Lupron Injection
Lupron Injection (Leuprolide acetate) and goserelin are synthetic peptide analogs of the natural hormone-gonadotropinrilizing (GnRH, LHRH) (chapters 36 and 39). These analogues are more powerful than the natural hormone, and act as agonists of GnRH, with the paradoxical result of the pituitary gland in the long-term treatment (or as depot preparations) – first stimulation followed by inhibition of the release of follicle stimulating hormone, and luteinizing hormone, which leads to reduce the synthesis of testicular androgens. This phenomenon causes the effectiveness of these agents in the treatment of metastatic carcinoma of the prostate.
Leuprolide compared with diethylstilbestrol (DES) with a standard hormone therapy of cancer last predstatatelnoy cancer. The suppression of androgen synthesis and a decrease in serum prostatic acid phosphatase (a marker of metastatic spread of cancer) in both drugs is approximately the same. However, painful gynecomastia, nausea, vomiting, edema, and thromboembolic events occur in the application of leuprolide at a much lower frequency. Leuprolide and goserelin is more expensive, but the cost differential disappears when assessing the overall cost of treating complications arising from the use of DES, or the cost of surgery and hospitalization for orchiectomy. When receiving goserelin leuprolina and once a month, is formed continuously acting depot. Endocrine effects of these funds can be used successfully for the treatment of hormone-receptor torpolozhitelnogo breast cancer, but this indication for further study required.
Gonadotropinrilizing hormone produced by arcuate nucleus of the hypothalamus and controls the release of gonadotropins FSH and LH from pituitary cells of three types: FSH-, LH – and FSH / LH-gonadotrofnyh cells. Secretion of GnRH pulse frequency, which selectively regulates gonadotropin gene transcription is one mechanism for production of two different hormones.
Chemical structure and pharmacokinetics Lupron Injection
A. Structure. GnRH decapeptide found in all mammals. In medical applications using synthetic GnRH. Analogs of the hormone (leuprolide, nafarelin, buserelin, goserelin and gistrelin) containing D-amino acid at position 6 and etilamidzameschayuschy glycine at position 10, more active and have a longer duration of action than native GnRH.
B. Absorption, metabolism and excretion. GnRH is administered intravenously and subcutaneously. Analogues of GnRH can be administered subcutaneously, intramuscularly, or by nasal spray. The half-life of intravenous GnRH is 4 minutes, by subcutaneous or intranasal administration counterparts – 3:00. Failure occurs in the hypothalamus and pituitary. Analogues of GnRH have an increased affinity for its receptor and to a lesser extent exposed to destruction.
Pharmacodynamics Lupron Injection
GnRH binds to receptors on pituitary gonadotropotsitah. Periodic bolus intravenous injection of the hormone every 1-4 hours stimulates the secretion of FSH and LH. In contrast, prolonged administration of GnRH or its analogs in the appointment of long-acting forms inhibits the release of gonadotropins.
Clinical Pharmacology Lupron Injection
A. Use in the diagnosis
Delayed sexual maturation of adolescents with gipogonadotropizmom may be a consequence of constitutional delay or hypogonadotropic hypogonadism. The reaction of LH (but not FSH) in response to GnRH administration allows to distinguish between these two states. LH levels measured in serum before and after 15, 30, 45, 60 and 120 minutes after intravenous or subcutaneous bolus injection of 100 micrograms GnRH. Peak concentrations of LH exceeding 6.15 IU / ml is normal and indicates the maturity, while the reduced LH-response indicates gipogonadotrop-ny hypogonadism, which is a consequence of the disease the pituitary or hypothalamus.
B. Therapeutic use
1. Stimulation. GnRH can stimulate the pituitary function, and hypogonadotropic hypogonadism is used for both sexes, delayed puberty and cryptorchidism. The system for intravenous GnRH was approved by the FD A in the 1990 kit, which contains a programmable pump and a battery-powered intravenous cannula allows “pulsing” the introduction of GnRH every 90 minutes during the follicular phase and luteal phase.
2. Suppression. Leuprolide, nafarelin, and goserilin gistrelin are GnRH-like agonists that are under long-term administration causes biochemical castration in adults with prostate cancer, uterine fibrosis, endometriosis, polycystic ovaries and premature puberty in children. Many programs for in vitro fertilization at first GnRH analogues are used to suppress the release of endogenous gonadotropins, and then exogenous gonadotropins to synchronize the maturation of the follicles.
GnRH analogues therapy to suppress the pituitary gland leads to a temporary increase in the concentration of sex hormones during the first two weeks of treatment. It can be harmful in the treatment of certain diseases such as prostate cancer. Currently being studied several analogs of GnRH antagonists. These substances cause an immediate suppression of pituitary function after complete blockade of receptors.
Dosing Lupron Injection
Recommended for leuprolide dose – 1 mg per day subcutaneously (Lupron) or 7.5 mg / month intramuscular injection (Lupron Depot) in prostate cancer, or 3.75 mg / month intravenously with endometriosis. Nafarelin administered as an aerosol of one or two doses (200 mcg / dose) intranasally twice a day. Goserelin is administered from a pre-filled syringe in the form of subcutaneous implants at a dose of 3.6 mg every 28 days. Gistrelin administered subcutaneously at a dose of 10 mg / kg daily.
Gonadorelin administered intravenously at a dose of 5 mg every 90 minutes during the 14-21 days prior to ovulation, otherwise the dose is increased. The corpus luteum may persist for 14 days by introducing a series of injections gonadorelina or human chorionic gonadotropin (hCG). Necessary to change the place of intravenous and ultrasonic method to investigate pelvic area.
Side Effect Lupron Injection
GnRH is used for diagnostic purposes, rarely causes headaches, abdominal discomfort or flushing to the face. Analogues of GnRH may significantly enhance bone pain in patients with prostate cancer and cause hot flashes in patients of both sexes. Their use in women should be limited to six months due to the risk of osteoporosis. Intravenous GnRH to ovulation, the call results in less ovarian hyperstimulation and multiple pregnancy than the use of human menopausal gonadotropin.
