NSAIDs & Non-Opioid Analgesics (Exam V) Flashcards
What is the cause of chronic inflammation?
What additional mediators are released?
WBC infiltration of the tissue in response to acute inflammation.
Interleukins
GM-CSF
TNF
Interferons
PDGF
What can block arachidonic acid production?
Corticosteroids
What is the most important autocoid involved in acute inflammation?
What are the other autocoid involved with acute inflammatory response?
Prostaglandin (most important)
Histamine
Serotonin
Bradykinin
Leukotrienes
What is the main pathway target when using NSAIDs?
What is the secondary pathway?
- COX pathway
- LOX pathway
Differentiate COX-1 & COX-2.
Essay Question
COX1 - Constitutive “always on” (stomach mucous secretion, renal blood flow, platelet function, macrophage differentiation “good effects”)
COX2 - Stimulus dependent, inflammatory response.
What drug class are usually the first line defense to relieve mild to moderate pain?
What can glucocorticoids suppress?
What drug can reverse the signs and symptoms on rheumatic disease?
Non-steroid Anti-inflammatory Drugs (NSAIDs)
Can treat acute or chronic pain.
Glucocorticoids can suppress immune response, chronic use can lead to toxicity.
Disease modifying antirheumatic drugs (DMARDs)- slow acting
What is the pharmacodynamics of NSAIDS?
What are the kinetic properties of NSAIDS?
Toxicity and side effects of NSAIDS?
Inhibit PG synthesis through COX-inhibition
Weak acids and well absorbed.
All NSAIDS can cause gastric irritants and can cause nephro/hepatotoxicity.
What function group on aspirin will bind irreversibly to COX-1 to prevent platelet aggregation?
How does ASA go through phase 1 metabolism?
How does ASA go through phase 2 metabolism?
acetyl group
Phase 1 through CYP450
Phase 2 through UGTs
How do NSAIDs treat headaches?
- Decrease sensitivity of brain vessels to bradykinin & histamine = CNS vasoconstriction.
Which NSAID irreversibly blocks COX-1, thus preventing platelet aggregation?
How long will this platelet inhibition last?
- Aspirin
- 8-10 days (the lifespan of the platelet)
Which NSAID is COX-1 selective?
Which NSAID is COX-2 selective?
Which NSAIDs block COX-1 & COX-2 with equal efficacy?
Which NSAIDs are both COX & LOX inhibitors?
Essay Question
COX-1 Selective:
-Aspirin (irreversible)
-Sulindac
-Piroxicam
COX 2 Selective: Celecoxib (Celebrex)
COX1 and COX2
- Ibuprofen
- Toradol
- Meclofenamate
COX and LOX
- Indomethacin
- Diclofenac
What are clinical uses of aspirin?
What are adverse effects of aspirin?
How was aspirin extracted prior to modern medicine?
Widely used to treat mild/moderate pain (12-1500 mg TID)
Rheumatoid Arthritis, Fever
Clot Prevention (81-325 mg/day)
GI upset d/t inhibition of GI protective PG
Increase gastric ulcers d/t decrease buffering
- Willow Bark extraction
Leukotrienes have power chemotactic effect on ______, ________, and ______.
Leukotrienes promote broncho_________.
Leukotrienes alters _____________.
Eosinophils, Neutrophils, and Macrophages
constriction
vascular permeability
Neutrophils produce _________.
How does this damage the membrane?
ROS (reactive oxygen species)
Hydrogen peroxide and hydroxyl radicals
ROS + AA =
Chemotactic metabolites
What can occur with chronic use of COX-2 selective agents?
- Thrombosis from ↑ PLT aggregation
COX-2 has prostaglandins that inhibit platelet aggregation.
What are the effects of COX-2 Selective Inhibitors?
Analgesic
Antipyretic
Anti-inflammatory
Adverse cardiovascular events are related to all NSAIDs except ________.
aspirin
Celecoxib (Celebrex)
Use:
Adverse:
Pharmacokinetics:
Other:
Celecoxib (Celebrex) - Selective COX-2 Inhibitor
Use: Arthritis
Adverse: CV Black Box Warning
Pharmacokinetics: Less GI issues , CYP2C9
Other: Sulfonamide, Very $$$
Diclofenac (Voltaren)
Use:
Adverse: What can you give to decrease GI issues?
Diclofenac (Voltaren) - Inhibits COX and LOX
Use: Pain, inflammation, fever
Adverse: 20% of pt have GI effects, but decrease incidence with misoprostol/cytotec (a synthetic prostaglandin)
Ibuprofen
Use:
Ibuprofen: Inhibits COX1 and COX2
Use: Pain, Inflammation
Indomethacin
Use:
Adverse:
Indomethacin: Inhibits COX and LOX
Use: Patent Ductus Arteriosus , Arthritis, Gout,
Adverse: GI issues
Acetaminophen
Use:
Adverse:
Other:
Acetaminophen: NOT A NSAID
Use: Pain and Fever
Adverse: Toxic levels @15 grams, Hepatotoxicity, ATN
Other: COX-2 inhibitor (primary effect is in the CNS, no significant anti-inflammatory effect)
What is the primary short-term use of glucocorticoid?
Suppression of Inflammation
Mobilize energy stores
Improve Cognitive Function - cortisol release
Salt and Water Retention
Crave carbohydrates for energy utilization.
