Flashcards in Therapy of Inflammation Lecture Deck (19)
What are the 3 distinct phases of inflammation?
1 acute transient phase, characterized by local vasodilation and increased capillary permeability
2 a delayed, subacute phase, most prominently characterized by infiltration of leukocytes and phagocytootic cells
3 a chronic proliferative phase, in which tissue degeneration and necrosis occur
Where is histamine stored and what are its pharmacologic actions involved in the acute inflammatory process?
Stored mainly in mast cells and basophils.
- it locally increases blood flow by capillary dilation
- it causes edema by increasing post capillary venule permeability
- it causes itching by sensitizing primary sensory neurons
What are the two kinins, what exnzymes produce them, what are their acute and chronic effect?
bradykinin and kallidin are produced by kallikreins.
-acute: effects of pain due to excitation of primary sensory neurons
- chronic: effects that are due to capillary dilation, increase in PCV permeability and activation of arachidonic acid release through stim of PLA2
What are the 3 major cytokines involved in inflammation?
Name two enzymes that act on arachidonic acid and what their products are?
Lipoxygenase: produce leukotrienes
COX: produce prostaglandins, prostacyclins, and thromboxanes
What are four major processes that COX 1 is involved in?
1 gastric cytoprotection
2 platelet aggregation
3 renal blood flow autoregulation
4 initiation of partuition
What arachidonic acid derivative is involved in protecting the gastric mucosa?
In which tissue is COX2 consitutively active and what does it do?
Renal: electrolyte homeostasis and blood flow maintenance
Describe the relationship between the doses needed to see analgesic vs anti inflammatory effects when using aspirin?
You need much higher doses to see antiinflammatory effects of aspiring almost 10x what is needed for analgesic
Is aspirin effective in relieving visceral pain?
How does aspirin reduce fever?
Blocks production of PGE2 in regions around hypothalamus
how does aspirin inhibit platelet aggregation?
by inhibiting TXA2 production
What is the toxic intermediate of acetominophen created by P450 enzymes in the liver. in therapeutic dosage what molecule is conjugated to this?
Why doesnt acetominophen have anti-inflammatory effects?
Poor ability to inhibit COX in the presence of high concentration of peroxides, as are found at sites of inflammation.
How is acetaminophen primarily metabolized?
Conjugation with sulfate and glucuronide
Does acetaminophen produce gastric side effects?
What is given to treat acetaminophen overdose?
Do coxibs have effects on platelet aggregation?