FARMAKOLOGI HORMON

TIROID
dr. Elly Nurus Sakinah, M.Si
Learning outcome

• Menjelaskan MOA dari obat tiroid dan

antitiroid
• Menjelaskan PK dari obat tiroid dan
antitiroid
• Menjelaskan efek samping obat  t.u
hepatotoksisitas
• Menjelaskan penggunaan klinis obat
tiroid dan antitiroid
 Kasus
• Seorang laki-laki usia 47 tahun datang
dengan keluhan palpitasi, tremor, penurunan
BB, intoleransi thd panas sejak 6 minggu yll.
Pmx fisik : HR: 110x/mnt, T: 150/80mmHg,
dan pembesaran kelenjar tiroid, fine tremor
dan eksoftalmus. Tes laboratorium : free T4:
40 pmol/L, free T3 : 10,6 pmol/L, tyroid
globulin meningkat, TSH tidak terdeteksi.

• Diagnosis ?
4
 Antithyroid Drugs

• Inhibit the formation of thyroid

hormones.
• Used in the treatment of
hyperthyroidism.
 Thioamides

• Propyithiouracil (PTU), methimazole.

• Inhibit the peroxidase enzymes catalyzing the
oxidation of iodide, thus reducing the synthesis of
thyroid hormones.
• PTU also inhibits the peripheral deiodination of T4 to
T3.
• Delay in onset (until preformed hormones have been
metabolized).
Mechanism of action
 Pharmacokinetic

PK PTU METHIMAZOLE
Absorbsi Rapid Rapid
Kadar puncak dalam 1-2 jam 1-2 jam
darah
DOA 12-24 jam Long acting
(diberikan 2-3x/hari) (single dose, 1x/hari)
Ikatan protein 80-90% dengan Free
albumin
Clinical use Thioamides
• Short term (week-months)
– Preparative therapy
– “Cool down” the patients prior to radioactive iodide radio
iodine
– Used for control of hyperthyroidism until surgery
• Long term (1-2 years)
– Primary therapy: Grave’s Dis’, pregnancy, pediatri. Bukan
Tx primer untuk toxic multinoduler goiter atau soliter
autonomic nodule.
– “remission”, that may or may not occur, usually followed
by radioiodine therapy
• The drugs are given PO.
 Antithyroid drug therapy
• Starting Doses à
– PTU: 100 mg tid
– methimazole: 10‐30 mg/day as a single dose
– Potency of methimazole as an inhibitor of
iodine utilization is 20‐50‐fold greater than PTU
• . Euthyroid state achieved in 4‐12 weeks
– depends on baseline severity
– à thyroid gland size
– à drug dose
 SIDE EFFECTS
• Currently, side effects from these drugs can be
classified as “minor” and “major” .
• Major side effect
– Agranulocytosis
– Hepatotoksisitas (methimazole : no hepatitis , dose
related)
• Minor side effects occur in 5‐10% of patients
and include:
– Rash, urticaria, pruritus
– Fever
– gastrointestinal distress
 PTU vs Methimazole in pregnancy
• Methimazole  teratogenik (aplasia cutis,
embryopathy including choanal atresia )
• Transplacental passage w. fetal hypothyroidism
• methimazole with congenital anomalies,
• propylthiouracil should be used as a first‐line drug,
if available, especially during first‐trimester
organogenesis.
• Methimazole may be prescribed if propylthiouracil
is not available or if a patient cannot tolerate or has
an adverse response to propylthiouracil.
 Aplasia cutis congenital
• On the scalp, the defect is hairless, ulcerated,
usually less than 3 cm diameter, and often heals
spontaneously
• . May require skin grafting
Atresia koana
 Breast feeding
• PTU crosses into milk < methimazole .
• Therefore PTU may be preferred .
• Both drugs have been shown to be safe
and lactating women with preservation
of normal neonatal thyroid function .
• both approved by the American
Academy of Pediatrics
 lodide
• Small amounts of iodine (75-100
ng/day) are required for hormone
synthesis.
• But high concentrations (+ 50 mg/day)
produce autoinhibition.
• lodide blocks the uptake of iodide,
inhibiting synthesis and release of
thyroid hormones.
• Diminishes vascularity of the gland.
 lodide
• Used only preoperatively to shrink the
gland. (prior to surgical removal of the
gland).
• It is given as Lugol's solution (iodine
and potassium iodide). 5% iodine +
10% potassium iodide,50–100 mg
iodine/d for a maximum of10 d)
• Effects are visible within 24 hours. It
is no longer used in long-term therapy.
 lodide
• Adverse reactions

• Hypersensitivity reaction .
• Drug fevers, metallic taste, bleeding
disordes.
• Gastric irritation.
• Long-term use can lead to sudden
disinhibition of hormone synthesis,
producing acute hyperthyroidism.
 kasus
• Setelah 7 minggu terapi dengan PTU
dan propranolol, pasien mengeluh
gatal, kemerahan maculopapular.
Terapi diganti dengan radioiodida.
• 3 bulan kemudian pasien mengeluh
letargi, lemah, kedinginan pada suhu
ruang. Hasil lab : T4 :8pmol/mL, T3 :
2pmol/mL, TSH : 25 mU/mL
• Diagnosis ?
 Terapi Hormon tiroid
• Thyroid hormones accelerate metabolism.
• Release hormon tyroid diatur oleh TSH
• Mekanisme feedback negatif
• Hormon tyroid :
– Thyroxine (T4)  paling dominan (90%)
– Triiodothyronine (T3) 10% tapi lebih aktif
karena afinitas thd reseptor 10x lebih tinggi,
lebih pendek masa kerjanya, lebih cepat
dieliminasi
– T4 is converted in part to T3
24
 Farmakologi
• Untuk tujuan terapi  T4 lebih dipilih
• Meskipun T3 lebih aktif dan lebih
cepat diabsorbsi GIT
• Karena T4  lebih konstan didalam
darah dan degradasinya lambat
• T4 bagus diabsorbsi dalam kondisi
perut kosong  diberikan ½ jam
sebelum sarapan pagi
 Replacement therapy of
hypothyroidism
• thyroid disease, or secondary, i.e.,
resulting from TSH deficiency
• Tx : oral administration of T4
• therapy is usually started with low
doses and gradually increased 
sampai eutyroid
• 150 μg/d)
 Thyroid Drugs
Adverse reactions

• Hyperthyroidism (or symptoms of

hyperthyroidism).
• Cardiovascular toxicity
(tachyarrhythmias, angina, and
infarction)
• CNS stimulation, insomnia.
 Levothyroxine
• Synthetic levo isomer of T4.
• PO and IV available.
• Preferred drug for hypothyroidism.
• Better standardization and stability and
long duration.
• Long half-life of T4.
• Facilitates maintenance of a steady
physiologic replacement.
 Liothyronine
• Synthetic L-T3.
• More difficult to monitor than T4.
• More expensive.
• Shorter duration of action.
• Treatment of choice for Mixedema
coma.
 Liotrix
• Combination of levothyroxine and
liothyronine.
• Ratio of 4:1.
• No advantage over levothyroxine.
 Terapi hormon tiroid
• Goiter struma  T4 atau garam iodine
(150–300 μg/d) to be met and effectively
prevents goiter
• Pada orang tua  hati2 pemberian iodine
jangka panjang  there is a risk of
provoking hyperthyroidism
• During chronic maximal stimulation,
thyroid follicles can become independent
of TSH stimulation (“autonomic tissue”).