Mechanism of action
At the molecular level, levothyroxine sodium acts as a prohormone. Upon entering the cell cytoplasm, thyroxine ($T_4$) undergoes conversion into triiodothyronine ($T_3$), which is 3–5 times more active than the parent compound.
The resulting $T_3$ penetrates the nucleus and stimulates intracellular receptors. This leads to the activation of mRNA transcription and, consequently, enhanced protein synthesis. Thus, the drug interferes with the basic processes of cellular metabolism, mimicking the work of the functional elements of the thyroid gland (follicles), where the iodination of thyroglobulin and condensation of iodotyrosines normally occur.
Pharmacological effects
The drug exerts a systemic effect on the body, regulating metabolism and growth processes. Within the framework of hypothalamic-pituitary regulation, levothyroxine sodium participates in a negative feedback mechanism: an increase in its blood level suppresses the secretion of thyrotropin-releasing hormone by the hypothalamus and thyroid-stimulating hormone (TSH) by the anterior pituitary.
Compared to preparations of pure $T_3$ (liothyronine), levothyroxine acts weaker and slower, but has an important clinical advantage — a less pronounced arrhythmogenic effect.
Indications for use
1. Replacement therapy The main goal is to replenish the deficiency of own hormones in endocrine hypofunction (hypothyroidism). Therapy does not eliminate the etiology of the disease, but relieves the manifestations of deficiency. The nature of use is long-term (often lifelong).
2. Non-cardiac indications
- Thyrotoxicosis: the drug has a pathogenetic effect by inhibiting the peripheral conversion of endogenous $T_4$ into the more active $T_3$.
- Neurology and psychiatry:
- Migraine: prevention of attacks by toning cerebral vessels and preventing their painful pulsation.
- Essential tremor: reduction of tremor due to blockade of $\beta_2$-receptors in skeletal muscle.
- Anxiety disorders: relief of panic attacks and fear due to a depressant effect on the central nervous system.
Side effects and risks
When prescribing the drug, its effect on various systems must be taken into account:
- Lipid profile: the drug has an atherogenic effect. The mechanism is associated with a decrease in endothelial lipoprotein lipase activity. As a result, the levels of triglycerides and VLDL rise, while the level of antiatherogenic HDL decreases.
- Sexual function: there is a risk of developing erectile dysfunction.
- Thyroid hormone metabolism: exogenous $T_4$ prevents the peripheral conversion of endogenous thyroxine into triiodothyronine.
Administration guidelines and prescription
The drug is prescribed orally, strictly in the morning 30 minutes before meals. The dosage is selected individually (usually from 0.000025 to 0.0001 g).
In clinical practice, levothyroxine sodium is often used as part of combination drugs. For example, with potassium iodide (Iodothyrox) or in a triple combination with liothyronine and potassium iodide (Tireokomb). There is also a combination of synthetic $T_4$ and $T_3$ — Thyreotome.
Example of a prescription: ```latin Rp.: Tab. Levothyroxini natrii 0.0001 D.t.d. N. 50 S. Orally 1 tablet in the morning 30 minutes before meals. ```
Briefly: answers to topical questions
What are the indications for the use of levothyroxine sodium?
Indications for the use of levothyroxine sodium (Levothyroxinum natrium) include replacement and suppressive therapy in various endocrine pathologies.
- Thyroid hypofunction — replacement therapy for hormone deficiency, including in pregnant mothers.
- Differentiated thyroid cancer — suppressive hormone therapy to improve survival rates.
- Cretinism — timely administration of hormones prevents the development of severe mental disability in children.
What side effects does levothyroxine sodium cause?
The side effects of levothyroxine sodium are primarily associated with the use of incorrect doses of the drug.
- Drug-induced thyrotoxicosis — occurs with overdose, is a risk factor for atrial fibrillation and osteoporosis in postmenopausal women.
- Fetal hypothyroidism — high-dose use increases the risk of hypothyroidism and enlargement of the thyroid gland in the fetus.
What are the contraindications for prescribing levothyroxine sodium?
Before starting therapy with levothyroxine sodium, adrenal insufficiency must be ruled out.
- Secondary adrenal insufficiency — if present or suspected, glucocorticoids are prescribed first, and only after that is levothyroxine sodium used. This is necessary to avoid the development of an adrenal crisis, as thyroxine accelerates cortisol metabolism.
What are the symptoms of levothyroxine sodium overdose?
Levothyroxine sodium overdose is assessed provided blood is drawn before taking the drug.
- Clinical manifestations of thyrotoxicosis.
- Free T4 — above or at the upper limit of the reference range.
- Free T3 — high level.
Levothyroxine sodium overdose is also a risk factor for atrial fibrillation and osteoporosis in postmenopausal women.
Class and exam questions
Why does the effect of levothyroxine develop slowly (maximum on days 10–15)?
The drug is a prohormone. To manifest full activity, it must penetrate the cell cytoplasm, convert into triiodothyronine ($T_3$), enter the nucleus, and trigger mRNA transcription for the synthesis of new proteins.
What is the advantage of levothyroxine over liothyronine?
Despite the fact that levothyroxine acts weaker and slower, it has a significantly less pronounced arrhythmogenic effect, making it safer for the cardiovascular system during long-term administration.
Why is levothyroxine used in thyrotoxicosis?
In this case, its pathogenetic effect is used: exogenous levothyroxine is able to inhibit the peripheral conversion of endogenous $T_4$ into the more active $T_3$.
What else to study on this topic
- Physiology of thyroid hormone biosynthesis: the role of thyroid peroxidase and thyroglobulin
- Hypothalamic-pituitary system: mechanisms of direct and negative feedback
- Comparative pharmacodynamics of levothyroxine and liothyronine
- Differences between replacement, symptomatic, and pathogenetic therapy
- Combination drugs for the treatment of hypothyroidism (Iodothyrox, Tireokomb, Thyreotome)
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