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Rheum/Musculoskeletal/Derm Week 2 > Pharm of crystallite arthritis > Flashcards

Pharm of crystallite arthritis Flashcards

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Dermatology Board Prep flashcards
1
Q

What is hyperuricemia?

A

uric acid conc in plasma over 7mg/dL

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2
Q

What are the causes of hyperuricemia?

A
  1. Metabolic (10%)

primary- associated with enzyme abnormalities

secondary- increased purine biosynthesis

  1. Renal (90%)
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3
Q

What are the types of renal causes of hyperuricemia?

A

a) primary- renal failure
b) secondary- long term diuretic use or toxemia or pregnancy

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4
Q
A
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5
Q

What are the therapeutic aims of gout treatment?

A
  1. Terminate an acute attack first
  2. Prevent recurrence of acute gouty arthritis
  3. Reverse or prevent complications of deposited ureate crystals
  4. Prevent other factors associated with the disease
  5. Prevent kidney stones
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6
Q

What is colchicine?

A

drug used as an alternative for NSAIDs that depolimerizes microtubules for treatment of acute gouty arthritis (prophylatic agent against these attacks)

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7
Q

Other therapeutic uses of cholchicine?

A
  • Familial Mediterranean Fever
  • a fib
  • pericarditis
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8
Q

Side effects of acute use of colchicine?

A

GI disturbances (dose limiting AE-common at high doses)

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9
Q

Chronic AE of colchicine use? Contraindications?

A

blood dyscrasia due to halting cells during mitosis and resultant neutropenia

-peripheral neuropathy

Contra: macrolides (can lead to cholchicine toxicity-GI pain, fever, myalgia, organ failure)

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10
Q

What is indomethacine (Indocin)?

A

a potent NSAID Cox inhibitor with analgesic and antipyretic and primarily anti-inflammatory properties (should not be used for minor aches and pains or fever)

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11
Q

What is Indomethacine used for in gout?

A

acute attack treatment

give 50mg 3x daily with antacid

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12
Q

AEs of Indomethacine?

A

N/V, GI ulcers (might want to give a PPI)

  • lithium retention (like other NSAIDs)
  • Severe CNS frontal headache sometimes with vertigo or blurred vision
  • effects on fetal heart

Side effects are pretty severe so Indomethacine is used primarily only on a short term basis

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13
Q

What drugs can Indomethacine antagonize?

A

Furosemide and HCTZ

-warfarin (can see raised INR)

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14
Q

What does allopurinol do?

A

competitive inhibitor of xanthine oxidase

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15
Q

What are the effects of allopurinol?

A

It increases plasma levels of uric acid precursors such as xanthine and hypoxanthine

-facilitates dissolution of uric acid crystals in the joints and kidneys

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16
Q

What kinds of gout is allopurinol good for?

A
  • primary hyperuricemia of gout due to enzyme abnormalities and in children with familial juvenile hyperuricemia nephropathy
  • secondary hyperuricemia due to heme disorders (such as MM) or chemo
17
Q

What are the AEs of allopurinol?

A
  • increased incidence of acute gout (give colchicine prophylatically)
  • hypersensitivity rxns, such as dermatitis (common)-SJS and toxic epidermal necrosis possible
  • elevated LFTs, hepatitis
  • Class C pregnancy

NOTE: allopurinol is a good alternative for uricosurics in renal insufficiency (and with stones) but dose should be adjusted

18
Q

What drugs are contraindicated with allopurinol?

A

-ampicillin and amoxicillin

19
Q

Allopurinol can impact the pharmacokinetics of what drugs?

A
  • Azathioprine and 6-mercaptopurine (reduce to 25% dose because these are typically inactivated by xanthne oxidase)- would lead to bone marrow suppression if not reduced
  • ACEIs
  • theophylline
  • warfarin
  • cyclosporine
20
Q

What is Febuxostat (Uloric)?

A

potent inhibitor of both the oxidized and the reduced forms of xanthine oxidase (highly effective)

21
Q

What are the uses of Febuxostat?

A

At its regular 80mg dose, febuxostat is more potent than allopurinol in lowering UA levels and has less AEs AND does not require dose changes in renal insufficiency so may be better than allopurinol and uricosurics

22
Q

Main indication of Febuxostat?

A

to lower ureate levels in patients who display AEs to allopurinol or those with renal insufficiency (which you need to adjust allopurinol dose in)

23
Q

AEs to Febuxostat?

A

2-3% patients have transaminase elevation 3x normal

24
Q

How do the kidneys handle uric acid?

A

filtered then reabsorbed in the proximal C.T. (pre-secretory reabsorption)

secreted, then partially reabsorbed (post-secretory reabsorption)

25
Q

What is Probenecid (Benemid)?

A

inhibits transport of organic (anions) across epithelial barriers and interfers with UA reabsorption by the organic acid transporter in the proximal tubule

26
Q

What are the clinical effects of Probenecid?

A

indicated to increase UA excretion in those who excrete less than 1g of UA/day, to dissolve uric acid crystals in joints (so basically you see less reabsorption by the kidneys)

given with adeuqate hydration to patients with good renal function

27
Q

AEs of Probenecid? Contraindications?

A

salicyclates inhibit probenecid

Probenecid increases longevity of medicine like captopril, indomethacin, quinolones, penicillins, acyclovir, methotrexate, naproxen (and more)

28
Q

What is Pegloticase (Krystexxa)?

A

IV Infusion every 2 weeks

a recombinant, PEGylated modfied pig type urate oxidase (which converts uric acid to allantoin in most mammals but not humans) used for severe, treatment-refractory chronic gout and disabling tophaceous gout

29
Q

AEs of Pegloticase? Contraindications?

A

Gout flares use to rapid drop in UA levels causing UA tophi to dissolve. These patients should be given colchicine, NSAIDs, or glucocorticoids concurrently

-Class C preg

Contra: G6PD deficiency- life-threatening hemolysis

Can only give short term because Abs are formed against it

30
Q

Note about Colchicine

A

there is not a specific antidote (watch out for AEs!)

31
Q

How is colchicine eliminated?

A

hepatically metabolized by de-acetylation and excreted through the biliary system (but up to 20% in urine)

32
Q

T or F. Dose-related GI effects are common in colchicine

A

T. Including N/V, diarrhea, anorexia, lactose intolerance, and cramping

33
Q

Chronic treatment with colchicine is associated with what?

A

bone marrow suppression

34
Q

Colchicine contraindications?

A

impaired renal and hepatic function leads to elevated serum drug levels.

NOT removed by dialysis

35
Q

What are the effects of colchicine toxicity in renal/hepatic toxicity?

A

can see myopathy (and elevated CPK), peripheral neuropathy, and rhabdomyolysis

36
Q

Things to monitor with colchicine?

A

CBC and serum ALP

Rheum/Musculoskeletal/Derm Week 2 (12 decks)

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