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Case Reports in Endocrinology 2015Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case...
Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16 mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.
PubMed: 25960894
DOI: 10.1155/2015/917869 -
The European Respiratory Journal Sep 2003Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular... (Review)
Review
Primary pulmonary hypertension (PPH) is characterised by sustained elevations of pulmonary arterial pressure without a demonstrable cause, leading to right ventricular failure and death. Hereditary mutations in the bone morphogenetic protein receptor type II (BMPR2) gene result in familial PPH transmitted as an autosomal dominant trait, albeit with low penetrance. The causes in cases without a BMPR2 mutation are unknown, but a syndrome of pulmonary arterial hypertension (PAH) similar to hereditary PPH is associated with systemic connective tissue disease, congenital heart disease, portal hypertension, and human immunodeficiency virus infection, or with the use of appetite-suppressant drugs. The authors identified a BMPR2 gene mutation in a 27-yr-old female who developed PAH after a short course of the appetite-suppressant drug amfepramone (diethylpropion). This allowed molecular genetic counselling and prevention of potentially harmful drug exposure in the patient's son treated for attention deficit disorder with methylphenidate, an amphetamine-related drug. No BMPR2 mutation was found in four additional, unrelated patients with appetite suppressant-related PPH. The findings provide strong evidence that amfepramone can trigger primary pulmonary hypertension in a bone morphogenetic protein receptor type II gene mutation carrier, and indicate that other genes are probably implicated in genetic susceptibility to appetite suppressants.
Topics: Adult; Appetite Depressants; Attention Deficit Disorder with Hyperactivity; Bone Morphogenetic Protein Receptors, Type II; Diethylpropion; Female; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Methylphenidate; Mutation; Protein Serine-Threonine Kinases; Receptors, Cell Surface
PubMed: 14516151
DOI: 10.1183/09031936.03.00095303 -
British Journal of Pharmacology Aug 1976The tolerance pattern to anorectic drugs was studied in starved rats by measuring two consecutive 2 h food intakes. 2 There was a reduction in the first 2 h food intake... (Comparative Study)
Comparative Study
The tolerance pattern to anorectic drugs was studied in starved rats by measuring two consecutive 2 h food intakes. 2 There was a reduction in the first 2 h food intake with development of complete tolerance after fenfluramine and phenmetrazine, and of partial tolerance after amphetamine, (+)-amphetamine and diethylpropion. 3 During the second 2 h intake, the anorectic effect was transient after fenfluramine and diethylpropion; while there was an absolute increase in the intake after amphetamine and (+)-amphetamine. 4 A pair-feeding experiment revealed that the increase in the second 2 h food intake was not a direct effect of the drug but a consequence of the deficit in food intake during the preceding 2 hours. 5 There was an overall correlation between the food and water intake. 6 A significant loss in body weight was observed after amphetamine, fenfluramine and phenmetrazine but not after (+)-amphetamine or diethylpropion. 7 The results indicate that so-called tolerance to the anorexigenic effect of drugs is apparent rather than real and that the duration of food access is a determining factor. The body weight changes may be brought about by the metabolic effects of these drugs rather than their effect on food and water intake.
Topics: Amphetamine; Animals; Appetite Depressants; Body Weight; Diethylpropion; Drinking; Drug Tolerance; Eating; Fenfluramine; Male; Phenmetrazine; Rats; Time Factors
PubMed: 963336
DOI: 10.1111/j.1476-5381.1976.tb10374.x -
British Medical Journal Jun 1968
Clinical Trial
Topics: Appetite Depressants; Clinical Trials as Topic; Diethylpropion; Fenfluramine; Humans; Phenethylamines; Placebos; Sleep; Substance-Related Disorders
PubMed: 4881584
DOI: 10.1136/bmj.2.5604.559-a -
British Medical Journal Aug 1974
Topics: 17-Ketosteroids; Adult; Depression, Chemical; Diethylpropion; Estrogens; Estrone; Gynecomastia; Humans; Hypothalamus; Luteinizing Hormone; Male; Spironolactone; Stimulation, Chemical
PubMed: 4414195
DOI: 10.1136/bmj.3.5929.520-b -
The European Respiratory Journal Jun 2016Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined...
Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment.
Topics: Adult; Aged; Antihypertensive Agents; Bosentan; Diethylpropion; Drug Therapy, Combination; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Patient Safety; Phenylpropionates; Pyridazines; Retrospective Studies; Severity of Illness Index; Sildenafil Citrate; Sulfonamides; Tadalafil; Time Factors; Treatment Outcome
PubMed: 26989105
DOI: 10.1183/13993003.02043-2015 -
Canadian Medical Association Journal Feb 1977
Topics: Adult; Appetite Depressants; Diethylpropion; Female; Humans; Middle Aged; Obesity; Phentermine; Psychoses, Substance-Induced
PubMed: 844014
DOI: No ID Found -
International Journal of Obesity (2005) Mar 2018Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care...
OBJECTIVE
Obesity is now the most prevalent chronic disease in the United States, which amounts to an estimated $147 billion in health care spending annually. The Affordable Care Act (ACA) enacted in 2010 included provisions for private and public health insurance plans that expanded coverage for lifestyle/behavior modification and bariatric surgery for the treatment of obesity. Pharmacotherapy, however, has not been included despite their evidence-based efficacy. We set out to investigate the coverage of Food and Drug Administration-approved medications for obesity within Medicare, Medicaid and ACA-established marketplace health insurance plans.
METHODS
We examined coverage for phentermine, diethylpropion, phendimetrazine, Benzphentamine, Lorcaserin, Phentermine/Topiramate (Qysmia), Liraglutide (Saxenda) and Buproprion/Naltrexone (Contrave) among Medicare, Medicaid and marketplace insurance plans in 34 states.
RESULTS
Among 136 marketplace health insurance plans, 11% had some coverage for the specified drugs in only nine states. Medicare policy strictly excludes drug therapy for obesity. Only seven state Medicaid programs have drug coverage.
CONCLUSIONS
Obesity requires an integrated approach to combat its public health threat. Broader coverage of pharmacotherapy can make a significant contribution to fighting this complex and chronic disease.
Topics: Anti-Obesity Agents; Humans; Medicaid; Medicare; Obesity; Patient Protection and Affordable Care Act; Prescriptions; United States
PubMed: 29151591
DOI: 10.1038/ijo.2017.287 -
Journal of Neurophysiology Jul 2015Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These...
Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds.
Topics: Action Potentials; Animals; Appetite Depressants; Benzazepines; Bupropion; Diethylpropion; Dopamine D2 Receptor Antagonists; Drug Interactions; Eating; Locomotion; Male; Nucleus Accumbens; Phentermine; Raclopride; Random Allocation; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, Dopamine D2; Sleep Initiation and Maintenance Disorders; Stereotyped Behavior; Weight Loss
PubMed: 25972577
DOI: 10.1152/jn.00012.2015 -
British Medical Journal Nov 1968
Topics: Amphetamine; Depression; Diethylpropion; Drug and Narcotic Control; Humans; Obesity; Phenmetrazine; Psychoses, Substance-Induced; Substance-Related Disorders
PubMed: 5722324
DOI: No ID Found