THYROID &

ANTITHYROI
D DRUGS
DR.AMMARA BUTT
Pharmacology
• Pituitary
• Thyroid
• Parathyroid
• Ad. Cortex
• Ad. Medulla
• Pancreas
• Ovaries
• Testes
Thyroid secretes 2 types of hormones:
• iodine-containing amino acids (thyroxine and triiodothyronine)
• and a peptide (calcitonin)

Thyroxine (T4) and triiodothyronine (T3) have broad effects on :

• Growth
• Development
• Metabolism

Calcitonin is important in calcium metabolism. (Inhibit osteoclastic activity,

thus reduces blood calcium levels)
We will discuss the drugs used in the treatment of hypothyroidism and
hyperthyroidism
Iodine  Required for synthesis of T4 & T3

Iodide ion Comes from  Food and iodide supplements

Goes into thyroid gland  Converted into iodine by peroxidases

Protein thyroglobulin  “Center of thyroid hormone synthesis”

Thyroglobulin contain “Tyrosine residues”

Iodine + tyrosine (present in thyroglobulin) = “iodine Organification”

Iodine + tyrosine = Monoiodotyrosine (MIT) or Diiodotyrosine (DIT)

DIT + DIT = T4

MIT + DIT = T3
Proteolysis causes  Release of T4 and T3 from thyroid gland

These released T4 & T3 are transported to blood via “thyroxine-binding globulin”

Peripheral conversion of T4 into T3 deiodinase 1 and 2

Thyroid function is controlled by

 Availability of iodide
 Thyrotropin (TSH)
Thyrotropin (TSH) stimulates the:
 Uptake of iodide as well as synthesis
 Release of thyroid hormone

Also has a growth-promoting effect that causes thyroid cell hyperplasia and
an enlarged gland (goiter)

Graves’ disease, an autoimmune disorder, B lymphocytes produce an

antibody that activates the TSH receptor and can cause a syndrome of
hyperthyroidism called thyrotoxicosis
Mechanisms of Action of T4 and T3
T3 is about 10 times more potent than T4.

Thyroid hormones bind to intracellular receptors that control the expression of genes
responsible for many metabolic processes

T3 synthesize different proteins depending on the involved tissues

these proteins include:

 Na+/K+ ATPase
 Specific contractile proteins in smooth muscle and the heart
 enzymes involved in lipid metabolism
 Important developmental components in the brain.
EFFECTS OF THYROID HORMONE

The organ-level effects include

 Normal growth and development of the nervous, skeletal, and reproductive
systems

 Control of metabolism of fats, carbohydrates, proteins, and vitamins

CLINICAL USES
Thyroid hormone therapy can be accomplished with either T4 or T3

Synthetic levothyroxine (T4) is usually the form of choice

T3 (liothyronine) is faster acting but has a shorter half-life and is more

expensive
TOXICITY
Thyrotoxicosis toxicities
Anti-thyroid Drugs
1. THIOAMIDES

Methimazole
Propylthiouracil (PTU)

 inhibit Blocking peroxidase-catalyzed reactions

 Iodination of thyroid hormone synthesis by:
 the tyrosine residues of thyroglobulin, and
 Coupling of DIT and MIT
USES

Propylthiouracil also inhibit peripheral conversion of T4 to T3

effective in young patients with small glands and mild disease

Methimazole is preferred  administered once per day

PTU is preferred in pregnancy and lactation  less likely than methimazole to

cross the placenta and to enter breastmilk
Toxic effects include skin rash (common) and severe reactions (rare) such as
vasculitis and liver dysfunction.

These effects are usually reversible.

2. IODIDE SALTS & IODINE
Iodide salts inhibit
 iodination of tyrosine and
 thyroid hormone release (by inhibiting proteolysis)

These salts also decrease the size and vascularity of the hyperplastic thyroid
gland

used in the management of thyroid storm (Severe thyrotoxicosis) and to

prepare patients for surgical resection of a hyperactive thyroid
The usual forms of this drug are
 Lugol’s solution (iodine and potassium
iodide) and
 saturated solution of potassium iodide.

Adverse effects include

 Rash
 Metallic taste
 Bleeding disorders
 and rarely, anaphylactic reactions
 It is taken up and concentrated in the thyroid gland so
properly that a large dose, to severely damage the gland,

3. can be given without endangering other tissues

RADIOAC Unlike the thioamides and iodide salts, an effective dose

TIVE of radioactive iodine can produce a permanent cure of
thyrotoxicosis without surgery
IODINE
Radioactive iodine should not be used in pregnant or
lactating women
4. ANION INHIBITORS
Thiocyanate (SCN–)
perchlorate (ClO4–)

Block the uptake of iodide by the thyroid gland through competitive

inhibition of the iodide transporter
USE AND TOXICITY

Their effectiveness is unpredictable and ClO4– can cause aplastic

anemia, so these drugs are rarely used clinically.
5. OTHER DRUGS
Beta-blockers:
 Controls tachycardia and other cardiac abnormalities of severe thyrotoxicosis

 Propranolol inhibits the peripheral conversion of T4 to T3 at doses greater than

160 mg/d

Amiodarone
 Iodine-containing antiarrhythmic drug

 can cause hypothyroidism through its ability to block the peripheral conversion of T4 to T3.
Iodinated radiocontrast media
 oral diatrizoate and intravenous iohexol

 rapidly suppress the conversion of T4 to T3 in the liver, kidney, and other

peripheral tissues.