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Flashcards in gout Deck (45):
1

can make dx of gout on

symptoms
serum uric acid levels

2

colchicine only works for

gout
not other arthritis

3

Primary gout is a familial disorder that is thought to result from genetically-determined errors of

purine metabolism or uric acid excretion that lead to increased circulating levels of uric acid.

4

secondary gout from

drugs, diet, disease states

5

uric acid is the major end product of

purine metabolism
(adenine, guanine)-->xanthine-->uric acid (no physio function) try to excrete

6

??? increase levels and catabolism of purines

-high purine diet, heavy alcohol consumption, surgery, certain drugs, etc--> can increase uric acid formation

7

90% uric is filtered at the ??

10%
-problem if..

glomerulus (~90%)

(~10%), by active secretion through the organic acid secretory system in the proximal tubule
-drugs may compete for transporter: low-dose ASA, diuretics

8

decreased function of kidney (hypo perfusion) caused by ??? may cause build up of uric acid

heart failure

9

about 75-90% of the uric acid/urate ion in the tubular fluid can be

reabsorbed in the proximal tubule by the anion exchange transport system
-if hard time reabsorbing uric acid-->potential gout

10

Normal values for plasma urate/uric acid

solubility of uric acid in water

pKa?

2.0-7.0 mg/deciliter or 120- 420 μM

0.68 g/L (approach solubility! about 5L blood in body)

pKa of 5.7
more soluble at high pH(alkaline)

11

factors contrib. to hyperuricemia/gout

Heredity
Diet
Alcohol (often a major factor)
Low fluid intake
Cancer
Radiation therapy
Drugs

12

hyperuricemia/gout inducing drugs

aspirin (low-moderate doses)
diuretics (especially thiazides)
sulfonamide antimicrobials
antineoplastics (anticancer drugs)
l-DOPA

13

25% of gout pts have attacks even though..

also, many ppl with mild hyperuricemia never...

their uric acid levels are in normal range

develop gout

14

steps in acute gout attack:

1. sodium urate crystals form in joint
2. phagocytosis by neutros and macros
3. neutro activation and release of inflamm. mediators (PGs, LKs, NO, Superoxide) triggers inflammatory reaction
also the generation of lactic acid and other acidic metabs lower pH-->inc. urate crystal formation

15

4 stages of gout

Asymptomatic hyperuricemia (may progress to gout)
Acute gouty arthritis
Intercritical (interval) gout
Chronic tophaceous gout (+/- progressive renal failure)

16

Chronic tophaceous gout dev. from

deposition of urate crystals in the kidney and renal calculi

17

pharm approach: suppress acute attack

1st: NSAIDs
indomethacin* (traditional)
ibuprofen
ketorolac (emerging!)

(acetaminophin: no anti-inflammatory)

2nd: Colchicine (Colcrys)

3rd: Corticosteroids - prednisone, methylprednisolone

18

indomethacin has a...

indol ring
can produce CNS effects that other NSAIDS don't
-behavioral diffs, hallucinations, diff concentrating
-cause ha
toxic to GIT, CV events
don't use chronically

19

if chronic problem of high uric acid (>7):

Increase excretion of uric acid

Probenecid (Benemid)
*not effective for tx acute attacks

20

Colchicine

unique anti-inflamm. classically assoc. w. gout
works in 12-24 hrs

binds to tubulin and prevents it's polymerization to microtubule-->reduces leukocyte migration, phago. and mitosis

also inhib. prod and rel. of proinflamm GPs from neutrophils

21

colchicine also used for..

familial Mediterrean fever

22

Colchicine adverse effects

*diarrhea: watery, sloughing of intestinal epi (rice-water)*

GI upset: N/V

23

colchicine dosage

0.5 - 1.0 mg every 2 hours until symptoms are relieved

Lower, less frequent doses are sometimes
used to prevent recurrence of attacks

24

colchicine removed from market for awhile

too cheap, company not making enough money
now: "Colcryst": $600/mo!

25

how to dose corticosteroids




quick onset?

fixed dose then taper for few weeks to avoid ACTH suppression
medrol dose pack

*can work w.in 4-6 hrs, 24 hrs symps gone!*
tolerated well short-term
may have recurrence when taper-->may have to lengthen dosage: Cushing's symps

26

if combo NSAID and corticosteroids

both GI SEs, don't used in combo
esp. indomethacin

27

ketorolac (toradol) for gout

injectable NSAID typ. only used pain man. (kidney stones) but can be used for acute gout attacks: analgesics + anti-inflamm.

main prob: GI irritation

28

Probenecid

Uricosuric Agent
*works bests in pts who do not normally pee out large amounts of uric acid

29

if chronic problem of high uric acid (>7):

inhibition of formation of uric acid

Allopurinol (Xyloprim)
Febuxostat (Uloric)

*both work best in pts who make too much uric acid (chemo) also good for pts w. existing kidney stones (gouty nephropathy)

30

target of uric acid levels

31

if chronic problem of high uric acid (>7):

Facilitate breakdown of uric acid (recombinant uricase enzymes that converts uric acid to allantoin)

Rasburicase (Elitek)
Pegloticase (Krystexxa)

*last resorts for refractory gout

32

in gout pts, avoid

ASA
inhibits uric acid pump (biphasic effect on uric acid excretion)

33

allopurinol



used for acute gout attacks?

older, cheaper
inhibits the enzyme xanthine oxidase-->reduces the
formation of uric acid

does not stop an acute gout attack, but over time it can greatly reduce the potential for future attacks

34

common reaction in early allopurinol therapy

increased frequency of gout attacks
-breakdown of crystals as the uric acid blood levels begin to fall
The acute attacks may necessitate the concomitant use of colchicine, etc

35

allopurinol SEs

elevation of liver enzymes: monitor every few mos

allergic reactions: skin

36

Febuxostat (Uloric)

similar to allopurinol, newer, more expensive, more effective according to Proz.

37

Probenecid (Benemid)

inhibits both the secretion and the reabsorption of organic acids

-more uric acid is reabsorbed (75-90%) than secreted (10%) by the tubule, so therefore: the net effect of probenecid is to increase uric acid excretion (good!)

38

Probenecid (Benemid) contraindicated in...

pts w. kidney stones (advanced gout: gout nephropathy)-->increased risk of stone formation in kidney as urate conc. in tubular fluid/urine increases

important to hydrate to maintain urine flow and prevent urate crystal formation!

recent surgery pts
put pts on allopurinol/febuxostat pre-op to prevent gout attack

39

Probenecid intial therapy may have

gout precipitates from breakdown, so may trigger attacks in early tx (like allopurinol)

40

Pegloticase (Krystexxa)

recombinant urate oxidase, metabolizes urate to allantoin
IV infusion
advanced gout, refractory, severe
2 hr admin
*Does not inhibit formation of uric acid

41

Pegloticase (Krystexxa) SEs

hypersn (foreign protein)
inf. from IV

42

Rasburicase (Elitek)

recombinant urate oxidase, metabolizes urate to allantoin
Do not inhibit formation of uric acid

43

while Pegloticase is used for adults with severe, refractory gout, Rasburicase is for....

pediatric patients with leukemia, lymphoma and solid tumor malignancies receiving anticancer therapy expected to result in tumor lysis and elevation of plasma uric acid

44

adverse effects of both Rasburicase and Pegloticase

fever, ha, rashes, N/V, bowel disturbs, GI pain, allergic reactions

45

for pts with severe, chronic gout/hyperuricemia, may be necessary to use ???

combo tx:
allopurinol and probenecid for hyperuricemia
+
cholchicine, NSAIDs, or steroids for acute attacks