1. Presented by-
ROHIT BISHT
M. 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 FAT
Fat is stored as triglycerides in adipose tissues and the
distributed mainly under skin in
Abdomen
Breast
Buttocks
Thighs
6. EPIDEMIOLOGICAL
DETERMINANTS
1. Age
-Increasing age
-one third obese from childhood
2. Sex
-women have higher propensity
-after menopause obesity risk
3. Genetic factors
- amount of fat is influenced by genetic factors
7. 4. Less Physical activity
- No energy expenditure through physical
activity.
- To burn 1 kg fat: 8000 kC required (approx.)
5. Socio-economic status
- high in affluent society
6. Eating habits
-Junk food
-Extra 100 Kcal/day consumption :5 kg wt
gain/year
8. 7. Psychological factors
-depression, anxiety, frustration, loneliness
overeating
8. Endocrine disturbances
-Cushing’s syndrome, GH deficiency
9. Alcohol
- increases fat in man (due to regular intake of alcohol
liver become fatty)
9. 10. Education
-inverse relation in affluent societies
11. Ethnicity
-affluent people of industrialized countries at
risk
12. Drugs
- Corticosteroids, contraceptives, insulin, ß
blockers promotes weight gain
10. Medications That Can Cause Weight
Gain
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 OBESITY
1. BY BODY WEIGHT:
• Mass Index (Quetelet’s 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 repeatability
3.Waist Circumference:
For Men: <90cm Low
90-102 High
>102 Very High
For Women: <80 Low
80-88 High
>88 Very High
4. Waist hip ratio: WHR : ≤1 (Men) and ≤ 0.85 (Women)
5.Measurement of Total Body Water, Total Fat Cells.
13. Below 18.5 Underweight
18.5 – 24.9 Normal
25.0 – 29.9 Overweight
Monitor for risk
30.0 -40.0 Obese
Increased health risk
40.0 and above Severely obese
Major health risk
14. Etiology is complex and incompletely understood
involved by many other factors. Three mechanism are
expressed, Which are
• The efferent system,
which generates signals from various sites. Its main
component are leptin (adipose tissue), insulin
(pancreas), gherlins (stomach), peptide Y (ileum and
colon).
Leptin reduces food intake, gherlin secretion
stimulates appetite and it may function as a meal initiating
signals. Peptide Y, which is released postprandial by
endocrine cells in the ileum and colon , it is a satiety
signals.
15. The hypothalamus processing system known as the
central melanocortin system, which integrates
different type of afferent signals and generates
efferent signals.
The efferent system that carries the signals generated
in the hypothalamus, which controls food intake and
energy expenditure.
16. PATHOPHYSIOLOGY OF OBESITY
ENERGY BALANCE
Energy stores will increase imbalance between intake and
expenditure.
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, white
and brown.
The primary function of white adipose tissue is lipid
manufacture, storage, and release. and brown have a ability to
dissipate energy via process of uncoupled mitochondrial
respiration.
17.
18. Role of Brain Neurotransmitters
Neurotransmitters govern the body’s response to
starvation and dietary intake.
Decreases in serotonin and increases neuropeptide Y
are associated with an increase in carbohydrate
appetite.
Neuropeptide Y increases during deprivation; may
account for increase in appetite after dieting.
Cravings for sweet high-fat foods among obese and
bulimic patients may involve the endorphin system.
19. HORMONAL REGULATION OF BODY
WEIGHT
Norepinephrine and dopamine—released by sympathetic
nervous system in response to dietary intake.
Fasting and semistarvation lead to decreased levels of
these neurotransmitters—more epinephrine is made and
substrate is mobilized.
20. Hormones and Weight
Hypothyroidism may diminish adaptive thermo genesis.
Insulin resistance may impair adaptive thermo genesis.
Leptin is secreted in proportion to percent adipose tissue
and may regulate (decrease) appetite.
21.
22. Effects of Various Neurotransmitters, Receptors,
and Peptides on Food Intake
23. PROBLEMS ENHANCING AFTER THE OBESITY
Short-term problems
Obesity 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 that
can seriously harm your health, such as:
24. • high blood pressure (hypertension)
• high cholesterol levels (fatty deposits blocking your arteries)
• Both conditions significantly increase your risk of developing a
cardiovascular disease, such as:
• coronary heart disease, which may lead to a heart attack
stroke, which can cause significant disability and can be fatal.
Another long-term problem that can affect obese people is type
2 diabetes.
Psychological problems
In addition to the day-to-day problems of obesity, many people
may also experience psychological problems such as:
• low self-esteem
• low confidence levels
• feeling isolated in society
• These can affect relationships with family members and friends
and may lead to depression.
25. GENERAL APPROACH FOR TREATMENT
Non pharmacological treatment
Behavior Modification-The primary aim is to help
patients choose lifestyles that are conducive to safe
and sustained weight loss.
Most such programs use self-monitoring of diet and
daily exercise both to increase patient awareness of
behaviour, and as a tool for the clinician to determine
patient compliance as well as patient motivation.
26. DIET- Numerous diet or nutrition plans exist to aid in
weight loss should low calorie intake..
Surgery- Surgery remains the most effective intervention
for the treatment of obesity.
• its related morbidity and mortality, this intervention is
reserved for those with BMI greater than 40 kg/m2 or 35
kg/m2 .
• 60−62 Surgical procedures either reduce the stomach
volume and/or reduce the absorptive surface of the
alimentary tract, resulting in some degree of
malabsorption. Currently, the three major types of
procedures are: stapled gastroplasty, adjustable gastric
banding, and conventional Roux-en-Y gastric bypass.
27. A combined intervention of behavior therapy, dietary
changes and increased physical activity should be
maintained for at least 6 months before considering
pharmacotherapy.
28. PHARMACOLOGICAL THERAPY
LIPASE INHIBITORS
Orlistat- Gastrointestinal (gastric, pancreatic, and
carboxylester) lipases are essential in the absorption of the
long-chain triglycerides commonly found in Western diets.
Orlistat is minimally absorbed and selectively inhibits
gastrointestinal lipases. Lipase inhibition results in
decreased formation of free fatty acids from dietary
triglyceride.
Orlistat induces weight loss by a persistent lowering of
dietary fat absorption.
clinical trials demonstrate that orlistat effectively increases
the amount of weight lost and decreases the amount of
weight regained during medically supervised weight loss
programs.
29. NORADRENERGIC-SEROTONERGIC AGENTS
Sibutramine- increase synaptic concentrations of
serotonin, norepinephrine (NE), and dopamine via reuptake
inhibition.
1 to 30 mg daily dose having a good result.
Recommended starting dose 10 mg daily.
Dry mouth, anorexia, insomnia, constipation, appetite
decrease, dizziness, nausea adverse effect, they also
increase systolic and diastolic B P.
It should not be used in patients with a history of coronary
arteries disease, stroke, C H F, arythmiasis, and patient who
receive M A O inhibitor.
30. NORADRENERGIC AGENTS
Phentermine- similar to Amphetamine, has less severe
CNS stimulation and lower abuse potential.
Its M/A is related to enhance NE and dopamine
neurotransmitter.
A single dose of 30 mg daily in the morning provide
effective suppression. Divided dose of 8 mg immediately
prior to meal.
other similar drugs having same M/A respectively
Amphetamine > methamphetamine > phentermine >
mazindol > diethylpropion
Ephedrine in combination with caffeine has enhanced
appetite suppression and thermo genesis.
31. Oral doses of 20 mg ephedrine and 200 mg caffeine up to
three times daily have good effect .
Side effects are tremor, agitation, nervousness, increased
sweating, and insomnia; palpitations and tachycardia have
also been reported.
SEROTONERGIC AGENTS
Serotonin is an important neurotransmitter involved in
many human physiological systems. Sleep-wake cycles,
sensitivity to pain, blood pressure, mood, and eating
behaviors have links to serotonin activity.
Increasing central serotonin levels decreases the amount
of food consumed and prolongs the time between food
intake.
32. Antidepressants: Selective Serotonin Reuptake
Inhibitors
fluoxetine (60 mg/day) demonstrate initial weight loss of
up to 2 to 4 kg.
sertraline (200 mg/day) as an adjunct to help maintain
weight lost with a very-low-calorie diet.
Fenfluramine and Dexfenfluramine- Both agents increased
synaptic serotonin concentration via reuptake inhibition
and possibly by increasing serotonin release.
33. PEPTIDES- Multiple different endogenous
peptides, which play a role in the regulation of food
intake.
Leptin originates in the adipocyte and is proposed to
function as a peripheral feedback messenger with respect
to fat storage.
NPY and galanin are two CNS peptides that appear to
similarly stimulate food consumption, but have differing
effects on preference of carbohydrate or fat, as well as
substrate metabolism.
NPY and galanin are thought to exert minimal effects on
protein intake.
Galanin activity, centering in the lateral pera ventricular
nucleus and medial preoptic areas, increases both
carbohydrate and fat intake with preferential effects on fat
34. NPY and galanin modulate the release of
insulin, corticosterone, and vasopressin, further affecting
nutrient intake behaviors and substrate metabolism.
NPY is associated with increased levels of
insulin, corticosterone, and vasopressin, where as
decreases are seen with galanin. The macronutrient
intake, energy use, and endocrine effects of NPY are most
consistent with those seen in chronic obesity.
35. MISLLENOUS DRUGS
Rimonabent- it is selective cannabinoid receptor-1 (CB-1)
antagonist which is newer used as antiobesity drug. It
blocks hunger promoting action of cannabis to Decrease
appetite and help in weight reduction by obese. psychiatric
disorder are the adverse effect of this drug.
B3 Agonists- B3 receptor generally present on adipose
tissue where selective agonists of B3 BRL 373 44 are
being developed as potential antiobesity drugs.
Olestra – it is a sucrose polyester which can be used as a
cooking medium in place of fat but is neither digested nor
absorbed,
