Flumazenil (also known as flumazepil, code name Ro 15-1788) is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (particularly in cases of overdose), through competitive inhibition. It was first characterized in 1981, and was first marketed in 1987 by Hoffmann-La Roche under the trade name Anexate. However, it did not receive FDA approval until December 20, 1991. The developer lost its exclusive patent rights in 2008; so at present, generic formulations of this drug are available. Intravenous flumazenil is primarily used to treat benzodiazepine overdoses and to help reverse anesthesia. Administration of flumazenil by sublingual lozenge and topical cream has also been tested. Medical uses
Flumazenil benefits patients who become excessively drowsy after use of benzodiazepines for either diagnostic or therapeutic procedures.The drug has been used as an antidote in the treatment of benzodiazepine overdoses. It reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine (BZ) recognition site on the GABA/benzodiazepine receptor complex. There are many complications that must be taken into consideration when used in the acute care setting. These include lowered seizure threshold, agitation, and anxiousness. Flumazenils short half-life requires multiple doses. Because of the potential risks of withdrawal symptoms and the drugs short half-life, patients must be carefully monitorered to prevent recurrence of overdose symptoms or adverse side effects. Flumazenil is also sometimes used after surgery to reverse the sedative effects of benzodiazepines.
Early puberty
Anastrozole is used at a dosage of 0.5 to 1 mg/day in combination with the antiandrogen bicalutamide in the treatment of peripheral precocious puberty, for instance due to familial male-limited precocious puberty (testotoxicosis) and McCune–Albright syndrome, in boys. Available forms
Anastrozole is available in the form of 1 mg oral tablets. No alternative forms or routes are available. Contraindications
Contraindications of anastrozole include hypersensitivity to anastrozole or any other component of anastrozole formulations, pregnancy, and breastfeeding. Hypersensitivity reactions to anastrozole including anaphylaxis, angioedema, and urticaria have been observed. Side effects
Common side effects of anastrozole (≥10% incidence) include hot flashes,
asthenia, arthritis, pain, arthralgia, hypertension, depression, nausea and vomiting, rash, osteoporosis, bone fractures, back pain, insomnia, headache, bone pain, peripheral edema, coughing, dyspnea, pharyngitis, and lymphedema. Serious but rare adverse effects (<0.1% incidence) include skin reactions such as lesions, ulcers, or blisters; allergic reactions with swelling of the face, lips, tongue, and/or throat that may cause difficulty swallowing or breathing; and abnormal liver function tests as well as hepatitis. Interactions
Anastrozole is thought to have clinically negligible inhibitory effects on the cytochrome P450 enzymes CYP1A2, CYP2A6, CYP2D6, CYP2C8, CYP2C9, and CYP2C19. As a result, it is thought that drug interactions of anastrozole with cytochrome P450 substrates are unlikely. No clinically significant drug interactions have been reported with anastrozole as of 2003.Anastrozole does not affect circulating levels of tamoxifen or its major metabolite N-desmethyltamoxifen. However, tamoxifen has been found to decrease steady-state area-under-the-curve levels of anastrozole by 27%.