Thyroid&

Antithyroid Drugs

By M. H. Farjoo M.D, Ph.D.Shahid Beheshti University of Medical Science

Thyroid & Antithyroid Drugs

Introduction Drugs in Hypothyroidism Drugs in Hyperthyroidism Adjuncts to Antithyroid

Therapy Thyroid malfunction and

Pregnancy Neonatal Graves' Disease Drug Pictures

Introduction Thyroid releases T3 & T4

The ratio of T4 to T3 is 5:1, so most of the hormone released is thyroxine

Most of the T3 in the blood is derived from thyroxine

T3 is three to four times more potent than T4

The affinity of the receptor site for T3 is about ten times higher than that for T4

Drugs in Hypothyroidism

Levothyroxine is the choice drug for hypothyroidism

T4 is converted to T3 intracellularly so levothyroxine produces both hormones

If angina pectoris or cardiac arrhythmia develops, it is essential to stop thyroxine immediately

Drugs in Hyperthyroidism

The antithyroid compounds include: Thioamides

Methimazole Propylthiouracil

Iodides Radioactive iodine

Thioamides

Their major action is blocking iodine organification Since the synthesis of hormones is affected, their

effect requires 4 weeks Propylthiouracil is preferable in pregnancy:

It crosses the placenta less readily Is not secreted in breast milk

The most common adverse effect is a maculopapular pruritic rash

The most dangerous complication is reversible agranulocytosis

Iodide

Iodides can induce hyperthyroidism (jodbasedow phenomenon) or precipitate hypothyroidism

In pharmacologic doses the major action is to inhibit hormone release

Improvement in thyrotoxic symptoms occurs within 2–7 days (iodide therapy in thyroid storm)

Iodides in pregnancy should be avoided, since they cross the placenta and can cause fetal goiter

Radioactive Iodine

Women in the childbearing period should be treated with I131 or subtotal thyroidectomy prior to pregnancy

I131 should NOT be administered to pregnant or nursing women

I131 is the preferred treatment for patients over 21 years

Hypothyroidism occurs in 80% of patients by radioiodine

Adjuncts to Antithyroid Therapy

Hyperthyroidism resembles sympathetic overactivity

Propranolol, will control tachycardia, hypertension, and atrial fibrillation

Diltiazem, can control tachycardia in patients in whom beta-blockers are contraindicated

Barbiturates accelerate T4 breakdown (by enzyme induction) and are also sedative

Thyroid malfunction and Pregnancy

In a pregnant hypothyroid patient, it is extremely important that the dose of thyroxine be adequate.

This is because early development of the fetal brain depends on maternal thyroxine

If thyrotoxicosis occurs, propylthiouracil is used and an elective subtotal thyroidectomy performed

Neonatal Graves' Disease

Is either due to passage of TSH-R Ab [stim], or to genetic transmission of the trait

If caused by maternal TSH-R Ab [stim], the disease is self-limited and subsides over 4–12 weeks,

Treatment is necessary because of the severe metabolic stress of the infant

Therapy includes : propylthiouracil, Lugol's solution, propranolol and careful supportive therapy

Iodinates Contrast MediaGastrografin

Iodinates Contrast Mediaiodixanol

Iodinates Contrast Media iodixanol

Iodinates Contrast Media iodixanol

Iodinates Contrast Media iohexol

Iodinates Contrast Media iohexol

Iodinates Contrast Media iohexol

Iodinates Contrast Media iohexol

Iodinates Contrast Media iohexol

Iodinates Contrast Media iopromide

Iodinates Contrast Media iopromide

Iodinates Contrast Media iopromide

Iodinates Contrast Media Urografin

SummaryIn English

Thank youAny question?

Hypothyroidism

Hypothyroidism can occur with or without thyroid enlargement (goiter). The laboratory diagnosis of hypothyroidism in the adult is easily made by the combination of a low free thyroxine (or low free thyroxine index) and elevated serum TSH

Infants and children require more T4 per kilogram of body weight than adults

Chronic overtreatment with T4, particularly in elderly patients, can increase the risk of atrial fibrillation and accelerated osteoporosis

Myxedema Correction of myxedema must be done cautiously to

avoid provoking arrhythmia, angina, or acute myocardial infarction.

myxedema coma: It is associated with progressive weakness, stupor,

hypothermia, hypoventilation, hypoglycemia, hyponatremia, water intoxication, shock, and death

It is important to give all preparations intravenously The treatment of choice in myxedema coma is to give a

loading dose of levothyroxine intravenously— usually 300–400 µg initially, followed by 50 µg daily

Opioids and sedatives must be used with extreme caution

Hyperthyroidism The most common form of hyperthyroidism is

Graves' disease, or diffuse toxic goiter The three primary methods for controlling

hyperthyroidism are antithyroid drug therapy, surgical thyroidectomy, and destruction of the gland with radioactive iodine

Antithyroid Drug Therapy the more severe reaction of agranulocytosis is often

heralded by sore throat or high fever Thyroidectomy

A near-total thyroidectomy is the treatment of choice for patients with very large glands or multinodular goiters

Hyperthyroidism Toxic Uninodular Goiter & Toxic Multinodular

Goiter These forms of hyperthyroidism occur often in older

women with nodular goiters. FT4 is moderately elevated or occasionally normal, but T3 by RIA is strikingly elevated

Subacute Thyroiditis episodes of transient thyrotoxicosis have been termed

"spontaneously resolving hyperthyroidism." Supportive therapy is usually all that is necessary, such as propranolol for tachycardia and aspirin or nonsteroidal anti-inflammatory drugs to control local pain and fever

Special Problems

Ophthalmopathy elevation of the head to diminish periorbital edema

and artificial tears to relieve corneal drying. Smoking cessation should be advised to prevent progression of the ophthalmopathy

If steroid therapy fails or is contraindicated, irradiation of the posterior orbit, using well-collimated high-energy x-ray therapy, will frequently result in marked improvement of the acute process

Special Problems

Nontoxic Goiter The most common cause of nontoxic goiter

worldwide is iodide deficiency, but in the USA, it is Hashimoto's thyroiditis. Less common causes include dietary goitrogens, dyshormonogenesis, and neoplasms

Thyroid Neoplasms

Some adenomas will regress following thyroxine therapy; those that do not should be rebiopsied or surgically removed. Management of thyroid carcinoma requires a total thyroidectomy, postoperative radioiodine therapy in selected instances, and lifetime replacement with levothyroxine.

Class Mechanism of Action and Effects

Indications Pharmacokinetics, Toxicities, Interactions

Thyroid Preparations  

  Levothyroxine (T4 ) Activation of nuclear receptors results in gene expression with RNA formation and protein synthesis

Hypothyroidism maximum effect seen after 6–8 weeks of therapy

  Liothyronine (T3) 

Class Mechanism of Action and Effects

Indications Pharmacokinetics, Toxicities, Interactions

Antithyroid Agents  Thioamides   Propylthiouracil (PTU) Inhibit thyroid peroxidase

reactions block iodine organification inhibit peripheral deiodination of T4 and T3

 

Hyperthyroidism Oral duration of action: 6–8 h delayed onset of action  Toxicity: Nausea, gastrointestinal distress, rash, agranulocytosis, hepatitis,hypothyroidism

Iodides   Lugol solution Inhibit organification and

hormone release reduce the size and vascularity of the gland

Preparation for surgical thyroidectomy

Oral acute onset within 2–7 days Toxicity: Rare (see text) 

  Potassium iodide

Beta blockers   Propranolol Inhibition of adrenoreceptors

inhibit T4 to T3 conversion (only propranolol) 

Hyperthyroidism, especially thyroid storm adjunct to control tachycardia, hypertension, and atrial fibrillation

Onset within hours duration of 4–6 h (oral propranolol) Toxicity: Asthma, AV blockade, hypotension, bradycardia 

Radioactive iodine 131I (RAI)      Radiation destruction of

thyroid parenchymaHyperthyroidism patients should be euthyroid or on blockers before RAI avoid in pregnancy or in nursing mothers

Oral  half-life 5 days onset of 6–12 weeks maximum effect in 3–6 months Toxicity: Sore throat, sialitis, hypothyroidism