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2H. Pharmacology > MOD 6- GOUT > Flashcards

MOD 6- GOUT Flashcards

1
Q

__________is a metabolic disease characterized by recurrent episodes of

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

Gout

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2
Q

What may also occur in Gout?

A

Uric acid renal calculi,

tophi, and interstitial nephritis
may also occur

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3
Q

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

A 
high serum uric
acid level (hyperuricemia
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4
Q

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

A

uricase

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5
Q

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

A

:)

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6
Q

The treatment of gout aims to________________.

A
  1. ** relieve acute gouty attacks and**
  2. prevent recurrent gouty episodes and urate lithiasis.
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7
Q

What is the pathophysiology of gout?

A

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).

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8
Q

Drugs active in gout inhibit_________________

A

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

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9
Q

What is again the pathophysio of gout?

A
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10
Q

what are the stages of Gout?

A
  1. Asymptomatic hyperuricemia
  2. Acute Gouty Arthritis: urate deposition
  3. Chronic Tophaceous: Chronic obstruction
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11
Q

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

A
  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
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12
Q

What are the common types of Arthritis?

A
  1. Rheumatoid Arthritis
  2. Osteoarthritis
  3. Gouty arthritis
  4. septic arthritis
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13
Q

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

A

Rheumatoid Arthritis

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14
Q

The distinuishing characteristic of Rheumatoid arthritis are?

A
  • symmetrical
  • bilateral
  • smaller joints are affected
  • extra articular manifestation
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15
Q

While in osteoarthritis, the distinguising feature is?

A
  1. large wt bearing joints
  2. unilateral
  3. asymmetrical
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16
Q

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

A

In septic there is presence of fever.

So important is to ask in history:

  1. trauma
  2. STD
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17
Q

How to tell if its pseudoGOUT/

A

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

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18
Q

What is the critical component in crystal induced inflammation?

A

PMN

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19
Q

Hyperuricemina results when?

A
  1. increase production
  2. decrease secretion
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20
Q

REMEMBER:

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

A
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21
Q

What are the two categories for the treatment of GOUT?

A
  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!!!!

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22
Q

Chronic tophaceous gout

tophus is loc deposit of monosodium urate crystal

Where is the classic location of tophi?

A

HELIX OF EAR

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23
Q

In Gout, what are the X-ray findings?

A
  1. DIP joint destruction
  2. phalangeal bone cysts
  3. bony erosions
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24
Q

What are the cardinal manifesstation of GOUT?

A
  1. arthritis
    • acute
    • chronic
  2. TOPHI
    • chronic
  3. Nephrolithiasis
  4. Nephropathy
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25
Q

drugs therapy of Gout

serum UA

>10 mg/ dL

A

annual: 70 %

5 year: 30 %

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26
Q

drugs therapy of Gout

serum UA

<7mg/dL

A

annual: 0.9 %

5 year:0.6%

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27
Q

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

A

xanthine oxidase

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28
Q

How to classify hyperuricemia

A
  1. serum UA
  2. urine UA excretion ( 24 hr)
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29
Q

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

A

both high

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30
Q

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

A

serum UA is HIGH

urine UA is normal or low

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31
Q

what are the 2 major category of DRUGS for GOUT?

A
  1. acute arthritis
  2. urate lowering drugs
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32
Q

What are the drugs under acute arthritis?

A
  1. colchicine
  2. steroids
  3. NSAIDS
  4. rest analgesia ice time
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33
Q

What are your URATE OWERING DRUGS?

A
  1. drugs for reduce UA production
  2. increase UA excretion
34
Q

Under lowering drugs there is two sub category?

A
  1. Reduce UA production
  2. Increase UA excretion
35
Q

What are your drugs that reduce UA production?

A

Allopurinoll

Febuxostat

36
Q

What are your lowering drugs that act on increasing UA excretion

A

Uricosuric Agents

PROBENECID

37
Q

What is your non pharmacologic treatment in GOUT?

A

rest + analgesic+time

38
Q

Why apply cold rather than warm?

A

COLD DISSOLVE THE CRYSTALS

Because warm will precipitate the crystal more

39
Q

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 .

A

colchicine

40
Q

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

A

2 hours

41
Q
  • Colchicine relieves the pain and inflammation of gouty arthritis
  • in 12–24 hours without_____________________
A
  • ** altering the metabolism or excretion of urates and **
  • **without other analgesic effects. **
42
Q

How does Colchicine produce its anti-inflammatory effects?

A

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.

43
Q

When is Colchicine indicated?

A

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.

44
Q

When do we use Colchicine?

A

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

45
Q

DOSE INDICATION

High dose is for?

A

ACUTE GOUT ARTHRITIS

46
Q

When to use Low dose?

A

Prevent recurrent Gouty Arthritis

47
Q

What are the adverse effects of Colchicine?

A

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 depression, as well as peripheral neuritis, myopathy, and,in some cases, death.
  • The more severe adverse events have beenassociated with the intravenous administration of colchicine.
    *
48
Q

What is the characteristic when there is Colchicine Acute overdose?

A

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.

49
Q

In prophylaxis (the most common use), the dosage of colchicine is_________________________.

A

0.6 mg one to three times daily

50
Q

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.

A
  1. 6 or 1.2 mg
  2. 6 mg every 2 hours until pain resolves, or nausea and diarrhea appear.
51
Q

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

A

:)

52
Q

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

A

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.

53
Q

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

A

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.

54
Q

___________ 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.

A

Probenecid and sulfinpyrazone

55
Q

Indications of Uricosuric therapy should be initiated in __________________

A
  • 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.

56
Q

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.

A

sulfinpyrazone

57
Q

What are the Contraindications & Cautions of Uricosuric agents?

A

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

58
Q

The preferred and standard-of-care therapy for gout during the
period between acute episodesis____________, which reduces total uric acid body burden byinhibiting xanthine oxidase.

A

ALLOPURINOL

59
Q

Allopurinol belongs to pregnancy category?

A

C

60
Q
A
61
Q

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

A
62
Q

When is Allopurinol indicated?

A

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.

63
Q

. 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.

A

:)

64
Q

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..

A

antiprotozoal agent

65
Q

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,

A
  • 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.
66
Q

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

A

Steven Johnson Syndrome

  • hypersensitivity
  • toxic eperdermal necrolysis
67
Q

Interactions & Cautions

When________________** **are given concomitantly with allopurinol, their dosage must be reduced by about 75%.

Allopurinol may also increase the effect of ________________

A

chemotherapeutic purines (eg, azathioprine)

** cyclophosphamide**.

68
Q

** Allopurinol inhibits the metabolism** of____________ and may increase hepatic iron concentration.

Safety in
children and during pregnancy has not been established.

A

probenecid and oral anticoagulants

69
Q

What durgs have interaction with allopurinol?

A
  • azathiaprime
  • cyclosphomide
  • probenecid
  • oral anticoagulants
70
Q

Dosage
The initial dosage of allopurinol is_________.

It should be titrated upward until serum uric acid is below 6 mg/dL; 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.

A

100 mg/d

71
Q

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

A

Febuxostat i

72
Q

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.

A

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

73
Q

Febuxostat is indicated for?

A

Indications
Febuxostat is approved at doses of 40, 80, or 120 mg the treatment of chronic hyperuricemia in gout patients.

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.

74
Q

What are the adverse effects of Febuxostat?

A

. 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.
75
Q

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

A

gout flares.

76
Q

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.

A
77
Q

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

A

PEGLOTICASE

78
Q

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.

A

Pegloticase

79
Q

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

A

Fuboxostat

80
Q

What drug speeds resolution of Tophi?

A

Pegloticase

81
Q
A

2H. Pharmacology (17 decks)

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