Term
| Characteristics of Inflammation |
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Definition
Redness
Swelling
Heat Pain
Loss of Function / Scars |
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Term
| Time Sequence of Inflammtion |
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Definition
Immediate (Minutes)
Acute (Hours)
Chronic (Months)
Oxidation Injury over time (Years) |
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Term
| Pathology of Inflammation |
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Definition
Dilation of Arterioles
Acceleration of blood flow
Slowing of blood flow
White cells bind vessel walls
White cells migrate through endothelial cell junctions |
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Term
| At what point do steroids block the inflammatory process? |
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Definition
| They block NF Kappa b Induction |
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Term
| Explain the causes of the cardinal signs of inflammation. |
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Definition
Redness -- Vasodilation
Heat -- Increased blood flow
Swelling -- Exudation of liquid
Pain -- Swelling |
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Term
| Where do most NSAIDs block the inflammation pathway? |
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Definition
| Most NSAIDs block both COX-I and COX-II enzymes |
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Term
| Describe the process by which cellular damage leads to prostaglandin production. |
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Definition
| Cellular damage >>> Membrane Phospholipid >>> Phospholipase A2 >>> Arachidonic Acid >>> COX-II >>> Prostaglandins |
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Term
| Describe the process by which leukotrienes are produced by cellular damage. |
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Definition
| Cell Damage >>> Membrane Phospholipid >>> Phospholipase A2 >>> Arachidonic Acid >>> Lipoxygenase >>> lipid peroxides >>> Leukotrienes C,D,E and slow reacitng substance P |
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Term
| What role does calcium concentration have in regulating the production of prostaglandins? |
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Definition
| If calcium concentrations are low, then prostaglandins are formed from the arachadonic acid pathway via cyclooxygenase. If the calcium concentration is high, then leukotrienes are formed via the lipoxygenase pathway. |
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Term
| What physiological mechanisms are regulated by COX-I? |
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Definition
**Vasodilation** and vasoconstriction
Prostacyclin -- Inhibits clotting
Thromboxane -- Causes clotting
Prostaglandin E -- Cytoprotection of the stomach |
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Term
| What physiolgical mechanisms are regulated by COX-II? |
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Definition
Inducible
Inflammatory system
Produces large amounts of prostaglandins
Increases pain and increases pain perception |
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Term
| How can diet affect the production of leukotrienes and prostaglandins? |
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Definition
| By changing the composition of the lipids (omega-3-fatty acids) in the cell membrane through diet, you can prevent the formation of prostaglandins and leukotrienes. |
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Term
| What are the three major oxidative systems? |
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Definition
1. Oxidative mechanisms of white cells cause killing of bacteria and produce oxidative damage to normal cells
2. Prostaglandin production (Induced)
3. Peroxynitrite production (Induced) |
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Term
| Where is NO synthase found and how is it induced? |
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Definition
| NO synthase is found in macrophages and is induced by antigen stimulation. |
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Term
| What two free radicals come together in macrophages in order to produce peroxynitrite? |
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Definition
| *O2- (superoxide) and *NO (Nitric oxide) |
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Term
| How is hypochlorous acid formed in neutrophils? |
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Definition
| Oxygen is converted to superoxide by membrane NADPH oxidase. Superoxide dismutase converts the superoxide into hydrogen peroxide. Cl- is added in the presence of myeloperoxidase (MPO), which results in the formation of hypochlorous acid (HOCl). |
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Term
| The induction of which proteins regulates the inflammatory process? |
|
Definition
Cytokines
Adhesion Factors
Chemokines
Enzymes |
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|
Term
| The induction of which proteins regulates the inflammatory process? |
|
Definition
Cytokines
Adhesion Factors
Chemokines
Enzymes |
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Term
| Which cytokines act as the master cytokines, which activate all the others during inflammation? |
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Definition
|
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Term
| What are the inducible inflammatory enzymes? |
|
Definition
Phospholipase A2
COX-II
NO synthase II |
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Term
| What are the non-inducible inflammatory enzymes? |
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Definition
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Term
| What is the transcription factor, which controls many of the key enzymes and cytokines of the inflammatory (induction) process? |
|
Definition
NF-Kappa B
It is inactive in inflammatory cells when no inflammation is present. |
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Term
| Describe the role of IkB-alpha in the activation of NF-Kb. |
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Definition
| When inflammation occurs, IKb-a is phosphorylated and it dissociates from the p50-p65 heterodimer. The activated P50-P65 heterodimer goes into the nucleus and bindes to the promoters at the NF-Kb sites, which induces the production of inflammatory proteins. Thus, Ikb is an inhibitory factor, which is released in the presence of inflammation. |
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Term
| What is the gold standard in anti-inflammatory drugs? |
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Definition
| The anti-inflammatory steroids. |
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Term
| What are the 2 major mechanisms of action of the steroidal anti-inflammatory drugs? |
|
Definition
1. They bind to the NF-Kappa B sites on the promoters of the inflammatory genes and block the induction of inflammatory proteins.
2. They cause IkB to go back to the P50-P65 heterodimer, bind, and inactivate the activated P50-P65 system.
These activities block the induction of inflammatory protein transcription. |
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Term
| What are the short-acting anti-inflammatory steroids? |
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Definition
|
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Term
| What are the intermediate acting steroids? |
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Definition
|
|
Term
| What are the long acting anti-inflammatory steroids? |
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Definition
dexamethasone
betamethasone |
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Term
| What are the advantages of using prednisone? |
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Definition
| It has an extra desaturation in its structure. This makes it 4x more potent as an anti-inflammatory. However, it also makes it less of a mineralocorticoid and thus it is causes less salt and water retention. |
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Term
| What is the most used steroidal anti-inflammatory? |
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Definition
|
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Term
| What adverse effects can result from long term steroid use? |
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Definition
1. It can cause diabetes because insulin release is dependent upon NF-kB release.
2. They can cause lower serum Ca levels and therefore result in bone breakdown.
3. They are immunosuppressive because they inhibit the oxidative mechanisms utilized by the immune system. Thus, patients are more susceptible to infections. |
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Term
| What drugs function as monoclonal antibodies to TNF-a? |
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Definition
|
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Term
| What drug functions as a TNF-a receptor blocker? |
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Definition
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Term
| What are the miscellaneous treatments available for arthritis, Crohn's Disease and Psoriasis? |
|
Definition
Monoclonal antibodies to TNF-a
TNF-a receptor blocker
Low dose methotrexate
Combination of a monoclonal antibody and methotrexate
Combination of TNF-a receptor and Low dose methotrexate |
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Term
| What are the side effects associated with the treatments for arthritis, Crohn's disease, and psoriasis? |
|
Definition
Increased risk of infections
Demyelinization
Heart Failure
Blood Dyscrasias
Lymphoma |
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Term
| Describe how uric acid is formed. |
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Definition
| Adenine and Guanine are broken down into hypoxanthine. Xanthine oxidase converts hypoxanthine into xanthine. Xanthine oxidase then converts xanthine into uric acid. |
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Term
| What type of drug is given to a patient with gout to inhibit pain? |
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Definition
|
|
Term
| What drugs may be given if a gout attack is caught early? |
|
Definition
Prednisone for pain
Allopurinol, which blocks all the steps in uric acid formation involving xanthine oxidase. |
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Term
| What drugs are given to a patient who is an under-secreter of uric acid? |
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Definition
Probenicid or Sulfinpyrazone
They increase urinary excretion of uric acid by blocking reuptake in the kidney |
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Term
| What drug is sometimes given for an acute attack of gout? |
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Definition
| Colchicine, which acts by preventing white cells from engulfing the uric acid crystals and blocks inflammation. |
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Term
| What side effect may be seen with allopurinol? |
|
Definition
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Term
| What side effect may be seen with colchicine? |
|
Definition
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