Aromatase inhibitors
Aromatase inhibitors
In postmenopausal women, estrogen is produced through aromatase, an enzyme that converts hormone precursors into estrogen. Aromatase inhibitors prevent androgen from being converted into estrogen in postmenopausal women, thereby blocking estrogen’s ability to activate cancer cells; limiting the amount of estrogen means that less estrogen is available to reach cancer cells and make them grow.
Two types
There are two types of aromatase inhibitors. Type 1, or steroidal, inhibitors include exemestane; type 2, or nonsteroidal, inhibitors include anastrozole and letrozole.
Pharmacokinetics
Aromatase inhibitors are taken orally (in pill form) and are usually well tolerated. Steady-state plasma levels after daily doses are reached in 2 to 6 weeks. Inactive metabolites are excreted in urine.
Pharmacodynamics
Aromatase inhibitors work by lowering the body’s production of estrogen. In about one-half of all patients with breast cancer, the tumors depend on estrogen to grow. Aromatase inhibitors are used only in postmenopausal women because they lower the amount of estrogen that’s produced outside the ovaries, such as in muscle and fat tissue. Because these drugs induce estrogen deprivation, bone thinning and osteoporosis may develop over time.
To reverse or not to reverse: That is the question
Type 1 inhibitors, such as exemestane, irreversibly inhibit the aromatase enzyme, whereas type 2 inhibitors, such as anastrozole, reversibly inhibit it. Type 1 aromatase inhibitors may still be effective after a type 2 aromatase inhibitor has failed.
Memory joggerRemember: Hormonal-dependent (gender specific) tumors are treated with hormonal therapies; tumors common to both genders are treated with corticosteroids.
Competitive advantage
Anastrozale and letrozole work by competitively binding to heme of the cytochrome P450 subunit of aromatase, leading to decreased levels of estrogen in all tissues; they don’t affect synthesis of adrenocorticosteroids, aldosterone, or thyroid hormones.
Pharmacotherapeutics
Aromatase inhibitors are primarily used to treat postmenopausal women with metastatic breast cancer. They may be administered alone or with other agents such as tamoxifen.
Drug interactions
Certain drugs may decrease the effectiveness of anastrozole, including tamoxifen and estrogen-containing drugs.
Warning!
Adverse reactions to aromatase inhibitors
Adverse reactions to aromatase inhibitors are rare. They may include dizziness, mild nausea, mild muscle and joint aches, and hot flashes.
Occasionally, aromatase inhibitors can also affect cholesterol levels; anastrazole may elevate both high-density and low-density lipoprotein levels.
Thanks for your visit..!