thyroid hormones and antithyroid drugs. normal amount of thyroid hormones are essential for normal...
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Thyroid hormones
and
antithyroid drugs
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normal amount of thyroid hormones are essential for normal growth and development by maintaining the level of energy metabolism in the tissue.
Either too little or too much thyroid hormones will bring disorders to the body.
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Part 1 Thyroid hormones
Two major thyroid hormones are: triiodothyronine ( T3, the most active form ) thyroxin ( T4 )
The characteristic of their chemical structure is that they all contain iodine as an essential part of the molecule.
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Structure
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inadequate secretion of thyroid hormone (hypothyroidism) can bring many disorders to the body (eg. bradycardia, poor resistance to cold, both mental and physical slowing.)
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[Synthesis, storage and release of thyroid
hormones]
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Synthesis
Iodine is the raw material of the thyroid biosynthesis. Once taken up by the thyroid gland, iodine undergoes a series of enzymatic reactions before it converts into active thyroid hormones.
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Synthesis; four steps1. iodine trapping :uptake of iodine by the thyroid
gland2. oxidation of iodine: (to its active form) thyroid peroxidase (key enzyme of the synthesis) 3. iodide organification :the iodination of tyrosyl gr
oups of thyroglobulin productions: MIT and DIT4. formation of T4 and T3 from MIT and DIT : thyroid peroxidase
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storage
store in the colloid droplets of thyroglobulin
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release
The hormones are released by proteolysis of thyroglobulin .
Enzyme: thyroglobulin hydrolase The ratio of T4 to T3 within thyroglob
ulin is about 5:1
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Differences between T3 and T4
the effect of T3 is much faster, stronger and shorter than that of T4.
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conversion T4 can converse to
T3 through deniodonite in peripheral tissues as well as in the thyroid.
(catalyzed by deiodinase)
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Regulation:
TRHTSH
T3,T4
Hypothalamus
pituitary
thyroid
Controled by HPT(hypothalamic-pituitary-thyroid) axis
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Regulation
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TRH (thyrotropin releasing hormone)
TSH (thyroid stimulating hormone or thyrotropin)
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[Pharmacokinetics]
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Pharmacological actions
Effects on growth and development Calorigenic effects : Hypersensitivity to catecholamine :
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Pharmacological actions
1.Effects on growth and development :
responsible for normal growth and maturation of human being , especially for nervous and skeletal tissues.
so the absence of thyroid hormones before birth leads to both mental and physical retardation ( cretinism )
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Pharmacological actions
2.Calorigenic effects: T3 /T4 can increase oxygen consumpti
on, promote metabolism and BMR( basal metabolic rate ) ,↓utility.
So hyperthyroidism will result in excess heat production and body wasting.
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Pharmacological actions
3. hypersensitivity to catecholamine
Cardiovascular effects: Tachycardia, hypertension nervous Effects: anxiety, nervous.
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mechanism
TR CBP NUCLEAR R
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Clinical uses
the major indications for the therapeutic use of thyroid hormones are for hormone replacement therapy in patients with hypothyroidism .
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Clinical uses
1.Cretinism :congenital hypothyroidism
often happens in newborn babies, mainly caused by iodine deficiency before birth .
Success in the treatment of cretinism depends on the age at which therapy is started.
The earlier, the better.
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Symptoms: 1.Physical slow: dwarf, with short extremities ,2.mentally retarded: inactive, uncomplaining
and listless. incidence :about 1 per 400 birthsPrevention and therapy: Prevention: Iodine replacement is the best
method prior to pregnancy. Therapy: thyroid hormones replacement(T4 is
more often used than T3)
Cretinism
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Clinical uses
2.Myxedema: adult hypothyroidism
Happens after individual development
Slow in mentality With special edema Mortality :60%
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Clinical uses
3.Simple goiter: A kind of prevalent disease ca
used by insufficient dietary iodine
TSH can promote hyperplasy and hypertrophy of thyroid gland.
4. Differential diagnosis of simple goiter and hyperthyroidism
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Simple goiter
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adverse reactions
hyperthyroidism
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Part 2 Antithyroid drugs
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Grave’s syndrome
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Treatment of hyperthyroidism
The goal of therapy is to decrease the additional hormone and attend to normal levels.
Can be accomplished by removing part of the gland Inhibiting synthesis Blocking releasing
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four categories of anti-thyroid drugs
Ⅰ Thioureas : ( 硫脲类 ) interfere directly with the synthesis of thyroid hor
mones Ⅱ High concentrations of iodine : decrease the release of thyroid hormones Ⅲ Radioactive iodine : damage the gland with ionizing radiation Ⅳ β- receptor antagonists: control the manifestations
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Ⅰ Thioureas( 硫脲类 )
Thiouracils: methythiouracil , propylthiouracil Imidazoles: methimazole , carbimazole.
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Ⅰ Thioureas Pharmacological action : Decrease the level of thyroid hormonesMechanism 1.inhibit the thyroid peroxidase : (key enzyme of synthesis) interfere the oxidation of iodine an
d the coupling of MIT and DIT to form T3/T4
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2. inhibit conversion from T4 to T3 3.immunosupressive effect: TSI
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Pharmacokinetics: Absorption Distribution Excretion Pass through placenta, milk
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Therapeutic uses 1.As definitive treatment to control hyperthyroi
dism 2.Preoperative preparations for subtotal thyroi
dectomy: to control the disorder in preparation for surgical treatment.
(thioureas plus large dose of iodine) 3. Thyroid crisis Propylthiouracil is the first ch
oice.
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Adverse reactions
1.allergic response 2.GI reaction
3.granulocytopenia (0.3%-0.6%)
4.Longterm use: goiter and hypothyroidism
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Drug interactions
↑ Li , sulfasulfonamide , PAS , para
minan (对氨苯甲酸), phenylbutazone , barbital , phentolamine , sulfonyl urea , vitB12
↓ iodine
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Ⅱ Iodine and iodide
Oldest agent have completely different
effects due to different doses
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Pharmacological effects
in small dose: ↑ synthesis of thyroid hormones in large dose : antithyroid 1) ↓the release of thyroid hormones into the cir
culation: strong Mechanism: Inhibit thyroglobulin hydrolase 2)↓synthesis of thyroid hormones: weakMechanism: Inhibit thyroid peroxidase
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Therapeutic uses
1.Simple goiter : in small dose2.In preparation for thyroidectomy : used after the hyperthyroidism has been controlle
d by thioureas, given for 7 to 10 days immediately preceding the operation. (The changes after a fairly long term of administration include: the vascularity of the thyroid gland is reduced, the gland becomes much firmer and smaller.)
3.Thryotoxic crisis
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Adverse reactions
1. Chronic iodism
2.Acute allergic action :angioneurotic edema and larynx edema
3. Thyroid dysfunction
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Ⅲ Radioactive iodine
131I : most often used isotope of iodine
γ rays ( 1% ) : β particles ( 99%):
destructive
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Effects on the thyroid gland
131I is rapidly and efficiently trapped by the thyroid gland and slowly emitsβparticles and γrays.
The destructive βparticles can destroy the thyroid cells with little damage to surrounding tissues (the penetration range is only 0.4-2.0mm).
Theγrays can pass through the tissue and be quantified by external detection
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Clinical uses
1.hyperthyroidism: administrated orally and the effective dose differs for individual patients.
2.diagnosis of thyroid functions
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Adverse reactions: hypothyroidism
contraindications pregnancy and milk mothers
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IV β-adrenergic receptor antagonists
------ adjuvant therapy many of the symptoms of hyperthyroidism are
associated with sympathetic stimulation, so β-R blockers are effective in antagonizing the catecholaminegic symptoms such as tachycardia, palpitations ,anxiety and tension.
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Action: (1)block 1-R of heart (2)block -R of CNS (3) block -R of presynaptic membra
ne of peripheral nerve. (4) Inhibit T4 converted into T3
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Uses: 1.Control the symptoms of hyperthyroidism before confirmed diagnosis 2.Thyroid crisis 3.Preoperation of hyperthyroidism 4.Hyperthyroidism
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Section 3 TSH and TRH
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Thank you!