1. Presented by- ROHIT BISHTM. Pharmacy( Pharmacology)

2. OBESITY It may be the illness where the health is adversely affected by excess body fat. Abnormal growth of the adipose tissue due to enlargement of Fat cells (hypertrophic) or an increase in fat cell number (hyperplastic) or a combination of both. A metabolic disorder that is primarily induced and sustained by an over consumption or under utilization of caloric substrate. 3. STORAGE OF FATFat is stored as triglycerides in adipose tissues and thedistributed mainly under skin in Abdomen Breast Buttocks Thighs 4. Android(Abdominal)obesity fat distributed in & around abdomen.Gynoid obesity fat distributed evenly & peripherally. 5. EPIDEMIOLOGICAL DETERMINANTS ObesityAge: Increasing ageFemales(specifically after menopause)Genetic factorsSedentary life, low physical activityIllnessJunk Food, eating frequently , sweets , refined foodsEndocrine disorder ( cushings syndrome ,GH defi. )Illiteracy in affluent societiesAlcoholDepression, anxiety, frustration, lonelinessEconomic statusDrugs: Corticosteroids, OCPs, Insulin, Beta blockers 6. EPIDEMIOLOGICALDETERMINANTS1. Age -Increasing age -one third obese from childhood2. Sex -women have higher propensity -after menopause obesity risk3. Genetic factors - amount of fat is influenced by genetic factors 7. 4. Less Physical activity- No energy expenditure through physicalactivity.- To burn 1 kg fat: 8000 kC required (approx.)5. Socio-economic status - high in affluent society6. Eating habits -Junk food -Extra 100 Kcal/day consumption :5 kg wtgain/year 8. 7. Psychological factors -depression, anxiety, frustration, lonelinessovereating8. Endocrine disturbances -Cushings syndrome, GH deficiency9. Alcohol- increases fat in man (due to regular intake of alcoholliver become fatty) 9. 10. Education -inverse relation in affluent societies11. Ethnicity -affluent people of industrialized countries atrisk12. Drugs - Corticosteroids, contraceptives, insulin, blockers promotes weight gain 10. Medications That Can Cause WeightGain Psychotropic medications Diabetes medications Tricyclic antidepressants Insulin Monoamine oxidase inhibitors Sulfonylureas (glipizide / glucotrol) Specific SSRIs Thiazolidinediones Atypical antipsychotics (pioglitazone ) Lithium Tamoxifen (anti-estrogen) Specific anticonvulsants Steroid hormones -adrenergic receptor blockers Glucocorticoids 11. MEASUREMENT OF OBESITY1. BY BODY WEIGHT: Mass Index (Quetelets Index):Weight(kg)/(Height) 2(m2) [ 18.5-24.99kgm-2] Broca Index - (Ideal Body Weight) = {Height(cm)100} Lorentz Formula:{Height(cm)100}{Height(cm) 150}/ 2(women) or 4(men) Corpulence Index- (Actual Weight/Desirable Weight) 1.2 Ponderal Index- Height(cm)/ (Weight)1/3 12. 2. Skin fold Thickness: Mid-triceps+ mid-biceps+ sub scapular + suprailiac = 50mm in women or 40 mm in men. It Impossible in Extreme obesity Poor repeatability3.Waist Circumference: For Men: 102 Very High For Women: 88 Very High4. Waist hip ratio: WHR : 1 (Men) and 0.85 (Women)5.Measurement of Total Body Water, Total Fat Cells. 13. Below 18.5 Underweight18.5 24.9Normal25.0 29.9Overweight Monitor for risk30.0 -40.0 Obese Increased health risk40.0 and above Severely obese Major health risk 14. Etiology is complex and incompletely understoodinvolved by many other factors. Three mechanism areexpressed, Which are The efferent system, which generates signals from various sites. Its maincomponent are leptin (adipose tissue), insulin(pancreas), gherlins (stomach), peptide Y (ileum andcolon). Leptin reduces food intake, gherlin secretionstimulates appetite and it may function as a meal initiatingsignals. Peptide Y, which is released postprandial byendocrine cells in the ileum and colon , it is a satietysignals. 15. The hypothalamus processing system known as thecentral melanocortin system, which integrates different type of afferent signals and generates efferent signals. The efferent system that carries the signals generatedin the hypothalamus, which controls food intake andenergy expenditure. 16. PATHOPHYSIOLOGY OF OBESITY ENERGY BALANCE Energy stores will increase imbalance between intake andexpenditure. Low Rates of Fat Oxidation. Low Metabolic Rate. Low Plasma Concentration of Leptin. Low Physical Activity. PERIPHERAL STORAGE AND THERMOGENESIS Adipose tissue generally is divided into two major types, whiteand brown. The primary function of white adipose tissue is lipidmanufacture, storage, and release. and brown have a ability todissipate energy via process of uncoupled mitochondrialrespiration. 17. Role of Brain Neurotransmitters Neurotransmitters govern the bodys response tostarvation and dietary intake. Decreases in serotonin and increases neuropeptide Yare associated with an increase in carbohydrateappetite. Neuropeptide Y increases during deprivation; mayaccount for increase in appetite after dieting. Cravings for sweet high-fat foods among obese andbulimic patients may involve the endorphin system. 18. HORMONAL REGULATION OF BODY WEIGHT Norepinephrine and dopaminereleased by sympatheticnervous system in response to dietary intake. Fasting and semistarvation lead to decreased levels ofthese neurotransmittersmore epinephrine is made andsubstrate is mobilized. 19. Hormones and Weight Hypothyroidism may diminish adaptive thermo genesis. Insulin resistance may impair adaptive thermo genesis. Leptin is secreted in proportion to percent adipose tissueand may regulate (decrease) appetite. 20. Effects of Various Neurotransmitters, Receptors,and Peptides on Food Intake 21. PROBLEMS ENHANCING AFTER THE OBESITY Short-term problemsObesity causes day-to-day problems such as: breathlessness increased sweating snoring difficulty sleeping inability to cope with sudden physical activity feeling very tired every day back and joint pains Long-term problems Obesity can also cause changes you may not notice, but thatcan seriously harm your health, such as: 22. high blood pressure (hypertension) high cholesterol levels (fatty deposits blocking your arteries) Both conditions significantly increase your risk of developing acardiovascular disease, such as: coronary heart disease, which may lead to a heart attackstroke, which can cause significant disability and can be fatal.Another long-term problem that can affect obese people is type 2 diabetes. Psychological problemsIn addition to the day-to-day problems of obesity, many peoplemay also experience psychological problems such as: low self-esteem low confidence levels feeling isolated in society These can affect relationships with family members and friendsand may lead to depression. 23. GENERAL APPROACH FOR TREATMENTNon pharmacological treatment Behavior Modification-The primary aim is to helppatients choose lifestyles that are conducive to safeand sustained weight loss. Most such programs use self-monitoring of diet anddaily exercise both to increase patient awareness ofbehaviour, and as a tool for the clinician to determinepatient compliance as well as patient motivation. 24. DIET- Numerous diet or nutrition plans exist to aid inweight loss should low calorie intake..Surgery- Surgery remains the most effective interventionfor the treatment of obesity. its related morbidity and mortality, this intervention isreserved for those with BMI greater than 40 kg/m2 or 35kg/m2 . 6062 Surgical procedures either reduce the stomachvolume and/or reduce the absorptive surface of thealimentary tract, resulting in some degree ofmalabsorption. Currently, the three major types ofprocedures are: stapled gastroplasty, adjustable gastricbanding, and conventional Roux-en-Y gastric bypass. 25. A combined intervention of behavior therapy, dietarychanges and increased physical activity should bemaintained for at least 6 months before consideringpharmacotherapy. 26. PHARMACOLOGICAL THERAPY LIPASE INHIBITORS Orlistat- Gastrointestinal (gastric, pancreatic, andcarboxylester) lipases are essential in the absorption of thelong-chain triglycerides commonly found in Western diets. Orlistat is minimally absorbed and selectively inhibitsgastrointestinal lipases. Lipase inhibition results indecreased formation of free fatty acids from dietarytriglyceride. Orlistat induces weight loss by a persistent lowering ofdietary fat absorption. clinical trials demonstrate that orlistat effectively increasesthe amount of weight lost and decreases the amount ofweight regained during medically supervised weight lossprograms. 27. NORADRENERGIC-SEROTONERGIC AGENTS Sibutramine- increase synaptic concentrations ofserotonin, norepinephrine (NE), and dopamine via reuptakeinhibition. 1 to 30 mg daily dose having a good result. Recommended starting dose 10 mg daily. Dry mouth, anorexia, insomnia, constipation, appetitedecrease, dizziness, nausea adverse effect, they alsoincrease systolic and diastolic B P. It should not be used in patients with a history of coronaryarteries disease, stroke, C H F, arythmiasis, and patient whoreceive M A O inhibitor. 28. NORADRENERGIC AGENTS Phentermine- similar to Amphetamine, has less severeCNS stimulation and lower abuse potential. Its M/A is related to enhance NE and dopamineneurotransmitter. A single dose of 30 mg daily in the morning provideeffective suppression. Divided dose of 8 mg immediatelyprior to meal.other similar drugs having same M/A respectively Amphetamine > methamphetamine > phentermine >mazindol > diethylpropion Ephedrine in combination with caffeine has enhancedappetite suppression and thermo genesis. 29. Oral doses of 20 mg ephedrine and 200 mg caffeine up tothree times daily have good effect . Side effects are tremor, agitation, nervousness, increasedsweating, and insomnia; palpitations and tachycardia havealso been reported. SEROTONERGIC AGENTS Serotonin is an important neurotransmitter involved inmany human physiological systems. Sleep-wake cycles,sensitivity to pain, blood pressure, mood, and eatingbehaviors have links to serotonin activity. Increasing central serotonin levels decreases the amountof food consumed and prolongs the time between foodintake. 30. Antidepressants: Selective Serotonin ReuptakeInhibitors fluoxetine (60 mg/day) demonstrate initial weight loss ofup to 2 to 4 kg. sertraline (200 mg/day) as an adjunct to help maintainweight lost with a very-low-calorie diet. Fenfluramine and Dexfenfluramine- Both agents increasedsynaptic serotonin concentration via reuptake inhibitionand possibly by increasing serotonin release. 31. PEPTIDES- Multiple different endogenouspeptides, which play a role in the regulation of foodintake.Leptin originates in the adipocyte and is proposed tofunction as a peripheral feedback messenger with respectto fat storage. NPY and galanin are two CNS peptides that appear tosimilarly stimulate food consumption, but have differingeffects on preference of carbohydrate or fat, as well assubstrate metabolism.NPY and galanin are thought to exert minimal effects onprotein intake. Galanin activity, centering in the lateral pera ventricularnucleus and medial preoptic areas, increases bothcarbohydrate and fat intake with preferential effects on fat 32. NPY and galanin modulate the release ofinsulin, corticosterone, and vasopressin, further affectingnutrient intake behaviors and substrate metabolism. NPY is associated with increased levels ofinsulin, corticosterone, and vasopressin, where asdecreases are seen with galanin. The macronutrientintake, energy use, and endocrine effects of NPY are mostconsistent with those seen in chronic obesity. 33. MISLLENOUS DRUGS Rimonabent- it is selective cannabinoid receptor-1 (CB-1)antagonist which is newer used as antiobesity drug. Itblocks hunger promoting action of cannabis to Decreaseappetite and help in weight reduction by obese. psychiatricdisorder are the adverse effect of this drug. B3 Agonists- B3 receptor generally present on adiposetissue where selective agonists of B3 BRL 373 44 arebeing developed as potential antiobesity drugs. Olestra it is a sucrose polyester which can be used as acooking medium in place of fat but is neither digested norabsorbed, 34. Herbal/Natural Products and FoodSupplements Used for Weight Loss