GOUT &

HYPERURICEMIA
{ Apt. Romauli Anna Teresia Marbun, S.Farm., M.Si
 What is Gout Arthritis

Gout is a kind of arthritis that occurs when

uric acid builds up in blood and causes joint
inflammation
 GOUT & HYPERURICEMIA
Definisi:

Hiperurisemia  kondisi asimtomatik dg  kons. as.

urat serum > 7,0 mg/dl   resiko
gout

Gout  spektrum penyakit yg meliputi :

hiperurisemia
serangan arthritis akut yang berulang
 kristal monosodium urat dlm leukosit
yg ditemukan dlm cairan sinovial
penyimpanan kr. urat dlm jar. (tofus)
peny. ginjal intersisial
nefrolitiasis as. urat
PATOFISIOLOGI
 As. urat (produk buangan)  degradasi purin
purin berasal dari  diet (coklat), konversi as. nukleat jar. menjadi
nukleotida purin, sintesa basa purin
adenin (6 aminopurin), guanin (2 amino-6 oksipurin), xantin (2,6-
dioksi purin), as urat (2,6,8-trioksi purin)
 Akumulasi  overproduksi – underekskresi as. urat
 Overproduksi :
abnormalitas enz. yg mengatur metabolisme purin
- pe aktivitas PRPP (fosforibosil pirofosfat)
-  HGPRT (hipoxantin-guanin fosforibosil transferase)
Guanin  as.guanilat kosubstrat &
hiposantin  as.inosinat PRPP utk sintesa as nukleat
defisiensi HGPRT  guanin & hiposantin diubah menjadi as urat
 ± 67% as.urat yg dihasilkan tubuh diekskresi dlm urin
normal  tbh menghasilkan as urat 600-800 mg/hari
ekskresi < 600 mg dlm urin
Gout: urate crystals (ordinary and polarized light microscopy)
• Penyimpanan kr. urat di cairan sinovial  inflamasi

Inflamasi : - vasodilatasi
-  permeabilitas vaskular
- aktivitas kemotaktik leukosit
polimorfonuklear

Fagositosis kr urat oleh leukosit  lisis sel sec cepat  pelepasan

enzim proteolitik ke sitoplasma  reaksi inflamasi :
- nyeri pd join
- eritema
- warmth
- swelling  membengkak

Nefrolitiasis  ekskresi as urat dlm urin >>

pengasaman urin
• Pd nefropati as urat akut  gagal ginjal akut
krn pengendapan di collecting duct & ureter
kronik  pengendapan jangka lama di parenchim ginjal
 Tempat penyimpanan as urat pd arthritis gout akut :
- jari kaki
- lutut
- tangan/pergelangan tangan
- helix telinga
- olecranon bursae
- tendon Achilles
 Obat-obat yg  Cl as urat :

diuretika, salisilat (dosis kecil), PZA, etambutol, as

nikotinat, levodopa, sitostatika
GAMBARAN KLINIK

Akut :

 Nyeri, swelling  inflamasi

mulai dari metatarsophalangeal joint (podagra) 
pergelangan kaki, tumit, lutut, pergelangan tangan, jari
tangan & siku
 Serangan malam hari px bangun tidur  nyeri

 Join  eritema, warm, swolen

 Demam dan leukositosis

TUJUAN TERAPI

 Mengurangi serangan akut

 Mencegah serangan berulang dari arthritis gout
 Mencegah komplikasi krn penyimpanan kr urat di jar.
Therapy acute gout attack.

 Aplikasi es lokal: pengobatan tambahan yang paling

efektif. Diet Suplemen (misalnya, biji rami, akar seledri)
tidak dianjurkan.
Dosage and Regimen
 TERAPI

 NSAID
- efek analgesika  menghambat pembentukan Pg (prostaglandin)
- efek antiinflamasi
-  suhu  interleukin-1 (pirogen endogen)
dr leukosit ke termoregular hipotalamus
Mekanisme kerja NSAID :
1. Ikatan kovalen ireversibel
asetosal + ggs serin enz. siklooksigenase
2. Rev. kompetitif inhibitor enz. siklooksi-
genase (ibuprofen, piroksikam)
3. parasetamol tdk ada efek antiinflamasi 
tdk  produk peroksida sitoplasma pd
inflamasi

ADR :
1.  Pg  PgE2 + PgI2   HCl,  mukosa gastrik,  aliran
darah gastrik  tdk ada sitoprotektif  ulser
Beri misoprostol  PgE1 dg NSAID
2. Nefrotoksik :
- PgE2 dan PgI2  disintesis dlm medulla dan glomeruli
ginjal  vasodilator renal kuat
-  PgE2 & PgI2 oleh NSAID   retensi Na,  aliran
darah ginjal gagal ginjal

3. Bronkospasme, rashes, alergi :

- krn lipooksigenase tdk diblok oleh NSAID  leukotrien
 LTD4 & C4 = SRS-A = slow reacting substance of
anaphylactic

4. lain-lain :
- as propionat : ibuprofen, fenbufen, naproxen  pilihan
pertama krn ADR kecil
- as asetat : indometasin  potent ADR  confussion,
blood dyscration, headache, ulser gastrik
° Kortikosteroid
- utk kasus yg resisten NSAID & kollkisin
- Prednison 30-60 mg/hari  withdrawal steroid
 tapering 5 mg 10-14 hari  stop
- ACTH (adrenocorticotropic hormone gel (i.m) 40-80 unit tiap 6-8
jam, 2-3 hari
- Triamsinolon hexasetonida 20-40 mg (intra artikular)

Profilaksis
Batu (litiasis) as urat  kons serum > 10 mg/dl
ekskr urin > 1000 mg/hari
1. Kolkisin 0,5-0,6 mg 2 kali sehari, ada attack 1 mg tiap 2 jam
0,5 mg 2 kali sehari 6-12 bl  as urat < 6 mg/dl
2. Urikosurika
- Probenecid, sulfinpirazon
-  Cl as urat dg menghambat reabs tubular renal
- dosis diawali rendah  utk menghindari urikosuria &
pembentukan batu
 - pemeliharaan  perhatikan aliran urin dan alkalinisasi urin (Na Bic)
- Probenecid 250 mg 2 kali sehari 1-2 minggu kmd 500 mg
2 kali sehari 2 minggu
- Sulfinpirazon 50 mg 2 kali sehari 3-4 hari kmd 100 mg
2 kali sehari
- e.s : iritasi GI, rash, hipersensitivitas
presipitasi AGA (Acute gouty arthritis)
pembentukan batu
- KI : alergi, fs ginjal  (Clcr < 50 ml/min)

3. Xantin oksidase inhibitor

- Allopurinol & oksipurinol (metabolit utama)
- menghambat konversi hipoxantin  xantin  as urat
-  kons PRPP intrasel
- t1/2 oksipurinol >  sehari sekali
- Dosis oral 300 mg sehari, 600-800 mg/hari
- allopurinol  obat pilihan antihiperurisemia pd px batu ginjal/ fs
ginjal
- e.s : skin rash, leukopenia, toksisitas GI
Therapy HYPERURICEMIA IN GOUT
 Xanthine oxidase inhibitors (Allopurinol, Febuxostat)
 Uricosuric (Probenecid)
 Pegloticase (Pegloticase)
ANTIIFLAMMATORY PROPHYLAXIS DURING INITIATION OF
URATE-LOWERING THERAPY

 low-dose oral colchicine (0.6 mg twice daily) and low-dose

NSAIDs (eg, naproxen 250 mg twice daily)- first line
Note: For patients on long-term NSAID prophylaxis, a PPI or
other acid-suppressing therapy is indicated to protect from
NSAID-induced gastric problems
 Low-dose corticosteroid therapy (eg, prednisone ≤10 mg/day)

 Continue, for at least 6 months or 3 months -> target serum uric

acid, whichever is longer. For patients with one or more tophi,

continue prophylactic therapy for 6 months after achieving the
serum urate target
EVALUATION OF THERAPEUTIC OUTCOMES

1. Check the serum uric acid level in patients suspected of having an acute gout attack, particularly if
it is not the first attack, and a decision is to be made about starting prophylaxis. However, acute
gout can occur with normal serum uric acid concentrations.
2. Monitor patients with acute gout for symptomatic relief of joint pain, as well as potential adverse
effects and drug interactions related to drug therapy. Acute pain of an initial gout attack should
begin to ease within about 8 hours of treatment initiation. Complete resolution of pain, erythema,
and inflammation usually occurs within 48 to 72 hours.
3. For patients receiving urate-lowering therapy, obtain baseline assessment of renal function, hepatic
enzymes, complete blood count, and electrolytes. Recheck the tests every 6 to 12 months in patients
receiving long-term treatment.
4. During titration of urate-lowering therapy, monitor serum uric acid every 2 to 5 weeks; after the
urate target is achieved, monitor uric acid every 6 months.
5. Because of the high rates of comorbidities associated with gout (diabetes, chronic kidney disease,
hypertension, obesity, myocardial infarction, heart failure, stroke), elevated serum uric acid levels
or gout should prompt evaluation for cardiovascular disease and the need for appropriate risk
reduction measures. Clinicians should also look for possible correctable causes of hyperuricemia
(eg, medications, obesity, malignancy, alcohol abuse)