antithyroid
TRANSCRIPT
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FARMAKOLOGI HORMON TIROID
dr. Elly Nurus Sakinah
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Yang Dibahas
• Terapi Hormon tyroid untuk kasus kekurangan hormon tiroid (hipotiroidisme)
• Antitiroid Drugs hipertiroidisme
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FISIOLOGI HORMON TIROID
• Kelenjar tiroid menghasilkan 2 hormon : T3 dan T4
• Fungsi : pertumbuhan, perkembangan, pemeliharaan jaringan tubuh yang optimal
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Hormon Tiroid• T3 dan T4 memasuki sirkulasi
dengan terikat protein plasma (99 %)
• 20 % T3 , sisanya T4, karena nanti T4 juga akan dikonversi menjadi T3 di perifer
• T4 juga bisa dikonversi menjadi rT3 (reversa T3)
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• Step One: Follicle cells actively (using ATP) take up iodide (I-) from the blood.
• Step Two: Follicle cells "oxidize" iodide (I-) to iodine (I). Remember, oxidation means to lose an electron!
• Step Three: Iodine is attached to tyrosine (Tyr) to give mono-iodotyrosine (MIT) and di-iodotyrosine (DIT).
• Step Four: MIT's and DIT's are joined together to form T3 (tri-iodothyronine) and T4 (thyroxine).
iodide uptake
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Terapi HIPERTIROID
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Antithyroid Drugs• Menghambat pembentukan hormon tiroid• Digunakan untuk pengobatan
hyperthyroidism.
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1. lodide • lodide menghambat uptake
(pengambilan) iodide menghambat sintesis dan release dari hormon tiroid
• Mengurangi ukuran dan vaskularisasi dari kelenjar yang hiperplastik berguna untuk pasien yang mau operasi tiroidektomi
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lodide• 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)
• Iodida berguna pada krisis tiroid ( eksaserbasi akut yang mengancam jiwa dari semua gejala tirotoksikosis)
• Tidak dapat digunakan untuk terapi hipertiroidisme jangka panjang karena efeknya cenderung menghilang
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Efek Samping lodide• Hypersensitivity reaction .• Drug fevers, metallic taste, bleeding
disordes.• Gastric irritation. • Long-term use can lead to sudden
disinhibition of hormone synthesis, producing acute hyperthyroidism.
• HATI – HATI PADA WANITA HAMIL : iodida dapat melewati sawar darah plasenta goiter pada janin
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Thioamides • Ada 2: Propyithiouracil (PTU), dan
methimazole.• Menghambat enzim peroxidase yang
mengkatalisis oksidasi iodida menurunkan sintesis hormon tiroid
• PTU juga menghambat deiodinasi dari T4 menjajadi T3.
• Biasanya diberikan per oral
– PTU: absorbsi cepat setelah 1 jam tapi tidak sempurna krn first past metabolisme
– Metimazole : absoebsi sempurna
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Efek Samping Thioamides• Mild maculopapular rash, joint pain,
headache, nausea, and loss of hair. • Jarang tapi berbahaya: agranulocytosis.
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Anti tiroid drugs
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Beta blocker• Digunakan untuk mengurangi bebrapa
keluhan : tremor, takikardia, palpitasi, cemas dan heat intolerance
• Mek kerja : menghambat sistem saraf simpatis melalui hambatan reseptor beta
• Sebagai terapi tambahan pada obat antitiroid yang lain ( grave disease, nodul toksik, pre operasi)
• Terapi primer tiroiditis
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Beta blocker• Dosis propanolol : 20-40 mg (4 x
sehari)
• Kontraindikasi : gagal jantung, cardiomiopati
• Efek samping : Nausea, vomiting, cemas, insomnia, bradikardi
• Jika terdapat kontraindikasi, beta blocker diganti dg CCB atau simpatolitik
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Pada kehamilan dan laktasi• Thioamida melewati placenta
hypothyroidism pada janin
• Tapi pada kehamilan lebih dipilih PTU , krn lebih kuat terikat protein shg tidak mudah menembus plasenta
• PTU juga tidak disekresi dalam ASI
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TERAPI HIPOTIROID
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Terapi Hormon tiroid• 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
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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
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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)
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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.
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Liothyronine • Synthetic L-T3.
• More difficult to monitor than T4.
• More expensive.
• Shorter duration of action.
• Treatment of choice for Mixedema coma.
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Liotrix • Combination of levothyroxine and
liothyronine.
• Ratio of 4:1.
• No advantage over levothyroxine.
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Thyroid DrugsAdverse reactions
• Hyperthyroidism (or symptoms of hyperthyroidism).
• Cardiovascular toxicity (tachyarrhythmias, angina, and infarction)
• CNS stimulation, insomnia.