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36 Cards in this Set
- Front
- Back
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What is the clinical use of TH (T3 and T4)?
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-Treatment of Myxedema coma
(combo of T4 and T3) Prevent Cretinism -T4 |
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What are the A/E of giving TH?
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-Thyroxine sensitizes the myocardium to catecholamines which can cause ARRYTHMIAS
-THYROTOXICOSIS |
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Which TH is fast acting?
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T3 -Liothyronine is fast acting, short half-life and costs more
T4 is used for maintenance purposes |
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What are the normal effect of T4 in the body?
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icr. Cardiac output
inc. Repriration rate inc. BMR potentiates effects of catecholamines (incr. sympathetic activity) promotes brain development thickens endometrium in females |
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What are the steps in TH synthesis?
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1. Iodine trapping in thyroid gland
2. Iodination of tyrosine residue bound to Thyroglobulin 3. Coupling reactions to form DIT, T3 and T4 4. Proteolitic release of T4 and T3 from being bound to thyroglobulin 5. Conversion of T4 to T3 in the peripheral tissues (using 5' deiodinase) |
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What drugs inhibit the 1st step in TH synthesis? What is the mechanism?
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PERCHOLATE, THIOCYNATE
and PERTECHNETATE They both block the transportation of iodine into the gland NB- They have the potential for aplastic anemia |
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How does radioactive iodine affect the thyroid gland?
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-Radioactive iodine is taken up and sequestered by the thyroid gland
-the intracellular iodine damages the tissues through emission of toxic beta particle It has NO other effect on other tissues Patients may develop HYPOthyroidism |
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What thyroid impairment is radiocative iodine used?
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HYPERthyroididsm- It is the ONLY therapy that produces permanent reduction in thyroid activity
Graves' disease-which is refractory to other antithyroid drugs Useful in young people NO evidence of radioactivity or cancer association with its use C/I in prgnant or nursing mothers |
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What drugs inhibit step 2 of TH synthesis-Iodination of tyrosine residues on thyroglobulin?
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PROPYL-THIOURACIL (PTU)
and METHIMAZOLE The thioamides They do this by inhibiting the Peroxidase enzymes |
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What else does the thioamides do?
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They decrease the coupling reaction of
DIT with MIT and DIT joining with another DIT This is the 3rd step in TH synthesis Formation of T3 and T4 is reduced |
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What is the clinical use of PTU?
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-used as a medical treatment in pregnant patients with HYPERthyroidism (relatively safe-its extensively protein bound)
-used in THROID STORM in combo with IV sodium iodine and glucocorticoids -blocks T4 conversion to T3 |
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What is a term used to describe the Thioamides?
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Goitrogens
They cause goitre |
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What are the A/E of Thioamides?
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Both drugs cause
Rash, arthralgia Agranulocytosis, Hepatotoxicity and vasculitis (rare) NB the vasculitis manifests as lupus |
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What is the A/E of PTU alone?
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Hypo-prothrombinemia
Methimazole is more preferred clinically since PTU has more serious A/E |
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What is the dosage of Thioamides?
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PTU - 3x daily
Methimazole- 1x daily both given orally |
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Can Methinidazole be used in a Thyroid storm?
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No.
It does not inhibit T4 conversion to T3 like PTU In fact it antagonizes this inhibitory action of PTU |
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Besides Thioamides, what other treatments block the 3rd step in TH synthesis?
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Iodide salts and Iodine
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What is the MOA of the iodide salts and Iodine?
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High levels of iodide inhibit TH synthesis by NEGATIVE FEEDBACK EFFECT.
The effect is only Transient and is Reversible |
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How long does the effect last? What is it called?
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The effect 'escapes' after 10-14 days (NOT used for long term)
It is called the WOLFF-CHAIKOFF effect |
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Before surgery to remove the gland, Iodide is given to?
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Iodide decreases the vascularity and size of the thyroid gland
This allows easy excision |
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How is Iodide used in a THYROTOXIC CRISIS
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Iodide is used in conjuction with
PTU and Beta blockers- Esmolol (short t1/2) controls tachycardias, tremors, sweating |
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What are the A/E of Iodide salts
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IODINISM (chronic iodide intoxication)
Anaphylactic reaction-angioedema, swelling of the larynx and eyelids BRASSY TASTE burning of teeth and gums ENLARGEMENT of Parotid and Maxillary glands |
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What drugs inhibit the 4th step in TH synthesis?
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Ipodate and Iodide
They inhibit the proteolytic release of T3 ant T4 from Thyroglobulin |
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What inhibits the 5th step in TH synthesis?
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Conversion of T4 to T3 via 5' deiodenase in periphral tissues, kidney and liver is inhibited by
IPODATE incr. dose of PTU |
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How is Ipodate effective in THYROTOXICOSIS?
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Ipodate rapidly reduces the T3 conc.
It has a fast action of anti-thyroid action by -inhibiting the release of TH from the gland -inhibiting the conversion of T4 to T3 |
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How is Iodinated radiocontrast media useful?
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It also inhibits the conversion of T4 to T3 in the peripheral tissues
May also play a role in inhibiting TH release from the gland |
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What drugs provoke auto-immune or destructive inflam thyroiditis causing HYPOthyroidism?
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AMIODARONE
LITHIUM IFN alpha and IL2 |
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How does Amiodarone provoke the thyroid gland to induce HYPOthyroidism?
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It is structurally similar to the TH
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How does Lithium provoke the thyroid gland to induce HYPOthyroidism?
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Increased levels of LIthium in the gland inhibits the release of hormones
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What 2 foods are Goitrogenic?
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Cabbage- contain thiocynate
Cassava- contains thiocynate |
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What are the therapeutic measures in Grave's disease?
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1. Surgery (iodide treatment b4 surgery to reduce the size and vascularity of the gland)
2. Radioactive Iodine to destroy the gland 3. Antithyroid drugs 4. Ipodate or iodine containing radiocontras media 5. Beta blockers ( in a thyrotoxic crisis) |
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What is the function of the Thyroid gland?
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take iodine from food and convert it into Thyroid hormones
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What is the enzyme that binds iodine to tyrosine residues in thyroglobulin molecues?
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Thyroperoxidase
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What other tissues contain the enzyme that converts T4 to T3
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The 5' deiodinase is found in
Peripheral tissues liver kidney pituitary gland brain brown fat |
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TH are usually bound to?
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THYROXIN- bindinG protein
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The End
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Yay!!!
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