Thyroid and Anti-thyroid Drugs Pharmacy Notes

physiological effects, and pharmacotherapy of hypothyroidism and hyperthyroidism.

Follicular cells

Which specific cells in the thyroid gland are responsible for the synthesis and secretion of $T_3$ (triiodothyronine) and $T_4$ (thyroxine)?

What hormone is secreted by the parafollicular cells of the thyroid gland?

Calcitonin

What is the primary regulator of iodide uptake and thyroid hormone formation in the thyroid gland?

$TSH$ (Thyroid-stimulating hormone)

Which transporter is responsible for the uptake of iodide into the thyroid gland?

$NIS$ (sodium iodide symporter)

What enzyme transforms iodide into its active form, hypoiodite, and catalyzes the incorporation of iodine into thyroglobulin?

Thyroid peroxidase ($TPO$)

What are the two intermediate products formed when hypoiodite reacts with the tyrosyl groups of thyroglobulin?

Monoiodotyrosyl ($MIT$) and diiodotyrosyl ($DIT$)

Identify the binding proteins responsible for transporting thyroid hormones in the circulation.

Thyroid Hormone-Binding Globulin ($TBG$) (∴ 70 \text{%}), Thyroxin binding Pre-albumin/transthyretin (∴ 15 \text{%}), and Albumin (∴ 15 \text{%})

Which membrane-bound enzyme is responsible for approximately 25 \text{%} of circulating $T_3$ and is downregulated in hypothyroidism?

$D1$ (Type 1 deiodinase)

Compare the affinity of thyroid receptors for $T_3$ versus $T_4$.

$T_3$ has $10 \times$ the affinity to thyroid receptors compared to $T_4$

How do high levels of thyroid hormones ($TH$) affect protein metabolism?

They increase protein degradation (high metabolic rate; energy)

What is the clinical term for severe hypothyroidism?

Myxedema

Why is Levothyroxine ($L-T_4$) the hormone of choice for thyroid replacement therapy?

Because of its consistent potency, prolonged duration of action, stability, low cost, and ease of laboratory measurement

Compare the oral bioavailability of $EUTHYROX$ tablets to $TIROSINT$ soft gel capsules.

$EUTHYROX$ has a bioavailability of 70-80 \text{%}, while $TIROSINT$ has a bioavailability of 98 \text{%}

What is the typical half-life ($t_{1/2}$) of Levothyroxine in a patient with euthyroidism?

$6-8$ days

Which drugs are known to increase the hepatic metabolism and degradation of thyroid hormones?

Nicardipine, phenytoin, carbamazepine, primidone, phenobarbital, rifampin, rifabutin, tyrosine kinase inhibitors, sertraline, and quetiapine

What is the primary cause of Grave's disease?

An autoimmune disorder in which antibodies ($Ab$) serve as agonists to the $TSH$ receptors

What are the three main management strategies for hyperthyroidism?

Antithyroid agents, Surgery, and Radioactive iodine ($131I$) treatment

What is the mechanism of action of thioamides like Propylthiouracil ($PTU$) and Methimazole?

They inhibit the thyroid peroxidase ($TPO$) enzyme, interfering with the oxidation of iodide, incorporation of iodine into thyroglobulin, and coupling of iodotyrosyl residues

Which thioamide is preferred for use in the first trimester of pregnancy and for the treatment of thyroid storm?

Propylthiouracil ($PTU$)

What is the most serious, although infrequent, adverse effect of thioamide therapy that manifests as a rapid drop in white blood cell count?

Agranulocytosis (0.1 - 0.5 \text{%} of patients)

What is the Wolff-Chaikoff effect associated with iodide treatment?

An autoregulatory phenomenon where a large amount of ingested iodide acutely decreases thyroid hormone levels within the follicular cells

Why are $\beta$-adrenoceptor antagonists, such as propranolol, used in hyperthyroidism?

To improve sympathetic symptoms (tachycardia, tremor, anxiety) and potentially decrease the peripheral conversion of $T_4$ to $T_3$