Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
94 Cards in this Set
- Front
- Back
|
What are the 2 components of the modern definition of inflammation?
|
1. Reaction of vascular living tissue to local injury
2. Protective response to noxious stimuli |
|
|
3 Physiological signs of Acute Inflammation:
|
-Vasodilation
-Increased vascular permeability -Recruitment of neutrophils |
|
|
What do the neutrophils and inflammatory cells that accumulate at sites of inflammation release?
|
Mediators
|
|
|
What are 5 mediators PMNs release?
|
Cytokines
Eicosanoids Platelet activating factor Proteinases Free radicals |
|
|
What is the result of mediator release?
|
Pain and tissue destruction
|
|
|
What is Chronic inflammation?
|
Inflammation with a prolonged duration of weeks to months or forever.
|
|
|
What makes Chronic inflammation different from Acute at the histologic level?
|
More diverse cell participation - lymphs, plasma cells, macrophages, fibroblasts and angioblasts
|
|
|
What is the purpose of inflammation in most cases?
|
To restore the body to health and then resolve.
|
|
|
Why do we give drugs for inflammation if it is meant to be a healing process?
|
Because there are some harmful effects of inflammation that can require treatment.
|
|
|
What are 2 potentially harmful effects of inflammation?
|
-Release of lysosomal enzymes that digest normal tissue
-Edema and swelling obstruction of airways and in the brain |
|
|
Why is treating inflammation difficult?
|
Because there are multiple Effects and Mediators, thus difficult to be specific.
|
|
|
What does the "Mediator Theory" state?
|
Signs/Symptoms of Inflammation are caused by the release of chemicals
|
|
|
What are the components of the Triple Response of Lewis? What is each caused by?
|
1. Red scratch - histamine
2. Red flare/flush around scratch - nerves involved 3. Red swollen area around flare - histamine |
|
|
What are the 8 main types of chemical mediators of inflammation to know?
|
HBC
CAC FL |
|
|
What is HBC CAC FL?
|
1. Histamine
2. Bradykinin 3. Complement 4. Cytokines 5. Adenosine 6. CAMs 7. Free radicals 8. Lipid mediators |
|
|
What are the 3 lipid mediators?
|
-Prostaglandins
-Leukotrienes -Steroids |
|
|
What cells store Histamine?
|
-Mast cells
-Basophils |
|
|
What is the physiological response to Histamine?
|
-Vasodilation
-Increased vascular permeability -Pain |
|
|
What is the mechanism of histamine?
|
GPCR activation
|
|
|
What pharmacologic agents are given to prevent histamine effects?
|
H1 antagonists (antihistamines)
|
|
|
What is an H1 antagonist?
|
Diphenhydramine
|
|
|
What is the cellular source of Bradykinin?
|
Endothelial cells
|
|
|
What are the 4 components of the physiologic response to Bradykinin?
|
1. Vasodilation
2. Increased vascular permeability 3. Pain 4. Activation of NF-kB to upregulate cytokines |
|
|
What is relevent pharmacology related to Bradykinin?
|
Bradykinin receptor antagonists are being made because they are upregulated in many diseases
|
|
|
What is the source of Complement?
|
The liver
|
|
|
What are the 3 main complement proteins involved in inflammation?
|
C3a, C5a, C3b
|
|
|
What is the physiological response to complement proteins in inflammation?
|
1. Chemotaxis
2. Release of PMN mediators 3. Increased vasc permeability 4. Tissue injury if excessive |
|
|
What are the main Cytokines involved in inflammation?
|
-IL1
-TNF-alpha |
|
|
What is the cellular source of cytokines?
|
Nearly all cells - inflammatory cells
|
|
|
What are 4 physiological responses to cytokines?
|
1. Increased CAM expression
2. Increased lipoxygenase 3. Fever 4. Fibrosis/tissue degeneration in chronic inflammation |
|
|
What causes the fever?
|
Increased cyclooxygenases
|
|
|
What causes the fibrosis and tissue inflammation?
|
Collagenase
|
|
|
What is the mechanism by which cytokines increase COX, LOX, CAMs and collagenase?
|
Cytokines activate NFkB and AP-1 which induces gene expression of these proteins
|
|
|
What are 2 pharmacologic drugs that act against cytokines?
|
-Etanercept
-Infliximab |
|
|
What does -mab mean?
|
Monoclonal antibody
|
|
|
What is the source of Adenosine?
|
All cells
|
|
|
What is Adenosine?
|
A purine nucleoside breakdown product of ATP
|
|
|
When/where is Adenosine increased and what effect does it have on inflammation?
|
-Increased extracellularly during injury
-Anti-inflammatory |
|
|
How does Adenosine mediate its anti-inflammatory effect?
|
By inhibiting cytokine action via specific GPCRs
|
|
|
What are 2 pharmacologic anti-inflammatory agents related to Adenosine?
|
-A2 agonists
-Methotrexate |
|
|
What is Methotrexate?
What is it used to treat? |
-A folic acid antagonist that releases adenosine
-Used to treat Rheumatoid arthritis |
|
|
What are 4 families of Cell adhesion molecules?
|
-Immunoglobulin like CAMS
-Integrins -Selectins -Cadherins |
|
|
What are 3 cellular sources of cell adhesion molecules?
|
-Endothelial cells
-Platelets -Leukocytes |
|
|
What are 2 important physiological responses to increased CAM expression?
|
-Leukocyte adhesion to tissue injury site
-Platelet adhesion to endothelium to allow clot formation |
|
|
What happens to CAMs during inflammation?
|
Their expression is increased
|
|
|
What is one CAM drug that is currently in use?
|
Abciximab
|
|
|
What is Abciximab?
|
An inhibitor of platelet glycoprotein IIb/IIIa integrin receptor
|
|
|
What is Abciximab used to treat?
|
Coronary artery disease - as an antiplatelet drug
|
|
|
What cells are sources of Free radicals?
|
All cells
|
|
|
What is the physiological response to Cytokines?
|
Cytotoxic - intracellular killing of bacteria by neutrophils
|
|
|
What are 3 mechanisms of free radical damage?
|
-Protein oxidation
-Lipid peroxidation -DNA mutation |
|
|
What is the main pharmacologic agent that reduces free radicals?
|
Antioxidants - Vit C and E
|
|
|
For what disease has the risk of getting it been shown to be reduced in people who take antioxidants?
|
Alzheimer's
|
|
|
What are the 2 main classes of lipid mediators?
|
-Eicosanoids
-Steroids |
|
|
What are the eicosanoids?
|
-Prostaglandins
-Leukotrienes |
|
|
What are Eicosanoids?
|
Prostaglandins and Leukotrienes
|
|
|
What are steroids?
|
Glucocorticoids
|
|
|
What is the cellular source of prostaglandins?
|
All cells
|
|
|
What are the 4 physiologic responses to Prostaglandins?
|
-Vasodilation
-Pain -Fever -Platelet aggregation |
|
|
What is the mechanism by which Prostaglandins mediate their physiologic response?
|
via specific GPCRs
|
|
|
What are 3 pharmacologic agents used to prevent the action of prostaglandins?
|
-NSAIDs
-COX2 inhibitors -Steroids |
|
|
What are the cellular sources of leukotrienes?
|
-Macrophages
-Neutrophils |
|
|
What are 3 physiological responses to Leukotrienes?
|
-Increased vascular permeability
-Chemotaxis -Bronchoconstriction |
|
|
What 3 leukotrienes are responsible for increased vascular permeability?
|
-LTC4
-LTD4 -LTE4 |
|
|
What leukotriene is responsible for chemotaxis?
|
LTB4
|
|
|
What is the mechanism by which Leukotrienes mediate their effects?
|
Specific GPCRs
|
|
|
What are 2 pharmacologic agents for inflammation that act against Leukotrienes?
|
-5Lipoxygenase inhibitors
-Leukotriene receptor antagonists |
|
|
What is a 5-LOX inhibitor?
|
Zileuton
|
|
|
What is a leukotriene receptor antagonist?
|
Zafirlukast
|
|
|
What is Lipoxygenase?
|
The enzyme that converts arachidonic acid to 5-HPETE
|
|
|
What is 5-HPETE?
|
The precursor to leukotrienes
|
|
|
What is the cellular source of Glucocorticoids?
|
Adrenal cortex
|
|
|
What are the 4 main physiologic responses to Glucocorticoids?
|
-Inhibition of cytokines
-Inhibition of Phospholipase2 -Inhibition of COX2 -Inhibition of adhesion molecules |
|
|
What is the mechanism by which Glucorticoids mediate their effects?
|
Via nuclear receptors and steroid response elements that induce or repress gene transcription.
|
|
|
What pharmacologic agents act against Glucocorticoids?
|
Steroids
|
|
|
Why are steroids important?
|
They are the most potent and effective agents for controlling chronic inflammatory diseases
|
|
|
What is an example of hos Steroids are used to treat chronic inflammation?
|
Asthma - inhaled steroids are the first line treatment for them.
|
|
|
So what are the 2 major groups of anti-inflammatory drugs available?
|
-STEROIDS
-NSAIDS |
|
|
What are 2 responses that can be seen in patients treated with steroids?
|
-Response
-Resistance |
|
|
What is the mechanism of resistance in the minority of patients that exhibit it?
|
Cellular defects in steroid responsiveness
|
|
|
What is the prototype nsaid?
|
Aspirin
|
|
|
What is NSAID again?
|
Nonsteroidal anti-inflammatory drug
|
|
|
What is the mechanism of action of NSAIDs?
|
Inhibition of cyclooxygenase
|
|
|
What are 2 other types of anti inflammatory drugs (other than Steroids and NSAIDs)?
|
-Leukotriene antagonists
-Cytokine inhibitors |
|
|
What are the 2 leukotriene antagonists?
|
-Zafirlukast
-Zileuton |
|
|
What is Zafirlukast?
|
The competitive antagonist of leukotriene receptors
|
|
|
What is Zileuton?
|
The inhibitor of 5-lipoxygenase - inhibits leukotriene synthesis
|
|
|
What are the 2 cytokine inhibitors?
|
-Etanercept
-Infliximab |
|
|
What is Etanercept?
|
An analog of the receptor for TNF-alpha that acts as a sink for it.
|
|
|
What is Infliximab?
|
Monoclonal antibody to TNF-alpha
|
|
|
What would be an example of an acute inflammatory attack?
|
Acute gout attack
|
|
|
What are 5 drugs that would be used to treat an Acute gout attack?
|
-NSAIDs
-Steroids -Uricosuric agent -Colchicine -Allopurinol |
|
|
What would be an example of a Chronic inflammatory disease?
|
Rheumatoid arthritis
|
|
|
What are the 3 first line drugs for treating RA?
|
-NSAIDs
-Steroids -Etanercept |
