Gout and hyperuricemia (BACH)

what is a breakdown product of purines

• waste product with no physiological purpose

uric acid

• endogenous purines manufactured by body

• exogenous obtained from food

• all mammals (except human ) have uricase that breaks down UA and easily remove from body

• body’s inability to process UA leads to hyperuricemia

metabolism of purines

humans excrete UA how?

renally

what is the normal serum UA levels

2.0-7.2 mg/dL

what is the hyperuricemia levels in males

>7.2 mg/dL

what is the hyperuricemia levels in females

>6.0 mg/dL

over production of UA

under-excretion of UA

leads to what ?

imbalance of production and elimination of UA

overproduction of uric acid is what hyperuricemia

primary hyperuricemia

Idiopathic

accelerated/excess purines nucleotide synthesis

is what hyperuricemia ?

primary hyperuricemia

• excessive purine intake through diet

• tissue catabolism

• accelerated ATP degradation

is what hyperuricemia

secondary hyperuricemia

increased purine nucleotide turnover is what

tissue catabolism

does higher uric acid mean gout

NO, higher uric acid doesn't mean gout

if you have serum UA level >9mg/dL what percentage you will most likely get gout

5%

liver, kidney, anchovies, trout, sardines, codfish, mussels, scallops, veal, venison, turkey, EtOH are which dietary sources of purines

best to avoid (HIGH)

conditions associated with hyperuricemia

obesity

excessive alcohol intake

diabetes

hyperlipidemia

chronic kidney

drugs that induce hyperuricemia

diuretics (thiazides & loop)

aspirin (low dose)

calcineurin inhibitors

pyrazinamide and ethambutol

drugs that decrease serum urate levels

losartan

statins

estrogen

SGC-2i

dihydropyridine (amlodipine)

increase in serum UA is more common with what

diuretics (hydrochlorothiazide)

effects can be minimized by concurrent treatment with what

ACE Inhibitor or ARB

better to switch HTN patient to what

ACE or ARB

what drug decreases UA levels through uricosuric effects (only ARB that is able to decreases UA levels)

losartan

how is acute gouty arthritis diagnosed

clinically by symptoms rather than labs

usually monoarticular with 1st metatarsophalangeal joint which is what that is most common

podagra

attacks generally begin when

at night

how long can it last if not treated

3-14 days

recurrent attacks of gouty are what

longer duration

polyarticular more common

soreness prodrom

precipitating factors for a gout attack

meds that decrease renal clearance of UA

stress

trauma

EtOH

infection

surgery

food

• monoarticular arthritis

• frequently attacks the first metatarsophalangeal joint, although other joints of the lower extremities are also frequently involved

• affected joint is swollen, tender, erythematous

classic acute gout (podagra)

• asymptomatic period between attacks

• also referred to as “intercritical period”

interval gout

•Deposits of monosodium urate crystals in soft tissues •Complications include soft tissue damage, deformity, joint destruction, and nerve compression syndromes such as carpal tunnel syndrome

topaceous gout

•Polyarthritis affecting any joint, upper or lower extremity •May be confused with rheumatoid arthritis or osteoarthritis

atypical gout

•Nephrolithiasis •Acute and chronic renal impairment

gouty nephropathy

goals of therapy

acute gouty attack

• relieve pain and inflammation

chronic gout

• prevent acute attacks

• decrease UA levels

  • <6.0mg/dL

nonpharm therapy of gout

cold compress

weight loss

avoid purine rich foods

avoid/limit EtOH

• no more than 2 drinks per day for males AND 1 drink per day for females

• no EtOH if having an attack

what are the drugs that should treat ACUTE gout attack

NSAIDs

Colchicine

corticosteroids

ACTH (adrenocorticotropic hormone)

• modifying plasma UA concentrations during acute gout attacks may precipitate another acute gouty attack

  • decrease in UA might mobilize UA stores

• conditionally recommended during acute flare

Is what kind of therapy that will precipitate another

urate lowering therapy initiation

what is the first NSAIDs that is first line treatment for ACUTE gout?

indomethacin (indocin)

what kind of side effects can indomethacin can cause

psychiatric side effects

when is NSAIDs be initiated for acute gout

within 24-48 hours

what NSAIDs can be used for acute gout

indomethacin (indocin)

naproxen (naprosyn)

sulindac (clinoril)

celecoxib (Celebrex)

what is ASA used for in gout

not used in treatment of gout

hyperuricemia is a risk factor for gout (t/f)

true

most patients with gout have what?

hyperuricemia

many patients with hyperuricemia do not develop what

gout

hyperuricemia should be used as diagnosis of what ?

gout

Do not treat asymptomatic hyperuricemia (t/f)

true

who gets urate lowering therapy?

frequent attacks of acute gouty arthritis (>2 attacks/year)

tophus or top deposists

evidence of radiographic damage of joints attributable to gout

goals of urate lowering therapy

treat to target serum urate levels <6 mg/dL

When the decision is made that ULT is indicated while the patient is experiencing a gout flare, starting ULT during the gout flare over starting ULT after the gout flare has resolved is conditionally recommended. is what

timing for the initiation of urate lowering drug therapy

most patients needing urate lowering therapy for how long

indefinite, should be continuous to remain effective

what labs should be monitored while on urate lowering therapy

BMP, liver enzymes, CBC

preventing acute gout attacks during initiation of ULT

1. colchicine —> favored

2. low dose NSAID

3. low dose CS

duration of prophylaxis of acute gout attacks

pts w/o tophi: 3-6 months after achieving target uric acid levels

pts with tophi: 6 months after achieving target uric acid levels

how long do you have to be on urate lowering therapy ?

indefinte

how long do you have to be on acute gout management ?

5-7 days

primary or idiopathic hyperuricemia leads to what

impaired excretion

diminished renal function is what type of hyperuricemia

secondary hyperuricemia

obesity

alcohol intake

diabetes

hyperlipidemia

chronic kidney

• ARE CONDITIONS OF WHAT

conditions associated with hyperuricemia

• these conditions either decrease renal clearance or cause overproduction of uric acid

drugs that induce hyperuricemia

diuretics

aspirin

ethanol

niacin

increase in serum UA is more common with what

diuretics (esp hydrocholorothiazide)

effect can be minimized by concurrent treatment with an ACE or ARB

• better to switch HTN to ace or arb

true

what HTN drug decreases UA levels

• only ARB able to decrease UA levels

losartan

how is acute gouty arthritis diagnosed

diagnosed clinically by symptoms rather than labs

what are the symptoms of acute gouty arthritis

rapid onset pain, erythema, warmth, swelling, tenderness

• aspiration of synovial fluid, look for urate crystals

what is the most common with acute gouty arthritis

monoarticular with 1st metatarsophalangeal joint (podagra)

when does acute gouty arthritis generally begin

at night

how long can acute gouty arthritis last if untreated

can last 3-14 days if left untreated

precipitating factors for a gout attack

meds that decrease renal clearance of Uric acid

stress

trauma

etoh

infection

food

surgery

asymptomatic period between attacks

referred as “intercritical period”

interval gout

deposits of monosodium urate crystals in soft tissues

complications include soft tissue damage, deformity, joint destruction, and nerve compression syndrome such as carpal tunnel syndrome

tophaceous gout

polyarthritis affecting any joint, upper or lower extremity

may be confused with rheumatoid arthritis or osteoarthritis

atypical gout

nephrolithiasis

acute or chronic renal impairment

gouty nephropathy

what is the goal of therapy for acute gouty attack

relieve pain and inflammation

what is the goal of therapy for chronic gout

prevent acute attack

decrease UA levels (<6.0)

nonpharm therapy for gout

cold compress

weight loss

diet": avoid purine rich foods

avoid/limit EtOH

• no more than 2 drinks per day for males and 1 drink per day for females

what is first line for acute gout attacks

NSAIDs

what is the management of acute gout attacks

NSAIDs

colchicine

corticosteroids

ACTH

modifying plasma UA concentrations during acute gout attacks may precipitate another gouty attack

true

what is recommended during acute flare

urate lowering therapy initiation

which NSAIDs is first line

indomethacin

which side effect can indomethacin cause

psychiatric side effects

which NSAIDs is good option for patients with high GI risks

celecoxib

when should NSAIDs be start with acute gout

within 24 hours of attack and continue until resolution (5-7 days)

which drug shouldn’t be given if allergic to aspirin

indomethacin

which drug is not used in treatment of gout

aspirin

what is the second option second line for acute gout

colchicine

what is the dose for colchicine

2 tablets followed by 1 tablet 1 hour later

what is the best statin to use with colchicine

rosuvastatin

what is the third line for acute gout

corticosteroids

what does corticosteroids do and is

immunosuppression

increase glucose

what should be used for acute gout if NSAIDs or colchicine not able to use

corticosteroids

how can corticosteroids be given

systemic (po or im)

intraarticular (IA)

avoid long term use due to side effects is what drug

corticosteroids

what is the last line for acute gout

adrenocorticotropic hormone

ACTH is the last line and is an injection. efficacy is same as indomethacin

true

risk factor for gout is what

hyperuricemia

most patients with gout have what

hyperuricemia

hyperuricemia should not be used as diagnosed of gout

true

do not treat asymotinatic hyperuricemia

true

who gets urate lowering therapy

frequent attacks of acute gouty arthritis (≥2 attacks/year)

topes or tophi deposits

evidence of radiographic damage of joints attributable to gout