Obesity and Medications PDF

 Topic INFLUENCE OF OVERWEIGHT AND OBESITY ON MEDICATIONS A good medical quote : “Obesity is not because it runs in the family… It is because no one runs in the family…”  DEFINITION Definition: “Abnormal or excessive fat accumulation that may impair health” In simp...

 Topic INFLUENCE OF OVERWEIGHT AND OBESITY ON MEDICATIONS A good medical quote : “Obesity is not because it runs in the family… It is because no one runs in the family…”  DEFINITION Definition: “Abnormal or excessive fat accumulation that may impair health” In simplest form, obesity can be considered to result from an imbalance between the amount of energy consumed in the diet and the amount of energy expended through exercise and bodily functions.  Conti…  Obesity is caused by increase in size and the amount of fat cells in the body.  It can cause complications such as metabolic syndrome, high blood pressure, atherosclerosis, cancer diabetes, sleep disorders etc.  Doctors measure BMI and waist circumference to screen and diagnose overweight and obesity.  Conti… Body mass index Waist circumference It is a person’s weight in It is accurate and simple kg divided by square of measure to find central his weight in meters. obesity or abdominal fat. A BMI greater then or  A WC of 102 cm or equal to 25 is overweight more in men and 88 cm A BMI greater than or or more in women leads equal to 30 is obesity. to various health problems.  Causes of obesity and overweight  CAUSES OF OBESITY AND OVERWEIGHT  Energy imbalance: Energy imbalance means that energy (calories) in does not equal to energy out. This imbalance cause body to store fats. The number and size of fat cells increases, leading to obesity.  Medical conditions: Some endocrinal disorders also cause obesity. For example:  Conti… Hypothyroidism: In this condition low level of thyroid hormones, is associated with ↓ metabolism and weight gain, even when food intake is reduced. Tumors: Some tumors such as craneopharingioma, can cause severe obesity because it develops near the part of the brain that control hunger. Cushing’s syndrome: In this disease, cortisol level become high and also have increase appetite, so that body also stores more fats in body.  Conti…  Medicines: Medicines such as antipsychotics, antidepressants, antihyperglycemic can cause weight gain and lead to overweight and obesity.  Genetics: Genes can directly cause obesity in such disorders such as Prader-Willi syndrome (which includes disruption in hypoglycemic pathways of satiety control resulting in hyperphagia and reduced energy expenditure). RISK FACTORS  MODIFIABLE RISK FACTORS  Lifestyle habits: Obesity develops gradually over time, as a result of poor diet and lifestyles changes such as eating large amount of processed food or fast food that is high in fat and sugar, use of alcohol that contains a lot of calories.  Smoking: Many people gain weight when they quit smoking as nicotine no longer speeds up the calorie burning process.  Conti…  Alcohol: Alcohol adds calories to the diet, increase appetite and may interferes with a person’s ability to make good choices about healthy meals and portion sizes.  Social factors: It may also leads to obesity. Poverty, causes people to buy processed food that cost less on healthier foods and their opportunities for exercise may be limited.  Conti…  Physical inactivity: Sedentary lifestyle may also leads to obesity because calories do not burn due to physical inactivity as a result energy stores in the form of fats in the body.  Lack of sleep: Not getting enough sleep or getting too much sleep can cause hormonal changes that increases appetite. It may also cause craving of food which are high in calories and carbohydrates, which lead to weight gain.  NON-MODIFIABLE RISK FACTORS  Age: As people age, the amount of calories needed also changes, often due to reduced activity levels and slowed metabolism.  Family history: Obesity tends to run in families. If one or both of parents are obese, your risk of being obese is increased.  Gender: Obesity is more common in women than in. Rate of obesity is more in Hispanics than Whites. COMPLICATIONS OF OBESITY  DIABETES  Diabetes is a disease in which the body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of CHO and elevated level of glucose in blood.  Currently 12% of adults in the US have diabetes. Insulin resistance develop during obesity which leads to glucose intolerance and then develop type 2 diabetes.  CARDIOVASCULAR DISEASES Dyslipidemia:  It is an abnormal amount of lipids in the blood.  Dyslipidemia may occur in children and adolescents as a result of obesity.  The most common abnormality of lipids and lipoproteins associated with obesity is an increase in triglycerides and decrease in HDL- cholesterol.  STROKE A stroke is a sudden interruption in the blood supply of the brain. Most strokes are caused by bleeding into brain tissue when a blood vessel bursts (hemorrhagic stroke) or abrupt blockage of arteries leading to brain (ischemic stroke). Obesity and high blood pressure is the leading cause of strokes.  CANCER Cancer is a disease caused by an uncontrolled division of abnormal cells in a part of body. It is estimated that obesity accounts for about 20% of all cancer cases such as colon, breast, kidney cancers etc. Obesity causes cancer by: increase level of insulin and insulin like growth factors  Conti… Extra fat in the body does not just sit there, its active form sending signals to body to divide more which can lead to cancer. So that, weight loss has been shown to reduce the risk of some cancers.  SLEEP APNEA Obstructive sleep apnea is a condition in which person can’t breathe normally because of upper airway obstruction. Improvement in obstructive sleep apnea, either by substantial weight loss or by other method such as continuous positive airway pressure during sleep, can lead to improvement of blood pressure elevation.  FERTILITY It is ability to conceive children or young. In men, obesity causes ↓sperm production and increase rate of erectile dysfunction. In women, it also leads to reduce fertility, poorer outcomes after fertility treatment and more pregnancy loss. (PCOS) is the primary cause of female infertility and increase the rate of pregnancy complications. TREATME NT OF OBESITY AND OVER- WEIGHT THROUGH MEDICATI ONS  TREATMENT 1. Orlistat: It promotes weight loss by inhibiting gastrointestinal lipases, thereby decreasing the absorption of fats from gastrointestinal tract. On average, 120mg of orlistat taken 3 times per day will decrease fat absorption by 30%. It is approved for adults and children under age 12 years.  Conti… Side effects: But high dose may cause diarrhea, gas & stomachache 2. Lorcasein: It is a selective serotonin receptor agonist, was approved by the FDA in 2012 as a long term treatment for obesity for adults. It may also reduce appetite. Side effects: But its high dose may cause constipation, cough, dry mouth and dizziness.  Conti… 3. Naltrexone: The combination tablet of bupropion and naltrexone was approved by FDA in September, 2014 for weight loss in adults. Side effects: But it may cause constipation, dizziness, headache, high blood pressure and liver damage, if it take in large amount.  Conti… Phentermine (was first FDA approved short term medication for weight loss, but it may also cause constipation, dry mouth, headache , raised pulse rate). Diethylpropion (it is also a short term drug for treating obesity) Benzphetamine and Phendimetrazine (also a short term medications to prevent obesity)  Drug Interactions  ABSORPTION & DISTRIBUTION 1. Absorption: Altered gastrointestinal transit time and a higher splanchnic blood flow It may modify drug absorption including a reduction in the bioavailability of drugs with high extraction ratios.  Distribution: The distribution of a drug throughout the body following absorption from the site of administration is determined by several factors – some related to the drug (e.g., lipophilicity, degree of ionization), others related to the body (e.g., blood flow, tissue-binding sites). Plasma protein binding, body composition, tissue size, tissue permeability, and drug affinity for various tissues each determine a drug’s distribution.  ELIMINATION The elements that determine elimination of a drug, whether through metabolism or excretion, may be altered in obese individuals. Increased cardiac output, fatty infiltration of the liver, portal inflammation and fibrosis, increased renal plasma and creatinine clearance are all known to occur in obesity  ELIMINATION 1. HEPATIC The fatty infiltration of the liver could affect hepatic metabolic activity. Fatty infiltration of the liver is more severe with increasing BMI and may impact on the organ’s metabolic activity. Using antipyrine as a marker of hepatic oxidative enzyme function, drug half-life was increased in obese individuals compared to lean volunteers.  EFFECT OF DRUG There may be increased sensitivity to some drugs such as glipzide, glyburide, prednisolone and triazolam And decrease sensitivity of to others such as atracurium, verapamil Receptor expression or affinity may be altered  IMMUNOSUPPRESSANTS The VD corrected to TBW is lower in obese individuals for both prednisolone and methylprednisolone without apparent changes in plasma protein binding to albumin or transcortin. However the CI of prednisolone is increased in obesity.  ANESTHETICS Local anesthetics administrated via the epidural route may ↓pain during active labor. Obese women often experience higher levels of epidural blockage. A prospective evaluation of bupivacaine showed that the effective drug concentration in obese patients (BMI 39.5 kg/m²) was only 60%  FLUROAUINOLONES The fluoroquinolone antimicrobials are widely used. The increased absolute VD for ciprofloxacin in obese individuals becomes slightly below that of controls, proportional to BMI, when normalized to actual body weight.This indicates that ciprofloxacin distributes less into the excess adipose tissue than into the fat-free tissues. ANTIVIRALS.  Non-response to interferon-a or peg interferon-a in patients with hepatitis C genotypes 1 and 4 viral infection is independently associated with BMI 30 kg/m2.  Due toincreased expression of an inhibitory factor (i.e., suppressor of cytokine signaling type 3) in obese compared with lean subjects  ANTIMICROBIALS Dosing of antimicrobials in obesity have been recently reviewed. Much is based on the degree of drug distribution into lean and fat mass and on the influence of obesity on drug clearance. Some studies have sought to optimize doses of moderately lipophilic antimicrobials in obese patients.