Peripherally-Acting Analgesics and Corticosteroids Flashcards
What are the effects of NSIADs?
Have central & peripheral effects
What are the principle action of NSAIDs?
blockade of prostaglandin production
What does the NSAIDs inhibit?
the activity of cyclooxygenase enzymes (COX-1 and COX-2) that are required for the production of prostaglandins
What is the primary MOAC of NSAIDs?
inhibiting the biosynthesis of prostaglandins by preventing the substrate arachidonic acid from binding to the COX enzyme active site
What is arachidonic acid?
present in cellular tissues and is released when the cellular membranes are disrupted by injury or disease
What is prostaglandins?
localized hormones that are responsible for inflammatory activity (vasodilation, erythema, edema, fever) and nociceptor sensitization
NSAIDS can be classified by ______ selectivity
COX
What are the two COX forms?
cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2)
What is COX1?
catalyzes production of prostaglandins that maintain physiologic functions: – maintain normal renal function, mucosal protection in GI tract, proaggregatory thromboxane A2 in platelets
What is COX2?
expression induced by inflammatory mediators in tissues, role in mediation of pain, inflammation, & fever; some anticoagulation activity, modulation of cell proliferation and pain sensitization
What is COX-1 activity?
- Hemostasis
- gastric mucosa protection
What is COX-1 inhibition benefits?
- possible reduced neuro inflammation targets at microglia
- cardio-protective anti coagulation
What is COX1- inhibition risks?
- can cause bleeding
- increased risk of gastric irritation & ulcers
What can COX-2 activity?
- inflammatory response
- fever
- pain sensation
- anticoagulation
- modulation of cell proliferation
What can COX-2 inhibition benefits?
- reduced inflammation
- reduced fever
- reduced pain sensation
- possible reduction in cancer progression
What CO2 inhibition risks??
Increase risk of thrombotic activity
What properties of NSAIDS?
Antipyretic, anti-inflammatory and analgesic properties
What are the characteristics of NSAIDs?
Weakly acidic, highly protein bound, lipophilic, low volume of distribution, and only the unbound portion is effective
What is the pKa of NSAIDs? What formed does it exist?
- NSAIDs are weak acids with pKa values typically lower than 5
- Exists mostly in the ionized form at physiologic pH
What is the protein bind of NSAIDs?
> 90% bound to albumin
What can occur from hypoalbuminemia with NSAIDs?
hypoalbuminemia & displacement by other drugs that are albumin bound can result in greater unbound NSAID & increased risk for toxicity
What is the elimination of NSAIDs?
Elimination via hepatic oxidation and conjugation (less than 10% eliminated via renal activity)
What some principles of NSAIDs?
- Decreased activation and sensitization of peripheral nociceptors
- Attenuation of the inflammatory response
- Absence of dependence or addiction potential
- Synergistic effects with opioids
- Preemptive analgesic effects
- Absence of respiratory depression
- Minimal N&V compared to opioids
- Long duration of action
- No effects on cognition
What is true about NSAIDs and hypersensitivity?
- Hypersensitivity reactions more common in individuals w/nasal polyps or asthma
- allergic reactions – bronchoconstriction, rhinitis, urticaria