THYROID + ANTITHYROID DRUGS Flashcards
PROPYLTHIOURACIL
METHIMAZOLE
MOA
Both of them
1) block iodination of thyroglobulin and
2) inhibit coupling reaction of DIT with MIT (T3) & DIT joining with another DIT (T4).
Hence, formation of T3 and T4 is reduced.
3) INHIBIT THYROPEROXIDASE
NOTE: They do not inhibit the preformed T4 / T3; as a result –slow onset of action. Takes 2-3 weeks for full effect.
PROPYLTHIOURACIL
USES
1) DOC FOR THYROID STORM b/c of its ability to inhibit 5’-DEIODINASE which results in a decrease in peripheral conversion of T4 to T3 conversion (T3 is more potent)
2) USED IN 1ST TRIMESTER B/C OF RARE TERATOGENICITY with methimazole
3) Is reserved for patients who are intolerant to methimazole; who are not fit for surgery, OR 131 radiactive Iodine
THIOAMIDES
ADVERS EFFECTS
• Thioamides are associated with rash and arthralgia; produce rare agranulocytosis, aplastic anemia, hepatotoxicity, hypoprothrombinemia and vasculitis.
Serious AE are much less with methimazole than with PTU; because of this methimazole is more preferred in clinical practice.
Methimazole is a teratogen –aplasia cutis congenita
IODINE + IODIDE SALTS
MOA
Large doses of iodide inhibit thyroid hormone synthesis (↓organification and release) via brief TPO inhibition.
–> This effect is called as Wolff-Chaikoff effect.
- Wolff-Chaikoff effect is gone after 10 - 14 days that can result in multinodular goiter, if large doses are continued (Jod-Basedow phenomenon).
IODINE + IODIDE SALTS
USES:
1) BEFORE SURGERY TO DECREASE VASCULARITY + SIZE OF GLAND
* Iodides decrease vascularity and size of the gland. They are used most often before surgery for easy thyroid excision.
2) THYROTOXIC CRISIS
* They are used in conjunction with PTU, and b- blockers in thyrotoxic crisis.
IODINE + IODIDE SALTS
Preps are available as?
• Preparations are available as:
1. Lugol’s solution – a mixture of iodine & potassium
iodide.
- Saturated solution of potassium iodide.
IODINE + IODIDE SALTS
ADVERSE EFFECTS
• Adverseeffects:
chronic iodide intoxication (iodism),
-anaphylactoid reaction –angioedema, swelling of larynx, eyelids; brassy taste, burning of teeth and gums; enlargement of parotid and maxillary glands.
RADIOACTIVE IODINE
MOA
Radioactive iodine (131I) is taken up and sequestered by thyroid gland. The intracellular 131I damage the tissue through emission of toxic β-rays, no effect on other tissues.
RADIOACTIVE IODINE
USES
Used in adults with
1) hyperthyroidism,
2) Graves’ disease
that has been refractory to other antithyroid drugs and persistent symptoms even after the subtotal thyroidectomy.
RADIOACTIVE IODINE
ADVERSE EFFECT
CONTRAINDICATIONS
The desired effect may not be obtained due to the difficulties to determine the dose. Patients may develop hypothyroidism.
It is the only medical therapy produces permanent reduction in thyroid activity.
There is no evidence of causing any cancer.
- Adverse effect: hypothyroidism.
- It is contraindicated in pregnant women and nursing mothers.
PROPANOLOL
ESMOLOL
USES:
β-blockers are useful in controlling the nervousness, palpitation, fatigue, weight loss, heat intolerance and tremors associated with hyperthyroidism, short-term management in pregnancy, preoperatively, and thyroid storm. Partial agonists are not used.
PROPANOLOL
MOA
nonspecific beta blocker prevents conversion of T4 to T3.
ESMOLOL
a short acting beta blocker can be used to control intra-operative thyroid storm.
Alternatives to β-blockers in thyroid storm for patients with asthma
1) CCB,
2) Diltiazem or
3) Verapamil.
WHAT IS THYROID STORM?
A life threatening medical emergency associated with extreme effects of hyperthyroidism.
It is caused by illness, surgery, and other stresses in patients suffering from thyrotoxicosis.
Beta-adrenergic blockers to manage CVS problems such as tachycardia, hypertension.
Propylthiouracil, I.V. sodium Iodine, and Glucocorticoids to inhibit peripheral conversion of T4 to T3.
DIATRIZOATE
IOHEXOL
What are they?
When are they used?
- they are Iodinated Radiocontrast Media, like
1) oral diatrizoate or
2) oral / I.V. iohexol
MOA: will suppress the conversion of T4 to T3 (5’-deiodinase) in the peripheral tissues, kidney and liver.
USES: It is useful in rapidly reducing (it has a fast onset of anti-thyroid action) the T3 concentration in thyrotoxicosis.
Also may play a role in the inhibition of hormone release from thyroid gland.
PERCHLORATE
THIOCYANATE
PERTECHNETATE
inhibit iodide concentration in the gland by blocking the transportation of iodine INTO the thyroid.
–> Ie it competitively inhibts the Na-I symporter
AE: Potential for aplastic anemia.
Note: cabbage + cassava contain thiocyanate (goitrogens)
DRUGS THAT PROVOKE AUTOIMMUNE/DESTRUCTIVE INFLAMMATORY THYROIDITIS, INDUCING HYPOTHYROIDISM
1. Amiodarone: has structural similarity with thyroxine.
(a) Iodine associated hyperthyroidism may occur –
can be treated with thiamides.
(b) Autoimmune mediated inflammatory version treated with steroids.
(c) Hypothyroidism: treated with levothyroxine
2. INTERFERON ALPHA + INTERLEUKIN 2
3. LITHIUM –> inhibits release of hormones (hypothyroidism and thyroid enlargement)
4. Goitrogens:
• Cabbage (contain thiocyanate)
• Cassava–containscarbohydrates+thiocyanate
5. Imatinib, Sunitinib (TKRI–Tyrosine Kinase Receptors) 6. Aminoglutethimide, sulfonylureas.
DRUGS THAT INHIBIT CONVERSION OF T4 –> T3
- Corticosteroids
- Propranolol
- Amiodarone
