Hyperstimulation

The molecular pathology of the (3-cell destruction in the course of insulin resistance is largely unknown. It has been suggested that the constant hyperstimulation of the (3-cell by glucose ( glucose toxicity ) or elevated fatty acids ( lipotoxicity ) may lead to cell damage. 

Hyperstimulation of the uterus during labor may lead to uterine Many with marked impairment of the uteroplacental blood flow, uterine rupture, cervical rupture, amniotic fluid embolism, and trauma to the infant. Overstimulation of the uterus is dangerousto both the fetusand the mother and may occur even when the drug is administered properly in a uterus that is hypersensitive to oxytocin. 

Systematic review concludes that misoprostol shows greater efficacy versus dinoprostone, but this benefit is offset by a greater incidence of side effects.46 Compared with dinoprostone, misoprostol is associated with a higher incidence of uterine hyperstimulation, alterations in fetal heart rate, and fetal distress.46 Misoprostol also has been associated with uterine rupture in patients with previous delivery by cesarean section and should be avoided in this population.44... 

De, L. A., MontaneUi, L., Van, D. J., et al. (2006) Presence and absence of foUicle-stimulating hormone receptor mutations provide some insights into spontaneous ovarian hyperstimulation syndrome physiopathology. J. Clin. Endocrinol. Metab. 91, 555-562. 

Pharmacokinetics Dimenhydrinate has a depressant action on hyperstimulated labyrinthine function. The precise mode of action is not known. The antiemetic effects are believed to be caused by the diphenhydramine, an antihistamine also used as an antiemetic agent. 

Labor and delivery - Misoprostol can induce or augment uterine contractions. A major adverse effect of the obstetrical use of misoprostol is hyperstimulation of the uterus, which may progress to uterine tetany with marked impairment of uteroplacental blood flow, uterine rupture (requiring surgical repair, hysterectomy, and/or salpingo-oophorectomy), or amniotic fluid embolism. 

Gonadotropins are used to treat infertility in women with potentially functional ovaries who have not responded to other treatments. The therapy is designed to simulate the normal menstrual cycle as far as is practical. A common protocol is daily injections of menotropins for 9 to 12 days, until estradiol levels are equal to that in a normal woman, followed by a single dose of hCG to induce ovulation. Two problems with this treatment are risks of ovarian hyperstimulation and of multiple births. Ovarian hyperstimulation is characterized by sudden ovarian enlargement associated with an increase in vascular permeability and rapid accumulation of fluid in peritoneal, pleural, and pericardial cavities. To prevent such occurrences, ovarian development is monitored during treatment by ultrasound techniques and by measurements of serum levels of estradiol. 

Serious or life-threatening allergic reaction characterized by hallucinations, hematuria, hyperstimulation after withdrawal, severe lower extremity edema, and parkinsonism. 

Recommended dosage and monitoring requirements According to Micromedex, the usual starting dose of Follistim is 150 to 225 lU per day injected intramuscularly or subcutaneously, adjusted accordingly on an individual basis. The initial dose of 75 lU per day for 7 to 14 days is employed in anovulatory women who have not responded to clomiphene citrate treatment. The initial dose of 150 lU per day, followed by a maintenance dose of 75 to 375 lU per day for 6 to 12 days, is employed for controlled ovarian hyperstimulation followed by assisted reproduction. 

G. Other applications Limited data show some beneficial effects of leuprolide in the treatment of breast cancer. According to Micromedex, there is good documentation that leuprolide is effective for bowel pain and nausea associated with irritable bowel syndrome. Leuprolide has been used for controlled ovarian hyperstimulation to enhance the in vitro fertilization-embryo transfer procedure. In endometriosis, the goal of treatment is pain relief and reduction of endometriotic lesions. In children with central precocious puberty, stimulated and basal gonadotropins are reduced to prepubertal levels. Testosterone and estradiol are reduced to prepubertal levels in males and females, respectively. 

Indications Inhibition of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation... 

Drug interactions Co-administration of dinoprostone in patients receiving intravenous oxytocic agents such as oxytocin may result in uterine hyperstimulation and is therefore contraindicated. Severe hypertension has been reported when oxytocin was given 3 to 4 hours following prophylactic administration of a vasoconstrictor in conjunction with spinal anesthesia. Oxytocin may enhance the neuromuscular blockade of succinylcholine. 

Inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation NA Af-acetyl-3-(2- naphthyl)-D- alanyl-4-chloro-D- phenylalanyl-3-(3- pyridyl)-D-alanyl-L- seryl-L-tyrosyl-9 N 9, AflO-diethyl-D- NA... 

FSH, LH, and hCG are commercially available in several forms. They are used in states of infertility to stimulate spermatogenesis in men and to induce ovulation in women. Their most common clinical use is for the controlled ovulation hyperstimulation that is the cornerstone of assisted reproductive technologies such as in vitro fertilization (IVF, see below). 

In women treated with gonadotropins and hCG, the two most serious complications are the ovarian hyperstimulation syndrome and multiple pregnancies. Overstimulation of the ovary during ovulation induction often leads to... 

SUPPRESSION OF GONADOTROPIN PRODUCTION Controlled Ovarian Hyperstimulation... 

Four synthetic decapeptides that function as competitive antagonists of GnRH receptors are available for clinical use. Ganirelix, cetrorelix, abarelix, and degarelix inhibit the secretion of FSH and LH in a dose-dependent manner. Ganirelix and cetrorelix are approved for use in controlled ovarian hyperstimulation procedures, whereas abarelix and degarelix are approved for men with advanced prostate cancer. 

When used for controlled ovarian hyperstimulation, ganirelix and cetrorelix are well tolerated. The most common adverse... 

Follitropin alfa Activates FSH receptors Mimics effects of endogenous FSH Controlled ovulation hyperstimulation in women infertility due to hypogonadism in men SC injection 3-7 x/wk Toxicity Ovarian hyperstimulation syndrome and multiple pregnancies in women gynecomastia in men headache, depression, edema in both sexes... 

Leuprolide Agonist of GnRH receptors Increased LH and FSH secretion with intermittent administration reduced LH and FSH secretion with prolonged continuous administration Ovarian suppression, controlled ovarian hyperstimulation, central precocious puberty advanced prostate cancer Administered IV, SC, IM or intranasally depot formulations are available Toxicity Headache, lightheadedness, nausea, injection site reactions t symptoms of hypogonadism with continuous treatment... 

Ganirelix Blocks GnRH receptors Reduces endogenous production of LH and FSH Prevention of premature LH surges during controlled ovulation hyperstimulation SC injection Toxicity Nausea, headache... 

Emotion Episodically strong Cholinergic hyperstimulation of amygdala and related temporal lobe structures triggers emotional storms which are unmodulated by aminergic restraint... 

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