Pharmacology and The mechanism of action of Anastrozole

Pharmacological group: anti-estrogen drugs; non-steroidal aromatase inhibitors.

Mode of action: the treatment of advanced breast cancer in women.

Systematic (IUPAC) name: 2,2′- [5- (1H-1,2,4-triazol-1-ylmethyl) -1,3-phenylene] bis (2-methylpropanenitrile)

Bioavailability: 83-85%

Protein binding: 40%

Metabolism 85% in the liver

The half-life: 46.8 hours

Isolation: 11% of renal

Formula: C17H19N5

Mol. weight: 293.366 g / mol

Anastrozole, available from AstraZeneca under the trade name Arimidex, is a nonsteroidal aromatase inhibitor approved for the treatment of breast cancer after surgery as well as in metastases in women in the pre- and post-menopause. Estrogen increases the severity of breast cancer, as hormones induce hyperplasia and differentiation on the estrogen receptor sites. Anastrozole works by inhibiting estrogen synthesis. The patent for Arimidex by AstraZeneca expired in June 2010.

 

Description

 

Anastrozole – antiestrogen drug developed for the treatment of advanced breast cancer in women. Anastrozole is the first drug in a class of aromatase inhibitors third generation. It acts by inhibiting the enzyme aromatase, and subsequently – by blocking the production of estrogen in the body. Since many forms of breast cancer cells are stimulated by estrogen, reducing levels of the hormone in the body can slow the progression of the disease. For these purposes, it is also often used tamoxifen citrate (Nolvadex), which blocks the action of estrogen receptors, and does not affect the actual endogenous estrogen production by the body. Anastrozole has a significant impact on the level of estrogen in a daily dose of 1 mg (usually one tablet) causes suppression of estrogen more than 80% of patients. Given the powerful effect the drug has on hormone levels, it is usually prescribed only in postmenopausal women. During therapy, may experience side effects such as hot flushes and hair thinning, which are much more likely to occur in premenopausal patients. Read more

 

Anastrozole in bodybuilding

 

Athletes who use steroids, Anastrozole is used in order to minimize the side effects associated with elevated levels of estrogen, is often observed when taking anabolic / androgenic steroids. Compared with traditional drugs such as Nolvadex and Proviron®, Anastrozole can significantly better control of estrogen levels.

 

Tamoxifen Anastrozole against

 

Test ATAC (Arimidex, Tamoxifen, alone or in combination) – an international, randomized, controlled study of 9366 women with localized breast cancer who took either anastrozole or tamoxifen or both drugs at once for five years, followed by five years’ observation. After 5 years of the study, patients of groups whose members received anastrozole, showed significant improvement in clinical outcomes compared to patients in the tamoxifen group. Researchers believe that anastrozole is more preferable as a medical therapy in postmenopausal women with localized estrogen receptor (ER) positive breast cancer. Another study showed that when taking anastrozole risk of relapse was reduced by 40%, but it increases the risk of bone fractures. The study concluded that ER-positive patients who have 2-saving treatment with tamoxifen was beneficial to switch from tamoxifen to anastrozole.

 

The mechanism of action of anastrozole

 

Anastrozole reversibly binds to the aromatase enzyme through competitive inhibition, and inhibits the conversion of androgens to estrogens in peripheral (vnegonadnyh) tissues.

 

History

 

Anastrozole was developed by Zeneca Pharmaceuticals, and in late 1995 was approved for use in the United States. The drug was developed as a new treatment for operable breast cancer in women, which previously, over time, used drug Tamoxifen. To move from the established trends were needed substantial reasons. Shortly after its launch, anastrozole was included in the very large-scale, multicenter, double-blind study, which is based in Rome. The study evaluated the use of anastrozole and tamoxifen, alone or in combination, from 9366 postmenopausal women after breast cancer surgery. The results demonstrate a significant benefit of anastrozole over tamoxifen. As a result, the treatment of patients observed regression of the disease and improve overall survival. After the publication of the study in 2002, anastrozole is becoming known as a new drug for the adjunctive treatment of breast cancer in postmenopausal women. Around the same time, the drug is also becoming popular among men (body builders and athletes), because the drug causes severe suppression of estrogen.

 

How Supplied

 

Anastrozole is often supplied in 1 mg tablets. See more

 

Structural Features

 

Anastrozole is classified as selective non-steroidal aromatase inhibitor. It has the chemical name 1,3benzenediatsetonitril, a, a, a ‘, a’-tetramethyl-5- (1 H-1, 2,4triazol-1-ylmethyl).

 

Anastrozole: side effects

 

Common side effects associated with the use of aromatase inhibitors include: hot flashes, joint pain, weakness, fatigue, mood swings, depression, high blood pressure, swelling of hands / feet, and headache. Aromatase inhibitors can also lead to a decrease in bone mineral density, which can trigger the development of osteoporosis and increase the number of fractures in susceptible patients. Some people may also experience side effects such as problems with the gastrointestinal system, nausea and vomiting. Aromatase inhibitors can harm fetal development, and should not be allowed to use them during pregnancy. When receiving the male (non-label), to reduce levels of estrogens during prolonged periods of steroid therapy, aromatase inhibitors can increase the risk of cardiovascular disease (CVD), holding a positive effect of estrogen on cholesterol levels. Studies have shown that the combination of steroids with a tendency to aromatization, such as testosterone enanthate, inhibitor of aromatase inhibition is more pronounced in high density lipoprotein (HDL, “good” cholesterol). Since an agonist / antagonist estrogen receptor Nolvadex does not usually as antiestrogen (negative) effect on the cholesterol levels, it is usually preferable to bodybuilders and male athletes who have problems with the cardiovascular system than aromatase inhibitors.

 

Anastrozole guide

 

Anastrozole is approved by the FDA as a means for further treatment of postmenopausal women with hormone-positive early breast cancer, as an agent for the treatment of postmenopausal women with hormone-positive or locally advanced metastatic breast cancer, and for the treatment of breast cancer in women in postmenopausal women after tamoxifen therapy. In all cases, the accepted dosage of 1 mg per day to stop disease progression. To mitigate the estrogenic side effects of anabolic / androgenic steroids, male athletes and body builders typically take anastrozole in a dosage of 0.5 mg to 1 mg per day. In some cases, to reduce the accumulation of sufficient estrogen dose is half a tablet (0.5 mg) every other day. When used in combination with an easy flavoring androgens, such as testosterone or methandrostenolone (Dianabol, Methandienone), the drug is able to effectively block gynecomastia and water retention. Furthermore, Anastrozole can be used as a fat burner, since the accumulation of fat is also related to estrogen levels. As a result of taking the drug, the user can expect improved physique that gets more pronounced, the dried kind. The product is of interest to athletes during the diet phase / drying. It should be noted that the absorption anastrozole not affect food intake, and the drug may be taken with meals or between meals.

 

Use of anastrozole for children

 

Anastrozole can be used off-label in children with precocious puberty or in children with pubertal gynecomastia. After the onset of puberty, epiphyseal plate begins to close due to the increased production of estrogen, avoid the local metabolism and spreading through the bloodstream. Anastrozole can help slow down the process and increase the predicted adult height in boys receiving peptide hormones based on proteins for the treatment of growth hormone deficiency.

 

Chemical synthesis of anastrozole

 

The synthesis begins with two nucleophilic substitution of benzylic bromides at a and a ‘dibromomesitilene (obtained by radical bromination mesitylene) by treatment with cyanide, potassium cyanide, under phase transfer conditions to form a dinitrile. Exhaustive methylation with methyl iodide and sodium hydride results in the replacement sidechain more acidic hydrogen atoms by methyl groups. The use of bromine in the presence of benzoyl peroxide results in the formation of the corresponding benzyl bromide. Reaction of this substance 1,2,4-triazole in the presence of a base completes the synthesis of the aromatase inhibitor.

 

Availability:

 

Anastrozole is widely available in the United States and many other countries as a prescription drug. In Russia, the drug is also released from pharmacies by prescription.