PERGHH SERAMNYA..!!!INILAH DIA Respon Bekas Suami Sari Yanti Kepada Sari Selepas 1 Jam Disatukan Dengan Pelawak Jep Yang Buatkan sari yanti TERGAMAM ! ?

PERGHH SERAMNYA..!!!INILAH DIA Respon Bekas Suami Sari Yanti Kepada Sari Selepas 1 Jam Disatukan Dengan Pelawak Jep Yang Buatkan sari yanti TERGAMAM ! ?

TERKINI-INILAH DIA Respon Bekas Suami Sari Yanti Kepada Sari Selepas 1 Jam Disatukan Dengan Pelawak Jep Yang Buatkan sari yanti TERGAMAM ! ?

Some anti-obesity drugs can have severe, even, lethal side effects, fen-phen being a famous example. Fen-phen was reported through the FDA to cause abnormal echocardiograms, heart valve problems, and rare valvular diseases.^[48] One of, if not the first, to sound alarms was Sir Arthur MacNalty, Chief Medical Officer (United Kingdom). As early as the 1930s, he warned against the use of dinitrophenol as an anti-obesity medication and the injudicious and/or medically unsupervised use of thyroid hormone to achieve weight reduction.^[49][50] The side effects are often associated with the medication's mechanism of action. In general, stimulants carry a risk of high blood pressure, faster heart rate, palpitations, closed-angle glaucoma, drug addiction, restlessness, agitation, and insomnia.

Another drug, orlistat, blocks absorption of dietary fats, and as a result may cause oily spotting bowel movements (steatorrhea), oily stools, stomach pain, and flatulence.^[51] A similar medication designed for patients with Type 2 diabetes is Acarbose; which partially blocks absorption of carbohydrates in the small intestine, and produces similar side effects including stomach pain and flatulence.^[52]

The limitation of - or knowledge gap concerning - drugs for obesity is that we do not fully understand the neural basis of appetite and how to modulate it. Appetite is clearly a very important instinct to promote survival.

Because the human body uses various chemicals and hormones to protect its stores of fat (a reaction probably useful to our ancestors when food was scarce in the past,) there has not yet been found a 'silver bullet', or a way to completely circumvent this natural habit of protecting excess food stores.

In order to circumvent the number of feedback mechanisms that prevent most monotherapies from producing sustained large amounts of weight loss, it has been hypothesized that combinations of drugs may be more effective by targeting multiple pathways and possibly inhibiting feedback pathways that work to cause a plateau in weight loss. This was evidenced by the success of the combination of phentermine and fenfluramine or dexfenfluramine, popularly referred to phen-fen, in producing significant weight loss but fenfluramine and dexfenfluramine were pulled from the market due to safety fears regarding a potential link to heart valve damage. The damage was found to be a result of activity of fenfluramine and dexfenfluramine at the 5-HT2B serotonin receptor in heart valves. Newer combinations of SSRIs and phentermine, known as phenpro, have been used with equal efficiency as fenphen with no known heart valve damage due to lack of activity at this particular serotonin receptor due to SSRIs. There has been a recent resurgence in combination therapy clinical development with the development of 3 combinations: Qsymia (topiramate + phentermine), Empatic (bupropion + zonisamide) and Contrave (bupropion + naltrexone).

Other classes of drugs in development include lipase inhibitors, similar to orlistat. Another lipase inhibitor, called GT 389-255, was being developed by Peptimmune^[53] (licensed from Genzyme). This was a novel combination of an inhibitor and a polymer designed to bind the undigested triglycerides therefore allowing increased fat expulsion without side effects such as oily stools that occur with orlistat. The development stalled as Phase 1 trials were conducted in 2004 and there was no further human clinical development afterward. In 2011, Peptimmune filed for Chapter 7 Liquidation.^[54]

Another potential long-term approach to anti-obesity medication is through the development of ribonucleic acid interference (RNAi). Animal studies have illustrated that the deletion of the RIP140 gene in mice by genetic knockdown results in the lack of fat accumulation, even when mice are fed a high fat diet.^[55] Similarly, another nuclear hormone receptor co-repressor, SMRT, has demonstrated an opposing effect in genetically engineered mice. Dr. Russell Nofsinger and Dr. Ronald Evans of the Salk Institute showed that disruption of the molecular interaction between SMRT and their nuclear hormone receptor partners leads to increased adiposity and a decreased metabolic rate.^[56] These studies suggest that new drugs targeting the molecular interaction between nuclear hormone receptors and their regulatory cofactors could provide a useful new category of therapeutic targets to be developed in an effort to control obesity.

Another approach is to induce a sense of satiety by occupying space in the gastric and intestinal cavities. One clinical trial involves a hydrogel (Gelesis) made of indigestible, food-grade materials.^[57] Another pilot study uses pseudobezoars.^[58]