Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.
 ...
PMID:Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss. 1020 59

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.
 ...
PMID:Pharmacologic options for the treatment of obesity. 1147 77

According to international surveys, the appetite suppressant phentermine has frequently been seized although its approval has been withdrawn in Germany. Phentermine is an isomer of methamphetamine though is not optically active such as e. g. amphetamine. The drug acts as a potent substrate at the norepinephrine transporter simultaneously promoting its release; it has a weaker activity at the dopamine transporter whereas its activity towards the serotonin transporter is negligible. Overall, its pharmacological action is comparable to that of amphetamine albeit less strong. Due to its declining effect with time and its addiction potential it has been recommended that phentermine should be used for a few weeks only. Phentermine hydrochloride is a readily soluble salt; absorption of the resinate compound is considerably slower. The drug is not extensively biotransformed; p- and N-hydroxyphentermine are the primary metabolites also being excreted as glucuronide conjugates. Gas chromatographic techniques to identify and to quantify phentermine in biological specimens are applicable following derivatization; however, liquid chromatography coupled to mass spectrometry is currently preferred for analysis of urine, serum or hair. Short-term clinical studies having been performed in the 80s and 90s revealed no serious harmful side effects. However, there are case reports proposing that phentermine usage might be associated with severe health risks due to hypertension, vasoconstriction and vasculopathy; in some individuals, mental illness had been observed. Apart from the legal consequences following purchase of drugs that have been withdrawn its user will simultaneously run serious and unpredictable health risks.
 ...
PMID:[Phentermine--a "weighty" or a dangerous substance?]. 2367 25

The prevalence and severity of obesity has increased markedly in recent decades making it a global public health concern. Since obesity is a potential risk factor in the development of hypertension, type-2 diabetes, cardiovascular diseases, infertility, etc., it is no more viewed as a cosmetic issue. Currently, only a few FDA-approved anti-obesity drugs like Orlistat, Lorcaserin and Phentermine-topiramate are available in the market, but they have considerable side effects. On the other hand, bariatric surgery as an alternative is associated with high risk and expensive. In view of these there is a growing trend towards natural product-based drug intervention as one of the crucial strategies for management of obesity and related ailments. In Asian traditional medicine and Ayurvedic literature a good number of plant species have been used and quoted for possible lipid-lowering and anti-obesity effects; however, many of them have not been evaluated rigorously for a definite recommendation and also lack adequate scientific validation. This review explores and updates on various plant species, their used parts, bioactive components and focuses multiple targets/pathways to contain obesity which may pave the way to develop novel and effective drugs. We also summarised different drugs in use to treat obesity and their current status. Nature is future promise of our wellbeing.
 ...
PMID:A review on possible therapeutic targets to contain obesity: The role of phytochemicals. 2674 Apr 73