-inflammatory activity
A. Block formation of inducible cox-2 isoenzyme to ↓ inflammatory PG’s - antipyretic activity
A. Block production of hypothalamic prostaglandins
1) stimulated by cytokines (TNF and Interleukins) - analgesic activity
A. Block formation of PGE2, PGF2 which ↓ pain “sensitization”
1) does not block original pain impulse but blocks intensity of pain
What are the 3 site affected by NSAID SE and which COX causes the SE
GI mucosa: COX1
Kidney: COX1/2
CV: COX 1/2
NSAIDS vs COXIBS
GI ulceration risk: which is higher/lower or same
Renal: which is higher/lower or same
CV Risk: which is higher/lower or same
GI: NSAIDS higher
Rena: Same risk w/LT use
CV: If patient has previous CVD and ↑ length of therapy = significant risk w/NSAIDS; COXIBS also high
GI ADR Presentations
- Abdominal pain, dyspepsia
- NVD
- Peptic ulcer disease, perforation
- blood in stool
- hematologic abnormalities
- NSAIDS can have (Renal or hepatotoxicity)
- What ↑ the risk of toxicity
- Presentation of ADR
- How to monitor for it
- RENAL
- Prolonged use
- Inhibition of local prostaglandins that promote vasodilation could cause water and Na retention –> ↑ blood pressure with NSAID toxicity
- monitor renal function w/prolonged use: Scr, CrCL
CV Risk and NSAIDS
- ↑ blood pressure
- Fluid retention and edema in HF patients, ↓diuretic efficacy
- Coronary artery disease, ischemic heart disease
A. Inhibition of prostacycline (PGI2) leads to prothrombotic risk and platelet aggregation - ↑ dose –> ↑risk
NSAID
DI
CI
DI
1. chronic oral NSAIDs given at the same time with cardioprotective doses of
ASA (81mg) ↓ antiplatelet effectiveness of ASA
- controlled clinical trials with NSAIDs and ASA for pain following CABG found an ↑ risk of MI and stroke
- displacement of plasma protein binding can lead to drug toxicities
Relative CI: All NSAIDs avoided/used with caution in Pregnancy
1. bleeding in fetus
2. Premature closure of the ductus arteriosus in the heart of some babies –> pulmonary hypertension in the fetus
celecoxib-Celebrex
Indications
MOA
Pharmacologic effects
ADR
CI
Indications
1. alternative to traditional NSAIDs for those who are at high risk for
GI toxicity
MOA: relative competitive reversible inhibition of cyclooxygenase-2 (COX-2)
with some COX-1 inhibition leading to a in the production of thromboxanes and prostaglandins
Pharmacologic effects
1. analgesic, antipyretic, anti-inflammatory
2. anti-inflammatory effect similar to ibuprofen 800mg and naproxen 500mg
3. does not inhibit platelet aggregation
A. does not have a cardiovascular benefit like ASA
B. may actually be demonstrating some prothrombotic effects especially at
higher doses (> 400mg)
ADR
1. > 50% reduction in GI event risk compared to non-selective NSAIDs
2. renal ADR/risk (1-5%) and mechanisms comparable to NSAIDs
3. ↑ CV thrombotic events ie stroke, MI with higher dose Celebrex®
A. Coxibs disproportionately inhibit endothelial cell PGI2 production and leave TxA2 production unaffected in the platelet
B. chronic Celebrex® is not recommended in higher doses (> 400 mg/day)
CI:
- bleeding disorders
- w/ warfarin-Coumadin®
- celecoxib-Celebrex® CI in sulfa allergy
