Flashcards in Exam 2 - Medchem 753, Delander Gout Deck (54)
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1
What is gout?
Inflammatory disease that results in urate crystals in joints and soft tissues
2
What causes the formation of crystals in gout?
Crystals form due to improper handling of uric acid which causes a supersaturated solution of urate precipitating crystals
3
How many people in the US are affected with Gout?
8 million (4% of population)
4
What factors are associated w/or are aggravated by Gout?
Genetics (big)
Obesity (Surface area?)
Age (older worse)
Adult Males
Potmenopausal women
HTN
Diet (high purine or high fructose)
5
What disease states might Gout be more prevalent in?
Lesch-Nyhan Syndrome
End Stage renal disease
Cancers w/ cell lysis
Major Organ Transplant
6
What Drugs may induce or exacerbate the presence of Gout?
Thiazides (Diuretics) - compete for transporters
Low dose Aspirin
Niacin
Immune Suppressants
Cytotoxic agents causing cell lysis
7
What is Lesch-Nyhan Syndrome?
A disease characterized by a lack of HGPRT which results in problems in the breakdown and removal of Urate. It is a Problem w/ Metabolic Process that some people have that does not have salvage pathway which results in higher amounts of Uric Acid and gout like symptoms.
8
What are the disease stages of Gout?
Acute
Intermittent
Chronic
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When do Acute phases of Gout generally occur?
At night while asleep, while not moving, increased likelihood of crystalizing out due to things cooling down.
10
What are the common characteristics of acute gout?
- Crystals form in joint(Very common in big toe)
- low grade fever
- typically resolves in 3-14 days
- May not have another attack for quite a while or ever
- Intense pain
11
What are the common characteristics of intermittent gout?
- Acute attacks x2 or more per year
- Usually in more than one joint (not always toe)
12
What are the common characteristics of chronic Gout?
Means that something is happening w/ disease state to cause other problems
- Start therapy
- Changes in renal
- permanent crystals setting in joints
- generally polyarticular (many joints)
13
What affect does change in diet have on disease state?
Generally very minimal effect
14
Where do Purines come from?
1. Our cells, constantly breaking down and forming it
2. Food
15
What is the enzyme animals have to break down Uric Acid?
Uricase (urate oxidase) which breaks down urate into Allantoin
16
What animal species do not contain Uricase?
Humans, Apes and Dalmations (dog)
17
What percentage of Uric Acid enters the Proximal tubule from glomerulus?
100%
18
What percentage of Uric Acid is reabsorbed by glomerular filtration?
98-100%
19
Due to secretion and reabsorption of Uric Acid, what percentage of Uric Acid is actually excreted in Urine?
8-12%
20
Due to secretion and reabsorption of Uric Acid, what percentage of Uric Acid is actually excreted in Urine?
8-12%
(increasing is current area of drug research)
21
What are Inflammasomes?
When there are high levels of Uric Acid in plasma, the uric acid cystallize and are phagocytized and form these, which release IL-1b, which activates a huge inflammatory response.
22
How much Uric Acid is the "magic number"? At what level is treatment usually started?
~7mg/dL
23
What are the chronic problems of gout that we are worried about with managing Gout?
- Renal - Nephrolithiasis (stones) and Interstitial Nephritis
- Arthritic - Deposition of Tophi, erosion of Cartilage and bone, loss of function
- Metabolic - associated w/ metabolic syndrome, stroke and other CVD
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What is the gold standard in diagnosing Gout? What else is used?
Visualization of Uric Acid Crystals in aspirated synovial fluid
Differential Diagnosis by using colchicine to treat
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What are the treatment goals of Acute Gout?
Resolve inflammatory process rapidly
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What are the treatment goals of intermittent/chronic Gout?
Decrease Uric Acid so we don't have long term problems of effects
New Guidelines state we don't try to control serum level, we treat to control symptoms.
27
What medication has traditionally been the go to therapy for Acute flares of Gout? Why is it no longer? What is the first line according to guidelines now?
Colchicine, Price
Steroid then NSAID
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Colchicine
1. MOA
2. Dosing
3. SE
4. Considerations
1. Decrease Microtubule formation, which limits chemotaxis
2. (1.2mg, prn 0.6mg an hour later) effective for 36hrs (1.2mg/day generally for 14 days)
3. GI upset (25%), Muscle Weakness (inc w/ statins), Bone Marrow Suppression (penias)
4. Price, Dose adjustments w/ Hepatic failure, inhibits 3A4 & PGP
29
What other drug classes are often prescribed for acute Gout flares?
NSAIDS
Steroids
IL-1 Antagonists (off label)
Adrenocorticotropic hormone (ACTH)
Opioids (?)
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