Food and Drug Administration Regulation of Drugs That Raise Blood Pressure
Although it is recognized that a systolic blood pressure (SBP) increase ≥2 mm Hg or a diastolic blood pressure (DBP) increase ≥1 mm Hg increases the risk of heart attacks and strokes in middle-aged adults, the Food and Drug Administration (FDA) lacks an adequate policy for regulating medications that increase blood pressure (BP). Some FDA reviewers consider a clinically significant increase in BP to occur only if a drug raises SBP ≥20 mm Hg or if a drug raises DBP ≥10 to 15 mm Hg. In recent years, numerous drugs have been regulated or taken off the market due to cardiovascular safety concerns. The list includes...
Source: Journal of Cardiovascular Pharmacology and Therapeutics - December 8, 2014 Category: Cardiology Authors: Blankfield, R. P., Iftikhar, I. H. Tags: Editorials Source Type: research
Antiobesity drugs in early pregnancy and congenital malformations in the offspring
Publication date: November–December 2014 Source:Obesity Research & Clinical Practice, Volume 8, Issue 6 Author(s): Bengt A.J. Källén Little information exists on the possible teratogenic effect of modern antiobesity drugs. The present study refers to orlistat, sibutramine, and rimonabant. Data in the Swedish Medical Birth Register were utilised. During the years 1998–2011, among 392,126 infants born, 509 had been exposed to antiobesity drugs in early pregnancy: 248 to orlistat, 242 to sibutramine, 12 to rimonabant, 13 to unspecified antiobesity drugs. Simultaneous use of orlistat and sibutramine occurred...
Source: Obesity Research and Clinical Practice - December 7, 2014 Category: Eating Disorders and Weight Management Source Type: research
Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome.
CONCLUSIONS: Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PCOS. The reduction in circulating androgens during metformin and sibutramine treatment might be implicated in this decline.
PMID: 24457404 [PubMed - indexed for MEDLINE] (Source: Hormones)
Source: Hormones - December 2, 2014 Category: Endocrinology Tags: Hormones (Athens) Source Type: research
Enantioselective N-Demethylation and Hydroxylation of Sibutramine in Human Liver Microsomes and Recombinant Cytochrome P-450 Isoforms
(Source: Journal of Toxicology and Environmental Health Part A)
Source: Journal of Toxicology and Environmental Health Part A - October 27, 2014 Category: Environmental Health Authors: ShindeKimJeongKimLeeShinKim Source Type: research
Pharmacological Strategies to Counteract Antipsychotic-Induced Weight Gain and Metabolic Adverse Effects in Schizophrenia: A Systematic Review and Meta-analysis
Conclusion: When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia. (Source: Schizophrenia Bulletin)
Source: Schizophrenia Bulletin - October 10, 2014 Category: Psychiatry Authors: Mizuno, Y., Suzuki, T., Nakagawa, A., Yoshida, K., Mimura, M., Fleischhacker, W. W., Uchida, H. Tags: Regular Article Source Type: research
Associations between the GNB3 C825T polymorphism and obesity-related metabolic risk factors in Korean obese women
Conclusions
The GNB3 825T polymorphism is significantly associated with greater visceral fat and higher serum lipids in Korean obese women and it suggests that the GNB3 C825T is a determinant of obesity-related metabolic traits in this population. (Source: Journal of Endocrinological Investigation)
Source: Journal of Endocrinological Investigation - October 4, 2014 Category: Endocrinology Source Type: research
The Effect of Sibutramine, a Serotonin-Norepinephrine Reuptake Inhibitor, on Platelets and Fibrin Networks of Male Sprague-Dawley Rats: A Descriptive Study.
Abstract
Abstract Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated...
Source: Ultrastructural Pathology - September 5, 2014 Category: Pathology Authors: van der Schoor C, Oberholzer HM, Bester MJ, van Rooy MJ Tags: Ultrastruct Pathol Source Type: research
Tolerability and Safety of the New Anti-Obesity Medications
Abstract
Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phen...
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research
Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?
Authors: Antel J, Albayrak O, Heusch G, Banaschewski T, Hebebrand J
Abstract
With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe afte...
Source: European Archives of Psychiatry and Clinical Neuroscience - August 26, 2014 Category: Psychiatry Tags: Eur Arch Psychiatry Clin Neurosci Source Type: research
Pharmacogenetics of Obesity Drug Therapy.
Abstract
As the prevalence and severity of obesity and its complications have risen significantly in worldwide populations, behavioral interventions alone have been inconsistent in promoting sufficient, sustained weight loss. Consequently, there has been intense interest in the development of anti-obesity medications as treatment strategies. When coupled with structured lifestyle modifications, pharmacotherapy can enhance weight loss. While less efficacious than bariatric surgery, drug therapy may be an alternative to surgery for some obese patients, and is an emerging strategy for weight maintenance. The ...
Source: Current Molecular Medicine - August 11, 2014 Category: Molecular Biology Authors: Guzman AK, Ding M, Xie Y, Martin KA Tags: Curr Mol Med Source Type: research
Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit
Abstract
Obesity is a major correlate of cardiovascular disease. Weight loss improves cardiovascular risk factors and has the potential to improve outcomes. Two drugs, phentermine plus topiramate and lorcaserin, have recently been approved by the US Food and Drug Administration for the indication of obesity; a third, bupropion plus naltrexone, is under consideration for approval. In clinical trials, these drugs cause weight loss and improve glucose tolerance, lipid profile, and, with the exception of bupropion plus naltrexone, blood pressure. However, their effect on cardiovascular outcomes is unknown. In defining appropri...
Source: Clinical Cardiology - August 1, 2014 Category: Cardiology Authors: Jonathan W. Cunningham, Stephen D. Wiviott Tags: Reviews Source Type: research
Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.
Abstract
The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake w...
Source: Diabetes Metab - July 28, 2014 Category: Endocrinology Authors: Vickers SP, Cheetham SC, Headland KR, Dickinson K, Grempler R, Mayoux E, Mark M, Klein T Tags: Diabetes Metab Syndr Obes Source Type: research
Role of hepatic blood flow and metabolism in the pharmacokinetics of ten drugs in lean, aged and obese rats.
Abstract
Abstract 1. The effect of age and obesity on the pharmacokinetics (PK), hepatic blood flow (HBF) and liver metabolism of 10 compounds was determined in rats. The animals fed a high-fat diet were defined as the diet-induced obese (DIO) group, while the animals that were aged similar to the DIO rats but not fed with high-fat diet were called the age-matched (AM) group. 2. The clearance (CL) values of high CL compounds (CL > 50 mL/min/kg, namely propranolol, diazepam, phenytoin, ethinylestradiol, lorcaserin and fenfluramine) decreased significantly (1.5- to 6-fold) in DIO and AM rats as ...
Source: Xenobiotica - June 20, 2014 Category: Research Authors: Subramanian M, Kurawattimath V, Pocha K, Freeden C, Rao I, Thanga Mariappan T, Marathe PH, Vikramadithyan RK, Abraham P, Kulkarni CP, Katnapally P, Nutakki R, Paruchury S, Bhutani P, Mandlekar S Tags: Xenobiotica Source Type: research
Dopamine reuptake transporter (DAT) "inverse agonism" - A novel hypothesis to explain the enigmatic pharmacology of cocaine.
We describe the experimental findings which suggest cocaine serves as a negative allosteric modulator to alter the function of the dopamine reuptake transporter (DAT) and reverse its direction of transport. This results in a firing-dependent, retro-transport of dopamine into the synaptic cleft. The proposed mechanism of cocaine is, therefore, different from other small molecule negative allostereric modulators of the monoamine reuptake transporters, eg SoRI-6238, which merely reduce the rate of inward transport. Because the physiological role of DAT is to remove dopamine from the synapse and the action of cocaine is the op...
Source: Neuropharmacology - June 19, 2014 Category: Drugs & Pharmacology Authors: Heal DJ, Gosden J, Smith SL Tags: Neuropharmacology Source Type: research
Influence of acute treatment with sibutramine on the sympathetic neurotransmission of the young rat vas deferens.
In conclusion, we showed that the acute treatment with sibutramine in young rats was able to affect the peripheral sympathetic nervous system by inhibition of noradrenaline uptake and reduction of the neuronal content of this neurotransmitter, leading to an enhancement of vas deferens sensitivity to noradrenaline.
PMID: 24886880 [PubMed - as supplied by publisher] (Source: European Journal of Pharmacology)
Source: European Journal of Pharmacology - May 30, 2014 Category: Drugs & Pharmacology Authors: Souza BP, Júnior ED, Jurkiewicz A, Jurkiewicz NH Tags: Eur J Pharmacol Source Type: research
