What Are the Signs of a Levothyroxine Overdose?

Levothyroxine can be absorbed by the gastrointestinal tract, but the absorption is incomplete and the absorption rate is uncertain, especially when taken with food. After T4 is absorbed into the blood, most of it binds to plasma proteins, only about 0.03% exists in free form, about 80% binds to thyroxine-binding globulin, and a small amount binds to thyroxine-binding protein or albumin.

Levothyroxine can be absorbed by the gastrointestinal tract, but the absorption is incomplete and the absorption rate is uncertain, especially when taken with food. After T4 is absorbed into the blood, most of it binds to plasma proteins, only about 0.03% exists in free form, about 80% binds to thyroxine-binding globulin, and a small amount binds to thyroxine-binding protein or albumin.
Drug Name
Levothyroxine
Alias
Thyroxine, levothyroxine, euthyroxine, levothyroxine sodium
Main indications
Cretinism and other hypothyroidism
Dosage
0.1 to 0.2 mg orally each time, 3 times a day

Introduction to levothyroxine compounds

Levothyroxine sodium is the sodium salt of levothyroxine. Levothyroxine, also called synthetic T4 or '3,5,3', 5'-tetraiodo-L-thyroxine is a synthetic form of thyroxine (thyroid hormone), used in patients with thyroid disorders Hormone replacement therapy. The natural thyroid hormone is, as in the pharmaceutical formulation, chemically chiral-L-configuration. D-thyroxine has been studied as an anti-cholesterol drug. But it was cancelled because of side effects on the heart.

Levothyroxine Basic Information

Chinese name: thyroid hormone
Chinese alias: 3,3 ', 5,5' '-tetraiodo-L-thyronine; 3,5,3', 5'-tetraiodothyronine; thyroxine and levothyroxine; D- -Tocopherol; D-ALPHA-tocopherol;
English name: L-thyroxine
English alias: L-Thyroxine; thx; L-Tyrosine, O- (4-hydroxy-3,5-diiodophenyl) -3,5-diiodo-; 3,5,3 ', 5'-tetraiodothyronine; THYROXINE;
CAS number: 51-48-9
Molecular formula: C 15 H 11 I 4 NO 4
Molecular weight: 776.87000
Exact mass: 776.68700
PSA: 92.78000
LogP: 5.25760

Physiochemical properties of levothyroxine

Appearance and properties: beige powder
Density: 2.635g / cm 3
Melting point: 235 ° C
Boiling point: 576.3ºC at 760mmHg
Flash point: 302.3ºC
Refractive index: 1.795
Water solubility: insoluble
Stability: Stable under normal temperatures and pressures.
Storage conditions: 2-8ºC [1]

Levothyroxine related drug label information

Levothyroxine Basic Information

[Alias] levothyroxine, levothyroxine, euthyroxine, levothyroxine sodium
[Indications] Mainly used to prevent myxedema, cretinism and other hypothyroidism (such as obesity with low basal metabolic rate and habitual abortion, etc.), sometimes also used for acne, acral arterial spasm (Raynaud Disease) and constipation. Because this product can inhibit the release of pituitary thyroid stimulating hormone, it can be used to treat thyroid cancer, and it has a certain effect on breast cancer and ovarian cancer.
[Dosage and usage] Myxedema: 0.1 to 0.2 mg each time, 3 times a day. Patients with coma were given a daily intravenous injection of 0.3 to 0.5 mg, and then changed to oral administration after waking. Obesity: Take 1-2mg orally 3 times a day. Children with congenital hypothyroidism, 0 to 6 months 25 to 50 g (8 to 10 g / kg); 6 to 12 months 50 to 70 g (6 to 8 g / kg); 1 to 5 years of age 75 to 100 g (5 to 5 6 g / kg); 150 to 200 g (2 to 3 g / kg) above 12 years old.
[Precautions] Overdose can cause toxic reactions, such as palpitations, sweating, agitation, tremor, weight loss, elevated body temperature, central excitement and insomnia, and severe cases can cause vomiting, diarrhea, fever, tachycardia and irregularities, angina pectoris, muscles Vibrations and even cramps, heart failure, etc. Once it occurs, the drug should be discontinued for 1 week, and then start with a small dose. Diabetes, coronary heart disease patients are contraindicated.
[Specifications] Tablet: 50g, 0.1mg; injection (sodium salt): 1mg / 10ml.

Levothyroxine pharmacological effects

When the thyroid function is normal, T4 in blood T1 / 2 is about 6 to 7 days, when hypothyroidism is 9 to 10 days, and when hyperthyroidism is about 3 to 4 days, thyroxine is deiodinated in the surrounding tissue to form T3 and anti- T3, part of thyroxine is metabolized in the liver, and metabolites are excreted by bile. Thyroid hormones include thyroxine (T4) and triiodothyronine (T3). The adult thyroid gland secretes about T480 100g and T35 8g daily. [2]

Levothyroxine kinetics

Target cell
The majority of thyroxine in the blood circulation binds to plasma proteins (mainly thyroxine-binding globulin TBG), and only about 0.03% of T4 and 0.3% of T3 exist in free form. Only free thyroid hormones can enter target cells to exert biological effects. Part of T4 is converted into T3 in the liver, kidney and other organs, and its amount accounts for about 70 to 90% of the total T3.
After free T3 and T4 enter the target cells, T4 is converted to T3, which has a 20-fold higher affinity with its receptor than T4. Therefore, T3 is the main active thyroid hormone, and T4 is regarded as a prohormone. Thyroid hormone has a wide range of effects on the body, has the role of promoting catabolism (thermogenesis) and anabolic metabolism, has an important impact on normal metabolism and growth and development of the human body, and is very important for the development of the central nervous system of infants and young children.
The basic role of thyroid hormone is to induce the synthesis of new proteins, including special enzyme systems, to regulate the three major substances of protein, carbohydrates and fats, as well as the metabolism of water, salt and vitamins. Because thyroid hormone induces the synthesis of Na + -K + pump in the cell membrane and enhances its vitality, energy metabolism is enhanced.
Thyroid hormone (mainly T3) binds to specific receptors in the nucleus. The latter undergoes a configuration change to form a dimer. The activated receptor combines with specific sequences on the DNA and thyroid hormone response elements to regulate genes. Transcription and expression (target genes of thyroid hormones) promote the synthesis of new proteins (mainly enzymes).

Levothyroxine indication

thyroid
Overview of thyroid hormones: alternative treatments for thyroid hormone deficiency (hypothyroidism or myxedema) caused by various reasons, excluding temporary subclinical hypothyroidism during the recovery period of subacute thyroiditis; non-endemic simple Goiter; prevention and treatment of thyroid nodules; adjuvant treatment of thyroid stimulating hormone (TSH) -dependent thyroid cancer;
Adjuvant drugs for antithyroid therapy to prevent the onset of hypothyroidism and further thyroid enlargement; Prevent the occurrence of thyroid cancer in patients with neck radiotherapy; Prevent goiter caused by certain drugs such as lithium, salicylic acid and sulfa drugs Effect; inhibitor of thyroid function test. This use is limited to T3.

Levothyroxine dosage

Levothyroxine orally

Blood vessel
Oral hypothyroidism in adults generally starts at a dose of 25 to 50 g per day and increases by 25 g every 2 weeks until the complete replacement dose, typically 100 to 150 g. The adult maintenance dose is about 75 to 125 g per day. For elderly patients, patients with cardiac insufficiency, and severe myxedema, the starting dose should be reduced to 12.5 to 25 g per day, and thereafter increased by 25 g every 2 to 4 weeks. It is not necessary to achieve a complete replacement dose, generally 75 to 100 g per day. Infants and children with hypothyroidism, the complete daily replacement dose is: 6 to 8 g / kg of body weight within 6 months; 6 to 12 months of 6 g / kg; 1 to 5 years of age 5 g / kg; 6 to 12 years of age 4 g / kg. At the beginning, 1/3 to 1/2 of the total replacement amount should be applied, and then gradually increased every 2 weeks.

Levothyroxine injection

Intravenous injection is suitable for patients with myxedema and coma. The first dose should be larger, 200 400g, and then 50 100g daily until the patient is awake and switched to oral administration. (1) The medication should be highly individualized, correctly grasp the dosage, and take the medicine daily on time. Those with hypothyroidism should generally be replaced for life. During treatment, they should be based on symptoms, signs and related laboratory tests (including T3, T4 or FT3, FT4, As a result, the dose was adjusted to maintain the FT3 or FT4 and the dose of the hypersensitivity TSH in the normal range as the optimal dose. (2) Avoid combination with other drugs, as it may interfere with the action of thyroid hormones.

Levothyroxine dose

heart
The equivalent doses of various commonly used thyroid hormone preparations are: thyroid powder 60mg, levothyroxine sodium 50 60g, and liothyronine sodium 20 25g. The contents of T3 and T4 in thyroid powder are not constant, and the ratio of the two is also uncertain. The actual effect is generally 90% to 110% of the standard dose. Thyroid replacement therapy generally uses thyroid powder or levothyroxine sodium (T4), and ioceronine sodium (T3) is only used in patients with thyroid hormone resistance syndrome or peripheral thyroid hormone metabolism disorders because of its unstable plasma concentration. Levothyroxine sodium should be the first choice for replacement therapy.

Taking levothyroxine

Patients with hypothyroidism with cardiovascular disease should pay attention to the occurrence of myocardial ischemia or arrhythmia. Thyroid hormones do not easily pass through the placenta, so patients with hypothyroidism do not need to stop medication during pregnancy. Trace amounts of thyroid hormones can be excreted from milk. T4 is used to treat low thyroid function. Due to its long half-life, the highest effect can be achieved 1 to 2 weeks after oral administration. The effect can be sustained for 1 to 3 weeks after stopping the drug. It only needs to be taken once a day. Because of its irregular absorption, it is best Taken on an empty stomach.

Levothyroxine adverse reactions

Levothyroxine (Figure 2)
If the thyroid hormone is used properly, there is no any adverse reaction. Excessive use can cause tachycardia, palpitations, angina pectoris, arrhythmia, headache, nervousness, excitement, restlessness, insomnia, osteopathic spasm, muscle weakness, tremor, sweating, flushing, fever, fever, diarrhea, vomiting, weight Reduce symptoms like hyperthyroidism. When T3 is excessive, adverse reactions occur faster than T4 or thyroid powder. Reduction or withdrawal can make all symptoms disappear. Caused by excessive T4, symptoms disappear slowly.
Adverse reactions are similar to hyperthyroidism, such as increased appetite, nervousness, various types of tachycardia, arrhythmia, and increased basal metabolism. Allergic reactions caused by pure thyroid preparations were first reported in 1986. Patients with hypothyroidism developed fever, abnormal liver function, and increased eosinophils, and symptoms generally disappeared after drug withdrawal. For young people with hypothyroidism, T4 may cause short-term pseudoencephalopathy. If T4 is continuously used, even if there is no local neurological defect, headache and bilateral optic nerve papillary edema will appear.
Acute thyroid poisoning may lead to the outbreak of clinical thyroid syndrome and death, but under normal circumstances, overdose will only cause temporary symptoms of hyperthyroidism. Dangerous conditions have been reported due to pharmacists mistakenly taking grams of T4 as a milligram dose to patients. T4, especially T3, is very dangerous to the heart if administered intravenously. Therefore, intravenous administration should be considered only in patients with life-threatening myxoid edema and with good cardiac monitoring. The use of dopamine drugs is more dangerous and should be used with caution.

Levothyroxine contraindications

Levothyroxine in elderly patients

Adrenal gland
Elderly patients are more sensitive to thyroid hormones, and those who are over 60 years of age need about 25% less thyroid hormone replacement.
The following situations should be used with caution:
Cardiovascular diseases, including patients with angina pectoris, arteriosclerosis, coronary heart disease, hypertension, myocardial infarction, etc .;
Patients with long course and severe thyroid hypothyroidism or myxedema should use caution when using this class of drugs, start with small doses, and then slowly increase until the physiological replacement dose;
Patients with anterior pituitary hypofunction or adrenal insufficiency should use corticosteroids first, and then use this medicine after adrenal cortex function returns to normal.

Levothyroxine special patients

For patients with heart disease and long-term hypothyroidism, the use of thyroid hormone replacement therapy is more dangerous, and adrenal insufficiency is often associated with hypothyroidism. If thyroid hormone replacement therapy precedes corticosteroid treatment, there may be Dyson's crisis, for patients with goiter, the secretion of thyroxine has always remained within the normal range. Due to the accumulation of endogenous thyroxine, a relatively small amount of exogenous hormones can cause excessive thyroid hormone and cause hyperthyroidism.

Levothyroxine drug interactions

globulin
(1) Patients with diabetes should appropriately increase the dose of insulin or hypoglycemic agents when taking thyroid hormones.
(2) When thyroid hormone is used in combination with anticoagulants such as dicoumarin, the latter's anticoagulant effect is enhanced, which may cause bleeding; the dose of anticoagulant should be adjusted according to the prothrombin time.
(3) When this class of drugs is combined with tricyclic antidepressants, the effects and toxic and side effects of both drugs are enhanced, and attention should be paid to adjusting the dose.
(4) Those taking estrogen or contraceptives, due to an increase in the level of thyroxine-binding globulin in the blood, the dose of thyroid hormone is appropriately increased when combined.
(5) Cholestyramine or cholestipol can reduce the effect of thyroid hormones. When two types of drugs are used, they should be taken at intervals of 4 to 5 hours, and the thyroid function should be measured regularly. (6) b Adrenergic blockers can reduce the conversion of T4 to T3 in peripheral tissues, and care should be taken when combined. T4 can increase the toxicity of cardiac glycosides and increase the effects of coumarins, anticoagulants and oral hypoglycemic agents. Clofibrate can increase the effect of T4.

Levothyroxine Specific Variety Information: Levothyroxine Sodium

About Levothyroxine

Levothyroxine sodium: Pharmacodynamics Thyroid hormone is a derivative of iodinated tyrosine, including thyroxine and triiodothyronine. Normal people release 75 and 25 ug of T4 and T3, respectively. Thyroid hormone is necessary for the normal growth and development of the human body, and its insufficient or excessive secretion can cause disease. When the thyroid function is insufficient, both physical and mental development are affected, which can cause a small disease (cretinism), and when adult thyroid insufficiency, it can cause myxedema. Thyroid hormone can also promote material oxidation, increase oxygen consumption, increase basal metabolic rate, and increase heat production. Nervousness, irritability, tremor, increased heart rate, increased cardiac output, etc., occur during hyperfunction, because thyroid hormones can enhance the heart's sensitivity to catecholamines. [3]

Levothyroxine kinetics

It is easily absorbed orally, and the plasma protein binding rate is over 99%. However, the affinity of T3 and protein is lower than T4, and its free amount can be 10 times that of T4. T3 has a fast and strong action and a short maintenance time, while T4 has a slow and weak action and a long maintenance time. The half-life is longer, T4 is 8 days, and T3 is 1 day. It is mainly deiodinated in the liver and kidney mitochondria, and is combined with glucaldehyde and sulfuric acid to be excreted by the kidneys.

Levothyroxine indication

Simple goiter (normal thyroid function); taken after goiter resection to prevent recurrence of goiter; can be used as a supplementary treatment for hypothyroidism caused by various reasons; adjuvant treatment of antithyroidism after thyroid function returns to normal ; Control and supplementary treatment of thyroid cancer, especially after thyroidectomy, can also be used for thyroid suppression experiments.

Levothyroxine dosage

glucose
Adults with simple goiter are 75-200ug / times / day, half an hour before breakfast, served with water, adolescents 50-150ug / times / day. Prevent goiter recurrence after goiter resection of 75-200ug / times / day. The initial dose of hypothyroidism in adults is 25-50ug / times / day, which is increased by 25-50ug every 2-4 weeks. Maintenance dose: 125-250ug / time / day. The initial dose for children is 25-50ug / times / day. The maintenance dose is 100-150ug / time / day. Adjuvant treatment of antihyperthyroidism 50-100ug / times / day. Thyroid suppression test 200ug / times / day. In children, if the heart function is normal, the full dose should be used at the beginning of treatment, but it should be started in small doses in adults and gradually increased to the optimal dose. Treatment course: Under normal circumstances, patients with hypothyroidism and patients with partial thyroidectomy will take medicine for life; for the treatment of goiter with normal thyroid function and prevention of goiter recurrence, they will take medicine for several months or for life; as a treatment for hyperthyroidism When used as an adjuvant therapy, the administration time is the same as that of antithyroid drugs; for thyroid suppression experiments, it should be taken for 14 days. Individual cases due to intolerance or overdose of the dose, especially due to intolerance or overdose of the dose, especially because the dose increased too fast at the beginning of treatment, may cause symptoms of hyperthyroidism, including: tachycardia, arrhythmia, Sweating, diarrhea, weight loss, insomnia. If there are symptoms of hyperthyroidism, the drug should be temporarily discontinued, once the adverse reactions have disappeared, the dose can be resumed by controlling the dose.

Levothyroxine considerations

Urticaria
Elderly patients and patients with severe or long-term hypothyroidism should start with a small dose, increase the dose slowly, and frequently monitor the status of thyroid hormones. Especially for patients with coronary heart disease, heart failure or rapid arrhythmia, active measures must be taken to avoid mild hyperthyroidism caused by this drug. Hypothyroidism secondary to pituitary disease must determine whether there is adrenal insufficiency and, if present, must be treated with glucocorticoids. Effects on pregnancy and lactation During pregnancy and lactation, special treatment with thyroid hormones should be adhered to. It is contraindicated that levothyroxine and antithyroxine are used to treat hyperthyroidism during pregnancy because antithyroid hormones can cross the placenta. , And can cause fetal hypothyroidism.
Contraindications: Hyperthyroidism due to various reasons.

Levothyroxine Specific Variety Information: Levothyroxine Sodium Tablets

About Levothyroxine

Amino acid
Levothyroxine sodium tablets: Pharmacodynamics Thyroid hormone is a derivative of iodinated tyrosine, including thyroxine and triiodothyronine. Normal people release 75 and 25 ug of T4 and T3, respectively. Thyroid hormone is necessary for the normal growth and development of the human body, and its insufficient or excessive secretion can cause disease. When the thyroid function is insufficient, both physical and mental development are affected, which can cause a small disease (cretinism), and when adult thyroid insufficiency, it can cause myxedema. Thyroid hormone can also promote material oxidation, increase oxygen consumption, increase basal metabolic rate, and increase heat production. Nervousness, irritability, tremor, increased heart rate, increased cardiac output, etc., occur during hyperfunction, because thyroid hormones can enhance the heart's sensitivity to catecholamines.

Levothyroxine kinetics

Mitochondria
It is easily absorbed orally, and the plasma protein binding rate is over 99%. However, the affinity of T3 and protein is lower than T4, and its free amount can be 10 times that of T4. T3 has a fast and strong action and a short maintenance time, while T4 has a slow and weak action and a long maintenance time. The half-life is longer, T4 is 8 days, and T3 is 1 day. It is mainly deiodinated in the liver and kidney mitochondria, and is combined with glucaldehyde and sulfuric acid to excrete through the kidneys.

Levothyroxine considerations

Elderly patients and patients with severe or long-term hypothyroidism should start with a small dose, increase the dose slowly, and frequently monitor the status of thyroid hormones. Especially for patients with coronary heart disease, heart failure or rapid arrhythmia, active measures must be taken to avoid mild hyperthyroidism caused by this drug. Hypothyroidism secondary to pituitary disease must determine whether there is adrenal insufficiency and, if present, must be treated with glucocorticoids. Effects on pregnancy and lactation During pregnancy and lactation, special treatment with thyroid hormones should be adhered to. It is contraindicated that levothyroxine and antithyroxine are used to treat hyperthyroidism during pregnancy because antithyroid hormones can cross the placenta. , And can cause fetal hypothyroidism.

Levothyroxine dosage

Adults with simple goiter are 75-200ug / times / day, half an hour before breakfast, served with water, adolescents 50-150ug / times / day. Prevent goiter recurrence after goiter resection of 75-200ug / times / day. The initial dose of hypothyroidism in adults is 25-50ug / times / day, which is increased by 25-50ug every 2-4 weeks. Maintenance dose: 125-250ug / time / day. The initial dose for children is 25-50ug / times / day. The maintenance dose is 100-150ug / time / day. Adjuvant treatment of antihyperthyroidism 50-100ug / times / day. Thyroid suppression test 200ug / times / day. In children, if the heart function is normal, the full dose should be used at the beginning of treatment, but it should be started in small doses in adults and gradually increased to the optimal dose. [4]
Plasma protein

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