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THYROID & ANTITHYROID

Akhmad Edy Purwoko


Bagian Farmakologi & Toksikologi
FK - UMY

Drug used in thyroid disease

Hipothyroidism

Thyroxin
T4

Triidothyronin
T3

Hiperthyroidism

Thioamide
Iodide
Ipodate
131i

I-

I-

Io

MIT-DIT-T3-T4
-

- Iodides
Proteolisis

Iodides,
Thioamides
PTU
Metamizol

Peripheral
Tissues
T4 T3
Ipodate,
Beta-blokers
T3

T4 T3
Blood

Thyroid Replacemen Therapy


Levothyroxin (a sodium salt of T4) is the
most commonly used drug for thyroid
replacement therapy drug of choice for
treatmen of hypothyroidism
Liothryronin (a salt of T3)and litotrix (a
mixture of T3 and T4) have also been
used to treat hypothyroidsm

Levotiroksin:
Tablet 25; 50; 75; 88; 100; 112; 125; 137;
150 ; 175; 200; 300 mcg
Kapsul 13; 25; 50; 75; 88; 100; 112; 125; 137;
150 mcg
Injeksi 100; 200; 500 mcg/vial

Mild Hipotiroid
1.7 mcg/kg or 100-125 mcg PO qDay; not to
exceed 300 mcg/day
>50 years (or <50 yr with CV disease)
Usual initial dose: 25-50 mcg/day
May adjust dose by 12.5-25 mcg q6-8Week
>50 years with CV disease
Usual initial dose: 12.5-25 mcg PO qDay
May adjust dose by 12.5-25 mcg q4-6weeks
until patient becomes euthyroid and serum
TSH concentration normalized; adjustments q68weeks also used
Dose range: 100-125 mcg PO qDay

Severe Hypothyroidism
Initial: 12.5-25 mcg PO qDay
Adjust dose by 25 mcg/day q2-4Week PRN

Subclinical Hypothyroidism
Initial: 1 mcg/kg PO qDay may be adequate
If replacement therapy not initiated, monitor
patient annually for clinical status

Myxedema Coma
200-500 mcg IV once, THEN 100-300 mcg 1
day later PRN; may consider smaller doses in
patients with cardiovascular disease

Levotiroksin t panjang diberikan


sekali sehari. Kadar steady state
(tunak) / Keadaan mantap dicapai setelah
6-8 minggu. Toksisitas ~ kadar tiroksin,
manifestasi klink: gelisah, palpitsi jantung
dan takikardi, intoleransi terhadap panas
dan berat badan turun tanpa sebab.

Liothyronin T3
Hypothyroidism
Initial: 25 mcg PO qDay; may increase by 25
mcg q1-2Weeks; not to exceed 100 mcg/day
Maintenance: 25-75 mcg PO qDay
May use 10-12.5 mcg T3 in combo with T4
(decrease T4 dose by 50 mcg)

Nontoxic Goiter
Initial: 5 mcg PO qDay; may increase by 5-10
mcg q1-2Weeks (5 mcg in elderly)
When reach 25 mcg PO qDay, may increase
by 12.5 mcg or 25 mcg q1-2Weeks
Maintenance: 75 mcg PO qDay

Myxedema
Initial: 5 mcg PO qDay; may increase by 5-10
mcg/day q1-2Weeks
When reach 25 mcg PO qDay, may increase
by 5-25 mcg q1-2Weeks
Maintenance: 50-100 mcg PO qDay

Myxedema Coma
Initial: 25-50 mcg IV
Patients with CVD: 10-20 mcg IV
Doses of at least 65 mcg/day IV associated
with lower mortality
Allow 4-12 hr between doses; not to exceed
12 hours

Adverse Effects 1-10%


Tachycardia (3%), Hypotension (2%),
Myocardial infarction (2%),Cardiopulmonary
arrest (2%)

<1%:
Congestive heart failure, Hypertension,
Twitching, Phlebitis, Angina, Fever

Antithyroid drugs
Propylthiourasil, Methimazole

inhibit thyroid synthesis (inhibit iodination of


tyrosin group and coupling these group to form thyroid hormon. Prohylthiourasil also inhibits the peripheral
conversion of T4 to T3)

Iodide salt and Iodide


Radioactive Iodine
Other drugs, -blockers

Propylthiouracil
Mechanism of Action
Inhibits synthesis of thyroid hormone by
blocking oxidation of iodine in thyroid gland;
blocks synthesis of T4 and T3
Pharmacokinetics
Absorption: 75%
Duration: 12-24 hr
Half-life elimination: 1-2 hr, increase in ESRD
Vd: 0.4 L/kg
Protein Bound: 80-85%
Concentration (200-400 mg single dose): 6-9 mcg/mL

Peak plasma time: 1-2 hr


Peak plasma concentration: (200-400 mg single
dose): 6-9 mcg/mL

Metabolism: liver, to glucuronide conjugates,


inorganic sulfates, sulfur metabolites
Total body clearance: 7 L/hr
Excretion: Urine (35%)

Dosing & Uses


Hyperthyroidism
300-450 mg/day PO divided q8hr initially (may
require up to 600-900 mg/day)
Maintenance: 100-150 mg/day divided q8hr

Thyrotoxic Crisis (Unlabeled)


Initial 200-300 mg PO q4-6hr initially on Day 1
(may require 800-1200 mg/day), then reduce
gradually; some practitioners propose an
initial dose of 600-1000 mg with gradual dose
reduction after initial response
Maintenance: 100-150 mg/day PO divided q812hr

Graves Disease
50-150 mg PO q8hr initially
Maintenance: 50 mg PO q8-12hr for up to 1218 months; then taper and discotinue if
euthyroidism restored (TSH) is normal

Renal Impairment
Dose adjustment not necessary

Adverse Effects Frequency Not Defined


Agranulocytosis, Aplastic anemia,
Dermatologic reactions, Hepatitis,
Polyarthritis, Drowsiness, Fever, Headache,
Vertigo, Alopecia, Erythema nodosum,
Exfoliative dermatitis, Skin rash, Skin ulcers,
Goiter,Weight gain, Constipation, Loss of
taste, Granulopenia, Leukopenia,
Thrombocytopenia

Black Box Warnings


Severe liver injury and acute liver failure,
some of which have been fatal, have been
reported in adult and pediatric patients
taking propylthiouracil
Closely monitor for symptoms and signs of
liver injury (eg, , anorexia, nausea,
vomiting, fatigue, pruritus, dark colored
urine, or jaundice), especially during first 6
months after initiating therapy

Reserve propylthiouracil use for those


unable to tolerate other treatments (eg,
methimazole, radioactive iodine, surgery)
Propylthiouracil may be the treatment of
choice during and just before the first
trimester of pregnancy (strong association
of methimazole with congenital
malformation during first trimester)

Inhibitor pelepasan hormon


Iodium menghambat iodinasi tirosin
simpanan tiroglobulin. Iodiom
menghambat pelepasan hormon tiroid
(mekanisme ?)
Iodium digunakan pada krisis tiroid yg
fatal, diberikan pada tindakan sebelum
bedah vaskularisasi tiroid.
Penggunaan jangka pendek (tidak
responsif setelah beberapa minggu)
ES < (bisul mulut & tenggorok, ruam
ulserasi mukosa & rasa logam di mulut