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;
74 Cards in this Set
- Front
- Back
|
What is the modern day definition of inflammation
|
Reaction of vascularized living tissue to local injury
Protective response to noxious stimuli |
|
|
What is responsible for the heat and redness in an inflammatory reaction? What about the swelling? What about the pain?
|
Vasodilation causes heat and redness
Increase in vascular permeability causes swelling Mediator release causes pain |
|
|
What are the 3 physiological signs of acute inflammation
|
Vasodilation
Increased vascular permeability Recruitment of neutrophils |
|
|
What is the key difference in chronic vs acute inflammation
|
chronic inflammation involves lymphocyte, plasma cells, macrophages, fibroblasts, and angioblasts
|
|
|
What are some examples of acute inflammation? Chronic inflammation?
|
Acute- sore throat, gout, insect bite
Chronic - ulcerative cholitis, tb, rheumatoid arthritis, chrohn's disease, asthma |
|
|
Is inflammation inevitable?
|
Body can usually moderate the inflammatory response- so inflammation is not seen at all in some cases. But other times, inflammation is never resolved.
|
|
|
What is the mediator theory?
|
Signs and symptoms of inflammation are caused by the release of chemicals
|
|
|
What are the harmful effects of inflammation
|
Inflammatory enzymes release lysosomal enzymes (collagenases, proteases) that can digest normal tissue
Inflammatory swelling may result in death- swelling that obstructs airways, swelling in the cranial cavity. |
|
|
What is the cell source of histamine?
|
Mast cells, basophils.
|
|
|
What is the physiological response of histamine?
|
Vasodilation, increased vascular permeability, pain
|
|
|
How does histamine work (mechanism). What are antihistamines?
|
Histamine activates GPCRs.
Antihistamines are H1 antagonists |
|
|
Bradykinin's chemical structure and cell source
|
Peptide and endothelial cells
|
|
|
Bradykinin's physiological response
|
Vasodilation
Increased vascular permeability Pain |
|
|
Mechanism of Bradykinin
|
Activation of GPCR
|
|
|
What is the cell source of complement protein
|
Synthesized by liver, circulate in blood
|
|
|
Physiological response of complement system
|
These plasma proteins
1) chemotaxis 2) release of mediators from neutrophils 3)increase vascular permeability 4) excessive activation may contribute to injury |
|
|
MOA of complement system
|
Activation of GPCR
and Complement protein complexes cause osmotic lysis |
|
|
Where is c reactive protein found?
|
In the plasma
|
|
|
What makes c reactive protein
|
Produced in liver in response to cytokines and also in adipocytes
|
|
|
C reactive protein is a marker of _____? What diseases are elevated crp associated with
|
inflammation.
Diabetes, hypertension, CV disease. Statins may be effective in patients with elevated CRP. |
|
|
What is the physiological response of c reactive protein
|
CRP is an acute phase reactant that activates the complement cascade and mediates phagocytosis.
|
|
|
What is the MOA of c reactive protein
|
Binds phospholipids in bacteria and damaged cells
|
|
|
What are the pro inflammatory cytokines?
|
These are proteins that are secreted - IL1 and TNFalpha by nearly ALL cells.
|
|
|
What physiological effects does TNF alpha have? IL1?
|
TNF - acute phase reaction, fever, sepsis
IL1 - acute phase reaction, fibroblast and lymphocyte proliferation, fever |
|
|
What is the mechanism of action of the cytokines
|
The cytokines activate NFkB and AP-1, which then induces gene expression of cyclooxygenase (fever), lipoxygenase, adhesion molecules, and collagenase
|
|
|
What are 2 cytokine inhibitors to know
|
Etanercept
Infliximab |
|
|
What cells make adenosine? What is it formed from
|
All cells.
Purine nucleoside formed from breakdown of ATP. |
|
|
What physiological response of adenosine
|
Inhibits cytokine action (anti-inflammatory) and is increased during injury
|
|
|
What is the mech of action of adenosine?
|
Activation of GPCRs
|
|
|
Adenosine in pharmacology
|
Adenosine A2 agonists
|
|
|
Cell adhesion molecules source
|
Endothelial cells, platelets, leukocytes.
|
|
|
Physiological response of CAMs
|
1) Leukocyte adhesion to endothelium pivotal in host defense and tissue repair
2) Endothelial adhesion molecules contribute to recruitment of activated platelets. |
|
|
What is the mechanism of CAMs
|
Contact molecules, calcium dependent.
|
|
|
What is the source of oxygen derived free radicals (Superoxide, hydroxy radicals)?
What is the physiological response and mechanism What are antioxidants used |
All cells.
Intracellular killing of bacteria by neutrophils Mechanism protein oxidation lipid peroxidation DNA mutation Vitamin C and E supplementation |
|
|
What is the source and physiological response of prostaglandins
|
all cells
vasodilation, pain, fever, platelet aggregation |
|
|
What is the mechanism of prostaglandins
|
Activation of GPCRs
|
|
|
What is the source of leukotrienes; what is the physiological response
|
Macrophages, neutrophils are sources of leukotrienes
Physiological response is to increase vascular permeability and cause bronchoconstriction. |
|
|
What is the mechanism for leukotrienes
|
GPCRs
|
|
|
What is the cellular source of glucocorticoids
|
Adrenal Cortex
|
|
|
What is the physiological response of glucocorticoids
|
1) inhibit cytokines
2) inhibit phospholipase A2 3) inhibit cyclooxygenase 2 4) inhibition of CAMs |
|
|
Glucocorticoids what is the mechanism of action
|
Nuclear receptors activated
|
|
|
The 2 major types of antiinflammatory drugs are
|
steroids and nsaids
|
|
|
steroids MOA
|
bind to cytoplasmic receptors, activated receptor-steroid complexes- localizes to nucleus/binds DNA
Then causes transcription of certain genes (induc/repression) |
|
|
what is the problem with steroids
|
most patients with chronic inflammatory conditions respond to steroids
but a small minority of patients are steroid resistant |
|
|
How do nsaids work
|
inhibit cox gene
|
|
|
What are the other anti-inflammatory drugs
|
zafirlukast
zileuton are both leukotriene antagonists cytokine inhibitors are etanercept and infliximab |
|
|
What does the term eicosanoids refer to?
|
Prostaglandins, leukotrienes, and related compounds (thromboxane)
these are 20 c essential fatty acids that have 3-5 double bonds |
|
|
What is the most abundant precursor of eicosanoids
|
arachidonic acid
|
|
|
What are the 3 fates of arachidonic acid?
|
COX to make prostaglandins, thromboxane, prostacyclins
lipoxygenase to make leukotrienes, hetes, lipoxins P450 metabolism |
|
|
What form does arachidonic acid exist in cells
|
Esterified to membrane phospholipids. Free AA is low.
|
|
|
The release of AA depends on
|
Calcium
|
|
|
What is the enzyme that frees Arachidonic acid from its esterified form?
|
Phospholipase A2
|
|
|
Compare and contrast COX 1 and COX 2
|
Both have the same 2 distinct activites, both are heme, membrane bound proteins. Cox 1 is constitutive; cox 2 is inducible. They are encoded on different chromosomes and the active site is larger in cox2
|
|
|
What are the 2 fns of COX
|
1) oxygenate and cyclize the precursor fatty acid to form PGG2.
2) peroxidase activity to convert PGG2 to PGH2 |
|
|
What is the fate of PGH2
|
Transformed into TXA2 (thromboxane), PGE2, and PGF2 as well as PGI2
|
|
|
What do lipoxygenases accomplish?
|
Convert fatty acids into corresponding lipid hydroperoxides
|
|
|
What is the most important lipoxygenase?
|
5-lipoxygenase - it leads to leukotriene synthesis
|
|
|
What does 5-lipoxygenase need to work
|
calcium
and 5-lipoxygenase activating protein |
|
|
What are some ways to inhibit phospholipase A2
|
Since Phospholipase A2 is activated by calcium, drugs that reduce availability of calcium will work to inhibit Phospholipase A2.
Glucocorticoids induce the synthesis of annexins that inhibit phospholipase A2 activity. |
|
|
What are some ways to inhibit COX
|
Aspirin and related NSAIDS inhibit both COX
COX2 selective drugs Glucocorticoids decrease expression of cox2 but not 1 |
|
|
What are the 2 ways to inhibit lipoxygenases
|
Zileuton inhibits 5-lipoxygenase
zafirlukast is a cysteinyl leukotriene receptor antagonist |
|
|
What is zileuton?
How long is its half life |
Half life 2.5 hrs
Inhibitor of 5-lipoxygenase. |
|
|
What is the mechanism of zileuton?
|
By inhibiting 5-lipoxygenase, you inhibit the production of leukotrienes that cause bronchoconstriction.
|
|
|
Side effects of zileuton?
Therapeutic use of zileuton |
Few side effects- increase liver enzymes
Prophylactic treatment of mild asthma |
|
|
What is zafirlukast. half life?
|
A cysteinyl leukotriene receptor antagonist. Half life 10 hours.
|
|
|
What is the therapeutic use of zafirlukast. adverse effects?
|
Prophylactic treatment of asthma. side effects are minimal
|
|
|
What are the two steps of eicosanoid catabolism?
|
1. oxidation of the 15-OH group by PG dehydrogenase followed by reduction catalyzed by Delta 13 pg reductase- this is rapid and results in most biological activity lost
The second step is a beta and omega oxidation of side chains that give a polar compound - slow step |
|
|
How do prostaglandins exert their action and why are they so diverse in action
|
They exert effect through g proteins. They have a wide diversity of effects because there are many receptors
|
|
|
What kind of receptors exist for the leukotrienes? How do they exert their action?
|
receptors for LTB4 and also for
the cysteinyl leukotrienes LTC4 and LTD4. They work through g proteins to increase intracellular calcium. |
|
|
What kinds of cells make eicosanoids?
|
Virtually every cell
|
|
|
What do PGE2, PGI2 do physiologically for pain? Mechanism?
|
They are involved in pain response- lower threshold of nociceptors (hyperalgesia- more responsive to bradykinin)
|
|
|
How does PGE2 play a role in fever?
|
An increase in cytokines leads to increased COX, which increases PGE2. This leads to increase in cAMP that triggers the hypothalamus to elevate body temperature.
|
|
|
How is TXA2 formed?
|
Activation of platelet membrane PLA2 causes release of arachidonic acid and its transformation into TXA2 by cox-1
|
|
|
What are the physiological effects of TXA2 for platelet aggregation
|
Promotes platelet aggregation by stimulating TP receptor that couples to increase in intracellular calcium
|
