Farmacos For the obesity?

The farmacological treatment of the obesity has to consider when it can not attain a loss of weight of 10% with the therapy of diet and the physical activity.


The effective medicines in the treatment of the obesity can act by different mechanisms such as the reduction of the consumption of foods, the inhibition of the absorption of fats, the increase of the termogénesis and the stimulation of the apoptosis of the adipocytes. At present, only we have two medicines commercialised for the treatment of the obesity.
So that the treatment of the obesity was successful, the patient has to accept continue the medical treatment and the therapy of exercises, as well as the treatment with medicines and the examinations and examinations of regular health.

Farmaco With sibutramina is an inhibidor of the recaptación of norepinefrina, dopamine and serotonin that inhibits the consumption of foods and increases the termogénesis.
The administration of sibutramina during a year can induce a loss of weight of the 4-7%.
The secondary effects are hipertensión, headache, sleeplessness and constipation. Orlistat Is an inhibidor of the pancreatic lipase that it can block the absorption of 30% of the fat ingerida. His administration induces the loss of weight and the reduction of the recovery ulterior of the weight.

Besides, this medicine improves the dislipidemia hipertensiva and help to warn the diabetes in 52% of the cases when it administers during four years.
The increase in the frequency of the depositions and the interference with the absorption of vitamins are his main secondary effects.
The similar peptide to the glucagón 1, that increases the sensitivity to the insulin and the satiety, the adiponectina and the agonistas of PPAR-gamma that reduce the resistance to the insulin and modulates the generation of adipocytes are the base of future therapeutic approaches of the obesity.
The inhibidores of the fosfatasa induce the phosphorylation of PPAR-gamma and the expression of UCP-1 that drives to an increase of the termogénesis and the reduction of the appetite. .

The obesity is a chronic illness that causes a big morbilidad and premature death to world-wide level.
The current farmacological treatments are not totally acceptable because of his little security and efficiency.
The obesity also associates with other grave complications, as diabetes mellitus, hipertensión, hiperlipidemia, hipercolesterolemia, cardiovascular illnesses, etc.

Because of his complex nature, exists the need of a farmacological treatment on a long-term basis safe and effective. An approach of treatment is not sufficient to administer the complex pathological circuit of the obesity. Recently, they have proposed several new aims that control the energetic homeostasis and warn the obesity.
Although the newest medicines are very far of the clinical use, the hope to realise investments of investigation to date is the translation to a safe farmacological treatment and effective in the future.

Farmacological treatment of the obesity?

The obesity now presents one of the greater problems of health of our time.
The diet and the exercise are better so much for the prevention as for the treatment; unfortunately, both require a lot of discipline and are difficult to keep.

The medicines offer a possible complement, but his effect is modest, are limited by the secondary effects and the loss of hard weight only while it takes the medicine, since so prompt as it interrupts the treatment, recovers the weight.

The farmaco sibutramina, a medication simpaticomimética that was available for the treatment on a long-term basis, is the most recent of the drugs that will withdraw of the market because of the secondary effects; in this case, it went a greater risk of cardiovascular events.
This document reviews the medicines that are available for the treatment of the obesity, included many of the recently take# out of the market.
Also it analyses some of the newest treatments that are investigating at present.

Although the obesity has been labelled like an illness by more than 200 years, only recently has recognised like a condition that deserves medical attention. This is especially some dice the increasing data on the correlation between the obesity and the diabetes type 2, the hipertensión, the dislipidemia, the cardiovascular illnesses, the accidents cerebrovasculares and the depression.

The obesity associates with osteoartritis, obstructive apnoea of the dream, increase of the risk of cancer and hepatic illness fat no alcoholic.
It is related with a variety of other complications, like the illness by backflow gastrointestinal, drop, headache, celulitis, chronic renal insufficiency, hipogonadismo and dysfunction eréctil, among others. On the other hand, the obesity associates with a reduction of the quality of life and the social stigmatisation.

Lamentably, the doctors keep on being reacios to mention the subject of the obesity when they visit patient in his clinic. Less than 50% of the obese patients even advises them lose weight .
This low implication by part of the doctor can have to, partly, to the fact that in this moment still does not exist a magic formula for the treatment of the obesity, and the diet and the exercise continue being the angular stone of the treatment. Given the frustrations that confront the doctors and the patients to attain results by means of the diet and the exercise, the therapy with medicines offers an attractive option, even if the results are modest. Unfortunately, in spite of the frantic research in this moment of farmacoterapia, at present exist few options.

In the last years, a lot of medicines that have been effective to go down of weight have had to be withdrawn of the market because of unacceptable secondary effects.

Indications for the medical therapy?

The obesity defines like an index of corporal mass (IMC, calculated like the weight in kilograms divided by the square of the height in metres) of 30 or more.
The guides of clinical practice for the handle farmacological and surgical of the obesity in primary attention have been published by the American College of Physicians (ACP) [10].

The guidelines include five recommendations?

Advise to all the obese patients (IMC ≥ 30 kg / m2) on the diet, the lifestyle and the aims of loss of weight.

Can offer farmacological therapy to those that did not attain the aims of loss of weight through the diet and the alone exercise.

The farmacological options include sibutramina, orlistat, fentermina, dietilpropion and two medicines that are not approved for the treatment of the obesity, fluoxetina and bupropión.

It has to consider the surgery bariátrica for patients with IMC ≥ 40 kg / m2 that have failed in the diet and the exercise (with or without farmacological treatment) and that have comorbilidades related with the obesity (hipertensión, intolerance to the glucose, diabetes mellitus, dislipidemia, dream apnoea).
The surgery bariátrica has to realise in centres of high volume with surgeons experienced. The NIH also suggests that they can use medicines to lose weight approved by the Administration of Foods and Medicines for use on a long-term basis or for patients with an IMC ≥27 accompanied of factors of risk or illnesses.

These factors of risk are hipertensión, dislipidemia, coronary illness, diabetes type 2 and apnoea of the dream .
It is possible that these recommendations change prompt, to the light of the new findings that relate to the sibutramina with a greater tax of cardiac events . The NIH also suggests that the adults with an IMC> 35 that have comorbilidades grave like diabetes, apnoea of the dream, miocardiopatía related with the obesity or severe articular illness also can be candidates for the surgery bariátrica.

You put of the therapy of Obesity?

Perhaps the most important appearance to initiate the farmacological treatment for the obesity is to establish realistic aims.
Given the difficulties of the diet, is almost impossible to reach the expectations of the patients. Numerous studies have showed that the obese people want to lose the equivalent to the 25-35% of his initial weight and expect to do it in roughly 1 year of treatment .

The people that do diet keep these expectations even when it informs them reiteradamente that is likely that lose only a 5-15% of the initial weight, that is the size of the typically induced losses by the interventions conductuales and farmacological current .
These data illustrate the dramatic disparity between the expectations of the patients and the professional recommendations and the need to help to the patients to accept results of loss of weight more modest.

An aim of realistic treatment is generally the loss of the 5-10% of the corporal weight initial during a period of 6 to 12 months, followed of the maintenance on a long-term basis of the weight reduced. The guidelines of the NIH recommend that the loss of weight exceed the 2 kg during the first month of therapy with medicines (2.5 Kg by week), fall more than 5% underneath of the initial level of three to six months, and remain in this level to consider effective.
If this does not attain , then the dose has to adjust or suspend the medicine. Although the loss of weight is an important result of the treatment, a main aim of the treatment of the obesity would have to be improve the factors of cardiovascular and metabolic risk to reduce the morbilidad and the mortality related with the obesity.

A loss of weight moderated so low like 5% of the corporal weight initial can drive to favourable improvements in the arterial pressure, the concentrations of lipids in serum, a greater sensitivity to the insulin and levels improved of glucose .

The patients that have intolerance to the glucose, diabetes type 2 or hipertensión are those that more benefit regarding the improvement of the factors of cardiovascular risk .

When initiating the farmacological therapy, is important that the patient comprise that once that it attains the therapeutic effect maximum, stabilises the loss of weight and that when it interrupts the farmacological treatment, recovers the weight .
Due to the fact that the body reduces his expense of energy to measure that loses weight, has to do more and more effort to keep the loss of weight . The increase of weight is the result of complex interactions between multiple factors, included physiological factors, environmental and psychological. The physiological factors include the reduction of the metabolic tax, so much in rest as in rest , and a greater activity of the lipoprotein lipase of the adipose fabric.

These mechanisms contrarreguladores protect against the starvation when causing an increase in the appetite and a decrease in the expense of energy, what does that it was very difficult to keep the stray weight. The patients also have to be conscious of the fact that the data on the use of these medicines are limited, since the longest essays for the sibutramina have a length of alone two years, and for orlistat a maximum of four years.
The essays for the remaining medicines are even more short. Therefore, if there is a good answer to the medicine and the patient wishes to continue, the decision has to be a discussion shared between the doctor and the patient.

?Medicines for the loss of weight?

Medicines for the diabetes that drive to the loss of weight The increase of the weight associated with a lot of medicines antidiabéticos commonly recetados, like insulin, sulfonilureas and tiazolidindionas, carries to a lot of doctors and patient to resist the intensification of the therapy as it was necessary . Fortunately, no all the medicines cause increase of weight, and recently have entered new medicines that in reality cause loss of weight.

Medicine Sibutramina-Sympathomimetic Drug, previously approved for use on a long-term basis The sibutramina (Meridia, Reductil) developed for the first time like an antidepressant, and although it was not effective for this, discovered that it reduced the corporal weight and the appetite. It is an inhibidor of the recaptación of noradrenalina and serotonin of central action that improves the loss of weight when increasing the satiety. Also it can have an effect termogénico in the human beings, but this keeps on being controversial.

All are derived of the amphetamine that drive to the loss of weight by means of the supresión of the appetite. To the equal that the amphetamines, are medicines of central action that increase the arterial pressure and the frequency of the pulse.
The fentermina is the medication to go down of weight recetada with more frequency. The fentermina administered of continuous form in a blind double essay of 36 weeks in 108 women caused a loss of 12,2 kg, in front of placebo, that went of 4,8 kg

Farmaco The Metformina investigated for the first time by his effects on the loss of weight in essays, but although the results were promising, the metformina descartó when the following year an essay that compared the metfor. They exist few essays controlled random big that evaluate the effect of the metformina on the weight like secondary result.

Farmaco Agonistas Of GLP-1: exenatida and liraglutida GLP-1 is a hormone secretada by cells L in the terminal ileum after the consumption of foods.
It diminishes the glucose in blood when inhibiting the secretion of glucagón and stimulate the secretion of insulin. GLP-1 also delays the gastric casting, reduces the consumption calórica and promotes the satiety. Exenatide (Byetta) Is an agonista of the receptor GLP-1 that shares a homology of 53% with GLP-1 and has a semivida much longer because it is resistant to the degradation mediated by dipeptidil peptidasa-4- (DPP-4).
It administers like injection subcutánea twice a day. It is approved to treat the diabetes type 2 and produces similar effects to the GLP-1, reducing the levels of glucose in ayunas and posprandiales, diminishing the HbA1c, diminishing the gastric casting and diminishing the consumption of foods in roughly 19%.

Farmaco Pramlintide Is an analogous of the amilina, a small hormone peptídica that frees in the bloodstream by the cells β of the pancreas together with the insulin in reply to the stimuli of nutrients.
It has showed that the amilina diminishes the gastric casting, reduces the increases posprandiales in the concentrations of glucose in blood and improves the concentrations of hemoglobin To1C in patients with diabetes type 1 and type 2. It has to administer by injection subcutánea, to a maximum dose of 120 microgramos with each food. Pramlintide Associates with a loss of weight moderated in patients with diabetes type 1. In one of these essays, where 651 patients with diabetes type 1 were assigned randomly to placebo or pramlintide subcutáneo in addition to to his insulin, the weight diminished 0.4 kg in the group pramlintida and increased in 0.8 kg in the group placebo .

Medicines anticonvulsivos

Farmaco Topiramato Is an agent anticonvulsivo approved around the middle of the decade of 1990 for the treatment of the refractory crises together with other agents anticonvulsivos.el topiramato also associates with a decrease of the bicarbonato sérico and the development of acidosis metabolic , an excretion of citrato urinary notably inferior and an increase of the urinary pH.

Farmaco Zonisamida Is another medicine antiepiléptico approved by the FDA in 2000 for the treatment of the partial crises in adults with epilepsy. Whereas the activity anticonvulsiva of the zonisamida thinks that is related with his activity bloqueadora of the channels of sodium and calcium , also knows that the drug exerts an activity dopaminérgica bifásica dependent of the dose and serotonérgica .
It observed loss of weight in the clinical essays for the treatment of the epilepsy [85], what caused an essay of obesity.

Antidepressant medicines

Farmaco Bupropion Is an inhibidor of the recaptación of norepinefrina and dopamine that is approved to treat the depression and quit smoking. The bupropión seems to have an effect of neutral weight for the majority of the people depressed of normal weight. However, the essays controlled with people depressed suggest that the RS of bupropión can be associated with the loss of weight in subjects with sobrepeso or obesity .
Besides, the increase of weight after the treatment to quit smoking was minor in the subjects treated with bupropión SR that in the subjects treated with placebo.

Farmaco fluoxetina, an inhibidor selective of the recaptación of serotonin (ISRS) approved for the treatment of the depression, also can drive to the loss of weight. In summary, can observe that, in average, the majority of the existent medicines drive to a loss of weight of roughly 5%, with the exception of the medicines simpaticomiméticos approved for use in the short term

Medicine Leptina The proteinaceous hormone leptina is produced by the adipose fabric and seems to indicate adiposidad and modulate the behaviour of ingestion .
A possible use of the leptina can be a complementary therapy for the maintenance of the loss of weight.
The reductions in the expense of energy and the concentrations of hormone tiroidea that occur with the loss of weight can be due to a descent in the concentrations of leptina and also can hinder the capacity to keep the loss of weight.

Medicine Peptide YY peptide of the intestinal hormone YY (PYY) sintetiza and cosecreta with GLP-1 by the cells L in the small intestine. It suppresses the appetite and diminishes the consumption of foods . The obese subjects had levels significantly lower of PYY in ayunas and the levels correlacionaron inversamente with the index of corporal mass. These observations suggest that the PYY has an important regulatory paper in the alimentary behaviour, that potentially offers an aim for the development of drugs .

Medicine Oxyntomodulin is a peptide produced in cells L of the track GI of the product of the gene of proglucagón. It frees to the blood in reply to the ingestion of foods and in proportion to the content calórico of the food . It has informed that the oxintomodulina reduces the consumption of foods in 19,3% during an intravenous infusion administered to people with normal weight, an effect that continues during but of 12 h after the infusion .

Agonistas Of the receptor of melanocortina-4 The system hipotalámico of melanocortina seems to improve the expense of energy and suppress the appetite. In a study in adults with normal weight, the administration intranasal of the central fragment MSH / ACTH4-10 of pro-opiomelanocortina during 6 weeks gave like result a significant reduction of the corporal weight in 1,7 kg.

Farmaco Lorcaserin The stimulation of receptors of specific central serotonin represents an effective farmacological mechanism to suppress the appetite. The serotonin and the agonistas that activate the receptors of the serotonin 2C (5-HT2C) promote the feelings of satiety, what reduces the consumption of foods [. Lorcaserin Is an agonista selective of 5-hidroxitriptamina (serotonin) (5-HT) 2C at present in clinical essays of phase 3 to treat the obesity. The subjects treated with Lorcaserin had cholesterol plasmático reduced, circumference of the waist, glucose in ayunas and sour úrico in serum.

Farmaco Tesofensine Is a simpaticomimético in the family of sibutramina initially developed for the treatment of the illness of Parkinson. Although his efficiency was limited for this application, observed that the subjects of the study experienced a loss of significant weight by the supresión of the appetite .

?Treatments combined?

Any of the medicines of only agent that have been approved or that seem to be next to the approval has been consistentemente able to attain a loss of weight of more than roughly 10% of the corporal weight.
The combination of fentermina and fenfluramina, that withdrew of the market in 1997, was able to attain a loss of roughly 15% of the corporal weight.
Recognising the complex pathophysiology of the obesity, the recent efforts have centred in therapies combined. The use of more than a medicine to treat the obesity is similar to the treatment of the hipertensión, where often need several medicines to reach the aims established.

Conclusion treatment Obesity

The obesity now presents one of the greater problems of health of our time. The diet and the exercise are better so much for the prevention as for the treatment; unfortunately, both require a lot of discipline and are difficult to keep.
The medicines offer a possible complement, but his effect is modest, are limited by the secondary effects and the loss of hard weight only while it takes the medicine, since so prompt as it interrupts the treatment, recovers the weight. The sibutramina, a medication simpaticomimética that was available for the treatment on a long-term basis, is the most recent of the drugs that will withdraw of the market because of the secondary effects; in this case, it went a greater risk of cardiovascular events.
They exist other available medicines, but is to expect that learn more on the combination of existent medicines and the development of new medicines provide a better treatment for this so difficult challenge.