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Thyroid & Anti-thyroid Agents Flashcards

1
Q

Steps in thyroid hormone biosynthesis

A
  1. Iodide Trapping (thyroid gland concentrates plasma iodide by active transport)
  2. Oxidation of iodide to iodine
  3. Binding of iodine to tyrosine residues in thyroglobulin to form mono- & di-iodotyrosines (MIT & DIT)
  4. Coupling of MIT & DIT to form tri- & tetra-iodothyronines (T3 & T4)
  5. Endocytosis of thyroglobulin by follicular cells
  6. Release of T3 & T4
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2
Q

Synthetic preparations of thyroid hormones

A
  1. Synthetic L-Thyroxine (T4)

2. Synthetic Liothyronine (T3)

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3
Q

Uses of synthetic thyroid hormones (2)

A
  1. Replacement therapy for Hypothyroidism (due to dyshormonogenesis, cretinism, hypothalamo-pituitary dysfunction, Hashimoto’s thyroiditis, post-irradiation myxoedema, non-toxic goitre)
  2. Suppress TSH release eg to treat TSH dependent thyroid cancers
  • T4 is preferred
  • T3 is reserved for treatment of myxoedemic coma
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4
Q

Toxicity of synthetic thyroid hormones (3)

A
  1. Children - insomnia, restlessness, accelerated growth, bone maturation
  2. Adults - increased nervousness, heat intolerance, palpitations, tachycardia, weight loss, monitor for signs & symptoms of cardiac arrhythmia/angina pectoris
  3. Drug interaction - interferes with absorption of thyroid hormones - Al-containing antacids, Sucralfate, Cholestyramine, Fe-containing supplements
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5
Q

Classes of anti-thyroid drugs & examples

A
  1. Ionic inhibitors (perchlorate ClO4, thiocyanate SCN, pertechnetate TcO4)
  2. Thioamides (Propylthiouracil, Carbimazole)
  3. Iodides (Lugol’s Iodine)
  4. Radioiodine (131 I)
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6
Q

Mechanism of action of ionic inhibitors

A

Inhibits trapping - competes with iodide for active transport into thyroid cells

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7
Q

Toxicity of ionic inhibitors (4)

A
  1. Fever
  2. Aplastic anemia
  3. Rashes
  4. Liver & kidney toxicity
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8
Q

Mechanism of action of thioamides

A

Antagonizes steps 2, 3, 4 - oxidation of iodide to iodine, binding of iodine to tyrosine to form MIT/DIT, coupling of MIT/DIT to form T3/T4 - by blocking activity of thyroperoxidase

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9
Q

Uses of thioamides (3)

A
  1. Definitive treatment of thyrotoxicosis (1-2 years)
  2. Pre-operatively
  3. Interim while waiting for the effects of 131 I
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10
Q

PTU vs carbimazole

A

Carbimazole is less strongly bound to plasma proteins - crosses the placenta & secreted in milk more readily

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11
Q

Toxicity of thioamides (7)

A
  1. Arthralgia
  2. Bone marrow suppression - leukopenia, agranulocytosis
  3. Cholestatic jaundice
  4. Drug rash
  5. Enlarged lymph nodes
  6. Fever
  7. Hypothyroidism - may have compensatory glandular enlargement
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12
Q

Mechanism of action of iodides

A
  1. Suppresses iodination of tyrosine & coupling of MIT, DIT - inhibits thyroid hormone synthesis
  2. Inhibits release of T3 & T4
  3. Decreases size & vascularity of the gland (1-2 weeks)
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13
Q

Uses of iodides (3)

A
  1. Prophylaxis against endemic goitre (supply iodide that is deficient)
  2. Treat thyroid storm (inhibit hormone release)
  3. Pre-op preparation to decrease size & vascularity of gland
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14
Q

Toxicity of iodides (2)

A
  1. “Iodism” from chronic overuse - bleeding disorders, conjunctivitis, fever, inflamed salivary glands, metallic taste, mucous membrane ulcerations, rash, rhinorrhea
  2. Fetal goitre - if taken longer than necessary during pregnancy - iodides can enter fetal circulation via placenta
  3. Severe exacerbation of thyrotoxicosis when gland escapes from iodide block (withdrawal of iodides)
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15
Q

Mechanism of action of radioiodine

A
  1. Taken up and concentrated in thyroid follicular cells
  2. Emits gamma & beta rays
  3. Beta particles emit rays with short path length that irradiate thyroid tissue (1-2mm), destroying follicular cells without damaging surrounding tissue
  • slow onset (1-2m)
  • only for >35 yo
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16
Q

Contraindications of radioiodine (2)

A
  1. Children - risk of genetic damage, carcinogenesis

2. Pregnancy (effect on fetal thyroid) & nursing mothers (neonates)

17
Q

Thyrotoxic Crisis/Thyroid Storm

A

characterised by

  1. Delirium
  2. Sweating
  3. Extreme Weakness
  4. Marked Tachycardia
  5. High Fever
  6. Tremors
  7. Occasionally heart failure
18
Q

Adjunct drugs used in the treatment of thyrotoxicosis

A

β-blockers - Propanolol

Relieve symptoms of sympathetic overactivity

  • while awaiting results of diagnostic tests
  • while awaiting response to thioamide
  • pre-operatively, with an iodide
  • thyroid storm
19
Q

Treatment of Thyroid Storm (5)

A
  1. IV iodides - rapidly block further release of thyroid hormone
  2. Anti-thyroid drugs (PTU) - reduce further synthesis of hormones, block conversion of T4 to T3
  3. Propanolol - block sympathetic overactivity
  4. Hydrocortisone - protect against shock & block conversion of T4 to T3
  5. Supportive therapy eg IV fluids, anti-pyretics, oxygen, digitalization

systemic pharmaco (18 decks)

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