The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK—carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity

Diagnosis and Treatment of Benign Prostatic Hyperplasia Practice Patterns of Primary Care Physicians

To define primary care physicians’ (PCPs) practices in managing patients with benign prostatic hyperplasia (BPH), and to compare these practices to portions of the Agency for Health Care Policy and Research BPH guideline and urologists’ practices. DESIGN: Mail survey. P ARTICIPANTS: Nationwide random sample of PCPs and urologists, selected from the American Medical Association Registry. METHODS: Initial mailing, postcard reminder, second mailing, telephone reminder, final mailing. MAIN RESULTS: Primary care physicians ( n = 444, response = 51%) reported seeing a median of 35 patients with BPH over the preceding year, in contrast to 240 for urologists ( n = 394, response = 68%). Regarding tests recommended by the guideline, two thirds of PCPs reported rarely or never using the American Urological Association (AUA) symptom index, nearly all reported routinely performing digital rectal examinations, and many (66%) reported routinely ordering tests to determine the serum creatinine level. Although considered “optional” by the guideline, more than 90% of PCPs reported routinely ordering a prostate-specific antigen test, while infrequently using other optional tests. Regarding “not recommended” studies, a substantial minority reported selectively or routinely ordering intravenous pyelography (34%) and renal ultrasound (33%), while two thirds reported rarely or never ordering these tests. Eighty-six percent of PCPs reported prescribing medications for BPH over the preceding year; α blockers to a median of 12 patients, and finasteride to a median of 2. Variation in urology referral thresholds was suggested in responses to two patient scenarios. CONCLUSIONS: Primary care physicians are actively managing patients with BPH. Some of their diagnostic evaluations vary from the recommendations of a national guideline and urologists’ practices. Referral thresholds appear to vary considerably. KEY WORDS: prostatic hyperplasia; primary care physicians; practice patterns; practice guideline.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72635/1/j.1525-1497.1997.012004224.x.pd