NSAIDs

Question 1

Define inflammation

Answer 1

A response characterized by pain, redness, heat, and swelling

Question 2

Inflammation can occur in response to what four things?

Answer 2

an infection, an allergic reaction, an injury, or metabolic imbalance

Question 3

What causes periodontitis?

Answer 3

bacteria help form dental plaque that causes inflammation and destruction of the gingival mucosa

Question 4

What characterizes acute inflammation?

Answer 4

• 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

Question 5

What characterizes chronic inflammation?

Answer 5

• 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

Question 6

Define eicosanoids

Answer 6

• products of arachidonic acid metabolism
  
  • include: prostaglandins, prostacyclins, thromboxanes, leukotrienes
  • can induce pain and fever
  • synthesis requires cyclooxygenase

Question 7

Compare and contrast cyclooxygenase I and II

Answer 7

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

Question 8

What is the mechanism of actions of NSAIDs?

Answer 8

Inhibit cycloxygenase enzymes > prevents synthesis of eicosinoids

Question 9

What are the adverse effects of NSAIDs?

Answer 9

• they are dose and time related
• Most common include:
  
  • gastropathy (irritation, nausea, bleeding, ulceration, erosions)
  • nephrotoxicity (acute renal failure)
  • idiosyncratic reactions (skin, delayed healing)

Question 10

Describe the pharmacokinetics of NSAIDs

Answer 10

organic acid with good lipid solubility and high oral bioavailability, but limited distribution due to extremely high plasma protein binding (V_D = 0.1-0.3L/kg)

• absorption enhanced in acidic environments (E.g. stomach, saliva )
• biphasic absorption in ruminants (stomach, then intenstine)

Question 11

Why might the uniformly high plasma protein binding of NSAIDs be a benefit to its therapeutic properties?

Answer 11

inflammatory exuate has high levels of plasma proteins > high protein sequesters NSAIDs in the exudate > may prolong drug persistence at inflamed sites

Question 12

Why are NSAIDs primarily eliminated solely by hepatic metabolism?

Answer 12

because protein bindings limits renal elimination