Methimazole is an oral antithyroid drug used to treat hyperthyroidism. It works by inhibiting the synthesis of thyroid hormones in the thyroid gland. Common side effects include skin rash, upset stomach, and loss of taste. Methimazole is readily absorbed from the gastrointestinal tract and metabolized in the liver. It has a half-life of 5-6 hours and is excreted in urine. Due to risks of harming an unborn baby, methimazole is contraindicated in pregnancy and breastfeeding without physician consultation.

1. METHIMAZOLE
ANTITHYROID DRUG
PRESENTED BY:
MEENAKSHI
M.Sc. 1st Year

2. HISTORY
• Antithyroid drugs were developed as derivatives of
thiourea, which was discovered to goiter in rats.
• ƒThiourea was the first drug used in man, followed by
thiouracil (after testing hundreds of compounds in rats)
(JAMA 1943)
• ƒBoth compounds caused agranulocytosis in
approximately 1% of patients
• ƒPropylthiouracil was found to have a lower risk of
agranulocytosis, and methimazole, introduced a few
years later, in 1949, seemed to have a lower rate still

3. HYPERTHYROIDISM
The over production of thyroid hormones.
Symptoms include fatigue, weight lose, rapid heart beat, anxiety,
swollen eyes, and sensitivity to hot temperatures.
Causes:
Grave’s disease, and autoimmune disorder in which antibodies
serve as agonists to the THS receptors on the thyroid’s surface,
causing thyroid growth and activation of hormone synthesis and
secretion.
Thyroid tumors which cause the uncontrolled synthesis and
secretion of thyroid hormones.
Thyroiditis, inflammation of the thyroid typically caused by
infection.

4. Symptoms:

5. Anti-thyroid drugs
Drugs used for the treatment of hyperthyroidism :
Inhibition of hormone synthesis : THIOAMIDES
• Propylthiouracil and Methimazole.
Blockade of hormone release :
• Iodides, Iodinated contrast media.
Radioactive Iodine 131
Anion Inhibitors :
• Perchlorates, Thiocynates.
Beta blocking drugs : Propranolol

6. Anti-thyroid agents
THIOAMIDES :
• Methimazole
• Propylthiouracil (PTU), Carbimazole
• MOA:
– inhibit synthesis by acting against iodide
organification
– coupling of iodotyrosines
– Blocks peripheral conversion of T4 to T3 (PTU)

7. Anti-thyroid drugs: THIOAMIDES
The thiocarbamide
group is essential for
antithyroid activity

8. THIOAMIDES :
• Pharmacokinetics:
– almost completely absorbed in the GIT
– serum half life: 90mins(PTU) ; 6 hours
(methimazole)
– excretion: kidney – 24 hours (PTU) ; 48 hours
(Methimazole)
– can cross placental barrier (lesser with PTU)
– Methimazole 10x more potent than PTU
– PTU more protein-bound

9. Pharmacological action:
Inhibition of the synthesis of T3 & T4
• Mechanism
• All thioamides inhibit peroxidase-catalyzing reactions
• Iodine organification
• Iodotyrosines condensation
• Propylthiouracil also inhibit T4 converting to T3
Characteristics
① Result appears slowly: in 3-4 w hyperthyroid ameliorated, and
in 2-3 months BMR normalized;
② Long-term use leads to thyroid hyperplasia
③ Methimazole is 10 times as potent as propylthiouracil

10. • Clinical use
• treatment of hyperthyroid
• 1. Mild hyperthyroid and surgery & 131I not permitted;
• 2. Operation preparation;
• 3. Thyroid crisis (comprehensive therapy).
• Adverse reactions
• 1. Long-term use leads to thyroid hyperplasia;
• 2. Pruritic maculopapular rash is the most common adverse
raaction
• 3. The severe adverse reaction is agranulocytosis

11. 11
Iodides (NaI, KI)
Pharmacological action
Inhibition of T3 & T4 release and synthesis
Decrease of size & vascularity of the hyperplastic gland
Clinical use
Ministrant treatment of hyperthyroid
1. Operation preparation;
2. Thyroid crisis.
Adverse reactions
1. Acneiform rash (similar to that of bromism);
2. Swollen salivary glands, mucous membrane ulcerations, and etc.

12. Radioactive iodine (131I)
12
131I is the only isotope for treatment of thyrotoxicosis.
Its therapeutic effect depends on emission of β rays with an effective half-life of
5 days & a penetration range of 0.4-2 mm.
Woman in pregnancy or lactation is forbidden!
β-adrenoceptor blockers
βblockers are effective in treatment of thyrotoxicosis.
Propranolol is the most widely studied and used.

13. ANION INHIBITORS :
• Monovalent ions like perchlorate, pertechnetate,
thiocyanate can competitively block the uptake of iodine.
• Anion inhibitors are uncommon in use because of
aplastic anemia.
• These are effective in iodine induced hyperthyroidism
IODINATED CONTRAST MEDIA: Diatrizoate / Iohexol :
• They are valuable in hyperthyroidism and as adjunctive in
thyroid storm.
• They inhibit the peripheral conversion of T4 into T3.
• Inhibition of hormone release is an additional mechanism

14. Other Anti-thyroid drugs :
• Propranolol is used in the management of
cardiac symptoms of thyrotoxicosis.
• Lithium is known to inhibit synthesis and release
of thyroid hormones.
• Amiodarone can also result in hypothyroidism.

15. Mechanism of action of anti
thyroid drugs

16. METHIMAZOLE
• IUPAC name: 1-methyl-3H-imidazole-2-thioneI
• Formula:C4H6N2S
• Mol. mass114.17 g/mol
• Melt. point146 °C (295 °F)
• Trade Name(s):
India- Methimez .
International- Mercazole, Thyrozole
• Brands: Tapazole , Metizol
• Routes: Oral
• PHARMACOKINETIC DATA:
• Bioavailability 93%
Metabolism: Hepatic
• Half-life 5-6 hours
• Excretion: Renal

17. METHIMAZOLE
• INDICATIONS:
• Methimazole is indicated in the medical treatment of
hyperthyroidism. Long-term therapy may lead to remission of
the disease.
• Category: D There is positive evidence of human fetal risk based
on adverse reaction data from investigational or marketing
experience or studies in humans.
• Can also be taken before thyroid surgery to lower thyroid
hormone levels.

18. PHARMACOKINETICS
ABSORPTION:
Bioavailability : Readily and rapidly absorbed from the GI tract
following oral administration.Peak plasma concentrations attained
within about 1 hour.
Distribution Extent:
• Readily crosses the placenta.
• Distributed into milk (in concentrations approximately equal to
those in maternal serum).
Metabolism: Metabolized in the liver.
Elimination Route: Excreted in urine; approximately 12% of dose
excreted in urine within 24 hours.
Half-life : 5–6 hours.
Storage: 15–30°C.

19. • DOSAGE
• Adult: The initial daily dosage is 15 mg.
• It may be increased upto 60 mg, divided into 3 doses at 8-hour
intervals.
• The maintenance dosage is 5 to 15 mg daily.
• Pediatric: Initially, the daily dosage is 0.4 mg/kg, divided into 3
doses and given at 8-hour intervals.
• ADMINISTRATION: Oral, with or without food
• Warnings and Precautions : Caution should be exercised in
patients with history of decrease in blood cells, liver disease,
any allergy, who are taking other medications, during
pregnancy and breastfeeding.
It may cause drowsiness, dizziness, or lightheadedness, do
not drive a car or operate machinery while taking this
medication

22. • SIDE EFFECTS: Skin - Rash, hives, abnormal loss of
hair, itching and skin pigmentation.
Gastrointestinal - Nausea, vomiting and stomach
upset.
Musculoskeletal - Joint/muscle pain.
Central Nervous System - Tingling, headache,
drowsiness, dizziness and fainting.
Miscellaneous - Loss of taste, swelling and jaundice.
Other Precautions : Avoid excess dosage.
Storage Conditions : Store it at controlled room
temperature (15° to 30°C), and in an airtight
container. Keep away from children.

23. COMMON ADVERSE EFFECTS:
• skin rash
• itching
• abnormal hair loss
• upset stomach
• vomiting
• loss of taste
• abnormal sensations (tingling, prickling, burning, tightness, and
pulling)
• swelling
• joint and muscle pain
• drowsiness
• dizziness
• decreased white blood cells
• decreased platelets

24. • List of Contraindications
• Methimazole and Pregnancy
• Contraindicated in pregnancy
USFDA pregnancy category D. Methimazole can harm an
unborn baby. Perform pregnancy tests before using
Methimazole. Use effective contraceptive modes to
prevent unintended pregnancies while taking
Methimazole.
• Methimazole and Lactation
• Methimazole can pass into breast milk and harm a
breast-feeding baby. Consult a physician before taking
Methimazole.
• Storage
• Store at 20-25°C.