Medications for Gout

Question 1

Urate/ uric acid?

Answer 1

end product of purine metabolism

Question 2

Hyperuricemia cause?

Answer 2

underexcretion, overproduction

Question 3

Gout?

Answer 3

deposition of monosodium urate crystals in tissues (joints and tendons)
cause inflammatory response/ mediator release

Question 4

what happens when synoviocytes phagocytose urate crystals?

Answer 4

secrete inflammatory mediators, attract polymorphonuclear leukocytes (PMN) and mononuclear phagocytes (MNP) (macrophages)

drugs active in gout inhibit crystal phagocytosis and polymorphonuclear r lecukocyte and macrophage release on inflammatory mediators

Question 5

Acute treatment of gout goal?

Answer 5

relieve pain, not stop the cause

dampen immune response, otherwise cause eroision and permanent damage

Question 6

Chronic treatment of gout goal?

Answer 6

lower and prevent recurrent uric acid

Question 7

Characteristics of gout?

Answer 7

exquistely painful
typically single joint 
-podagra(big toe), first MTP joint
result of an imbalance btw uric acid production and renal excretion
-hyperuricemia
Asymptomatic hyperuricemia
-does not always cause gout

Question 8

Characteristics of gouty arthritis?

Answer 8

sudden onset
intense inflammation
distal joints
severe pain
middle aged males
recurrent episodes
influenced by diet and comorbidities
bony eroisions on xray
hyperuricemia
-durgs may exacerbate, thaizedes, loops, salicylates

Question 9

Acute gouty arthritis?

Answer 9

precipitation of monosodium urate crystals

acute inflammatory response

Question 10

Chronic?

Answer 10

chronic arthritis
joint destruction
tophi
renal calculi and damage
-nephrlithiasis and neuropathy

Question 11

First attack?

Answer 11

short duration
-resolves within a few days to several weeks (if untreated)
typically involves one joint
subsequent attacks may last weeks and involve many joints

Question 12

Without prophylaxis?

Answer 12

asymptomatic periods become shorter
more frequent attacks
chronic joint symptoms cause permanent erosive joint deformity

Question 13

Manage asymptomatic hyperuricemia?

Answer 13

lifestyle mod and risk reduction
-diet, alcohol
Comorbid disease management
-hypertension, obesity, diabets, alcoholism, hyperlipidemia

Question 14

Treatment aims for Gout?

Answer 14

1. prompt relief of acute attacks
2. prevention of recurrent attacks
   prevent/ reverse crystal depositis in
   -joints, urinary tract, renal intersitium, tissue and paranchymal organs (tophi)

Question 15

Acute treatment?

Answer 15

inhibit immune response

-nasaids, corticosteroids, colchicine

Question 16

Prevention?

Answer 16

inhibit uric acid synthesis
-allopurinol
increase uric acid elimination
-probenecid

Question 17

NSAIDs?

Answer 17

first line therapy for most patients
fast-acting (hrs)
decrease inflammtory response

Question 18

MOA Nsaids?

Answer 18

mainly inhibit prostaglandin synthesis

Question 19

General properties of NSAIDS?

Answer 19

analgesic
antipyretic
anti-inflammatory

Question 20

Indomethacin?

Answer 20

drug of choice for acute attacks
significant GI and CN side effects

prostaglandin synthase inhibitor

Question 21

Other nsaids?

Answer 21

ibuprofen, naproxen

Question 22

Avoid aspirin with gout?

Answer 22

low dose- cause renal retention of uric acid

high dose- uricosuric action increases risk of renal calculi

Question 23

Colchicine?

Answer 23

treat acute attacks
slower onset than NSAIDS
GI side effects (narrow therapeutic index)
Antiinflammtory- blocks cellular response to crystals
not an analgesic
not uricosuric
-not effect uric acid serum levels
-not stop destructive aspects of gout

Question 24

Colchicine MOA?

Answer 24

binds to tubulin
cause antimitotic effect, interferes with microtubules and spindle formation, neutrophils and GI epithelium
inhibits luekocyte migrattion, phagocytosis, and leukotriene B4 formation
can’t activate immune cells, cant cause inflammatory response

Question 25

High dose of colchicine?

Answer 25

treat gouty arthritis, can do even with narrow TI, because only short use, acute

Question 26

Low does colchicine?

Answer 26

prevent recurrent attacks, particularly in early stages of antithyperuricemic therapy, better tolerated

Question 27

Colchicine toxicity?

Answer 27

``` GI (primary) -drug use for acute attacks -diarrhea (can be severe), nausea, vomit, ab pain Hematological -bone marrow suppression myopathy (chronic use) ```

Question 28

Corticosterioids?

Answer 28

for acute attacks antiinflammatory steroids intra-articular injections (one or 2 joints) PO/parenteral (systemic) use -can't take nsaids or colchicine -pts not candidates for intra-artiuclar injections toxicity limits chronic use (last resort)

Question 29

Xanthine oxidase?

Answer 29

prevent uric acid formation by inhibiting it

Question 30

Hypoxanthine and xanthine?

Answer 30

they will accumulate because of inhibited xanthine oxidase but is water soluble

Question 31

Indications for uric acid lowering drug therapy?

Answer 31

``` frequent/diabling attacks clin/radiographic signs of joint disease tophaceous deposits gout with renal insufficiency recurrent uric acid stones not recommend for asymptomatic no role in managing acute attacks ```

Question 32

Allupurinol clin use?

Answer 32

``` chronic treatment of gout (1st choice) prevent stone formation protect kidneys eliminate tophi cancer chemo ```

Question 33

Allupurinol effectiveness?

Answer 33

in both underexcetors/ overproducers ease of use (once daily) effective in renal insufficiency (elderlu, dose adj)

Question 34

Hypoxanthine analog?

Answer 34

competitive inhibitor of xanthine oxidase | inhibits uric acid production

Question 35

Allupurinol inhibits metabolism of? (caution with these other drugs)

Answer 35

6-mercaptopurine (anticancer agent) Azathioprine (immunosuppressive agent) Both metabolized by xanthine oxidase reduce doses of these drugs

Question 36

Allopurinol adverse effects?

Answer 36

generally well tolerated most common issue is hypersentivity can cause acute gouty attacks

Question 37

hypersensitivity?

Answer 37

mostly rashes but can be more serious may occur after months or years desentization possible in 50% pts

Question 38

acute gouty attacks? prevent them?

Answer 38

mobilizes tissue stores of uric acid | use NSAIDs or colchcine (low dose) when starting therapy

Question 39

Febuxostat?

Answer 39

``` xanthine oxidase inhibitor may be better for pts with mild to moderate chronic kidney disease -no dose adjust -allupurinol- watch GFR and adjust dose may have increased CV risk high cost ```

Question 40

Uricsuric agents?

Answer 40

second line patients that are underexcretors acoid use where nephrolithiasis or neprhropathy might occur, likely ineffective in pts with renal impairment, less effective in elderly pts requires bid or tid dosing (less compliant) for patients resistant to or intolerant of allopurinol(hypersensitivity)

Question 41

Uricosuric agents?

Answer 41

urate excretion reabsorption redominates, trasnporter mediated these drugs are weak organic acids inhibit urate-anion exchangers in proximal tubule decrease uric acid reabsorption

Question 42

Probenecid?

Answer 42

decrease serum uric acid level block tubular reabsorption or uric acid enhance urine uric acid excretion (increase uric acid level in urine, increase risk of nephrolothiasis) not used in pts with renal disease frequent but mild, side effects

Question 43

Contraindications Probenecid?

Answer 43

history of nephrolithiasis existing renal disease avoid use in pts that excrete a large amount of UA already, renal calculi is a risk (DONT USE IF URINARY URATES ARE TOO HIGH) urine flow is low/history or renal calculi less effective in elderly 2-3 times a day dosing (compliance)

Question 44

Drug Drug interactions Probenecid?

Answer 44

can interfere with renal excretion of other drugs -penicillin, cephalosprins, quinolones, loops, NSAIDs aspirin can diminish probenecid's effect

Question 45

Adverse effects Probenecid?

Answer 45

generally well tolerated (some GI, hypersentivity, uric acid stone formation) May cause acute attack of gout - until theurpeutic levels are reached, may happen give nsaids/ colchicine before to reduce risk