Willard H Dere

Selective Estrogen Receptor Modulators: An Alternative to Hormone Replacement Therapy

Abstract Estrogen is a key regulatory hormone, which in addition to its role in reproduction, affects a number of physiological systems, including the skeleton and cardiovascular system. The important role of estrogen in various tissues is perhaps most evident in postmenopausal women who, in addition to menopausal symptoms, experience increases in osteoporosis and coronary heart disease as their estrogen levels decline. Estrogen replacement, while effective against osteoporosis and heart disease, produces a number of side effects associated with the breast and uterus which limits compliance. Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, produce beneficial estrogen-like effects on bone and lipid metabolism, while antagonizing estrogen in reproductive tissue. SERMs can be distinguished from each other in reproductive tissue, particularly the uterus, by their activity profile. For example, while triphenylethylenes like tamoxifen behave as partial agonists, raloxifene (a benzothiophene) behaves as a complete antagonist in the uterus. The SERM profile is distinct from that of full estrogens (i.e. 17β-estradiol or 17α-dihydro-equilenin) which behave as estrogen agonists in all tissues and pure estrogen antagonists (i.e. IC1-164,384) which exhibit only an estrogen antagonist profile in a battery of tissue types. The precise mechanism by which SERMs produce this tissue-selective pharmacology remains a question. It is clear, however, that for raloxifene, both the estrogen agonist effects on bone and cholesterol metabolism as well as the estrogen antagonist effects in uterine and mammary tissue involve high affinity interaction with the estrogen receptor. The estrogen antagonist activity is mediated via classical pharmacological competition for estrogen receptor binding. The estrogen agonist activity, in bone for example, appears to involve novel post-receptor pathways and non-classical estrogen response element(s) which are activated by SERMs. These novel response elements may represent natural pathways which respond to estrogen metabolites in vivo.

Acute bronchitis: Results of U.S. and European trials of antibiotic therapy

Abstract Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection. It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain. Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics. Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral β-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin. Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents. Loracabef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate. Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis.