Thyroid hormones regulate metabolism and are essential for growth, development, and maintaining body temperature and energy levels. Levothyroxine and liothyronine are used to treat hypothyroidism by replacing deficient hormones, while thioamides, iodides, radioactive iodine, and beta blockers are used to treat hyperthyroidism by inhibiting hormone synthesis or action. Specifically, thioamides inhibit thyroid peroxidase and deiodination of hormones, while iodides suppress hormone synthesis and release; radioactive iodine damages the thyroid through beta particle emission; and beta blockers alleviate hyperthyroidism symptoms.

1. Anti thyroid and thyroid drugs
By :Diriba Dereje
Email : dirroodare@gmail.com

2. objective
At the end of this presentation you should be able to:
Explain physiology of thyroid hormone.
Describe mechanism of action and effect of thyroid hormone.
Differentiate pharmacologic effect of thyroid and anti thyroid drugs.
Identify therapeutic uses of thyroid and anti thyroid drugs.

3. PHYSIOLOGY OF THYROID GLAND
• Secretes three hormones essential for proper regulation of metabolism.
-Thyroxine (T4)
-Triiodothyronine (T3)
-Calcitonin
• T3 contain 59% of iodine as essential component of the molecule and T4 ,65%.
• The recommended daily adult intake of iodine is 150µg (200µg during pregnancy).

4. Chemical structure of T3,T4

5. Effects of Thyroid Hormones
The thyroid hormones are responsible for :
• Optimal growth
• Development ,Function and
• Maintenance of body temperature and energy level.
NB: Iodine and thyroglobulin are important for synthesis of
T3,T4.

6. Thyroglobulin synthesis

7. Biosynthesis of thyroid hormone

8. Biosynthesis of thyroid hormone

9. Storage and release of T3,T4.

10. Regulation of thyroid hormone

11. Transport of thyroid hormone
• T3 and T4 transported in plasma by binding to protein called thyroxin
binding globulin.
• Only about 0.02% of total T4 and 0.5% of total T3 found in free form.
• Estrogen, chlofibrate, methadone, heroin, tamoxifen, liver disease, porphyria,
and HIV infection increase binding of thyroxine to thyroxine binding
globulin.
• Glucocorticoid, androgen, salicylate, mefenamic acid, furosemide,
inheritance, can decrease the binding.

12. Interferon vs thyroid dysfunction
• According to the study done in Pakistan to identify effect of TPO Antibodies in
Non-Interferon Treated Hepatitis C Patients in Pakistan.
• Independent of patient's gender and increasing with advancing age, about 25% of
local untreated HCV patients are TPO-Ab positive and are at greater risk of
developing thyroid disorders during and after interferon treatment.

13. Mechanism of action of TH.

14. Peripheral metabolism of T4
T4 is peripherally
metabolized into T3 by
enzyme called
deiodenase ,
are three in number
i.e.:
• D1
• D2
• D3

15. Thyroid Preparations
1. levothyroxine (Synthroid, Levothyroidl)-Synthetic thyroid hormone T4
2. liothyronine (Cytomel) -Synthetic thyroid hormone T3
3. liotrix (Thyrolar)-Synthetic thyroid hormone T3-T4 combined
4. Thyroid Desiccated (dried) animal thyroid gland

16. Thyroid Preparations
Therapeutic use:
• Cretinism.
• Myxedema coma.
• Primary hypothyroidism.
• Secondary hypothyroidism.
• To maintain thyroid hormone after surgery
and radiation.
• Levothyroxine vs obesity.
Mechanism of Action:
 To replace what the thyroid
gland cannot produce to achieve
normal thyroid levels (euthyroid)
 Thyroid drugs work the same
way as thyroid hormones.

17. Thyroid Preparations
Adverse effects:
• Cardiac dysrhythmia is the most significant adverse effect
• May also cause: Tachycardia, palpitations
• angina, hypertension, insomnia, tremors, headache, anxiety
• nausea, diarrhea,, weight loss, appetite changes, sweating, heat intolerance
• menstrual irregularities

18. Anti thyroid agents
A number of compound that are capable of interfering directly and indirectly with
synthesis, release, and action of thyroid hormone.
Anti thyroid drug include:
1. Thioamides
2. Iodides
3. Radioactive Iodine
4. Anion Inhibitors
5. Adrenoceptor-Blocking Agents

19. Thioamides
Pharmacokinetics:
• Propylthiouracil is rapidly absorbed and the bioavailability is 50-
80%
• Methimazole is completely absorbed
• Both thioamides cross the placental barrier, PTU is less.
• The onset of these agents is slow, often requiring 3-4 weeks
Mechanism of action:
• Prevent hormone synthesis by inhibiting TPO.
• Inhibiting the peripheral deiodination of T4 and T3.

20. Thioamides
Therapeutic uses:
• Thyrotoxicosis (Grave disease).
• Adjuvant to radiation therapy
• Before preparation for subtotal thyroidectomy.
• Thioamide vs pregnancy.
Adverse effects:
• Hypothyroidism
• Agranulocytosis(MML).
• Neonatal
hypothyroidism(MML).
• Severe liver injury (PTU).

21. Iodides
• Also called strong iodine solution or lugol’s solution. Is mixture of 5% iodine and 10% KI.
Mechanism of action:
• decreasing iodide uptake by thyroid.
• Inhibit thyroid hormone synthesis by suppressing both
-iodination of tyrosine and
-coupling of iodinated tyrosine
• Inhibit hormone release
• Decrease the size and vascularity of the hyperplastic gland

22. Iodides
Pharmacokinetics:
• To produce the effect iodide should be at high dose i.e. greater than 6 g/d.
• Increase in intraglandular store of iodine which may:
-Delay onset of thioamide therapy or
-Prevent the use of radioactive iodine for several weeks.
• Better to initiate after onset of thioamide therapy.
• Better avoid using with radioactive iodine seems likely.

23. Iodides
Therapeutic uses:
• In thyrotoxic crisis.
• For preparation for thyroidectomy.
• Why do we need iodide prior to surgery?
Side effect:
• Iodism - syndrome result from chronic ingestion of iodine.
• Corrosive and can injury GIT if overdosed.
• Acneiform rash similar to that of bromism, swollen slivery gland, conjunctivitis, rhinorrhea,
drug fever, bleeding disorder, and rarely anaphylactoid reaction.

24. Radioactive iodine
• 131I is the only isotope used for treatment of
thyrotoxicosis.
Mechanism of action:
• 131I is concentrated in thyroid gland.
• Cause distruction of thyroid tissue mainly by
emission of  particle.
• Also produce gamma rays even though it is
relatively harmless.
• How damage to surrounding tissue is protected?
Pharmacokinetics:
 Radioactive decay of 131I
occur rapidly within half
life of 8 days.
 Reduction of thyroid
gland is gradual.
 Full effect develop in 2-3
months.

25. Radioactive iodine
Advantage include:
• low cost.
• Patient spared risk such as discomfort
from surgery.
• Death after treatment is extremely rare
and.
• No tissue other than thyroid injured.
Therapeutic uses:
 grave disease
 Patient who does not respond to
anti thyroid and subtotal
thyroidectomy.
 Young children are not candidate.
 contraindicated in pregnancy and
lactation because it can damage
immature thyroid.

26. Anion Inhibitors
Include:
• Perchlorate (ClO4-)
• Pertechnetate (TcO4-)
• Thiocyanate (SCN-)
Mechanism of action:
• By inhibition of iodide uptake.
• Do you know how goiterogen food causes goitre?

27. To what extent goiterogen can cause goitre?
• According to the study done on concentrations of thiocyanate and goitrin in
human plasma, their precursor concentrations in brassica vegetables, and
associated potential risk for hypothyroidism.
• The consumption of typical serving sizes of raw Chinese cabbage
correspond to progoitrin- and thiocyanate-generating indole glucosinolate
exposures at concentrations far lower than those likely to impair thyroid
function.

28. β-Blocking Agents
 Beta blockers cause clinical
improvements of hyperthyroid
symptoms but do not typically alter
thyroid hormone level.
 But propranolol at doses greater than
160 mg/d may also reduce T3 level
approximately by 20% by inhibiting
the peripheral conversion of T4 to T3.
 Contraindicated in asthma and heart
failure
 Include : methoprolol, propranolol,
atenolol.
 Are effective adjuvants in management of
thyrotoxicosis since many of this
symptoms mimic those associated with
symphatetic stimulation.
 Propranolol has been the beta blockers
most widely studied and used in therapy
of thyrotoxicosis.

29. Summary of mechanism of anti thyroid

30. Summary
• Normal thyroid gland secrete sufficient amount of T3,T4 to control normal growth, and development, body
temperature and energy level.
• Levothyroxine and liotyronine used to treat hypothyroidism by activation of nuclear receptor which result in
gene expression in RNA formation protein synthesis which produce or modulate effect of thyroid hormone.
• Thioamides used to treat hyperthyroidism by inhibiting TPO reaction, blocking iodine organification, and
inhibit peripheral deiodination of T4 (primary PTU).
• Iodide like lugol’s solution and potassium iodide and potassium iodide are used to treat hyperthyroidism by
inhibiting organification and hormone release.
• Beta blockers used as an adjuvant therapy in treatment of hyperthyroidism associated symptom and also
propranolol can inhibit T4 to T3 conversion.
• Radioactive iodine are beneficial in hyperthyroidism by causing distruction of thyroid parenchyma and had
half life of 10 days but onset of action is 6-12 week.

31. References
1. Goodman and Gilman the pharmacological bases of therapeutic 12th edition.
2. Basic and clinical pharmacology 13th edition.
3. Pharmacology of nursing care 8th edition.
4. Guyton textbook of medical physiology 13th edition.
5. Lippincott's pharmacology 5th edition.
6. Rang and Dale pharmacology 8th edition.
7. https://www.ncbi.nlm.nih.gov/pubmed/27790523
8. https://www.ncbi.nlm.nih.gov/pubmed/21198738
9. https://www.ncbi.nlm.nih.gov/pubmed/26437220
10. http://nutritionreviews.oxfordjournals.org/content/74/4/248.full-text.pdf

32. Any question