thyroid and antithyroid drugs -...
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Thyroid and Antithyroid Drugs
Department of Pharmacology
Dr. Yunita Sari Pane, MSi
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HYPOTHALAMIC – PITUITARY –
THYROID AXIS
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T3 and T4 are synthesized in the
thyroid gland. Inorganic iodine is
trapped with great avidity by the
gland, oxydized and attached to tyro-
sine. Combination of mono- and/or-sine. Combination of mono- and/or-
di-iodinated tyrosine forms T3 and
T4. The thyroxine peroxidase is im-
portant both in the initial oxidation
and the final combination steps.
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Mono-iodtyrosine (MIT)
Tyrosine
Inorganic iodine Thyroxine peroxidase
Mono-iodtyrosine (MIT)
Di-iodtyrosine (DIT)
Thyroxine peroxidaseInorganic iodine
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MIT + DIT T3Thyreoglobulin
DIT + DIT T4Thyreoglobulin
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TyrosineI
CH2-CHHO
NH2
COOH
Di-iodtyrosine
CH2-CHHO
NH2
I
I
COOH
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CH2-CH
NH2
I
O
I
HO
COOH
T4 = L-Thyroxine
II
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Synthesis and release of T3 and T4
are controlled by the anterior pitu-
itary hormone, thyrotrophin (TSH -
thyroid-stimulating hormone). Its
secretion is controlled by the hypo-secretion is controlled by the hypo-
thalamic thyrotrophin-releasing
hormone (TRH) and somatostatin.
Circulating T3 and T4 exert a nega-
tive feeback on the TSH and TRH.
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Adenohypophysis
TSH
Hypothalamus
TRH Somatostatin
������������ ((((−−−−))))
Glandula Thyreoidea
TSH
������������((((−−−−))))
������������
((((−−−−))))
((((−−−−))))
p l a s m aT3 < I > I T4
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80 mcg T4
24 hrs:24 hrs:
80 mcg T4
40 mcg T3
200 mcg I
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Circulating thyroid hormones are
highly protein-bound to TBG
(thyroxine-binding globulin).
Less than 0.1% from T4 is free.
Only the free fraction can
bind to specific cell receptors.
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PlasmaT4: 95% T3: 5%
Thyroxine-binding
globulin
99.91 - 99.97%
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AGENTS INLFUENCING PROTEIN-
BOUND OF L-THYROXINE
AGENTS INLFUENCING PROTEIN-
BOUND OF L-THYROXINE
INCREASE
•estrogens
DECREASE
•glucocoricoids•estrogens
•methadone
•heroin
•clofibrate
•tamoxifen
•glucocoricoids
•aspirin
•phenytoin
•carbamazepine
•furosemide
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T3 is much more biologically activethan T4. The plasma half-life of
T3 is 36 h. T4 has t1/2 168 h.
T4 is a prohormone. After entering
into cells it is converted to T3 which into cells it is converted to T3 which
binds to receptor protein and inte-
racts with DNA in the cell nucleus,
causing the synthesis of new messen-
ger RNA and hence of new proteins.
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TRbeta1
THYROID RECEPTORSTHYROID RECEPTORS
TRbeta2 adenohypophysisadenohypophysis
TRalfa2
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The main effects of T3 and T4:
•Stimulating of metabolism (which
resulting in a raised basal meta-
bolic rate).
•Promotion of normal growth and•Promotion of normal growth and
maturation, particularly of the
CNS and skeleton.
•Sensitization to the effects of cate-
cholamines (DA, NA, A).
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1. THYROID
DRUGS
1. THYROID
DRUGS
Thyroxine (T4) and
tri-iodthyronine (T3)
DRUGSDRUGS
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T3&T4 - indications:
•hypothyroidism
•T3 is reserved for•T3 is reserved for
patients with
myxoedema coma.
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EFFECTS OF T.H.
T.H. are responsible for optimal :
- Growth
- Development
- Function
- Maintenance
of all body tissues
- Maintenance
Excess ���� thyrotoxicosis or hyperthyroidism.
Inadequate ���� hypothyroidism
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T.H. is important in infancy for growth and development of the nervous system
Congenital deficiency of TH.
Cretinism ���� mental retardation
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TH regulates general body metabolism and
energy expenditure, and also some enzymes :
In adult :
- Na+ - K+ - ATPase
- For catabolic and anabolic ���� body
temperatur increases
- Resemble the effects of symphathetic - Resemble the effects of symphathetic
stimulation.
Low level of TH.
- Lethargy
- Myxedema ���� - Hypometabolic
- Dry skin
- Coarse voice
- Cold intolerance
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Jodthyrox (T4 + < I)
Levothyroxine (T4)
- tabl. 25 mcgLiothyronin (T3)- tabl. 25 mcgLiothyronin (T3)Thyreoidea siccata
Thyrotrophin (TSH)
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•Thioureas agents
•Beta-blockers
2. ANTITHYROID
DRUGS
2. ANTITHYROID
DRUGS
They are used to treat
hyperthyroidism.
•Beta-blockers
•Radioactive iodine (131I)
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Thioureas agentsinhibit thyroxine peroxidase,
and therefore synthesis of T3
and T4. Because of long half-life and T4. Because of long half-life
of T4, changes in rate synthesis
takes several weeks to low circu-
lating concentrations to normal.
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•Carbimazole (prodrug)
Methimazole
(thiamazole)(thiamazole)
•Propylthiouracil
•Thiamazole
- tabl. 5 mg
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Thioureas – adverse effects
•Nausea, taste disturbance
•Agranulocytosis•Agranulocytosis
•Placentar transfer and secretion
in breast milk can produce neo-
natal hypothyroidism (small
doses are probably safe).
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Beta-blockers have immediate
symptomatic effect on palpitation and
tremor but do not alter the rate of T3
& T4 synthesis.
131I (t1/2 8 days) is used to treat
multinodular toxic goitres. It is
taken up by the abnormal tissue.
Monday, 17th March 2008 in Medan
08.00-08.50
10.30-11.20