1

INS TIATY
Departemen Farmakologi & Terapeutik FKUI
2008
TIROID dan OBAT ANTITIROID
Sintesis hormon tiroid
1. Iodide trapping =
transport iodida ke
kel tiroid
2. di oksidasi - thyroidal
peroxidase iodium
3. iodinasi residu
tirosin di molekul
tiroglobulin
monoiodotirosin (MIT)
& diiodotirosin (DIT)
4. 2 mol DIT bergab di
antara mol tiroglobu
lin L-tiroksin (T4)
1 mol MIT+1mol DIT
T
2
! Uptake Iodida

Diham"at oleh# thio$%anate &S 'N

(
)* per$hlorate
&'l+,
(
)

Diurangsang oleh TS -

Iodide dalam plasma# 0!2(0!, m$g.d/

Iodide dlm kel! Tiroid# 20(00 1 kadar dlm plasma

2! +ksidasi dan Iodinasi
T2+
3
Iodida &I
(
) (((((((((((( Iodine &I
2
)
3
Iodine 4 Th%roglo"ulin 5IT 6 DIT
3
Dirangsang oleh TS -*
3
Diham"at oleh 2TU* 5etima7ole dan
amino"en7ene
3
Sintesis hormon tiroid
3. Organification (Pembentukan T3 dan T!
"
#ou$%ing &IT ' DIT T3
"
#ou$%ing DIT ' DIT T
"
Dihambat o( PT) dan methima*o%e
. Sekresi dan kon+ersi

Tiroid terutama mensekresi T, teta$i

T3 memi%iki $otensi bio%ogis -ang
%ebih besar
4
Sintesis hormon tiroid
Sintesis hormon tiroid
.. /on+ersi di 0aringan $erifer
"
Sebagian T dikon+ersi men0adi T3
di ke%. tiroid
"
123 kon+ersi ter0adi di hati dan gin0a%
"
/on+ersi dirangsang o( TS4
"
Dihambat o( PT), dan beta5b%oker
5
Struktur 5olekular dan kon8ersi
6
Inakti+asi
Akti+asi
!"!# triiodot$%rosine (T)
5. 6 more $otent than T
!#!"# triiodot$%rosine
(re&erse T)
Tetraiodot$%ronine (T4)
7armakokinetik hormon tiroid

T8 ikatan $rotein besar

Terutama $d a5g%obu%in (9 1.3!, and

$rea%bumin

4an-a : 3 T bebas (7T!

T3 re%atif tidak terikat $d $rotein %ama

ker0a singkat

T:(; T8

norma% 8 <5= hari

hi$ertiroidisme 8 35 hari

hi$otiroidisme 8 >5:2 hari

7
7armakokinetik hormon tiroid

&etabo%isme8

?i+er8 kon0ugasi, deiodinasi, deaminasi ,

dekarboksi%asi

@in0a%8 deiodinasi

/on0ugasi8 dg g%ukoronida dan su%fat

sirku%asi enterohe$atik

Akskresi8

)rine, feces
8
5ekanisme Ker9a
T
,
& T
:
di"a;a ke sel
target o. protein plasma

-ormon "e"as memasuki

sitoplasma sel target dlm
"entuk T
,
atau T
:
!
T
,
dikon8ersi men9adi T
:

di dlm sitoplasma o.k
han%a T
:
%g "eker9a di
nukleus
T
:
"erikatan dg DNA &
merangsang transkripsi
DNA m<NA sintesis
protein
9
10
7ISIO?O@I 4OR&ON TIROID
:. Afek ka%origenik8 tingkatkan B&R
;. Afek katabo%ik (dosis tinggi!8
"
Otot ke%emahan, kreatinuria
"
Tu%ang osteo$orosis
3. &etabo%isme karbohidrat

absor$si #4O, g%ukosa darah,

g%ikogen hati
. &etabo%isme $rotein8
Dosis keci%8 efek anabo%ik
Dosis tinggi8 katabo%ik
7ISIO?O@I 4OR&ON TIROID
0! 5eta"olisme lipid #

/ipolisis ;eight loss in h%perth.

S intesis kolesterol * meta"! kolesterol o.

hati kolesterol darah

&D(th%ro1in# antih%perlipidemi$ agent)

=! 2enting dlm proses pertum"uhan
De>isiensi saat "a%i kretinism
?! S istem sara>#
Irrita"ilitas* restlessness* peningkatan re>leks
tendo dalam
11
7ISIO?O@I 4OR&ON TIROID
8! T- and Norepinephrine &N@)

T- # tingkatkan sekresi N@

T- memiliki e>ek sama dg N@ &tetapi

le"ih lam"at)

@>ek Kardio8askular dapat diham"at

oleh "loker
12
13
Regulasi Fungsi Tiroid
Abnorma%itas 7ungsi Tiroid
14
'I'T(M )I*(+ )I*,
/BS
Takhikardia , fibri%asi
atria%, gaga% 0antung
Bradikardia
/u%it
4angat, %embab,
berkeringat, tidak tahan
$anas
Pucat, dingin, ku%it kering,
tidak tahan dingin
&ata,
Ca0ah
e6o$hta%mus Adema $eriorbita% , $tosis,
@I
Appetite , diare Appetite , konsti$asi,
ascites
#NS
Nervousness,
hi$erkinesia, emosi %abi%
?etargi, $er%ambatan $roses
menta%

4i$ertiroidisme
"
4i$otiroidisme
15
Abnorma%itas 7ungsi Tiroid
'I'T(M )I*(+ )I*,
&usku%ar Deakness and fatigue,
hi$er ref%eksia,
hi$erka%semia,
osteo$orosis
Otot kaku dan fatigue,
hi$oref%eksia , non $iting
edema
Re$roduksi &ens irregu%arit-,
$enurunan ferti%itas
4-$ermenorrhea,
inferti%itas, %ibido ,
o%igos$ermia
&etabo%ik Peningkatan B&R Penurunan B&R
4ormon Tiroid

Sediaan

?e+oth-ro6ine (T!8 .2, :22 mcg tab%ets

?ioth-ronine (T3!8 ., ;., .2 mcg tab%ets

?iothri6 (a 8: ratio of T and T3!

Th-roid dessicated (anima% origin!

Indikasi

Re$%acement thera$- $d
hi$otiroidisme, kretinism

Su$$ression thera$- u( goiter non toksik

16
+"at Antitiroid

Thionamides

Anion Inhi"itors

Iodida dan Iodinated $ontrast media

Iodine <adioakti>

2engham"at reseptor adrenergik

17
T4IONA&IDAS
(Pro$-%thiouraci%, methima*o%e, carbima*o%e!
18

&ekanisme ker0a

Inhibisi th-ro6ine $ero6idase8

Inhibisi oksidasi iodida men0adi

iodine

Inhibisi iodinasi th-rog%obu%in

Inhibisi organifikasi ( $embentukan

T3 dan T!

PT) (methima*o%e tidak! 8 hambat

deiodinasi T di $erifer

Tidak mem$engaruhi u$take iodida

o%eh tiroid
19
20
"
7armakokinetik
E
Absor$si8 @I tract
E
7irst $ass metabo%ism bioa+ai%abi%itas
.25123
E
&etabo%isme8 g%ukoronidasi di hati
E
Distribusi8
"
Terkonsentrasi di ke%en0ar tiroid
"
P%acenta% $assage8 &ethima*o%e 99 PT)
PT) bisa digunakan $ada Canita
hami%
"
Akskresi8 urine, breast mi%k
"
PT) d%m 0um%ah keci% diekskresi ke ASI

da$at diberikan $d ibu men-usui

Aaktu paruh plasma #

3
2TU ?0 menit >rekuensi dosis ( , 1.
hari
3
5ethima7ole ,(= 9am 1.hari

@>ek samping &relati> rendah)

Agranulositosis &methima7ole B 2TU)

2apular rash* Arthralgia

S ediaan #

2rop%lthioura$%l &2TU)# ta"let 00 mg

5ethima7ole # ta"let 0* 0 mg

'ar"ima7ole

5eth%lthioura$il 21

Indikasi

Pengobatan hipertiroidisme

Terapi definitif Graves disease

Thyroid storm

Th/ supresi sebelum pembedahan

Supresi TSH pada non toxic goiter

22
Ionic B%ockers

-am"at transpor akti> Iodida ke kel tiroid

Carang digunakan

Thio$%anate &S 'N()

2er$hlorate &'l+,()

Nitrate &N+:()

2erte$hnetate &T$+,()

Fluoro"orate &DF,()
23
Iodide and Iodinated ontrast !edia

Iodide" obat antitiroid tertua

#iperlukan dlm $umlah kecil u/ sintesis TH

#lm dosis lebih tinggi inhibisi sekresi TH

%fek samping"

Hipersensitivitas& iritasi GI

!etallic taste& erupsi kulit

'aI& (I" tersedia sbg sediaan oral

ontrast media
)ugol solution " (I * I
+
24
Radioacti+e Iodine

I
131

Cepat terkonsentrasi di kel tiroid terutama dlm

kondisi hipertiroidisme

T1/2 : 8 hari

Ekskresi: Urine

Hipotiroidisme: 85-9! diekskresi dlm 2" #am

Eutiroid : $5!

Hipertiroidisme : 5!
25

Indikasi #

-ipertiroidisme &khususn%a pd pasien

usia tua)

Era8eFs disease# persisten* relaps atau

gagal terapi setelah tiroidektomi

To1i$ nodular goiter

Karsinoma tiroid metastatik

Diagnostik nodul tiroid &hot* ;arm* $old)

Kontraindikasi#

Kehamilan

2asien usia muda

26

@>ek S amping#

<isiko peru"ahan neoplastik

-ipotiroidisme

Dosis# 0!0: m$g I

:
& , m'i) dosis
tunggal

S ediaan# NaI
:
kapsul u. oral* dan
solution u. pem"erian IntraGena
27
T@<I5A KASI-
28

29
30
P,-,TH.-/I# H/-!/'% and ,)I0!
!%T,1/)IS!
2 alsium is important for normal function of
nerve and muscle& blood clotting& en3yme
function& etc
2 1lood calsium is regulated by three
hormones" parathyroid hormone& calcitonin&
and vitamin #4
2 PTH is the most important endocrine
regulator of calcium and phosphorus
concentration in extracellular fluid4
Physiologic %ffects of PTH

5o"ili7ation o> $al$ium >rom "one# stimulate

osteo$lasts to rea"sor" "one mineral*
li"erating $al$ium into "lood!

@nhan$ing a"sorption o> $al$ium >rom the

small intestine "% indire$tl% stimulating
produ$tion o> the a$ti8e >orm o> 8itamin D in
the kidne% &Gitamin D indu$es s%nthesis o> a
$al$ium("inding protein in intestinal epithelial
$ells that >a$ilitates e>>i$ient a"sorption o>
$al$ium into "lood)!

S uppression o> $al$ium loss in urine and

stimulate loss o> phosphate ions in urine
31
32
#ontro% of PT4 Secretion and #a
metabo%ism
33
Indi$ation o> 2T-

Diagnosti$ test o> pseudo h%po2T-

&insensiti8it% o> target $ell to 2T-)

Administration o> 2T- Dlood 'a

44
in$rease

2seudo h%po 2T-# no 'a

44
response to 2T-
34
35
#a%citonin
"
Secreted from #5ce%%s of the th-roid g%and.
"
#a%citonin reduces the acti+it- of osteoc%ast
decreases $%asma ca%cium concentration
"
#a%citonin $%a-s a minor ro%e in ca%cium
metabo%ism and on%- acts Chen the $%asma
ca%cium concentration is +er- high
(h-$erca%cemia!.
"
Administration8 im, nasa% s$ra-
Indi$ation o> 'al$itonin

-%per$al$emia due to h%per 2T-

idiopathi$ h%per$al$emia

+steoporosis

Done resorption due to immo"ili7ation

Git! D into1i$ation
36
Gitamine D

Gitamin D is produ$ed "% the skin in response to

e1posure to sunlight!

<eall%* Gitamin D is a hormone!

The 8itamin D must "e $hemi$all% altered "% the li8er

and then the kidne%s to "e$ome "iologi$all% a$ti8e!

A$ti8e meta"olite o> 8it! D:

Git! D in$reases 'a a"sorption >rom EI

37

38
Bisphosphonate
O!""""O""""!O
O# $#3 O#
O# O# O#
O!""""O""""!O
O# R2 O#
O# R1 O#
%tidronate
!a&idronate
O!""""O""""!O
O# $#2 O#
$#2"$#2"'#2
O# O# O#
O!""""O""""!O
O# $#2 O#
'#2
O# O# O#
Risedronate
DIS2-+S2-+NAT@
BISP4OSP4ONATA

5e$hanism o> a$tion

S uppress osteo$last a$ti8it% on ne;l% >ormed

resorption sur>a$e

De$rease >ormation o> osteo$last progenitors

De$rease osteo$last re$ruitment

2romotion o> apoptosis o> mature osteo$last

Anti apoptoti$ e>>e$t on osteo"lasts and

osteo$%tes
39
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BISP4OSP4ONATA
/INATI#S
"
Poor%- absorbed from @IT. 7ood or
be+erages can decrease bioa+ai%abi%it-
significant%-
"
Pamidronate8 gastric irritation gi+en ora%%-
i+
"
4igh affinit- to bone tissue and ha+e %ong
bone retention
"
Not metabo%ised
"
A6creted b- the kidne-
BISP4OSP4ONATA

S ide @>>e$ts

@sophageal irritation H risk o> per>oration should

"e taken in sitting position ;ith su>>i$ient ;ater
drinking

Arthralgia

-%persensiti8it%

'ontraindi$ation

-%persensiti8e to "isphosphonate

-%po$al$emia

S e8ere renal impairement &''T I :0 ml.min!)

A$ti8e uper EI pro"lems

2regnan$%
41
BISP4OSP4ONATA

Indi$ations

+steoporosis

2re8ention o> "one metastasis

2agetFs disease

-%per$al$emia asso$iated ;ith malignan$%

Administration

To "e taken "e>ore meal &a"t :0 min)

Keep sitting >or at least :0 min

42
BISP4OSP4ONATA

2reparation and Dose

<isedronat# ta"! 0 mg

0 mg.da%

Alendronate# ta"! 0 mg

0 mg.da%

2amidronate# 8ial 0 mg.0 ml

=0(J0 mg single in>usion e8er% , ;eeks

'lodronate# $ap ,00 mg* in>usion =0 mg.ml 1

0 ml* amp :00 mg.0 ml

Koledronate# 8ial , mg
43
44