ANTI-THYROID DRUGS

Dr. Mozna Talpur

ANTITHYROID DRUGS
 Thyroid follicles are the structural & functional units of the
thyroid gland.
 Thyroid hormones are mainly synthesized in colloid while
the simple cuboidal epithelium undertaking thyroglobulin
production, iodide intake &thyroid hormones release.
 Synthesis of thyroid hormones:
 Step 1: Iodide is trapped by sodium-iodide symporter
 Step 2: Iodide is oxidized by thyroidal peroxidase to iodine
 Step 3: Tyrosine is iodinated and forms MIT & DIT
 Iodotyrosines condensation with thyroglobulin. MIT+DIT→T3;
DIT+DIT→T4
MIT: monoiodotyrosine, triiodotyrosine (T3) DIT:
diiodotyrosine, tetraiodotyrosine (T4, thyroxine)
3
THYROID HORMONES
Increases basal metabolic
rate.
Potentiates brain
development.
Potentiates the beta
effects of catecholamines.
HYPERTH HPYOTHY
YROIDISM ROIDISM
●
Nervousness ●
Depression
●
Irritability ●
Difficulty in concentrating
●
Insomnia ●
dry, coarse or itchy skin, thinning of hairs and feeling
●
Hyperkinesia of cold especially in the extremities
●
Warm & moist skin ●
Drooping of eyelids; periorbital edema
●
increased perspiration ●
Puffy nonpitting facies and large tongue
●
Heat intolerance ●
Fatigue, exhaustion
●
Thinning of skin ●
excessive weight gain
●
Fine brittle hairs
●
Retraction of upper lid with wide stare; Exophthalmoses
●
Constipation
●
Muscular weakness
●
Muscle cramps
●
Increased heart rate and cardiac output
●
Increased menstrual flow
●
weight loss despite a good appetite more frequent periods
●
less frequent menstrual periods
●
Infertility/miscarriage
●
Increased BMI; hyperglycemia, decreased cholesterol. ●
Decreased BMI, hypoglycemia, increased cholesterol.
DRUGS USED IN HYPOTHYROIDISM

 Levothyroxine (Synthetic Thyroxine/T4):

The most popular and commonly prescribed
thyroid hormone replacement drug is
Levothyroxine, a synthetic form of thyroxine.
 T4 is converted into T3 in target cells

 Liothyronine (Synthetic Triiodothyronine/T3):

 T3 is ten times more potent than T4
 MECHANISM OF ACTION:
The predominant actions of thyroid hormone are mediated via
binding to nuclear thyroid hormone receptors (TRs) and
modulating transcription of specific genes.

Thyroid hormones have two important functions.

 They are crucial determinants of normal development of body,
especially in the central nervous system (CNS).

 In the adult, thyroid hormones act to maintain metabolic

homeostasis (BMI), affecting the function of virtually all organ
systems.
ANTI-THYROID DRUGS

Drugs used for the treatment of hyperthyroidism :

Inhibition of hormone synthesis (Thioamides) :
 Propylthiouracil, carbimazole and Methimazole.

Blockade of hormone release :

 Iodides(Lugol’s iodine, potassium iodide).

Radioactive Iodine 131

Anion Inhibitors:
 Perchlorates, Thiocynates.

Beta blocking drugs : Propranolol, metaprolol,

atenolol.
THIOAMIDES

Mechanism of Action
Inhibit synthesis of thyroid hormones
 By inhibiting peroxidase enzyme that catalyzes the
iodination of tyrosine residues in the thyroglobulin &
couples iodotyrosines to form T3 & T4.(blockes
organification)
 They block the deiodination of T4 to T3 within the thyroid
& in peripheral tissues.
 Since it blocks the synthesis the onset of action is slow. (3-4
weeks T4 stores are depleted)
 ADVERSE EFFECTS
 GI upset (early)
 Cutaneous reactions ( maculopapular rash(4-6%) with fever)

 Urticaria, vasculitis, lymphadenopathy, hypoprothrombinemia,

arthalgia.
 Hepatotoxicity ( cholestatic jaundice, altered taste mainly with
methimazole)
 Most dangerous complication is agranulocytosis (granulocytes
<500cells/mm3 occur within 90 days of treatment)
 IODIDES:

It was the major class of drug used before thioamides.

Mechanism of action

 Inhibit thyroid hormone organification and release.

 Decrease size and vascularity of hyperplastic gland.
 Block the peripheral conversion of T4 to T3 .
 In susceptible individual may cause hyperthyroidism.
 Inhibit thyroglobulin proteolysis.
 Improvement in symptoms occur within 2-7 days.
 CLINICAL USES

 Thyroid storm
 Prior to thyroid surgery to decrease vascularity of the gland .
 Following radio active iodine therapy.
PRECAUTIONS /TOXICITY:
 Should not be used as a single therapy

 Should not be used in pregnancy

 May produce iodism ( acniform rash, swelling of

salivary glands, mucous membrane ulceration,
metallic taste, bleeding disorders, conjunctivitis,
rhinorhea, drug fever and rarely anaphylaxis ).
 RADIOACTIVE IODINE
I isotope ( therapeutic effect due to emission of β
 131
rays )

 Accumulates in the thyroid gland and destroys

parenchymal cells . Clinical improvement may take 2-3
months

 Half-life 5 days
 Cross placenta & excreted in breast milk

 Easy to administer ,effective , painless and less

expensive
RADIOACTIVE IODINE ( CON.)
 Available as a solution or in capsules
 Clinical uses

 Hyperthyroidism mainly in old patients (above 40)

 Patients with toxic nodular goiter
DISADVANTAGES
 High incidence of delayed hypothyroidism
 Large doses have cytotoxic actions (necrosis of the
follicular cells followed by fibrosis )
ADRENOCEPTOR BLOCKING
AGENTS:
 Adjunctive therapy to relief the adrenergic
symptoms of hyperthyroidism such as tremor,
palpitation, heat intolerance and nervousness.
 E.g. Propranolol, Atenolol , Metoprolol.

 Propranolol is contraindicated in asthmatic patients

THYROIDECTOMY
 Sub-total thyriodectomy is the treatment of choice in very
large gland or multinodular goiter
 THYROID STORM:
 A sudden acute exacerbation of all of the symptoms of
thyrotoxicosis, presenting as a life threatening syndrome.

 There is hyper metabolism, and excessive adrenergic activity,

death may occur due to heart failure and shock.

 Is a medical emergency .
 Propranolol 1-2mg slows IV or 40-80 mg orally every 6 hours
 Potassium iodide 10 drops orally daily or

 Propylthiouracil 250 mg orally every six hours or 400 mg

every six hours rectally.

 Hydrocortisone 50 mg IV every 6 hours to prevent shock.

THYROTOXICOSIS DURING
PREGNANCY
 Therapy with 131I or subtotal thyroidectomy
prior to pregnancy to avoid acute
exacerbation during pregnancy or after
delivery

 Duringpregnancy radioiodine is
contraindicated.

 Propylthiouracil is the better choice during

pregnancy.