MOD 6- GOUT

Question 1

__________is a metabolic disease characterized by recurrent episodes of

• *acute arthritis** due to deposits of monosodium urate in joints and
• *cartilage.**

Answer 1

Gout

Question 2

What may also occur in Gout?

Answer 2

Uric acid renal calculi,

tophi, and interstitial nephritis
may also occur

Question 3

Gout is usually associated with a _______________), a poorly soluble substance that is the
major end product of purine metabolism

Answer 3

high serum uric
acid level (hyperuricemia

Question 4

What enzyme is present in most mammals but is absent in humans which
__________-converts uric acid to the more soluble allantoin

Answer 4

uricase

Question 5

While clinical gouty episodes are associated
with hyperuricemia,most individualswith hyperuricemia may
never develop a clinical event from urate crystal deposition

Answer 5

:)

Question 6

The treatment of gout aims to________________.

Answer 6

1. ** relieve acute gouty attacks and**
2. prevent recurrent gouty episodes and urate lithiasis.

Question 7

What is the pathophysiology of gout?

Answer 7

Pathophysiologic events in a gouty joint.
Synoviocytes phagocytose urate crystals and then secrete inflammatory
mediators, whichattract and activate polymorphonuclear leukocytes
(PMN) and mononuclear phagocytes (MNP) (macrophages).

Question 8

Drugs active in gout inhibit_________________

Answer 8

crystal phagocytosis and polymorphonuclear
leukocyte and macrophage release of inflammatory mediators.
PG, prostaglandin; IL-1, interleukin-1; LTB 4 , leukotriene B 4

Question 9

What is again the pathophysio of gout?

Question 10

what are the stages of Gout?

Answer 10

1. Asymptomatic hyperuricemia
2. Acute Gouty Arthritis: urate deposition
3. Chronic Tophaceous: Chronic obstruction

Question 11

What are the characteristics of **Gout **arthritis?

Answer 11

1. sudden onset
2. middle age MAN
3. severe pain
4. distal joins; can tell what type of arthritis
5. intense inflammation
6. recurrent episodes
7. influenced by diet
8. bony erosiions on Xray

Question 12

What are the common types of Arthritis?

Answer 12

1. Rheumatoid Arthritis
2. Osteoarthritis
3. Gouty arthritis
4. septic arthritis

Question 13

This is a type of arthritis that is autoimmune and with extra articular manifestation?

Answer 13

Rheumatoid Arthritis

Question 14

The distinuishing characteristic of Rheumatoid arthritis are?

Answer 14

• symmetrical
• bilateral
• smaller joints are affected
• extra articular manifestation

Question 15

While in osteoarthritis, the distinguising feature is?

Answer 15

1. large wt bearing joints
2. unilateral
3. asymmetrical

Question 16

Gouty and Septic Arthritis have the same manifestation. What is the difference ?

Answer 16

In septic there is presence of fever.

So important is to ask in history:

1. trauma
2. STD

Question 17

How to tell if its pseudoGOUT/

Answer 17

presence of Calcium oxalate instead of Monosodium urate crystals found in Gout arthritis.

Question 18

What is the critical component in crystal induced inflammation?

Answer 18

PMN

Question 19

Hyperuricemina results when?

Answer 19

1. increase production
2. decrease secretion

Question 20

REMEMBER:

The amount of uric acid obtained dietary is not as significant as endogenous production.

Question 21

What are the two categories for the treatment of GOUT?

Answer 21

1. Drugs inhibit production
2. Drugs that facilitate excretion

” KASI NGA DBA, PROBLEM IS EITHER IMBALANCE OF INCREASE PRODUCTION OR DECREASE SECRETION”

SO THAT WILL BE YOUR TARGET!!!!

Question 22

Chronic tophaceous gout

tophus is loc deposit of monosodium urate crystal

Where is the classic location of tophi?

Answer 22

HELIX OF EAR

Question 23

In Gout, what are the X-ray findings?

Answer 23

1. DIP joint destruction
2. phalangeal bone cysts
3. bony erosions

Question 24

What are the cardinal manifesstation of GOUT?

Answer 24

1. arthritis
   
   • acute
   • chronic
2. TOPHI
   
   • chronic
3. Nephrolithiasis
4. Nephropathy

Question 25

drugs therapy of Gout ## Footnote serum UA \>10 mg/ dL

Answer 25

annual: 70 % 5 year: 30 %

Question 26

drugs therapy of Gout serum UA \<7mg/dL

Answer 26

annual: 0.9 % 5 year:0.6%

Question 27

conversion of hypoxanthine to xanthine and to uriac acid requires what enzyme?

Answer 27

xanthine oxidase

Question 28

How to classify hyperuricemia

Answer 28

1. serum UA 2. urine UA excretion ( 24 hr)

Question 29

When the problem is overproduction, what will be the found in urine and serum?

Answer 29

both high

Question 30

If the problem is undersecretion, what will be the serum and urine UA findins?

Answer 30

serum UA is HIGH urine UA is normal or low

Question 31

what are the 2 major category of DRUGS for GOUT?

Answer 31

1. acute arthritis 2. urate lowering drugs

Question 32

What are the drugs under **acute arthritis?**

Answer 32

1. colchicine 2. steroids 3. NSAIDS 4. rest analgesia ice time

Question 33

What are your URATE OWERING DRUGS?

Answer 33

1. drugs for reduce UA production 2. increase UA excretion

Question 34

Under lowering drugs there is two sub category?

Answer 34

1. Reduce UA production 2. Increase UA excretion

Question 35

What are your drugs that reduce UA production?

Answer 35

Allopurinoll Febuxostat

Question 36

What are your lowering drugs that act on increasing UA excretion

Answer 36

Uricosuric Agents PROBENECID

Question 37

What is your non pharmacologic treatment in GOUT?

Answer 37

rest + analgesic+time

Question 38

Why apply cold rather than warm?

Answer 38

**COLD DISSOLVE THE CRYSTALS** Because warm will precipitate the crystal more

Question 39

Although **NSAIDs are now the first-line drugs for acute gout,** \_\_\_\_\_\_\_\_\_\_ was the **primary treatment for many years.** This is an is an alkaloid isolated from the autumn crocus, **Colchicum autumnale .**

Answer 39

colchicine

Question 40

Colchicine is absorbed readily after **oral administration**, reaches **peak plasma levels** within \_\_\_\_\_\_\_\_\_\_\_\_\_, and is eliminated with a serum **half-life of 9 hours**. Metabolites are excreted in the **intestinal tract and urine**

Answer 40

2 hours

Question 41

* Colchicine **relieves the pain and inflammation of gouty arthritis** * in **12–24 hours** **without\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

Answer 41

* ** altering the metabolism or excretion of urates and ** * **without other analgesic effects. **

Question 42

How does Colchicine produce its anti-inflammatory effects?

Answer 42

Colchicine produces its anti-inflammatory effects by binding to the intracellular protein tubulin, thereby preventing its polymerization into microtubules and leading to the inhibition of leukocyte migration and phagocytosis. It also inhibits the formation of leukotriene B4. Several of colchicine’s adverse effects are produced by its inhibition of tubulin polymerization and cell mitosis.

Question 43

When is Colchicine indicated?

Answer 43

Indications Although **colchicine is more specific in gout than the NSAIDs**, NSAIDs (eg, indomethacin and other NSAIDs **[except aspirin])** are **sometimes used in its stead because of the troublesome *_diarrhea associated with colchicine therapy_*****.**

Question 44

When do we use Colchicine?

Answer 44

Colchicine is now used **between attacks (the “intercritical period”) for prolonged** **prophylaxis (at low doses)**. NOTE: It is effective in preventing attacks of acute Mediterranean fever and may have a mild beneficial effect in sarcoid arthritis and in hepatic cirrhosis. ( Although it has been given intravenously, this route is no longer approved by the FDA [2009].) However today its sole purpose if for GOUT

Question 45

DOSE INDICATION High dose is for?

Answer 45

ACUTE GOUT ARTHRITIS

Question 46

When to use Low dose?

Answer 46

Prevent recurrent Gouty Arthritis

Question 47

What are the adverse effects of Colchicine?

Answer 47

Adverse Effects * Colchicine often causes diarrhea and may occasionally cause nausea,vomiting, and abdominal pain. * Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures havealso been observed. * Colchicine may **rarely cause hair loss and bone** * **marrow depressio**n, as well as **peripheral neuritis, myopathy, and,in some cases, death.** * **The more severe adverse events have beenassociated with the intravenous administration of colchicine.** *

Question 48

What is the characteristic when there is Colchicine Acute overdose?

Answer 48

Acute overdose is characterized by **burning throat pain, bloody** **diarrhea, shock, hematuria, and oliguria**. Fatal ascending central nervous system depression has been reported. Supportive care is the mainstay of treatment.

Question 49

In prophylaxis (the most common use), the dosage of colchicine is\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Answer 49

**0.6 mg one to three times daily**

Question 50

For terminating a gouty attack, traditional dosing has been an **initial colchicine dose** of\_\_\_\_\_\_\_\_\_\_\_\_\_\_, followed by\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ However, a regimen of 1.2 mg followed by a single 0.6 mg oral dose was shown to be as effective as the higher dose therapy noted above . Adverse events were less with this lower dose regimen. In February 2008, the FDA requested that intravenous preparations containing colchicine be discontinued in the USA because of their potential life-threatening adverse effects. Therefore, intravenous use of colchicine is not recommended.

Answer 50

0. 6 or 1.2 mg 0. 6 mg every 2 hours until pain resolves, or nausea and diarrhea appear.

Question 51

In addition to inhibiting prostaglandin synthase**, indomethacin** and **other NSAIDs** also **inhibit urate crystal phagocytosis.**

Answer 51

:)

Question 52

Why of all NSAID aspirin is not used for Gouty arthritis?

Answer 52

Aspirin is not used because it causes renal retention of uric acid at lowdoses (≤ 2.6 g/d). NOTE : It is uricosuric at doses greater than 3.6 g/d.

Question 53

What NSAID is commonly used in the initial treatment of gout as a **replacement for colchicine**.

Answer 53

Indomethacin Note : For acute gout, 50 mg is given three times daily; when a response occurs, the dosage is reduced to 25 mg three times daily for 5–7 days.

Question 54

\_\_\_\_\_\_\_\_\_\_\_ and __________ are uricosuric drugs employed to **decrease the body pool of urate** in patients with **tophaceous gout orin those with increasingly frequent gouty attacks**. In a patient who **excretes large amounts of uric acid, the uricosuric agents should not be used.**

Answer 54

Probenecid and sulfinpyrazone

Question 55

Indications of Uricosuric therapy should be initiated in \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Answer 55

* gouty patients with * **underexcretion of uric acid** **when allopurinol or febuxostat is contraindicated** * or **when tophi are present**. Therapy should not be started **until 2–3 weeks after an acute attack.**

Question 56

Adverse Effects Uricosuric Agents **Adverse effects do not provide a basis for preferring one or the other of the uricosuric agents.** Both of these organic acids cause GI irritation, but ___________ is more active in this regard. A rash may appear after the use of either compound. **Nephrotic syndrome has occurred after the use of probenecid.** Both sulfinpyrazone and probenecid may rarely cause aplastic anemia.

Answer 56

sulfinpyrazone

Question 57

What are the Contraindications & Cautions of Uricosuric agents?

Answer 57

It is essential to maintain a large urine volume to minimize the possibility of stone formation.

Question 58

The preferred and standard-of-care therapy for **gout during the period between acute episodes**is\_\_\_\_\_\_\_\_\_\_\_\_, which reduces total uric acid body burden by**inhibiting xanthine oxidase.**

Answer 58

ALLOPURINOL

Question 59

Allopurinol belongs to pregnancy category?

Answer 59

C

Question 61

Allopurinol is approximately 80% absorbed after oral administration and has a terminal serum half-life of 1–2 hours. Like uric acid, allopurinol is metabolized by xanthine oxidase, but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long enough duration of action so that allopurinol is given only once a day

Question 62

When is Allopurinol indicated?

Answer 62

Indications Allopurinol is often the **first-line agent for the treatment of** **chronic gout in the period between attacks** and it **aims to prolong the intercritical period.**

Question 63

. When initiating allopurinol, colchicine or NSAID should be used until steady-state serum uric acid is normalized or decreased to less than 6 mg/dL and they should be continued for 3-6 months or even longer if required. Thereafter, colchicine or the NSAID can be cautiously stopped while continuing allopurinol therapy.

Answer 63

:)

Question 64

In addition to gout, allopurinol is also used as an \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ (see Chapter 52 ) and is indicated to prevent the massive uricosuria following therapy of blood dyscrasias that could otherwise lead to renal calculi..

Answer 64

antiprotozoal agent

Question 65

Adverse Effects See above for prophylaxis against an acute attack during the initiation of allopurinol, which can occur as a result of acute changes in the serum uric acid level. Among the side effects,

Answer 65

* GI intolerance including nausea, vomiting, and diarrhea, * peripheral neuritis and necrotizing vasculitis, * bone marrow suppression, and rarely aplastic anemia may also occur. * Hepatic toxicity and interstitial nephritis have been reported. * An **allergic skin reaction characterized by pruritic maculopapular lesions occurs in 3%** of patients. * Isolated cases of exfoliative dermatitis have been reported. * In **very rare cases, allopurinol has become bound to the lens, resulting in cataracts.**

Question 66

What do you call the syndrome that occurs as adverse effect in taking allopurinol?

Answer 66

Steven Johnson Syndrome * hypersensitivity * toxic eperdermal necrolysis

Question 67

Interactions & Cautions When\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_** **are given concomitantly with allopurinol, their dosage must be reduced by about **75%**. Allopurinol may also increase the effect of **\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_**

Answer 67

chemotherapeutic purines (**eg, azathioprine)** ** cyclophosphamide**.

Question 68

** Allopurinol inhibits the metabolism** of\_\_\_\_\_\_\_\_\_\_\_\_ and may **increase hepatic iron concentration**. Safety in children and during pregnancy has not been established.

Answer 68

probenecid and oral anticoagulants

Question 69

What durgs have interaction with **allopurinol?**

Answer 69

* azathiaprime * cyclosphomide * probenecid * oral anticoagulants

Question 70

Dosage The initial dosage of allopurinol is\_\_\_\_\_\_\_\_\_. It should be titrated upward until serum uric acid is below **6 mg/d**L; this level is commonly achieved at 300 mg/d but is not restricted to this dose; doses as high as 800 mg/d may be needed. As noted above, colchicine or an NSAID should be given during the **first several weeks of allopurinol therapy to prevent the gouty arthritis episodes that sometimes occur.**

Answer 70

100 mg/d

Question 71

\_\_\_\_\_\_\_\_\_--is a non-purine xanthine oxidase inhibitor that was approved by the FDA in February 2009.

Answer 71

Febuxostat i

Question 72

What is the MOA Febuxostat? In clinical trials, **febuxostat at daily dosing of 80 mg or** **120 mg was more effective** in lowering serum urate levels than allopurinol at a standard 300 mg daily dose. The **urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion.**

Answer 72

potent and selective inhibitor of xanthine oxidase, thereby reducing the formation of xanthine and uric acid without affecting other enzymes in the purine or pyrimidine metabolic pathway

Question 73

Febuxostat is indicated for?

Answer 73

Indications Febuxostat is approved at doses of **40, 80, or 120 m**g the treatment of **chronic hyperuricemia in gout patient**s. Although it appeared to be **more effective then allopurinol as urate-lowering therapy, the allopurinol dosing was limited to 300 mg/d**, thus not reflecting the actual dosing regimens used in clinical practice . At this time, the dose equivalence of allopurinol and febuxostat is unknown.

Question 74

What are the adverse effects of Febuxostat?

Answer 74

. The most frequent treatment-related adverse events are * liver function abnormalities, diarrhea, headache, and nausea. * Febuxostat appears to be well tolerated in patients with a history of allopurinol intolerance. * There **does not appear to be an increase risk of cardiovascular events.**

Question 75

In Febuxostat as with allopurinol, prophylactic treatment with colchicine or NSAIDs should be started at the **beginning of therapy to avoid** \_\_\_\_\_\_\_\_\_\_\_

Answer 75

gout flares.

Question 76

Dosage The recommended starting dose of febuxostat is **40 mg daily.** Because of the concern for cardiovascular events in the original phase 3 trials, the FDA approved only 40 mg and 80 mg dosing. **No dose adjustment is necessary for patients with renal impairment since it is highly metabolized into an inactive metabolite by the liver.**

Question 77

Pegloticase is the newest **urate-lowering therapy**; it was approved by the FDA in September 2010 for the treatment of refractory chronic gout.

Answer 77

PEGLOTICASE

Question 78

Chemistry \_\_\_\_\_\_\_\_\_\_\_\_ is a recombinant mammalian uricase that is covalently attached to **methoxy polyethylene glycol (mPEG**) to prolong the circulating half-life and diminish immunogenic response.

Answer 78

Pegloticase

Question 79

What drug for Gout that has a function in decreasing the production can be used in patients with RENAL PROBLEMS?

Answer 79

Fuboxostat

Question 80

What drug speeds resolution of Tophi?

Answer 80

Pegloticase