Antithyroid

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Anti-thyroid drugs

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Content
Thyroid inhibitors
• Classification thyroid inhibitors
• Pharmacology of antithyroid drugs
• Advantages and disadvantages of antithyroid drugs
• Pharmacological actions of iodides, iodines,
radioactive iodines and beta blockers

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Objectives
At the end of this lecture, student will be able to
• Classify thyroid inhibitors
• Explain the pharmacology of antithyroid drugs
• List the advantages and disadvantages of
antithyroid drugs
• Describe the actions of iodides, iodines, radioactive
iodines and beta blockers

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Thyrotoxicosis
• Excessive secretion of thyroid hormones
• Grave’ s disease,
• Autoimmune disease
• IgG Ab to TSH receptor
• Exophthalmos
• Toxic nodular goiter
• Produce thyroid hormones
• Independent of TSH

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Thyroid inhibitors
• Inhibit Hormone synthesis : Propylthiouracil, methimazole, carbimazole
• Inhibits iodide trapping (Ionic inhibitors): Thiocyanates, perchlorates,
nitrates
• Inhibits hormone release: Iodine, Iodides of sodium and potassium,
organic iodide
• Radioactive iodine

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Antithyroid drugs
• Binds to hyroid peroxidase
• Prevent oxidation of iodide or iodotyrosil residues
• Inhibits iodination of tyrosine residues
• Inhibits couping of iodotyrosine to form T3 and T4
• Thyroid colloid depleted over time
• T3 and T4 blood level are reduced
• Do not interfere on iodide trapping, release or peripheral
actions
• Propyl thiouracil – inhibits peripheral conversion of T4 to T3

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Antithyroid drugs
Pharmacokinetics
• Quickly absorbed
• Widely distributed- enter milk, cross placental barrier
• Reversible hypothyroidism
ADR
• GIT intolerance, skin rashes, joint pain
• Loss/ graying of hair, loss of taste
• Rare – liver damage, serious agranulocytosis

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Uses
• Thyrotoxicosis: Grave’s disease, toxic nodular goiter
• Improvement starts after 1 or 2 weeks
• Initial control with antithyroid drugs
• 1 or 2 weeks gap – radioactive iodine
• Antithyroid drugs resumed after 5-7 days
• Gradually withdrawn over 3 months

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Advantages and disadvantages
• Advantages
• No surgical risk
• Hypothyroidism
• Can be used in children and young adults
• Disadvantages
• Prolonged treatment (Relapse)
• Not practicable in un co-operative patient
• Drug toxicity
• Radioactive iodine – contraindicated in pregnancy

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Ionic inhibitors- Inhibits iodide trapping
• Inhibits iodide trapping by NIS – T3 & T4 is not
synthesized.
• Toxic & not clinically used these days.

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Iodine and Iodides
• Iodine – fastest acting thyroid inhibitor
• Inhibition of hormone release – thyroid constipation
• Endocytosis of colloid and proteolysis of thyroglobuline
halt
• Attenuation of TSH and cAMP induced thyroid +++
• Excess iodide inhibits its own transport and alter the
redox potential of cells

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Iodine and Iodides
• Interferes with iodination
• Reduce T3 and T4 synthesis (Wolffchaikoff effect)
• Preparation: 5% iodine in 10% KI solution

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Uses
• Preoperative preparation for thyroidectomy
• 10 days preceding surgery
• To make gland firm, less vascular, easy to operate
• Thyroid storm: Sodium or potassium iodide i.v or orally –
to stop further release
• Prophylaxis of endemic goiter: iodized salt

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ADR
• Acute reaction in sensitive individuals: Swelling of lips,
eyelids, angioedema of larynx, fever, joint pain, petechial,
hemorrhage, thrombocytopenia, lymphadenopathy
• Chronic (Iodism): inflammation of mucous membrane,
salivation, rhinorrheoa, sneezing, lacrimation, swelling of
eyelids, burning sensation in mouth, headache, rashes, GI
symptoms
• Long term – hypothyroidism and goiter
• Flaring and acne in adolescents
• Pregnant/ nursing mother – Foetal/ infantile goiter

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Radioactive Iodine
• Stable isotope 121I, 131I – physical half life 8 days
• 123I (13 days), 125I (60 days)
• 131I emits X rays and β particles
• β particles – destructive effect on thyroid cells
• Concentrated by thyroid gland, incorporated in colloid
• Emits radiation within follicles & penetrate 0.5 – 2 mm of
tissue
• Follicle undergo pyknosis, necrosis, fibrosis

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Uses
• Therapeutic: Hyperthyroidism due to grave’s disease,
toxic nodular goiter (3-6 m curie)
• High dose – toxic multinodular goiter
• 131I ˃35 years old, patients with CHF, angina
• Metastatic carcinoma of thyroid: 131I palliative therapy
after thyroidectomy

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Advantages and disadvantages
• Advantages
• Simple, inexpensive
• No surgical risk
• Once controlled – cure permanent
• Disadvantages
• Hypothyroidism
• Long latent period of response
• Contraindicated in pregnancy
• Not suitable in young patients

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β adrenergic blockers
• Propranalol – Rapidly alleviate manifestation of
thyrotoxicosis (sympathetic overactivity)
• Decrease palpitation, tremor, nervousness, severe
myopathy, sweating
• Uses
• Thyrotoxic crisis
• While awaiting response to carbimazole
• Alongwith iodide for preoperative preparation before
subtotal thyrotectomy

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Summary
• Thyrotoxicosis: Excessive secretion of thyroid hormones
• Antithyroid drugs: Propylthiouracil, methimazole,
carbimazole
• Ionic inhibiotrs inhibits iodide trapping with the similar
hydrated ionic size
• Radiactive iodine β particles produce destructive effect on
thyroid cells
• β adrenergic blockers: Rapidly alleviate manifestation of
thyrotoxicosis (sympathetic overactivity) and decrease
palpitation, tremor, nervousness, severe myopathy,
sweating