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Pharmacology > Rx Gout > Flashcards

Rx Gout Flashcards

1
Q

what level of urate is considered hyperuriemia?

A

> 6.8 mg/dL
Patients can be hyperuricemic may not develop clinical gout symptoms - the treatment of leukemia and lymphomas increase the risk of hyperuricemia and gout.

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2
Q

Characteristics of chronic gouty arthritis include

A

Uric acid deposits in the kidney

Tophi - deposits in the skin

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3
Q

Gout pathophysiology

A

Purine metabolism -> urate crystals

Most gout patients are under-excretors

The crystals trigger neutrophils and an inflammatory response

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4
Q

which gender is gout more common in?

A

Male - 6.9% prevalence

Female - 2% prevalence

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5
Q

What type of substances reduce excretion of uric acid?

A

diuretics - loop and thiazides

nicotinic acid

Salicylates at 2g per day (hard to meet) - a gout patient with MI history should stay on their aspirin

Calcineurin inhibitors - cyclospoine, tacrolimus (immunosuppressive drugs)

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6
Q

explain the inflammation associated with Gout

A

happens 10-30 years after asymptomatic hyperuricemia

urate crystals are ingested by macrophages and synoviocytes, this leads to the activation of NLRP3 inflammasome and secretion of Il-1beta

Neutrophils are recruited, the major driving force on inflammation.

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7
Q

crystals of uric acid

A

needle-like

negatively birefringent

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8
Q

Acute Gouty Arthritis

A

usually in the first MTP joint - podagra - can also affect other joints of the lower limbs

can be accompanied by fever, chills and malaise

inflammation resolves spontaneously over 10 to 14 days

serum uric acid may not be elevated during an acute episode

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9
Q

Chronic Gouty Arthritis

A

tophi - larger aggregates of Uric acid crystal deposition (in skin). Can grow between attacked.

Chronic inflammation erodes bone and cartilage - appear like osteoarthritis

10 or more years after acute intermittent gout

it’s chronic gout when the inbetween periods are no longer pain free

kidney damage

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10
Q

kidneys and gout - what is the damage?

A

nephrolithiasis

stones - some uric acid stones, calcium stones are 10x more common in gout patients

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11
Q

what type of things should gout patients avoid?

A

avoid organ meats, high fructose corn syrup, and when uncontrolled - alcohol

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12
Q

what type of things should gout patients limit?

A

servings of beef, pork, lamb, sardines and shellfish

servings of naturally sweet fruit juices

sugar, salt

alcohol

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13
Q

whats the first line treatment of acute gout?

A

NSAIDS

Corticosteriods - has many side effects, not preferred

colchicine - anti-gout, anti-inflammatory

ACTH

main therapeutic goal is to control inflammation

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14
Q

Urate-lowering therapy

A

aim to reduce serum uric acid

xanthine oxidase inhibitors - allopurinol and febuxostat

uricosuric drugs - Probenecid, (sulfinpyrazone), lesinurad

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15
Q

what is transition therapy in gout?

A

administration of anti-inflammatory and ULT

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16
Q

If a patient is on ULT and has an acute attack how should their prescription change?

A

ULT should not be discontinued but the anti-inflammatory should be added on

17
Q

NSAIDs

A

MOA - inhibits prostaglandin synthesis and urate crystal phagocytoses

used for acute management of gout

toxicties include GI ulcers and bleeding

can be poorly tolerated in elderly, renal insufficiency or GI disorders.

18
Q

Corticosteroids

A

MOA - suppression of immune response

used for the acute management of gout and also 2nd line for transition to ULT

toxicities - insomnia, mood changes, hyperglycemia and fluid retention

gout requires a larger dose, oral is most common

19
Q

Colchicine

A

MOA - inhibits inflammatory response by inhibiting microtubule polymerization

clinical use - acute management of gout, transition, rarely long lerm propholaxis

toxicities - nausea, vomiting, diarrhea; continued use leads to neuropathy and bone marrow suppression

A LOT of drug interactions

Rx needs to be initiated within 36 hours of onset

20
Q

ACTH

A

for patients that cannot take oral therapy

25-40 IU subQ

expensive

21
Q

what are the common doses for NSAIDs when treating Gout?

A

Indomethacin 50 mg 3 times daily

Naproxen 750 mg at first, then 3 times daily

Ibuprofen 800 mg three times a day

22
Q

Dosage of Colchicine

A
  1. 2 mg starting dose

0. 6 mg in an hour

23
Q

treatment for severe acute attack

A

Gout - combination therapy for intense pain or polyarticular

colchicine + NSAIDs
colchicine + oral steroids
intra-articular steroids + anything

NSAIDS and Oral Steroids should NOT be prescribed because of synergistic GI toxicities

24
Q

What are the indications for ULT?

A

An established dx of Gout and:

Tophi
frequent attacks
Chronic Kidney Disease - stage 2
History of urolithiasis

25
Q

when should ULT be started?

A

After an acute attack has resolved or during asymptomatic periods

goal is for serum urate is < 6mg/dL

26
Q

initiation of prophylaxis

A

first line is low dose colchicine and NSADS

second line is low dose prednisone

treatment for at least 6 mo, depends on finding on PE

27
Q

Allopurinol - MOA, Use and Metabolism

A

MOA - reduces uric acid formation through competitive inhibition of xanthine oxidase

used for the chronic management of gout or cancer related hyperuricemia

metabolized to oxypurinol, which also inhibits xanthine oxidase

28
Q

Febuxostat

A

MOA - nonpurine inhibitor of xanthine oxidase

for chronic management of gout

inactive metabolite - no renal adjustments

29
Q

Uricosuric agents

A

compete with uric acid for the transporter which inhibits reabsorption, avoid in uric acid over-produces

30
Q

Probenecid

A

used for chronic management of gout

causes rash, precipitation of gouty arthritis and nephrolithiasis

31
Q

Lesinurad

A

Required to be given with Allopurinol

MOA - inhibits URAT1 and OAT4

used for hyperuricemia

toxicities- headache, increased serum creatine and GERD

interacts with CYP2C9 inhibitors and CYP2C9 inducers and REDUCES EFFICACY OF HORMONAL CONTRACEPTIVES

32
Q

Allopurinol - toxicities, dose, drug interactions and monitorings

A

toxicities - dyspepsia, headache, diarrhea and pruritic maculopapular rash

hypersensitivity - HLAB58:01

initial dose - 100 mg/day, titrate as needed, adjust in renal insuffeiciency

interacts with acathioprine and mercaptopurine (immunosuppresants)

monitor liver function and serum creatinine and CBC

33
Q

Febuxostat - toxicities

A

toxicities - nausea, msk pain, rash, increased risk for thromboembolic events in patients with history of CV events

34
Q

Febuxostat - toxicities and interactions

A

toxicities - nausea, msk pain, rash, increased risk for thromboembolic events in patients with history of CV events

interacts with azathioprine and mercaptopurine

35
Q

IL-1 Inhibitors

A

Anakinra
Rilonacept
Canakinumab

alternatives for gout …. somehow.

36
Q

Uricase

A

pegloticase
Rasburicase

enzyme for digesting uric acid

Pharmacology (23 decks)

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