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IMSCP2 Pharmacology > Thyroid Drugs > Flashcards

Thyroid Drugs Flashcards

1
Q

What are the two thyroid hormones?

A

T3 - Triiodothyronine
T4 - Thyroxine

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2
Q

What are the 5 functions of TSH?

What messenger molecule does it act through?

A

Acts through cAMP

  1. Increases blood flow to thyroid
  2. Increases uptake of iodine into thyroid
  3. Increases iodination of tyrosines on thyroglobulin
  4. Increases formation of thyroglobulin-associated T3 and T4
  5. Increases release of stored T3 and T4
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3
Q

What is thyroglobulin ?

A

Protein made by follicular cells of the thyroid.

Has many tyrosines, on which iodine radicals join to form MIT+DIT

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4
Q

What dietary form do we get iodine?

A

Iodide - transported into cells via active transport.

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5
Q

Describe the formation of MIT and DIT from iodine.

A

Peroxidase converts iodine into an iodine radical by stripping an electron.

The radical searches for an electron in tyrosine, and bonds, forming monoiodotyrosine (MIT). Another iodine radical can join to form diiodotyrosine (DIT)

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6
Q

How are T3 and T4 formed from MIT and DIT?

A

Thyroperoxidase cleaves MIT/DIT from thyroglobulin and attaches them together:

MIT + DIT = T3 (triiodothyronine)

DIT + DIT = T4 (thyroxine)

Proteases release the T3 and T4 into circulation.

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7
Q

What is the action of T3 and T4, once released into circulation?

A

T4 is converted into T3 in the liver and other cells.

T3 is ligand for thyroid hormone receptor

Effect:

  • Growth and maturation
  • Increased metabolic rate (uptake of AAs and glucose, production of ATP)
  • Adrenergic facilitation
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8
Q

What receptor is also involved in the T3 + thyroid hormone receptor interaction?

A

Retinoid-X-Receptor (RXR) - regulates activity of nuclear receptor by forming heterodimer.

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9
Q

What are 4 causes of hypothyroidism?

A
  1. Autoimmune thyroid disease
  2. Iodine deficiency
  3. Surgical removal / radio-iodine treatment
  4. Drug induced (lithium, amiodarone)
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10
Q

What are 4 causes of hyperthyroidism?

A
  1. Graves Disease (TSH receptor auto-antibodies)
  2. Thyroid adenoma
  3. Thyroid hypertrophy (iodine sufficiency after insufficiency)
  4. Over-production of TSH (rare)
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11
Q

What are the two types of thyroid hormone replacement and their delivery?

A

T3 replacement:

  • Rapidly effective
  • Eliminated rapidly, short half-life (2 days)
  • IV formulation to immediately treat life-threatening hypothyroidism

T4 replacement:

  • Longer half-life (6 days)
  • Oral formulation
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12
Q

What are 3 side effects of thyroid hormone receplacement?

A
  • Angina
  • Restlessness
  • Arrhythmia
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13
Q

What are the 5 methods of treating hyperthyroidism?

A
  1. Remove gland and replace T4
  2. Irradiate gland and replace T4
  3. Inhibit thyroperoxidase
  4. Prevent peripheral deiodination of T4
  5. Interfere with sympathetic nervous system action of T3/T4 (beta-adrenergic-blockade)
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14
Q

How does irradiation of the thyroid gland help treat hyperthyroidism?

What are the consequences of this treatment?

A

131-Iodine, taken orally.

Incorporated into thyroid epithelium producing radiation that kills thyroid tissue.

Ultimately, the patient becomes hypothyroid and requires T4 replacement.

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15
Q

How does inhibiting thyroperoxidase help treat hyperthyroidism?

What are the drugs used to do this?

A

Thyroperoxidase is responsible for building T3 and T4 from MIT and DIT.

Thiourylenes are used

  • Methimazole, carbimazole (pro-drug for methimazole)
  • Propylthiouracil
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16
Q

Prophylthiouracil is a drug that inhibits thyroperoxidase action.

What additional synergistic effect does it have on treating hyperthyroidism?

What is a severe adverse effect that can come with it?

A

Along with thyroperoxidase suppression, it also reduces peripheral deiodiniation of T4.

However, it can be associated with severe liver toxicity.

17
Q

What are some adverse effects of thyroperoxidase inhibiting drugs?

A

Oversuppression - hypothyroidism

Immunological effects - marrow aplasia, skin rashes

18
Q

Why is beta-adrenergic blockade useful in hyperthyroidism?

A

Hyperthyroidism induces sympathetic nervous system mediated effects, such as tachycardia, tremor and tachyarrhythmias.

Beta-adrenergic blockade antagonises this, suppressing the above listed manifestations.

19
Q

Removal/irradation of the thyroid gland or anti-thyroid drugs can result in hypothyroidism, which requires T4 replacement.

What is the best way to monitor T4 replacement?

A

TSH level is the best indicator, dependent on feedback from T3

  • High TSH = little negative feedback produced from little T4 in circulation = need more T4 or less anti-thyroid drug
  • Low TSH = needs less T4 or more anti-thyroid drug

IMSCP2 Pharmacology (17 decks)

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