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Pharm III Unit II > 6 Gout > Flashcards

6 Gout Flashcards

1
Q

Gout is a disease caused by…

A

An increase in the amount of uric acid in the body

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2
Q

What are the two categories of gout patients?

A

Overproducers of uric acid - larger body pool of uric acid (polycythemia vera, myeloid metaplasia, leukemia, lymphoma)

Underexcretors of uric acid - renal excretion is somehow low (lead neuropathy, glycogen-storage disease, sickle cell disease)

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3
Q

Only _______ drugs affect uric acid

A

Acidic drugs

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4
Q

WHat are the two distinct objectives in the treatment of gout?

A

Terminate the inflammatory process of an acute attack

Reduce hyperuricemia to prevent formation of urate deposits and acute attacks of gouty arthritis and to promote resolution of tophi

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5
Q

How is termination of the inflammatory process of an acute attack of gout accomplished?

A

By use of colchicine, indomethacin, and other anti-inflammatory agents

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6
Q

How is reduction of hyperuricemia accomplished?

A

By uricosuric agents that reduce the pool of uric acid in tophaceous gout and secondary hyperuricemia (probenecid and sulfinpyrazone) and by allopurinol which decreases the formation of uric acid

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7
Q

Acute attacks of gout follow the deposition of _______ in peripheral joints

A

Uric acid crystals

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8
Q

In acute attacks of gout, uric acid crystals are phagocytosis by ________, initiating an inflammatory reaction mediated by ________ and __________

A

Synoviocytes

Prostaglandins and cells of the immune system

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9
Q

What classes of drugs are used for acute management of gout?

A

NSAIDs (indomethacin and others)

Colchicine

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10
Q

What drugs are used for chronic prevention of gout?

A

Uricosuric agents (probenecid)

Xanthine oxidase inhibitors (Allopurinol, febuxostat)

Enzyme converting uric acid to allantoin (rasburicase, prgloticase)

Glucocorticoids

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11
Q

What is the primary NSAID used in the treatment of gout

A

Indomethacin

Can also use Naproxen and Sulindac but Indomethacin is DOC

Can also use specific reversible inhibitors of COX-2

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12
Q

Which NSAIDs are CONTRAINDICATED for the treatment of gout?

A

Aspirin and other salicylates

They are acids so they decrease urate excretion

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13
Q

Colchicine is derived from …

A

Colchicum autumnale or the autumn crocus

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14
Q

MOA for colchicine

A

Binds to tubulin and inhibits the assembly of microtubules

Produces it’s anti-inflammatory effect by inhibiting leukocyte migration and phagocytosis —> inhibition of the formation of leukotriene B4

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15
Q

Colchicine has an anti inflammatory effect but no …

A

No analgesic effect
No effect on COX enzymes
No effect on urate excretion

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16
Q

How is colchicine used?

A

To reduce the pain and inflammation of an acute attack of gouty arthritis

Administered orally (IV has increased toxicity)

17
Q

Adverse effects of colchicine

A

DIARRHEA**
Nausea
Vomiting
Abdominal pain

Side effects produced by the inhibition of tubulin polymerization

18
Q

Drug used to reduce inflammation in acute gout by binding to tubulin —> inhibiting the assembly of microtubules

A

Colchicine

19
Q

How do uricosuric agents work?

A

Increase the urinary excretion of uric acid by blocking the active reabsorption of uric acid in the proximal tubule

20
Q

When using uricosuric agents, _________ should be maintained

A

A large urine volume

This is minimize the possibility of kidney stone formation

Also, keep the pH above 6.0 (alkali administration)

21
Q

Initial administration of a uricosuric agent may trigger a gouty attack. What should you do to prevent this?

A

Prophylactic colchicine therapy is indicated

22
Q

Are uricosuric agents effective in acute attacks of gouty arthritis?

A

NO

In fact, they may aggravate symptoms

Control the attack with colchicine or NSAIDs and start the uricosuric agent after they’ve recovered

23
Q

Main side effect of uricosuric agents

A

GI irritation

24
Q

When should you initiate probenecid?

A

2-3 weeks after an acute attack (it’s a uricosuric agent so it will exacerbate symptoms if administered DURING an attack)

25
Q

Probenecid will decrease excretion of …

A

Many acidic compounds or metabolites

EX: 
Penicillin
Methotrexate
Clofibrate
Glucuronides of NSAIDs
26
Q

Urate transporter (URAT1) inhibitor

A

Lesinurad (Zurampic)

Combined with a xanthine oxidase inhibitor (ie Allopurinol, Febuxostat)

27
Q

Which gout drugs inhibit the synthesis of uric acid?

A

Allopurinol and Febuxostat

28
Q

MOA for Allopurinol and Febuxostat

A

Inhibit synthesis of uric acid through inhibition of xanthine oxidase

Effective in both primary and secondary forms of gout

29
Q

What are the serious side effects of xanthine oxidase inhibitors (Allopurinol, febuxostat)?

A

Vasculitis
Agranulocytosis
Hypersensitivity reactions

30
Q

What may happen with initial allopurinol/febuxostat therapy?

A

May provoke acute gouty attack

Colchicine prophylaxis may be necessary

31
Q

Possible drug interactions with xanthine oxidase inhibitors (Allopurinol/Febuxostat)

A

ALUMINUM HYDROXIDE decreases the absorption of allopurinol

Increases the effect of chemotherapeutic mercaptopurines 6-MP** and Azathioprine (Imuran)

Increases the effect of cyclophosphamide (Cytoxan)

Inhibits the elimination of chlorpropamide (Diabinese)

Inhibits the metabolism of WARFARIN** and PROBENECID**

Inhibits activation of FLUOROURACIL (5-FU)***, thus reducing it’s therapeutic effect

32
Q

Recombinant form of urate oxidase —> catalyze enzymatic oxidation of uric acid into a readily excreted metabolite allantoin

A

Rasburicase (Fasturtec)

33
Q

Urate oxidase is ________ in humans

A

Not endogenous

34
Q

What is the most important contraindication for Rasburicase (Fasturtec)

A

Patients with hematological malignancies or solid tumors are at particular risk for TUMOR LYSIS SYNDROME and thus hyperuricemia and related complications, especially after chemotherapy initiation

35
Q

Adverse effects of Rasburicase (Fasturtec)

A

Severe hypersensitivity including anaphylactic shock and anaphylactic reactions

N/V
Fever
HA
Abdominal pain
Constipation
Diarrhea
36
Q

Pegylated, recombinant, mammalian urate oxidase enzyme

A

Pegloticase (Krystexxa)

Converts uric acid into allantoin, which is easily excreted

37
Q

What is the boxed warning on Lesinurad (Zurampic)

A

Risk of acute renal failure - this is more common when lesinurad is administered as a monotherapy and with higher than approved doses

Should always be used in combo with a xanthine oxidase inhibitor

Pharm III Unit II (8 decks)

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