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• Asam urat adalah produk akhir dari metabolisme

protein (purin)
• Hiperurisemia : konsentrasi asam urat yang larut
dalam darah berlebih ( > 6.8 mg/dl)
– Akibat overproduksi asam urat atau ekskresi
(pengeluaran) yang berkurang
– Kelainan konsentrasi zat dalam serum yang cukup
sering ditemukan
The classification of hyperuricemia
a. Asymptomatic hyperuricemia
- Never develop gout or stones
- Treatment is not recommended
- Hyperuricemia therapy
*patients receiving cytolytic treatment → treated pro-phylactically to
prevent acute uric acid nephropathy
*Indicated when SUA concentration > 9 mg/dL
assosiated with increasing joint changes, arthritis, gout and renal
complication
b. Symptomatic hyperuricemia
- Gout, uric acid stones, uric acid nephropathy
- Treatment is recommended
Distribution of Serum Uric Acid in Black Africans and Its Association
With Cardiovascular Risk Factors, 2017
a. Metabolic syndrome
dyslipidemia, impaired fasting glucose, hyperuricemia,-obesity
- Hyperuricemia  an independent risk factor for CVD
- Impaired glucose utilization (insulin resistance syndrome) has a relationship with
hyperuricemia because of reduced renal excretion of sodium and urate in hyper-insulinemia
b.Renal Dysfunction
- Uric acid excretion  decreased in renal dysfunction due to decreased glomerular filtration
hyperuricemia
- The hyperuricemia does not need to be treated unless patients manifest gouty arthritis
c. Ethanol Consumption
- Attributed to reduced renal urate excretion when acute alcohol intake causes lactic acidosis,
degradation of the purines in beer and other alcoholic beverages increases uric acid
production
– Inflamasi dan nyeri sendi yang mendadak,
biasanya timbul pada malam hari
• Nyeri hebat, bengkak, kemerahan, panas
• Demam, menggigil, nyeri badan
– Hilang dalam 3-10 hari walau tanpa
pengobatan
– 90% serangan pertama menyerang 1 sendi saja
Tissue nucleic acid

Dietary Purin Endogenous purin sintesis

Urate
Underexcretion Overproduction
Hyperuricemia

Silent tissue Gout Renal Association


deposition manifestasion cardiavaskular
events &
mortality
 Uric Acid Disposition
- UA has no biological function ( anti oxidant )
- UA is the end product of purine metabolism
- Primarily is excreted renally, also eliminated through GIT
- Increased SUA concentrations  over production and under
excretion or combination
• Overproduksi
– Primer / idiopatik
– Sekunder
• Intake tinggi
• Peningkatan turnover purin
• Peningkatan degradasi protein
• Hipoekskresi
– Primer / idiopatik
– Sekunder
• Gangguan fungsi ginjal
• Hipertensi, hiperparatiroid
• Akibat kadar yang tinggi di cairan ekstraseluler terbentuk kristal
urat monosodium
• Sendi dan jaringan lunak
• Kondisi yang
diakibatkan
pengendapan kristal
asam urat pada sendi
• Ditandai peningkatan
asam urat dalam
darah & peradangan
sendi berulang
(artritis)
• Terbanyak menyerang
usia dekadi 4-6 (Pria :
9x dibanding wanita)
• Terjadi dalam beberapa tahun pasca serangan pertama
• Disebabkan hiperurisemia yang tidak terkontrol pasca
serangan & tidak mendapat pengobatan adekuat
 endapan kristal bertambah  artritis kronis
• Sendi bengkak, kaku, tidak nyaman  persisten
– Intensitas nyeri lebih kurang daripada serangan awal
• Kadang-kadang diselingi serangan akut
• Perubahan bentuk sendi
• Timbul benjolan berisi endapan asam urat pada
jaringat ikat (TOPHI)
Cyclosporine Decreased urate renal clearance, either via a Cyclosporine-induced hyper-
tubular mechanism or decrease in GFR uricemia  cause gout in
patients with risk factors (renal
dysfunction, concurrent diu-
retics, and male gender).
Cytotoxic Rapid cell lysis Occurs primarily with lympho-
chemotherapy mas and leukemias  uric acid
nephropathy, acute renal failure,
nephrolithiasis.
Diuretics Secondary to volume contraction and Dose and duration-dependent
increased uric acid reabsorption in the elevations in uric acid
proximal tubules for all diuretics; thiazides
may also competitively inhibit proximal tubular
secretion
Ethambutol Decreased urate renal clearance Hyperuricemia and gout have
been demonstrated. A majority
of patients were receiving 20
mg/kg/day orally.
Pyrazinamide Inhibition of renal tubular urate secretion Hyperuricemia is more common
with daily than with intermittent
administration. Gouty attacks
have occurred in those with a
history of gout.

Aspirin (low Inhibition of proximal tubular secretion of urate Doses <1 g/day cause
dose) hyperuricemia.
Laboratorium
– Kadar asam urat  bisa normal / tinggi
– Pemeriksaan cairan sendi  Gold
Standard
• Ditemukan kristal yang mengendap pada
sendi

Gambar kristal yang mengendap.. Sumber Koda Kimble


• Mengatasi serangan akut dengan segera
– Obat: analgetik, colcichine, kortikosteroid
• Program pengobatan untuk mencegah serangan berulang
– Obat: analgetik, colcichine dosis rendah
• Mengelola hiperurisemia (menurunkan kadar as.urat) &
mencegah komplikasi lain
– Obat-obat penurun asam urat
– Lifestyle
Non Farmakologi
Farmakologi

- Allopurinol
Febuxoxtat Product
Raburicase SUA
- uricosuric agent
Probenesid Exrect
Sulfinpyrazone SUA ↑
Benzbromarone
Ascorbic acid
1. Hyperuricemia
• Pengatasan hiperurisemia dilakkan dgn terapi non farmakologi & farmakologi
• Goals of hyperuricemic therapy :
o Elimination of acute gout attacks and the mobilization of urate crystals from
soft tissue
o The target of SUA concent. : <6 mg/Dl
o Overproducer HU  should be treated with a drug that inhibits production of
uric acid (e.g., xanthine oxidase inhibitors)
o Underexcretor  should be treated with a drug that increases excretion of
uric acid ( e.g probenicid)
a. Non farmakologi
• Weight reduction (a caloric- and carbohydrate-restricted diet) → decreased
SUA
• Avoid the excessive dietary intake of purine-rich foods
• No alcohol consumption
b. Farmakologi
 Xanthine Oxidase Inhibitors
Allopurinol
o Inhibits the production of uric acid  decreases SUA concentrations.
o First-line therapy of HU
o Dose :initiated at a 100 mg once daily dose and increased by 100 mg/day increments every 2 to 4
weeks until the SUA <6 mg/dL
o Dose related :200 to 300 mg/day mild disease
400 to 600 mg/day more severe disease
o SUA levels → begin to fall within 1 to 2 days after initiation of allopurinol therapy
o Maximal uric acid suppression → 7 to 10 days
o Once-Daily Dosing allopurinol has t½ <2 hours, but its active metabolite (oxypurinol) has a serum t½
of 13 to 18 hours.
o In renal impairment, oxypurinol accumulates and dosage adjustments should be done
Adverse Effects
- GI intolerance, bone marrow suppression, renal or hepatic toxicities,mild skin rash
Hypersensitivity Reactions
o Mildly erythematous, dusky red purpuric, scaly maculo-papular skin eruptions
o The cutaneous reactions necrosis of the skin and mucous membranes, exfoliative dermatitis, SJS,TENs
 hepatomegaly, jaundice, hepatic necrosis, renal impair-ment often accompanied these reactions
o Patients with renal insufficiency, those receiving thiazide and with chronic alcoholism or severe liver
disease induce this syndrome
Febuxostat
 Non purine xanthine oxidase inhibitor
 Phase III trials (awaiting FDA approval )
 More selective than allopurinol for xanthine oxidase inhibitor
 Does not inhibit other enzymes involved in purine and
pyrimidine metabolism
 In a double-blind, randomized, 52-week multicenter trial, oral
febuxostat (80 or 120 mg/day) was significantly more
effective than allopurinol (300 mg/day) in decreasing SUA
concentrations from >8 mg/dL to an end point of <6 mg/dL
 Higher-dose febuxostat treatment  prevalence of gout
flares and adverse events
 Rasburicase
 Recombinant urate oxidase enzyme  enhances the solubilized uric acid
metabolic product into the urine
 Now approved for the management of hyperuricemia in children who are
susceptible to hyperuricemia resulting from chemotherapy and tumor
lysis
 In a multicenter, randomized trial of 52 children with leukemia or
lymphoma, IV rasburicase (0.2 mg/kg once daily), during initial
chemotherapy, decreased serum urate concentrations more effectively
and with a quicker onset of action than oral allopurinol (median doses of
300 mg/day).
 Rasburicase reserved for patients who cannot under-take allopurinol
therapy and who are at high risk for tumor lysis syndrome
Uricosuric Agents
o Probenecid and sulfinpyrazone  alternatives to allopu-rinol for patients who are unable to
tolerate allopurinol
o It should not be administered to patients with impaired renal function or urolithiasis

* Probenecid
o Well absorbed orally, Cpmax 2 to 4 hours,t½ 6 to 12 hours, its active metabolites extend the
duration of action
o The usual initial dose of probenecid (250 mg twice daily for the first week of therapy) can be
increased to 500 mg twice a day. Maximal dose 2 g/day
o It should begin with small doses  excretion of large amounts of uric acid increases the risk
of urate stone formation in the kidney
o High fluid intake to maintain urine flow of at least 2 L/day also minimizes renal stone
formation
o Clcr < 50 ml/mnt avoid use
o Drug Interactions  Probenecid inhibits secretion of penicillins into the renal tubule
prolongs t½ penicillin and penicillin serum concent.
Sulfinpyrazone
-Inhibits the tubular secretion of uric acid at low doses and inhibits the
tubular reabsorption of uric acid

Benzbromarone
-Not available in the USA hepatotoxicity

Ascorbic Acid
- Hypouricemic effect  competition with urate for renal tubular
reabsorption
- In a study of 184 healthy, nonsmoking adults, ascorbic acid 500 mg
daily for 2 months significantly decreased SUA concentrations
2. Primary gout
- Pemberian uricosuric or xanthine oxidase inhibitors sete-lah fase akut terlewati
3. Nephrolithiasis,urate nephropathy
- Allopurinol is the mainstay of drug therapy in patients with hyperuricemia who develop uric acid
stones and urate nephropathy
4. CKD
- Hypeuricemia terjadi krn underexcretion
- Pemberian dosis allopurinol disesuaikan sesuai Clcr
* Clcr 10 ml/mnt : 100 mg every 2 days
* Clcr 20 ml/mnt : 100 mg daily
* Clcr 40 ml/mnt : 150 mg daily
5. Heart failure
• Pd HF tjd peningkatan xanthine oxidase → uric acid ↑
• Significant hyperuricemia (ie, serum UA ≥9.5 mg/dL) is present in 25% of patients with HF and
reduced ejection fraction
• Pemberian allopurinol diberikan bila UA ≥9 mg/dL
1. Drug related problem
a. Unresponsive drug
o Dosis obat dlm rentang terapeutik tapi outcome
klinik blm tercapai ( persistent) , hal ini dpt tjd krn :
riwayat HU sblmnya yg cenderung tinggi dan
underlying disease ( CKD)
b. Dosis subterapeutik
o Keluhan pasien semakin bertambah
c. Drug induce hyperuricemia
o Pemberian diuretika ( thiazide, furosemida),
ethambutol, pyrazinamide, aspirin dosis rendah
memicu peningkatan HU
o losartan, probenecid → inhibit urate reabsorption
o pyrazinamide, nicotinic acid → stimulate urate
reabsorption
2. Rekomendasi
a. Unresponsive drug
o Tingkatkan dosis, bila perlu sampai dosis maksimum ( allo-
purinol : 800 mg/hari)
o Switch dgn agen lain mis. Probenecid
b. Dosis subterapeutik
o Tingkatkan dosis
c. Drug induce hyperuricemia
o Hentikan obat penyebab atau bila tdk mungkin dihentikan
berikan xantine oxidase inhibitor ( allopurinol ) or
uricosuric ( probenecid)
d. Overdose
o Turunkan dosis obat HU sesuai Clcr ( pada CKD), CPS (
pada hepatic failure)
e. Adverse drug reaction
o stop obat pemicu, bila ADR teratasi lakukan dechallenge
o switch ke obat penurun HU yg lain dan lbh aman
o + kan anti dotum  antihistamin, kortikosteroid
3. Konseling
oIndikasi dan ADR diberikan terutama
pasien hendak pulang
oKepatuhan konsumsi obat
oLife style modification ( rendah
makanan pyrine )