•DEFINITION•ETIOLOGY•PATHOPHYSIOLOGY•SIGNS & SYMPTOMS•TREATMENT R.MADHURI BY PHARM-D ,II YEAR ROLL NO:05 1
It is defined as excess of adipose tissue that impartsHealth risk ,obesity means too much of body fat. It is not .Thesame as being overweight. A body weight of 20percent excessover ideal weight for age, sex &height obesity is an illnesswhere health & hence lifestyle is adversely affected by excessbody fat. Most widely used method to evaluate obesity is BMI.Which is equal to weight in kg by height in square meter, for ahealthy individual BMI value ranges from 18-25. BMI greaterthan 40 individuals are said to be overweight or morbidly obese. 2
Category “BMI” Range• Acceptable range(low risk) 20.0-25.0 kg/m2• Mildly overweight(increased risk)25.1-27.0 kg/m2• Moderately overweight 27.1-30.0 kg/m2• Markedly overweight/obese 30.1-40.0 kg/m2• Morbidly obese >40.0 kg/m2 The distribution of body fat is probably the most important factor in health and disease. The three types of fat distribution include:• Upper Body• Normal• Lower Body An excess deposition of adipose tissue focused on the trunk isUpper Body Obesity or ANDROID Obesity. Upper body obesity, more 3 specifically, visceral body fat distribution is related to disease etiologies.
OBESITY results when calorie intake exceedsutilization. Taking in more calories than body canburn can lead to obesity because the body storesthe unused calories as fat.•Eating more food than the body requirement•Drinking too much alcohol•Not getting enough exercise•TRUNKAL OBESITY : Where the body fataccumulates chiefly on the trunk (abdomen etc….)•Other type is where fat deposition occurs chiefly 5on the buttocks & limbs
•SECONDARY where obesity is due to a known disorder( ex: CUSHING‟S syndrome, hypothalamic disorder)•PRIMARY (no specific cause),the probable causes are…. : •Over eating •Genetic hereditary •Hypothalamic set point: •Hypothalamus has a set point regarding body weight . •If body fat is lowered the person develops ravenous appetite. They eat more until set point is achieved. • If body fat amount exceeds the set point the appetite decreases till the body fat amount is restored. • It may be noted that this set point may alter in one‟s lifetime. Thus, in a middle aged person, the set point may be elevated and 6 the person gains weight. Hypothalamic set point may be determined by genetic factors..
•LEPTIN AND NUEROPEPTIDE Y: LEPTIN is a poly peptide hormone discovered recently ¤tly under intense research. Obesity, Ischemic heart diseases& even cancer may be related to LEPTIN.•NEUROPEPTIDE Y is a neurotransmitter found in neurons ofcertain areas of brain. Injection of NEUROPEPTIDE Y in tohypothalamus increases appetite and food intake. LEPTIN is produced by adipose tissue, when adiposity ofbody rises, more LEPTIN is produced LEPTIN is carried viablood reaches hypothalamus ultimate result isdecreased food intake. Probably LEPTIN causes suppression of NEUROPEPTIDE Ysynthesis. IT APPEARS HUMAN OBESITY IS DUE TO LACK OFLEPTIN RECEPTORS. 7
The way we eat when we are children can affect the way we eat as adults, The way we eat over many years becomes a habit. It affects what we eat, when we eat & how much we eat. Many people do not have time to plan & take healthy meals. More people work desk jobs compared to more active jobs in the past. Sometimes medical problems and treatment cause weight gain including: . Other factors are For women: : Women may gain 12 to 15 pounds during 8 menopause, and not losing weight they gained during pregnancy.
The lipid storing cells, comprise the adipose tissue &are present in compartment in the body. Besides their role in fat storage, cells also release•Energy regulatory hormone(• Insulin sensitivity regulating factors• B.P. regulating agent Adipose mass may be increased due to enlargement of adipose cells due to excess of intracellular lipid deposition as well as due 9 to increased number of
:•„ob‟ gene and its protein product leptin•„db‟ gene and its protein product leptin receptor. The fine balance of body weight is maintained by aninternal set point or lipostat that can sense the quality of the energystores and appropriately regulate the food intake as well as theenergy expenditure. The neurohumoral mechanisms regulate theenergy equation and therefore influence body weight. : :•Generates humoral signals from the adipose (leptin), pancreas(insulin) and stomach (ghrelin)•Located primarily in hypothalamus which integrates the afferentsignals. 10 Carries out “orders” from the hypothalamicnuclei in the form of feeding behaviour and energy expenditure.
•Insulin and activate catabolic circuits Produced in the stomach, ghrelin levels rise sharplybefore every meal and fall promptly when the stomach is “filled”.•leptin has a more important role than insulin in the central nervoussystem control of energy homeostasis.•Adipocytes communicate with the hypothalamus centers thatcontrol appetite and energy expenditure by secreting leptin, amember of the cytokine family.•When energy is stored in the form of adipose tissue, the resultanthigh levels of leptin cross the blood-brain barrier, binding to leptinreceptors. Leptin receptor signalling has two effects: 11.
•The net effect of leptin is to reduce food intake and promote energyexpenditure.•This cycle is reversed when adipose tissue is lost and leptin levelsare reduced below a threshold. 12
communicate with the hypothalamic centre that controlappetite & energy expenditure by secreting polypeptide hormonecalled LEPTIN. acts as mediates its affect by binding to & activating inthe•In experimental animals , is controlled at least in part by that increase the release of that whenstimulated by cause fatty acid hydrolysis & also 13uncouple energy production by storage.•Thus fats are literally burned & the energy so produced -dissipated as
• Large body frame.• Difficulty in doing daily activities.• Lethargy• Breathlessness• Disproportionate facial features• Breast region adiposity - (sagging fat cells) inboys• Big belly (abdomen)• Male external genitalia may appeardisproportionately small• Early arrival of puberty• Flabby fat in the upper arms and thighs• Knock-knees (Genu valgum) is common• Menstrual problem• Increased sweating 15• Snoring• Difficulty in sleeping
SEQUELAE OF OBESITY: Marked obesity is a serious health disorder & may predispose toa number of clinical disorders & pathological changes as describedbelow.......MORPHOLOGICAL FEATURES: Obesity is associated with increased adipose stores insubcutaneous tissue, skeletal muscles, internal organs such as kidney,heart, liver. FATTY LIVER is also most common in obese individuals. METABOLIC CHANGES:There is increase in both size & number of adipocytes i.e. there is both • HYPERINSULINAEMIAhypertrophy & hyperplasia. • NON ALCOHOLIC FATTY LIVER DISEASE• TYPE II DIABETES MELITUS • CHOLELITHIASIS• HYPERTENSION • HYPOVENTILATION SYNDROME• HYPERLIPOPROTEINAEMIA • OSTEOARTHRITIS •CANCER•ATHEROSCLEROSIS 16
MANAGING OBESITY-TREATMENTLIFESTYLE MODIFICATION1. Dietary changes2. Low fat high carbohydrate diets3. Fixed energy deficit diets4. Meal replacements5. Very low calorie diets6. High protein low carbohydrate diets PHYSICAL ACTIVITYBEHAVIORAL MANAGEMENTANTI OBESITY DRUGSThere are currently two categories of antiobesity drugs: Those that 18act on the gastrointestinal system (pancreatic lipase inhibitors) andthose that act on the central nervous system to primarily suppress
Drugs acting on the gastrointestinal system: pancreatic lipase inhibitors Orlistat inhibits pancreatic and gastric lipase thereby decreasing ingested triglyceride hydrolysis. It produces a dose dependent reduction in dietary fat absorption: weight loss in obese subjects largely results from reduction in fat intake to avoid gastrointestinal effects. Vitamin supplementation (especially of vitamin D) may be considered if there is concern about deficiency of fat soluble vitamins. Centrally acting antiobesity drugs Sibutramine promotes a sense of satiety through its central action as a serotonin and norepinephrine reuptake inhibitor. In addition, it may mitigate against the fall in thermogenesis through stimulation of peripheral norepinephrine receptors. It is used in the adjunctive management of obesity in individuals with a BMI of 30 kg/m2 or more (and no associated comorbidity) or in individuals with a BMI of 27 kg/m2 or more in the presence19 of other risk factors such as type 2 diabetes or hypercholesterolaemia.
SIBUTRAMINE•Sibutramine, originally intended as an antidepressant,•The drug inhibits the reuptake of serotonin and noradrenaline atthe hypothalamic sites that regulate food intake.•Its main effects are to reduce food intake and cause dose-dependent weight loss.•Produces a reduction in waist circumference (i.e. a reduction invisceral fat), a decrease in plasma triglycerides and VLDL, but anincrease in HDL•There is some evidence that the weight loss is associated withhigher energy expenditure, possibly through an increase inthermogenesis mediated by the sympathetic nervous system.Unwanted effects• Increases heart rate and blood pressure.•The drug is contraindicated if cardiovascular disease is present or if 20the systolic or diastolic pressure is raised by 10 mmHg or more.•Other unwanted effects include dry mouth, constipation and insomnia.
ORLISTAT•Orlistat reacts with serine residues at the active sites of gastric andpancreatic lipases, irreversibly inhibiting the enzymes and therebypreventing the breakdown of dietary fat to fatty acids and glycerols.It therefore causes a dose-related decrease in fat absorption and acorresponding increase in faecal fat excretion•Orlistat is also reported to be effective in patients suffering from type 2 diabetes and other complications of obesity, to reduce leptin levels and blood pressure,to protect against weight loss-induced changes in biliarysecretion, to delay gastric emptying and gastric secretion, to improve several important metabolic parameters, and not to interfere with the release or action of thyroid and otherimportant hormoneso •Abdominal cramps, •faecal incontinence 21 It does not induce changes in energy expenditure Unwanted •flatus with dischargeeffects
•Phentermine 30 mg in the morning or 8 mg before meals (Adverse effects e.g., increased blood pressure, palpitations,arrhythmias,•Diethylpropion(25 mg before meals or 75 mg of extended-release formulation everymorning)Diethylpropion is one of the safest noradrenergic appetite suppressantsand can be used in patients with mild to moderate hypertension orangina, but it should not be used in patients with severe hypertension orsignificant cardiovascular disease.•Rimonabant is a recently developed anti-obesity drug. Italso acts centrally on the brain and decreases appetite. It may alsoact peripherally by increasing thermogenesis and thereforeincreasing energy expenditure.•Fen-phen Increases serotonin release that then activates serotonin 22receptors in the brain to regulate food intake and body weight, butunfortunately, this drug also causes lesions in heart valves,
OVERVIEWAll of these drugs induce several adverse effects.Although most of these adverse effects are mild andtransient, the prolonged use of adrenergic orserotonergic anorectic drugs, or their use ascombination treatment, may induce serious andpotentially life-threatening complications, such asprimary pulmonary hypertension or valvular heartdisease. The adrenergic appetite-suppressing drugsare not recommended for the treatment of obesity,since their safety has never been evaluated in long 23term clinical trials, and because of their stimulatoryeffects on the cardiovascular and nervous systems.
SURGICAL TREATMENTIMPORTANT CONSIDERATIONS FOR AllWEIGHT LOSS SURGERY-Surgery should not be considered until allother options have been evaluated1. Weight loss surgery is not a cosmetic surgery.2. The decision to elect surgical treatment requires an assessment of the risk and benefit to you and the meticulous performance of the appropriate surgical procedure.3. The success of weight loss surgery is dependent on your long term lifestyle changes in diet, exercise and behavior modification.4. In a survey of over 10,000 patients, the mortality rate for weight loss surgery was 0.30%What defines successful weight loss surgery? 24The ability to achieve and maintain loss of at least 50% of excessbody weight without having substantial adverse effects.
Laparoscopic approach to weight loss surgery All the procedures are performed Laparoscopically. When aLaparoscopic operation is performed, a small video camera inserted intothe abdomen allows the surgeon to conduct and view the surgery on avideo monitor. The camera and surgical instruments are usually inserted throughsmall incisions made in the abdominal wall. Laparoscopic Sleeve Gastrectomy•. Approximately 2/3 of the stomach is stapledoff. This results in a stomach, which is roughlythe size and shape of a banana or Sleeve.• It reduces hunger because hunger stimulating hormone producing part of stomach is removed.• 90-98% resolution of Diabetes, Hypertension, hyperlipidemia,Sleep apnea,knee joint pain and much quality of life. 25• Provides satiety with small amount of food.• No malabsorption
Laparoscopic Gastric Banding1. The gastric banding is the least invasive of all procedures.2. An adjustable silicon band is placed around the stomach to create a small stomach. Small quantity of food can fill up the small stomach providing satisfaction/satiety to the person.• Narrow outlet of this small stomach delaysprogression of food into intestine – personfeels full for longer period.• The size of the stomach opening can beadjusted by injecting saline through a buttonunder the skin. Person is able to eat smallermeals at long interval.• The mean weight loss at two years after surgery is 40-55% of excess weight. 26
Intra Gastric Balloon The Intra Gastric Balloon is a soft, expandable, silicone balloon that is placed inside the stomach via endoscopy that enters through the mouth and into the stomach with or without sedation.reduces the capacity of the stomach. This creates a feeling of fullnessfor the patient and does not allow for overeating, therefore allowingthe patient to effectively diet without feeling continuously hungry.This procedure generally takes 20 minutes.•Digestion and absorption is normal.•When eating less the body draws the requiredenergy from its own fat•The mean weight loss at six months 27after is 15-25 Kgs
Gastric Imbrication•The Gastric Imbrication is a laparoscopic (keyhole) procedure.•It is a reversible procedure which involves only 3 tiny cuts on theabdomen and the stomach is folded over itself and stitched.•The tiny cuts are so small that they don‟t require any stitches and thepatient walks home the next morning.•The procedure results in reducing the capacity of the stomach to 100-150 ml and as a result the patient gets a feeling satiety with a smallmeal. not require any stapling,•It doesdisconnecting or reconnecting theintestines and food absorption isnormal. 28
Liposuction , Also known as lipoplasty ("fat modeling"), liposculpture suction lipectomy ("suction-assisted fat removal") or simply lipo is a cosmetic surgery operation that removes fat from many different sites on the human body.• Areas affected can range from abdomen, thighs and buttocks, to the neck, backs of the arms and elsewhere. Possible Liposuction Risks 1. Infection 2. Extended healing time 3. Fat or blood clots 4. Excessive fluid loss can lead to shock 5. Fluid accumulation 6. Friction burns 29 7. Damage to the skin or nerves 8. Damage to vital organs
•Pathological basis of disesase. ROBBINS 7th edition 2005•RANG & DALE’S pharmocology 6th edition•Text book of pathology HARSH MOHAN 6th edition•Concise medical physiology by CHAUDHURI 3rd edition•Pharmacotherapeutics by DIPIRO•www.bellenews.com•www.geniusbeauty.com•www.diabetespharmacist.com•www.healthheap.com•www.coolhealthtips.com•www.lowdensitylifestyle.com•www.medscape.com•www.life123.com•www.teenobesity.net•Obesityinformations.info•www.mrhealthtips.com•www.immortalhumans.com 30