Thyroid & Anti-thyroid Agents Flashcards Preview

systemic pharmaco > Thyroid & Anti-thyroid Agents > Flashcards

Flashcards in Thyroid & Anti-thyroid Agents Deck (19):
1

Steps in thyroid hormone biosynthesis

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

2

Synthetic preparations of thyroid hormones

1. Synthetic L-Thyroxine (T4)
2. Synthetic Liothyronine (T3)

3

Uses of synthetic thyroid hormones (2)

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

4

Toxicity of synthetic thyroid hormones (3)

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

5

Classes of anti-thyroid drugs & examples

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

6

Mechanism of action of ionic inhibitors

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

7

Toxicity of ionic inhibitors (4)

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

8

Mechanism of action of thioamides

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

9

Uses of thioamides (3)

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

10

PTU vs carbimazole

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

11

Toxicity of thioamides (7)

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

12

Mechanism of action of iodides

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)

13

Uses of iodides (3)

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

14

Toxicity of iodides (2)

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)

15

Mechanism of action of radioiodine

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

16

Contraindications of radioiodine (2)

1. Children - risk of genetic damage, carcinogenesis
2. Pregnancy (effect on fetal thyroid) & nursing mothers (neonates)

17

Thyrotoxic Crisis/Thyroid Storm

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

18

Adjunct drugs used in the treatment of thyrotoxicosis

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

Treatment of Thyroid Storm (5)

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