Thalidomide is an immunomodulating drug currently used mainly in the treatment of multiple myeloma. It was introduced in 1957 as a sedative and hypnotic drug, intended mainly for pregnant women. At that time, it was not known that the use of thalidomide in the first 3-6 weeks of pregnancy was associated with malformation in the developing fetus.

Thalidomideis a chemical derivative of alpha-N-phthalimidoglutarimidic acid and is produced as a racemic mixture of two enantiomers - the therapeutic R-enantiomer and the potent teratogen S-enantiomer.

The biological half-life of thalidomide is approximately 5 to 7 hours. So far, the mechanism of drug elimination from the body has not been known, but it is known that it is metabolized by non-enzymatic hydrolysis to many metabolites.

Thalidomide: action

The mechanism of thalidomide action is complicated and not fully understood. It is known that it inhibits angiogenesis - it induces apoptosis of cancerous blood vessels.

This is done by reducing the synthesis of the basic Fibroblast Growth Factor (bFGF) and the Vascular Endothelial Growth Factor (VEGF).

In addition, this drug by inhibiting cyclooxygenase 2, tumor necrosis factor alpha, inhibiting the secretion of interleukin 6 and 8 and increasing the activity of interleukin 4, 5, 10 and 12 reduces the synthesis and activity of cytokines that regulate the function of bone marrow cells .

Additionally, it has been shown that thalidomide increases cellular immunity by stimulating cytotoxic T lymphocytes, enhances the anti-tumor response of Th1 helper lymphocytes and NK cells, and inhibits erythropoiesis.

Thalidomide: indications, contraindications, interactions

Thalidomide is currently used mainly in the treatment of multiple myeloma. Other indications include the treatment of leprosy, skin lesions in the course of lupus erythematosus, as well as Hodgkin's lymphoma and myelofibrosis resistant to other treatments.

Due to the fact that this drug causes severe deformities and even death of the fetus, it must not be taken by pregnant women or women who could become pregnant during the fetus.reception. Therefore, a pregnancy test is essential before starting therapy. It is worth knowing that thalidomide cannot be used during breastfeeding.

Thalidomide enhances the effects of alcohol, chlorpromazine, reserpine, barbiturates and drugs causing peripheral neuropathy.

Thalidomide: dosage

Thalidomide is taken orally in the evening 1 hour after a meal. The recommended dose in the treatment of multiple myeloma and Hodgkin's lymphoma refractory to other treatments is 100 mg daily, in myelofibrosis refractory to other treatments, 50 mg daily, and in the treatment of leprosy erythema nodosum, 100 to 300 mg daily. Remember to reduce the dose of the drug in patients whose body weight is less than 50 kg.

It is worth mentioning here that the duration of drug use depends on the response to treatment and treatment tolerance - it is usually recommended to evaluate the effectiveness of therapy after a month of using the drug. The maximum effect of the therapy is achieved after 2-3 months of taking the drug - if there is no response to treatment after this time, it is worth considering increasing the dose of thalidomide.

Thalidomide: side effects

The primary side effects of thalidomide are weakness, fever, and weight loss.

In addition, the following symptoms are very common in patients taking thalidomide:

on the part of the nervous system:

  • numbness and tingling in limbs
  • muscle tremors
  • lack of motor coordination
  • peripheral neuropathy
  • sleepiness
  • confusion syndrome

digestive system:

  • diarrhea
  • constipation
  • nausea
  • vomiting
  • stomatitis

This drug increases the risk of thrombosis (most often in the form of thrombophlebitis complicated by pulmonary embolism), disturbs the functioning of the circulatory system - it can cause both hypotension and arterial hypertension and induce bradycardia.

In addition, thalidomide exhibits myelotoxicity, which may include anemia, thrombocytopenia, and neutropenia, as well as nephrotoxicity.

May contribute to the development of hypocalcaemia, hypophosphatemia, hypoproteinemia, hyperuricemia and hyperglycaemia, as well as hypothyroidism, skin rashes and Stevens-Johnson syndrome.

Thalidomide is highly teratogenic

Thalidomide was introduced in 1957. as a sedative and hypnotic drug intended mainly for pregnant women. The first suspicions of a teratogenic effect of thalidomide appeared in 1961.

It had itassociated with the sharp increase in the incidence of the so-called focomelia (seal limbs), i.e. inhibition of the development of long bones of the upper and lower limbs in newborn babies.

The drug was withdrawn from sale in the same year - unfortunately, by that time about 10,000 children with limb deformities were born. Interestingly, studies on the toxicity of thalidomide were carried out in mice, which later turned out to be resistant to the toxic effects of this drug.

Moreover, the detailed analyzes carried out at that time showed that the period of the greatest exposure to the teratogenic effects of the drug falls on days 21-36 of pregnancy.

This means that many women may have taken this drug without knowing they were pregnant. After detecting its teratogenicity, all hypnotics containing thalidomide were withdrawn from the market.

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