How Physiological Changes Associated with Obesity Affect Drug Metabolism
Obesity is known to have a significant impact on many organ systems that are crucial in drug metabolism. As the prevalence of obesity continues to rise, clinicians are being challenged with the problem of dosing in the extreme overweight population. This review article discusses the different physiological changes associated with obesity and how they affect absorption, distribution, drug metabolism and clearance in morbidly obese patients.
The changes that occur in the organs of the body do not correlate linearly with BMI, but also includes factors such as time and individual body composition. For example, in the kidney of an obese patient, renal clearance is initially enhanced by a compensatory hyperfiltration and hyper-perfusion, though, eventually, this declines as a result of a constantly elevated intra-glomerular pressure which leads to chronic kidney disease. Likewise, cardiac output is increased in obese patients in order to provide oxygen and nutrients to the excess tissue. This should mean that that blood flow to the liver increases, however due to non-alcoholic fatty liver disease resulting in steatosis, together with sinusoidal narrowing, blood flow may actually decrease over time.
Obesity also has an effect on the gastric emptying and gut permeability, meaning that drugs are absorbed at different rates to normal. Drug penetration into tissue is also affected, meaning that a higher dose may be needed in order to reach effective concentrations. For example, with antibiotics to treat a local infection, obese patients may require a much higher dose, which can then introduce issues of drug toxicity.
What is clear from these few examples is that with a growing number of obese patients, there needs to be a quantitative system in place that can derive drug dosing recommendations for obese patients. Currently there is a lack of understanding of how obesity affects the pharmacokinetics and pharmacodynamics of drugs, which leads to improper and potentially dangerous dosing of obese patients.
To learn more about obesity, its prevention, and its treatment please look at CCH’s Postgraduate Academic Courses in Lifestyle Medicine (Obesity Care), and CPD Short Courses in topics such as childhood obesity and behaviour change, designed to up-skill health professionals in this vitally important, and often overlooked, area of care.
Read MoreFamine Exposure During Early Life May Lead to an Increased BMI in Adulthood
It has been previously reported in epidemiologic studies that famine exposure during early life is associated with overweight or obesity in adulthood. In this systematic review and meta-analysis of 20 studies, this paper set out to determine whether exposure to famine in early-life had any association with overweight or obesity in later life.
This study was conducted according to the Cochrane methodology, and included research from a variety of different famines across the world with considerations for gender and age. It found that there was a significant correlation between early life exposure to famine and being overweight in later life, and that this association was stronger in females, individuals less than 50 years of age and individuals who experienced foetal exposure.
The mechanisms for this phenomenon are still not clear, however the author goes on to discuss the different systems that the famine could affect, including a formatting of the HPA neuroendocrine access that controls energy intake and expenditure, epigenetic changes sustained during famine causing behavioural differences, as well as psychological damage to the individual, which will affect their behaviour and attitude towards food.
Read MoreEfficacy, Safety, and Mechanisms Of Herbal Medicines Used In The Treatment Of Obesity: A Protocol For Systematic Review
There is a huge amount of conflicting evidence over the potential efficacy of herbal remedies for the treatment of obesity. Although several systematic reviews have been conducted, the market is saturated with poorly evidenced claims, and a huge number of different remedies. This study sets out a protocol for a comprehensive systematic review into herbal remedies and their efficacy at treating obesity.
Herbal medicines can cause weight loss through 5 different mechanisms, namely appetite control, stimulation of thermogenesis, inhibition of fat absorption as well as decreasing lipogenesis.
Efficacy has been evaluated before, however, the authors feel a new systematic review, focussing on clinical trials data is needed. This systematic review will be seen as an update, with all new data plus any new research on active components and methods of action.
Herbal remedies are defined as raw or refined products derived from plants or parts of plants, in this case used for the treatment of obesity. The primary outcomes expected will be an improvement in BMI, waist circumference, waist-hip ratio, body fat and appetite. Secondary outcomes will focus more on the metabolic features of obesity, meaning improvements to cholesterol, low-density lipoprotein, high-density lipoprotein, blood pressure, triglycerides and blood sugar.
The increasing number of randomised controlled clinical trials means that a new and updated review of the mechanisms of action and efficacy of these treatments is needed. They have the potential to become a cheap new therapy in the treatment of obesity or if proven otherwise, then this systematic review will put to rest the debate over their efficacy.
Read MoreCardiorespiratory fitness as a Determinant Factor for the 30% of Obese Individuals That are Metabolically Healthy
Previous studies have shown that individuals can be obese and metabolically healthy, or of normal weight with an unhealthy metabolic profile. The metabolically healthy obese (MHO) phenotype currently represents 30% of obese individuals. However, major studies have so far failed to consider the possible impact of cardiorespiratory fitness on metabolic health.
MHO individuals are characterised by having low abdominal adiposity, low inflammation level and low risk of developing metabolic comorbidity. This study hypothesised that cardiorespiratory fitness, is a determinant factor for the MHO phenotype. It aimed to investigate the associations between fitness, abdominal adiposity and low-grade inflammation within different BMI categories. Data from 10,976 individuals on waist circumference (a surrogate measurement for abdominal adiposity), cardiorespiratory fitness and C-reactive protein levels (a measure of low-grade inflammation) were analysed.
In both men and women, this study found a strong inverse association between fitness and waist circumference adjusted for age, education, smoking, alcohol and BMI. It also found that fitness reduced levels of inflammation regardless of BMI. Furthermore, a positive association between waist circumference and C-reactive protein, in both men and women in all BMI categories. This study demonstrates that there is a considerable difference in the values for abdominal adiposity, fitness and low-grade inflammation in people with the same BMI. Therefore, in order for clinicians to obtain a more accurate identification of individuals who are healthy despite obesity and individuals who are at metabolic risk despite the normal weight, additional measurements of waist circumference, CRP and fitness should be taken in to account.
Read MoreThe Effectiveness of a School Intervention Program. A Panacea against Obesity?
A large randomised controlled trial was conducted in the West Midlands, looking into the effectiveness of a school and family based healthy lifestyle programme, in comparison to usual practice. 1,467 year 1 pupils aged 5 to 6 years (control, 778 pupils), were randomised into the study, with follow-ups at 15 months and 30 months. The intervention consisted of encouraging healthy eating and physical activity, which included a daily additional 30-minute school time physical activity opportunity and a 6-week interactive skills programme in conjunction with Aston Villa football club. There was also signposting of family physical opportunities and termly workshops looking at healthy eating cooking skills.
The main outcome measured in the study was BMIz score at 15 and 30 months respectively. They also looked at other anthropometric, dietary, physical activity and psychological measurements. Unfortunately, at 15 and 30 months follow up, there was no statistically significant improvement in any of the outcomes measured. Despite this rigorous in-school intervention, the primary analysis suggests that it was in fact, ineffective. Although this study was inconclusive, the authors go on to point out that it highlights the difficulty of the task of reducing weight in children, and that schools alone may not be the answer. A holistic approach that incorporates school, home, environment and policy is one that is most likely to succeed, and the idea that school-based interventions will solve the problem is likely oversimplifying the issue.