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NAPLEX Review > Gout > Flashcards

Gout Flashcards

1
Q

What is gout?

A

Gout is a type of arthritis caused by a buildup of uric acid (UA) crystals, primarily in the joints

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2
Q

How is uric acid produced?

A

Uric acid is produced as an end-product of purine metabolism. Purines are present in many foods, and they make up one of the base pairs of DNA. Under normal conditions, UA is excreted renally (mainly) and via the GI tract

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3
Q

What is a normal serum UA level?

A

2-6.5 mg/dL in females and 3.5-7.2 g/dL in males

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4
Q

What can happen with increasing levels of UA?

A

When UA builds. up in the blood, the patient can remain asymptomatic (many people with high UA or hyperuricemia never get gout) or the UA can crystallize in the joints, resulting in a severe, painful gout attack with burning and swelling of the affected joint. Gout attacks have a sudden onset

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5
Q

Where does gout typically occur and what can happen if left untreated?

A

Gout typically occurs in one joint, most often the metatarsophalangeal joint (MTP, the big toe). If left untreated, the attacks can occur repeatedly and damage the joints, tendons and other tissues

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6
Q

What are risk factors for gout?

A

Male sex, obesity, excessive alcohol consumption (particularly beer), hypertension, chronic kidney disease, lead intoxication, advanced age and using medications that increase UA

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7
Q

What are some medications that increase uric acid?

A
  • Aspirin, lower doses
  • Calcineurin inhibitors (tacrolimus and cyclosporine)
  • Diuretics (loops and thiazides)
  • Niacin
  • Pyrazinamide
  • Select chemotherapy (with tumor lysis syndrome)
  • Select pancreatic enzyme products
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8
Q

What are some foods to avoid with gout?

A

Foods to avoid include organ meats, high-fructose corn syrup and alcohol. Foods that should be limited include fruit juices, table sugar, sweetened drinks, desserts, salt, beef, lamb, pork and seafood with high purine content (sardines, shellfish)

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9
Q

What are some non-pharmacological ways to reduce risk of gout?

A

A healthy diet, including low-fat dairy products and vegetables, reduces gout risk. Weight control, smoking cessation, exercise and hydration are other ways to reduce risk

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10
Q

Is asymptomatic hyperuricemia treated with drugs?

A

Asymptomatic hyperuricemia is not treated with drugs

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11
Q

When is preventative medications considered for gout?

A

Preventative medications are considered after multiple/frequent gout attacks have occurred, if there is radiographic evidence of advanced disease or if there are tophi present

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12
Q

What do drugs that are used for acute attacks target?

A

Pain and inflammation

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13
Q

What are prophylactic drugs used for in gout?

A

The prophylactic drugs are used to lower UA levels, with a gaol UA level of < 6 mg/dL

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14
Q

What are medications that are used to treat acute pain with gout?

A

Treat acute pain with anti-inflammatory drugs: Colchicine, Steroids (including intra-articular injections), NSAIDs (often with a high starting dose)

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15
Q

What medications are used to treat chronically to prevent future attacks once gout has struck?

A

Xanthine oxidase inhibitor (XOI): allopurinol (preferred) or febuxostat

*An acute gout flare can occur when an XOI is started, so give initially with colchicine or an NSAID

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16
Q

What should be done if XOI didn’t work well enough and UA remains > 6 mg/dL?

A
  • Add on probenecid or lesinurad to daily XOI

- Replace the XOI with IV pegloticase (Krystexxa)

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17
Q

What single drug is recommended when a gout attack occurs?

A

NSAID, systemic steroid or colchicine

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18
Q

What should the treatment be for a gout attack in more severe disease?

A

Combination treatment usually includes colchicine with either an NSAID or an oral steroid

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19
Q

What should be done if the gout attack is localized to one or two joints?

A

An intra-articular steroid can be helpful

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20
Q

Should urate-lowering therapy be continued if an acute attack occurs?

A

If an acute attack occurs in a patient using chronic urate-lowering therapy (ULT), they should continue the ULT during the acute attack

*Topical ice applied to the affected joints reduces pain and inflammation

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21
Q

hat are some contraindications of colchicine?

A

Do not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment

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22
Q

What are some warnings associated with Colchicine?

A

Myelosuppression, neuromuscular toxicity (including rhabdomyolysis), if possible, do not use with cylcosporine, diltiazem, verapamil, gemfibrozil or statins as these drugs increase myopathy drugs

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23
Q

What are some side effects associated with Colchicine?

A

Diarrhea, nausea, myopathy, neuropathy (dose-dependent), decreased vitamin B12

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24
Q

What are some notes associated with Colchicine?

A
  • Start within 36 hours of symptom onset (for treatment)
  • Wait 12 hours after a treatment dose before resuming prophylaxis dosing
  • Increased risk of myelosuppression, GI and neuromuscular adverse effects in elderly with CrCl < 30 mL/min; decrease dose and monitor, or use steroid as an alternative
  • Maintain adequate fluid intake
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25
Q

What are some examples of NSAIDs used for acute gout attacks?

A

Indomethacin (Indocin), Naproxen (Aleve, Naprosyn), Sulindac, Celecoxib (Celebrex)

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26
Q

What are some notes associated with NSAIDs?

A
  • Avoid use in severe renal disease (UA is renally cleared and patients with gout often have renal insufficiency) and CVD risk, bleeding (risk of lower with shorter duration of use)
  • Indomethacin, naproxen and sulindac are approved for gout; other NSAIDs can be used
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27
Q

What are some steroids used for gout?

A

Prednisone/prednisolone, methylprednisolone, triamcinolone

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28
Q

What are some notes about steroids?

A
  • Acute side effects of steroids, including increased BG, increased BP, insomnia, increased appetite
  • Intra-articular steroid injections stay localized and do not cause systemic side effects; repeat injections can cause joint damage
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29
Q

What is a key drug interaction of Colchicine?

A
  • Colchicine is a major substrate of CYP450 3A4 and P-gp
  • Fatal toxicity can occur if colchicine is combined with strong CYP3A4 inhibitors, such as clarithromycin, or a strong inhibitor of P-gp
  • If colchicine is used with a strong CYP3A4 inhibitor, the dose is reduced and repeated no earlier than three days. If using a moderate CYP3A4 inhibitor, the maximum dose for acute treatment is 1.2 mg (2 tablets)
30
Q

When should chronic ULT be started?

A

Chronic ULT should be started in all patients with gout who have experienced multiple or frequent gout attacks, have evidence of joint damage or have tophi (UA crystals that form under the skin)

31
Q

What should be used when starting chronic ULT?

A

When starting chronic ULT, colchicine, steroids or NSAIDs should be used as prophylaxis to reduce the risk of attacks, which can occur when UA is lowered rapidly (possibly due to mobilization of the urate crystals)

32
Q

What is the first-line ULT?

A

Allopurinol, a xanthine oxidase inhibitor. Blocking the xanthine oxidase enzyme stops the production of UA and produces a non-toxic end product

33
Q

What should be done for patients at high risk of a severe allopurinol hypersensitivity reaction?

A

Screened for the HLA-B*5801 allele prior to use

34
Q

What is another alternative treatment option for ULT?

A

Another XOI, febuxostat, is available as an alternative treatment option. XOIs are titrated up slowly to lower the UA to a target level of < 6 mg/dL

35
Q

What is considered second-line treatment for ULT?

A

Probenecid is a uricosuric and a second-line treatment that can be used if XOIs are contraindicated or not tolerated, or can be added when the UA level is not at goal despite maximal doses of XOIs

36
Q

What is the MOA of Probenecid?

A

Probenecid inhibits reabsorption of UA in the proximal tubule of the nephron, which increases UA excretion. It requires adequate renal function to b. effective, which many patients with gout do not have

37
Q

What is another option when XOI treatment is inadequate?

A

Lesinurad is a uricosuric that is taken with teh XOI

38
Q

What is the MOA of Pegloticase?

A

Pegloticase is a recombinant uricase enzyme, which converts UA to an inactive metabolite that can be easily excreted. Pegloticase is reserved for severe, refractory disease

39
Q

What is the effect caused by xanthine oxidase inhibitors?

A

Decreases uric acid production

40
Q

What are some examples of xanthine oxidase inhibitors?

A

Allopurinol (Zyloprim, Aloprim), Febuxostat (Uloric)

41
Q

What is the MOA of uricosurics?

A

Inhibit reabsorption of uric acid in the kidneys, which increase uric acid excretion

42
Q

What are some warnings associated with Allopurinol?

A

Hypersensitivity reactions, including severe rash (SJS/TEN, DRESS); HLA-B*5801 testing prior to use if high risk (especially for patients of Asian descent) and do not use drug if positive, hepatotoxicity, bone marrow suppression

43
Q

What are some side effects of Allopurinol?

A

Rash, acute gout attacks, nausea, diarrhea, increased LFTs

44
Q

What are some monitoring parameters of Allopurinol?

A

CBC, LFTs, renal function

45
Q

What are some notes about Allopurinol?

A
  • Higher doses used for tumor lysis syndrome

- Due to the high rate of gout attacks when beginning ULT, use with colchicine or an NSAID for the first 3-6 months

46
Q

What is a boxed warning of febuxostat?

A

Increased risk of cardiovascular (CV) death compared to allopurinol in patients with established CV disease; use should be limited to those who cannot tolerate allopurinol or if allopurinol is not effective

47
Q

What are contraindications of febuxostat?

A

Do not use with mercaptopurine or azathioprine

48
Q

What are some warnings associated with Febuxostat?

A

Hepatotoxicity, possible MI or stroke, gout attack, hypersensitivity and serious skin reactions including SJS/TEN, DRESS

49
Q

What are some side effects of febuxostat?

A

Rash, nausea, increased LFTs, arthralgia

50
Q

What are monitoring parameters of Febuxostat?

A

LFTs

51
Q

What are some notes associated with febuxostat?

A

Due to the high rate of gout attacks when beginning ULT, use with colchicine or an NSAID for the first 3-6 months

52
Q

What are some examples of uricosurics?

A

Lesinurad (Zurampic), Probenecid

53
Q

What is a boxed warning associated with Lesinurad?

A

Acute renal failure, more common if used alone; only use with XOI

54
Q

What are some notes associated with Lesinurad?

A

Use only with XOI if UA goals not reached with XOI alone; keep hydrated

55
Q

What are some contraindications of Probenecid?

A

Do not use with aspirin therapy, blood dyscrasias, UA kidney stones (nephrolithiasis), children < 2 years, initiation in acute gout attack

56
Q

What are some warnings associated with Probenecid?

A

Decreased effectiveness with CrCl < 30 mL/min, do not use with G6PD deficiency

57
Q

What are some side effects of Probenecid?

A

Hypersensitivity reactions, hemolytic anemia

58
Q

What are some notes associated with Probenecid?

A

Probenecid can be used to increase beta-lactam levels by decreasing beta-lactam renal excretion

59
Q

How does a recombinant uricase work?

A

Converts uric acid to allantoin, which is excreted

60
Q

What is an example of a recombinant uricase?

A

Pegloticase (Krystexxa)

61
Q

What are some boxed warnings associated with Pegloticase?

A

Anaphylactic reactions: monitor and premedicate with antihistamines and steroids, risk is higher if UA is > 6 mg/dL; life-threatening hemolytic reactions and methemoglobinemia may occur with G6PD deficiency

62
Q

What is a contraindication of Pegloticase?

A

G6PD deficiency

63
Q

What are some warnings associated Pegloticase?

A

Acute gout flares can occur upon initiation; an NSAID or colchicine should be given 1 week prior to infusion and continued for at least 6 months

64
Q

What are some side effects of Pegloticase?

A

Antibody formation, gout flare, infusion reactions, nausea, bruising, urticaria, erythema, pruritus

65
Q

What are some notes associated with Pegloticase?

A

Do not use in combination with allopurinol, febuxostat or probenecid (increased risk of anaphylaxis)

66
Q

What are some key xanthine oxidase inhibitor drug interactions?

A
  • Allopurinol and febuxostat increases the concentration of mercaptopurine, the active metabolite of azathioprine. Do not use either drug with allopurinol or febuxostat, or decreased dose and monitor for toxicity
  • Avoid use with didanosine; allopurinol and febuxostat can increase didanosine levels
  • Antacids decrease allopurinol absorption
67
Q

What are some key Probenecid drug interactions?

A
  • Probenecid decreases the renal clearance of other medications when taken together, including aspirin (do not use salicylates concurrently), methotrexate, penicillins, cephalosporins and carbapenems
  • Probenecidis sometimes used with beta-lactams to increase the concentration of the antibiotic; this will increase the risk of adverse reactions. This is occasionally done with penicillin when treating neurosyphilis or other penicillin-treated infections
  • Probenecid decreases the efficacy of loop diuretics, but increases the risk of loop diuretic toxicity
68
Q

What is tumor lysis syndrome?

A

Tumor lysis syndrome is an acute, potentially life-threatening complication of some types of chemotherapy. When cells are lysed open, purines are released into the blood and quickly converted to Ua. This can cause acute gout and significant electrolyte abnormalities, which can lead to renal failure, cardiac arrhythmias, seizures and potential death

69
Q

What is Rasburicase (Elitek)?

A

Rasburicase is a urate-oxidase enzyme used in the treatment of TLS. It is contraindicated with G6PD deficiency. Discontinue immediately and permanently in any patient developing hemolysis

70
Q

What are some key counseling points of Colchicine?

A
  • At the first sign of an attack, take two tablets. Take one more table in one hour. Do not use more than three tablets in an hour, and do not use more than four tablets in 24 hours. Do not take the second dose if you have upset stomach, nausea or diarrhea
  • Can cause nausea and diarrhea and muscle damage
71
Q

What are some key counseling points of Allopurinol?

A
  • Can cause mild or severe rash, liver damage, nausea

- Take after a meal to reduce stomach upset (higher doses can be divided). Drink plenty of fluids

NAPLEX Review (45 decks)

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