This presentation includes drugs used in treatment of hyperthyroidism/ thyrotoxicosis.

1. ANTI-THYROID DRUGS
Dr. Rupali A. Patil
Associate Professor, Pharmacology Department
GES’s Sir Dr. M. S. Gosavi College of Pharmaceutical Education & Research,
Nashik

2. THYROID INHIBITORS
• Thyrotoxicosis : excessive secretion of TH.
• Main Causes : Graves’ disease and toxic nodular goiter.
• Graves’ disease: an autoimmune disorder: IgG class of antibodies to the TSH receptor
are detected in blood. They bind to & stimulate thyroid cells, & produce other TSH like
effects.
• Due to feedback inhibition, TSH levels are low.
• Exophthalmos is due to autoimmune inflammation of periorbital tissues.

3. 1. Inhibit hormone synthesis (Antithyroid drugs)
• Propylthiouracil, Methimazole, Carbimazole Goitrogens
2. Inhibit iodide trapping (Ionic inhibitors)
• Thiocyanates (SCN–), Perchlorates (ClO4
–), Nitrates (NO3
–).
3. Inhibit hormone release
• Iodine, Iodides of Na and K, Organic iodide.
4. Destroy thyroid tissue
• Radioactive iodine (131I, 125I, 123I).

4. Hypothyroidism/goiter as a side effect by high doses of some drugs for prolonged periods
• • Lithium: inhibits thyroid hormone release.
• • Amiodarone: inhibits peripheral conversion of T4 to T3; also interferes with thyroid hormone
action.
• • Sulfonamides, para-aminosalicylic acid: inhibit thyroglobulin iodination and coupling reaction.
• • Phenobarbitone, phenytoin, carbamazepine, rifampin: induce metabolic degradation of T4/T3.
• Goitrin—found in plants (cabbage, turnip, mustard, etc.),
• Cause of goiter in cattle who feed on these plants.
• May contribute to endemic goiter in certain iodine deficient regions.

5. CLASSIFICATION
Inhibitor of hormone
synthesis
 Carbimazole
 Methimazole
 Propylthiouracil
Inhibitor of hormone release
 Iodine
 Iodides of Na, k
 Organic iodides
Radioactive iodine
131I (Radioactive iodine)
Ionic inhibitors
 Thiocynate (SCN-)
 Perchlorates (ClO4
-)
 Nitrates (NO3
-)
β-blockers: Propranolol

6. 1. HORMONE SYNTHESIS INHIBITORS/
ANTITHYROID DRUGS/THIOAMIDES
 Methimazole (carbimazole)
 Propyl thiouracil (PTU)
✓ Major drugs used in the treatment of thyrotoxicosis
(Carbimazoles converted to methimazole in vivo).
MOA: Inhibit thyroid hormone production by
• inhibiting thyroid peroxidase required in intrathyroidal oxidation of Iodide.
• by inhibiting the iodination of tyrosine
• by inhibiting coupling of MIT and DITto form thyroid hormones
Thyroid colloid is depleted over time & blood levels of TH are progressively lowered.
Propylthiouracil inhibits peripheral conversion of T4 to T3 by inhibiting DID-1
enzyme

7. CARBIMAZOLE
• More potent given in a single daily dose
• Completely absorbed & readily accumulated in thyroid gland
• Excreted in urine but slower than PTU.
• Has some immunosuppressive action leading to decrease in serum TSH
receptor antibodies.
• Has little effect on conversion of T4 to T3
• Crosses placenta.
• Excreted in breast milk.

8. PROPYL THIOURACIL ( PTU)
 Dose is 10 times that of Carbimazole given every 6-8 hrs.
 Rapidly absorbed with a bioavailability of 50-80 %
 Excreted in urine within 24 hrs
 Has no immunosuppressive effect
 Inhibits the peripheral conversion of T4 to T3
 Crosses placenta less readily, Preferable in pregnancy
 Not excreted in breast milk

9. USES
 Control thyrotoxicosis in both Graves disease & toxic nodular goiter.
 Clinical improvement starts after 1-2 weeks
 Propylthiouracil : 50-150mg TDS followed by 25-50 mg BD-TDS for
maintenance
 Carbimazole: 5-15 mg TDS initially
 Maintenance dose : 2.5-10mg daily in 1-2 divided doses

10. Propylthiouracil Carbimazole
Dose to dose less potent About 5 × more potent
Highly plasma protein bound Less bound
Less transferred across placenta and in milk Larger amounts cross to foetus and in milk
Plasma t½ 1–2 hours 6–10 hours
Single dose acts for 4–8 hours 12–24 hours
No active metabolite Produces active metabolite—methimazole
Multiple (2–3) daily doses needed Mostly single daily dose
Inhibits peripheral conversion of T4 to T3 Does not inhibit T4 to T3 conversion

11. 2. IODIDE SALTS AND IODINE
 Iodide salts inhibit organification (iodination of tyrosine) & thyroid hormone release.
 Also decrease the size & vascularity of the hyperplastic thyroid gland.
 Iodide salts inhibit the release as well as the synthesis of the hormone, their onset
of action occurs rapidly within 2-7 days.
 This effect is transient because the thyroid gland escapes from iodide block after
several weeks of treatment.
 Wolff-Chaikoff effect : Excess iodide inhibits its own transport into thyroid cells by
interfering with expression of NIS on the cell membrane. Attenuates TSH & cAMP
induced thyroid stimulation.
 Excess iodide rapidly & briefly interferes with iodination of tyrosil & thyronil
residues of thyroglobulin (probably by altering redox potential of thyroid cells)
resulting in reduced T3/T4 synthesis.

12.  Iodide salts : Used in thyroid storm (severe thyrotoxicosis) &
To prepare the patient for surgical resections of hyperactive thyroid.
 Saturated solution of KI.
 Lugols solution (iodine & KI): 5% iodine in 10% KI solution : 5- 10drops/day
 Iodide salts (Na / K): 100-300 mg/day (therapeutic),
5–10 mg/ day (prophylactic) for endemic goiter
 Colloid Iodine 10%: 5–10 drops/day

13. USES
1. Preoperative preparation for thyroidectomy in Graves’ disease:
Iodine for 10 days just preceding surgery.: to make the gland firm, less vascular &
easier to operate on. Propranolol additionally for rapid control of symptoms.
2. Thyroid storm Lugol’s iodine (6–10 drops) or I2 containing radiocontrast media
(iopanoic acid/ipodate) orally to stop further release of T3/T4 from the thyroid & to
decrease T4 toT3 conversion.
3. Prophylaxis of endemic goiter : as “iodized salt”.
4. Antiseptic As tincture iodine, povidone iodine

14. Adverse effects
• Acute reaction : Occurs only in individuals sensitive to iodine.
• Swelling of lips, eyelids, angioedema of larynx (may be dangerous), fever,
• Joint pain, petechial haemorrhages, thrombocytopenia, lymphadenopathy.
• Chronic overdose (iodism): Inflammation of mucous membranes, salivation,
rhinorrhoea, sneezing, lacrimation, swelling of eyelids, burning sensation in mouth,
headache, rashes, g.i. symptoms, etc.
• Long-term use of high doses: hypothyroidism and goiter.
• Iodide : cause flaring of acne in adolescents.
• Pregnant or nursing mothers: foetal/infantile goiter and hypothyroidism.
• Thyrotoxicosis may be aggravated in multinodular goiter.

15. IODINATED CONTRAST MEDIA (IPODATE)
 Suppresses conversion of T4 to T3 via 5’deiodinase in the liver, kidney & other
peripheral tissues.
 Ipodate : Useful in rapidly reducing T3 concentration in thyrotoxicosis
(in thyroid storm)

16. 3. RADIOACTIVE IODINE
 Administered as sodium salt of 131I , dissolved in water & taken orally.
 Stable isotope of iodine is 127I.
131I : emits x-ray as well as β particles .
 x-ray : useful in tracer studies, they traverse the tissues and can be monitored
by a counter,
β particles : utilized for their destructive effect on thyroid cells.
 131I is concentrated by thyroid, incorporated in colloid- emits radiation from
within the follicles.
 β particles penetrates around 0.5-2 mm of tissue
 Thyroid follicular cells are affected within undergoes pyknosis & necrosis followed
by fibrosis when a large dose is given.

17. USES
 Diagnostic: 25-100 mcCurie : no damage to thyroid cells occur at this dose
 Therapeutic:
 Hyperthyroidism due to Graves’ disease or Toxic nodular goitre.
 Average therapeutic dose: 3-6 milli curie
 Response is slow, starts after 2 weeks & gradually increases reaching peak at
3 month.

18. Advantages
1. Treatment with 131I is simple, conveniently given on outpatient basis & inexpensive.
2. No surgical risk, scar or injury to parathyroid glands/recurrent laryngeal nerves.
3. Once hyperthyroidism is controlled, cure is permanent.

19. • Disadvantages
1. Hypothyroidism: 131I in Graves’ disease : hypothyroid (may require supplemental
thyroxine treatment).
2. Long latent period of response.
3. Contraindicated during pregnancy—cretinism during first trimester.
4. Not suitable for young patients: hypothyroidism later & would then require life-
long T4 treatment. Chances of genetic damage/cancer.
131I : treatment of choice after 25 years of age and if CHF, angina or any other
contraindication to surgery is present.
Metastatic carcinoma of thyroid (papillary / follicular carcinoma which concentrate
iodine), 131I may be used as palliative therapy after thyroidectomy.

20. 4. IONIC INHIBITORS
 Certain monovalent anions inhibit iodide trapping by NIS into thyroid
because of similar hydrates ionic size.
 Inhibition of T4 & T3 synthesis
 Very toxic --- not used.
 Eg: Thiocyanates, Perchlorates

21. 5. Β-BLOCKERS
• Propranolol is used to rapidly alleviate manifestations of thyrotoxicosis that
are due to sympathetic overactivity.
• eg: Palpitation, tremor, nervousness and sweating,
• They reduce peripheral conversion of T4 to T3

22.  β-blockers are used in hyperthyroidism in following situations:
a) while awaitng response to propylthiouracil / carbimazole
b) along with iodide for preoperative preparation before subtotal thyroidectomy
c) thyrotoxic crisis (Thyroid storm): emergency situation

23. THYROID STORM:
• Presents with extreme symptoms of hyperthyroidism.
• Treatment of thyroid storm: same as that for hyperthyroidism
• But the drugs are given in higher doses and more frequently.
• β-blockers: metoprolol or propranolol : blunt the widespread sympathetic stimulation
in hyperthyroidism.

24. Treatment of Thyroid storm
• • Nonselective β blockers (e.g. propranolol): symptomatic relief.
They reduce peripheral conversion of T4 to T3.
• Propranolol 1–2 mg slow i.v. may be followed by 40–80 mg oral every 6 hours .
• • Propylthiouracil 200–300 mg oral 6 hourly: reduces hormone synthesis as well as
peripheral T4 to T3 conversion.
• • Iopanoic acid (0.5–1 g OD oral) or ipodate : potent inhibitors of thyroid hormone release
from thyroid, as well as of peripheral T4 to T3 conversion.
• • Corticosteroids (hydrocortisone 100 mg i.v. 8 hourly followed by oral prednisolone): help to
tide over crisis, cover any adrenal insufficiency & inhibit conversion of T4 to T3 in periphery.
• • Diltiazem 60–120 mg BD oral : if tachycardia is not controlled by propranolol alone, or
when it is contraindicated.
• • Rehydration, anxiolytics, external cooling & appropriate antibiotics are the other
measures

25. REFERENCES
• Rang HP, Ritter JM & Flower RJ & Henderson G, Rang & Dale's Pharmacology, 8th
Edition, Churchill Livingstone, 2015.
• Tripathi KD, Essentials of Medical Pharmacology, 7th edition, Jaypee Brothers Medical
Publishers (P) Ltd, 2013.
• Katzung BG, Lange & Katzung Basic & Clinical Pharmacology, 14th edition, McGraw Hill
Professional, 2018.
• Barar FSK, Essentials of Pharmacotherapeutics, 6th revised edition, S. Chand &
Company Ltd., New Delhi, 2011.

26. THANK YOU