NSAIDs Flashcards
Define inflammation
A response characterized by pain, redness, heat, and swelling
Inflammation can occur in response to what four things?
an infection, an allergic reaction, an injury, or metabolic imbalance
What causes periodontitis?
bacteria help form dental plaque that causes inflammation and destruction of the gingival mucosa
What characterizes acute inflammation?
- Causative agent: bacteria, pathogens, injured tissues
- Major cells involved: neutrophils, basophils, eosinophils, mononuclear cells
- Primary mediators: vasoactive amines, eicosanoids
- Onset: immediate
- Duration: a few days
- Outcomes: resolution, abscess, chronic inflammation
What characterizes chronic inflammation?
- Causative agent: persistent acute inflammation due to non-degradable pathogens, foreign bodies, or autoimmune reactions
- Major cells involved: mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts
- Primary mediators: INFY, cytokines, growth factor, ROS
- Onset: Delayed
- Duration: Days to months to years
- Outcomes: Tissue destruction, necrosis
Define eicosanoids
- products of arachidonic acid metabolism
- include: prostaglandins, prostacyclins, thromboxanes, leukotrienes
- can induce pain and fever
- synthesis requires cyclooxygenase
Compare and contrast cyclooxygenase I and II
I: constitutively active at low levels in many cells; inhibition viewed as causing adverse side-effects
II: inducible expression, stimulated by cytokines and pro-inflammatory mediators; inhibition viewed as therapeutic
What is the mechanism of actions of NSAIDs?
Inhibit cycloxygenase enzymes > prevents synthesis of eicosinoids
What are the adverse effects of NSAIDs?
- they are dose and time related
- Most common include:
- gastropathy (irritation, nausea, bleeding, ulceration, erosions)
- nephrotoxicity (acute renal failure)
- idiosyncratic reactions (skin, delayed healing)
Describe the pharmacokinetics of NSAIDs
organic acid with good lipid solubility and high oral bioavailability, but limited distribution due to extremely high plasma protein binding (VD = 0.1-0.3L/kg)
- absorption enhanced in acidic environments (E.g. stomach, saliva )
- biphasic absorption in ruminants (stomach, then intenstine)
Why might the uniformly high plasma protein binding of NSAIDs be a benefit to its therapeutic properties?
inflammatory exuate has high levels of plasma proteins > high protein sequesters NSAIDs in the exudate > may prolong drug persistence at inflamed sites
Why are NSAIDs primarily eliminated solely by hepatic metabolism?
because protein bindings limits renal elimination
