PHARMACOLOGY OF THYROID AND ANTITHYROID DRUGS

• Normal Thyroid gland is responsible for the synthesis and

release of THYROXINE /T4 and TRIIODOTHYRONINE / T3.

• Iodine containing amino acid analogues and regulate the rate

of oxidative processes.

• ANTITHYROID DRUGS / ATD

• Hyperthyroidism>>> Excess of circulating thyroid hormones.

• ATD - Interferes with synthesis and release of thyroid

hormones.

7th semester -2012 Pharmacology of Hormonal drugs - Part 2 1

 PHYSIOLOGICAL / PHARMACOLOGICAL EFFECTS
OF THYROID HORMONES.
• These are METABOLIC
STIMULANTS affecting almost
all tissues of the system.
1. Calorigenic effects : Stimulates oxygen
consumption in all tissues / BMR except
in brain, gonads, lymph nodes, spleen,
thymus and dermis.
2. Growth : Essential for Intrauterine and
extra uterine growth and diffrensiataion.
( Deficiency- Cretinism, mental
retardation)

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PHYSIOLOGICAL / PHARMACOLOGICAL
EFFECTS OF THYROID HORMONES.
3. METABOLIC ACTIONS : ANABOLIC EFFECT –
Promotes growth and protein synthesis,
Increases Glucose absorption from GIT, and Entry
- intracellular utilization of glucose. Enhances
cholesterol synthesis by liver, rate of Biliary
secretion, water and electrolyte metabolism.
4. CARDIOVASCULAR SYSTEM : Stimulates the rate
and force of myocardium contraction , Increases
cardiac output.
5. CENTRAL NERVOUS SYSTEM : Essential for
myelination of CNS – Excess – irritability,
tremors, hyperkinesia Etc.
( Deficiency – Mental retardation, slow tendon
reflexes, convulsions and psychosis.)

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PHYSIOLOGICAL / PHARMACOLOGICAL
EFFECTS OF THYROID HORMONES.
5. GIT : Overall health of GIT and peristaltic
movement - Xs – Diarrhea/ Less –
constipation and Achlorhydria.
6. REPRODUCTIVE TRACT AND BREAST : Affects
gonadal function in both men and women,
Menstruation and fertility in women.
7. HEMOPOIETIC SYSTEM : Hypo- anemia,
megaloblastic anemia
8. SKIN : LESS – Deposition of
mucopolysaccharide in the connective tissue
of skin – leading to pallor and rough skin
( Myxoedema)

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PHYSIOLOGICAL / PHARMACOLOGICAL
EFFECTS OF THYROID HORMONES.
• OTHER MINOR EFFECTS : Xs – impairs conversion of
Creatine to Creatinine and leads to formation of
Phosphocreatinine, defective conversion of carotene to vit
A, Myopathies Etc.

• ADME : Both T3 and T4 – well absorbed from GIT,

Absorbed from stomach, ( Empty), concentrates in Liver
and Kidney, Deiodinated – iodine – reutilized .
•
• Adverse Effects : Diarrhea, wt Loss, Palpitation, tremors,
hyperkinesia, irritability, angina pain, osteoporosis. Etc.

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 MECHANISM OF ACTION OF THYROID HORMONES – Via RECEPTORS

PLASMA MEMBRANE INNERMEMBARNE OF

MITOCHONDRIA NUCLEUS
• Stimulates entry
of amino acids • Stimulates oxidative
• Delayed / late to
and calcium into metabolism directly manifest.
the cell. >>> Increased • Stimulates -
energy production Transcription – Protein
• Stimulates • RAPID and FIRST synthesis- like Na k ATP
Adenylate Cyclase effect
ase.
activity. • Increase in SIZE and
Number of
Mitochondria.

7th semester -2012 Pharmacology of Hormonal drugs - Part 2 6

 DISORDER OF THYROID HORMONES FUNCTIONS

• Clinical disorders – due to Deficient or Excess production of

Thyroid hormones – Enlarged gland – Neoplastic changes. –
Combination of one / more.
• HYPOTHYROIDISM. – can be congenital – Athyrotic cretinism.
Can be acquired – Defective synthesis and release –
Secondarily due to Thyroidectomy, Thyroiditis, antithyroid
drugs or autoimmune disease.
• By birth – CRETINISM
• HYPERTHYROIDISM : Excess production. / Goiter ( Graves
Disease).
• Therapeutic utility : As replacement therapy ( Hypo) in
Cretinism , As well in adults. Non toxic Goiter, Thyroid
carcinoma Etc ANTITHYROID DRUGS – To interfere with
synthesis and release of thyroid hormones.

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 Therapeutic use of thyroid drugs
1. AS REPLACEMENT THERAPY - In cretinism and adult

hypothyroidism.

2. TO PREVENT ENLARGEMENT AND INCREASED

VASCULATURE OF TOXIC GOITER OF Graves disease.

3. AS A SOURCE OF IODINE AND TO CORRECT MILD

HORMONAL DEFICIENCY In case of non – toxic goiter.

4. AS A SUBSTITUTE OF RADIOACTIVE IODINE After surgery.

5. IN THYROID SUPPRESSION TEST.

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 ANTI THYROID DRUGS
• Act by INTERFERING WITH THE SYNTHESIS AND RELEASE of
thyroid hormones – THUS REDUCING THYROID ACTIVITY in
case of hyperthyroidism of any etiology.
• Classification
1. GOITERIGENS : - Ionic inhibitors ( Pot. Percholrate,
thiocynates) and Organic Antithyroid drugs. Thioamides
like Propyl –Thiouracil, Methimazole , carbimazole,
Methylthiouracil, Iothiouracil.
Others like – Sulfonamides, PAS, Amino- Gluthamide,
Resorcinol
2. IODIDES and LITHIUM
3. RADIOACTIVE IODINE

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 ANTI THYROID DRUGS
PHARMACOLOGY OF INHIBITORS OF
HORMONE SYNTHESIS

Includes Thioamides like Propyl thiouracil, Thiouracil ,

Methimazole , carbimazole, Methylthiouracil, Iothiouracil.
MOA :
Blocks thyroidal hormonal synthesis by Inhibiting
Coupling of iodotyrosines, Conversion of
Monoiodotyrosine into Diidothyronine and
formation of Monoiodotyrosine, itself.

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 ANTI THYROID DRUGS
Propyl thiouracil >>> Inhibits the peripheral conversion of T4 to
T3.
carbimazole >>> produces Remission by suppressing
autoimmune Response. Interferes with feed back inhibition
of pituitary TSH secretion by reducing amount of circulating
Thyroxine ( T4) and Triiodothyronine ( T3) .
ADME : Rapidly absorbed on oral administration and
accumulates in the thyroid glands , Duration of action< 8 hrs,
can cross BBB and secreted in the milk also. Partly
metabolized and excreted in the urine.
Adverse effects: RARE : Skin rashes, Edema of the feet, hair loss ,
arthralgia, Liver damage, ;Leucopenia, Agranaulocytosis.

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 IONIC INHIBITORS AS
ANTI THYROID DRUGS

- Inhibits the thyroid function and produce goiter.

- By competitive inhibition of iodine concentrating

mechanism in the thyroid gland.

- Percholrate concentrates and not thiocynates.

- Aplastic anaemia restricts the use.

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 RADIOACTIVE IODINE AS ANTI THYROID DRUG
• I (1/2 life of 8 days,) ( Commonly used).
131

• 130 I (1/2 life of 12.3 hours ) ( Experimental purposes)

• 125 I ( ½ Life of 60 days ) (Experimental purposes )

• MOA : 131 I like stable iodine is trapped by thyroid gland , gets

incorporated into Thyroxine and Triiodothyronine and stored as colloid.

• Subsequently EMITS β rays to the depth of 0.5 mm- 2mm – It is like radiation
therapy . However, have to be restricted to parenchyma of the gland. ( √ rays
also emitted - with limited use).

• Available for ORAL, IV and also as single use capsule.

• Effect can be seen within 3-4 weeks and maximum effect by 3-6 months.
• Dose repeated at the end of 4th or 6th week.

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 RADIOACTIVE IODINE AS ANTI THYROID DRUGS –
ADVANTAGES AND DISADVANTAGES

ADVANTAGES
 Convenient, Highly effective, inexpensive and avoids surgery.
DISADVANTAGES
 Chances of Hypothyroidism in children.
 Not suitable in women in the reproductive age group.
 Slow acting.
 Chances of developing Thyroid carcinoma.
 Will be under observation for long time.

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 IODIDE AS ANTITHYROID DRUG
• Oldest and fastest ( effect within 24 hours) and result is similar to
surgical removal of thyroid -as indicated by ↓ Basal Metabolic
Rate.
• Maximum clinical effect within 10-14 days.
• Effect seems wear off within a short period and can produce only
partial control of hyperthyroidism.
• MOA :
1. Appears to rapidly shutoff release of preformed thyroid
hormones.
2. Inhibits binding of Iodine
3. Inhibits release of T3 and T4 from Thyroglobulin.
4. Decreases response of iodine rich gland to the circulating TSH.

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 IODIDE AS ANTITHYROID DRUG
THERAPEUTIC USES
1. as a pre-operative preparation of hypothyroid patient to reduce
vascularity of thyroid gland.
2. To block thyroid uptake prior to administration of radioactive
iodine.
ADVERSE EFFECTS
 IODISM – characterized by skin rashes, Rhionrrhea, lacrimation ,
increased salivation.
 Prolonged use in Asthmatics – Results in Myxoedema and Goiter.
 Since can cross BPB - may result in GOITEROUS CRETINISM in fetus
 Can precipitate THYROTOXICOSIS.

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