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Gout in Clinical Prac - Ce: 16/06/54 Kiattisak K. Md. Pornanan D. MD
Gout in Clinical Prac - Ce: 16/06/54 Kiattisak K. Md. Pornanan D. MD
Gout in Clinical Prac - Ce: 16/06/54 Kiattisak K. Md. Pornanan D. MD
in
Clinical
Prac.ce
16/06/54
KIATTISAK
K.
MD.
PORNANAN
D.
MD.
Case 1
A 65 year-old man presented with severe right knee arthri:s for 1 day, he had HT and was treated with amlodipine 10 mg/d and HCTZ 25 mg/day. PE: BT 39 degree C, BP 148/68 mmHg Marked swelling, tender of right knee. No tophi What s next management ?
Inves:ga:on
MSU
crystals
in
PMN,
G/S
:
nega:ve
BUN
14
/
Cr
1.0
Uric
acid
:
9.2
Hb
13.7
gm/dl,
WBC
14,500/cu.mm
(PMN
99%)
adequate
platelet
smear
Chol
120
LDL
80
HDL
32
TG
110
FBS
80
HbA1C
6
Diagnosis ?
Management ?
Hyperuricemia
Serum
urate
level
>
6.8
mg/dL
When
uric
acid
levels
are
high
enough,
needle
shaped
monosodium
urate
crystals
form
The
crystals
commonly
deposit
in
.ssues
with
limited
blood
ow,
such
as
tendons,
car:lage,
ligaments,
bursa,
and
the
skin
in
areas
that
are
cooler
or
around
distal
joints
UA
overproduc.on
UA
underexcre.on
Primary
Idiopathic
Idiopathic
hyperuricemia
Inherited
enz.
(HGPRT,PRPP)
def.
Common
gene:c
variants
Risk
of
gout
Age
and
sex
(estrogen
=
uricosuric
agent)
Serum
uric
acid
:
degree
and
dura:on
Serum
urate
mg%
incidence 5 yrs
< 6 6.0 6.9 7.0 7.9 8.0 8.9 9.0 9.9 > 10
Risk
of
gout
BMI
:
BMI
risk
Alcohol
:
acetate
acetyl
coA
adenosine
nucelo:de
+
uric
acid
produc:on
Beer
:
most
potent
risk
(guanosine
uric
)
MSU
deposi:on
Urate
conc.
>
6.8
mg/dL
Temperature
NF-KB
IL6 TNF a
Caspase I
Endothelial ac:va:on
Apopto:c bodies
TGF-beta, (NO, IL-10) Endothelial inac:va:on Inhibi:on of inammatory response to MSU crystals
Mature macrophage
Progression
of
Gout
4
stage
1.
Asymptoma:c
hyperuricemia
2.
Acute
gouty
arthri:s
3.
Intercri:cal
or
interval
gout
4.
Chronic
tophaceous
gout
Management
5
steps
1.
Educa:on
and
advise
2.
Treat
acute
inamma:on
3.
Prevent
recurrent
4.
Long
term
uric
acid
lowering
5.
Treat
complica:on
and
co-morbid
diseases
Diets
Low
purine
diet
rela:vely
ineec:ve
(reduces
urinary
urate
but
liqle
eect
on
serum
level)
Calorie
restricted
diet
reduced
saturated
fat-complex
carbohydrate
Dairy
products
rather
than
meat
protein
Rx
of
Acute
inamma:on
Colchicine
NSAIDs
Steroids
and
ACTH
Oligo-poly
joints
Renal
and
liver
disease
Normal
:
renal
and
liver
Single joint
Oral
Prednisolone
30-60
mg/day
then
taper
o
in
2
wks
IV
ACTH
sc
or
IM
40
iu
q
12
hrs
1-3
days
Solumedrol
IM,IV
100-150
mg/d
x
1-2
days
NSAIDs
< 10 or HD Ovoid Or signicant hepatobiliary dysfunc:on aged 70 yrs 50% of usual dose
Management
of
Hyperuricemia
Indica.on
1.
acute
aqack
3
:mes/yr
2.
tophi
+
3.
uric
acid
>
9
mg/dL
4.
24
hr
urine
for
uric
acid
>
800
mg/day
or
renal
stone
Goal
:
uric
acid
5.5
6.8
mg/dL
If
tophi
<
5
mg/dL
dura:on?
Uricosta:c
drugs
Allopurinol
Xanthine
oxidase
inhibitor
Use
in
increase
synthesis
and
low
excre:on
OD
dose
Renal
adjustment
Metabolism
:
CYPs
(P450)
oxypurinol
Ini:al
:
100
mg/d
increase
dose
100mg/
2wk
100 mg AD or 300-400 mg biweekly: immediately aber HD Maintain plasma oxypurinol levels < 100 mmol/L (15.2mg/L)
Uricosta:c
drugs
Oxypurinol
Ac:ve
metabolite
of
allopurinol
Cross
reac:on
:
allopurinol
30%
Renal
adjustment
Uricosta:c
drugs
Febuxostat
Xanthine
oxidase
inhibitor
(another
pathway)
Not
inhibit
other
enzymes
Metabolism
:
liver
excre:on
in
renal
and
fecal
route
(50%)
avoid
in
CCr
<
30
DI
:
6MP,
azathioprine
and
theophilline
Initail
:
40
mg/day
OD
dose
S/E
:
hepa::s,
diarrhea,
arthralgia
and
headache
Uricoly:c
drugs
Uricase
Uric
allantoin
Use
in
tumor
lysis
syndrome
Rapid
ac:on
and
very
potent
drug
Metabolism
:
non
CPYs
S/E
:
1.
hemoly:c
anemia
in
G6PD
def.
2.
acute
aqack
Uricoly:c
drugs
1. Rasburicase
:
IV
con:nuous
infusion
anaphylatoid
reac:on
,
alloan:body
(recombinant
unmodied
aspergillus
avus
uricase
)
2. Peglo.case
(Krystexxa)
IM,IV
and
SC
8mg
q
2
wk
FDA
approved
in
severe
gout
and
poor
response
with
conven:onal
treatment
Uricosuric
drugs
1.
Probenicid(500
mg-2g/d)
2.
Sulphinpyrazone
3.
Benzbromarone(50-200
mg/d)
combina:on
therapy
with
allopurinol
rela:vely
ineec:ve
Contraindicate
hyperexcretors
&
renal
stone
formers
Uricosuric
drugs
Probenecid
Dose
250
mg
rising
to
500-
1000
mg
2-3
:mes
daily(max
3g/d)
Increases
urinary
calcium
excre:on
Numerous
drug
interac:on
esp.
ASA
(block)
Indicate
in
allopurinol
allergy
with
CCr
>
60
ml/min
S/E
:
nephro:c,
N/V
Uricosuric
drugs
Sulphinpyrazone
Dose
50
mg
bid
rising
to
100-200
mg
3-4
:me
daily(max
800
mg/d)
CCr
>
30
ml/min
Potent
than
probenacid
:
5x
Uricosuric
drugs
Benzbromarone
50-200
mg/days
Liver
metabolism,
urinary
excre:on8%
Contraindicate
:
liver
disease
renal
stones
low
GFR
(<30ml/min)
hyperexcretor>700
mg/d
DI
:
an:-TB
and
ASA
(block)
,
coumadin
(1/2)
S/E
:
diarrhea,
skin
rash
and
hepa::s
Other
drugs
Increase
urine
uric
excre.on
losartan,
fenobrate*
and
atorvasta:n
IL-1
inhibitor
(anakinra)
IL-1B
an:body
(canakinumab)
***
Etanercept
,
iniximab
Study
drugs
PDE4-TNF-a
inhibitor,
BCX-4208
(purine
nucleoside
phosphorylase
inhibitor
)
Co-morbids
Dyslipidemia
HT
T2DM
Obese
CKD
Atherosclerosis
Metabolic
syndrome
Complica:ons
Renal
disease
acute
uric
acid
nephropathy
chronic
urate
nephropathy
uric
acid
nephrolithiasis
(nidus)
Hypertension
Insulin
resistance
Cardiovascular
risk
Musculoskeletal
complica:on
Case 2
An elderly male 70 yrs old with crystal- proven gout has a history of 4 aqacks during the previous year and uric acid level 10 mg/dL Cr 0.7 GFR 90 Now he was prescribed allopurinol 200 mg/day for 1 week He comes to hospital today for evalua:on about skin lesion
Allopurinol
PNAS 2005;4134-39
PNAS 2005;4134-39
Ethics
Africans
Caucasian
Asian
Indians
Chinese
Prevalence
(%)
2-4
1-6
3-15
8.8-10.9
OR
348.3
0.8
0.4
3.3
0.4
0.3
0.3
0.2
95%
CI
19.2-6336.9
0.2-2.7
0.1-1.7
0.5-20.7
0.04-3.4
0.03-2.2
0.06-1.1
0.03-1.9
P
value
1.61x10-13
0.68
0.18
0.19
0.37
0.19
0.06
0.13
http://pharmacology.md.kku.ac.th/
Case 3
A 54-year-old KT man with gout his serum urate level is 11 mg/dL , has a history of 6 aqacks during the previous year current medica,on cyclosporin A, prednisolone 15 mg/day amlodipine 10 mg, enalapril 20 mg Cr = 1.4 mg/dL How should his gout be managed?
Treatment of gout in
INCIDENCE
Hyperuricemia
in
organ
transplant
pa:ent
with
cyclosporine
about
30-80%
Developed
gout
about
3.5-25%
Cyclosporine
decrease
renal
excre:on
hyperuricemia
Gout
in
KT
pa.ents
Post
KT
about
5
years
develop
gouty
arthri:s
Cyclosporine
use
with
diure:cs
increase
incidence
<thiazide,
loop
diure:cs>
Oligo
to
polyarthri:s
more
common
typical
presenta:on
Early
develop
tophi
Hip,
shoulder,
sacroiliac
joint
arthri:s
Gout
in
KT
pa.ents
Check
baseline
renal
func:on
before
treatment
Cau:on
with
NSAIDs
usage
Kidney,
heart,
lung
transplanta:on
Non-pharmacological
treatment
Advice
and
educa:on
about
Lifestyle
,
nutri.on,
adjunc.ve
therapies
Find
out
atherosclero:c
risk
and
treatment
if
indicated
DM,
insulin
resistance,
hypertension,
metabolic
syndrome,
dyslipidemia