obesity management

Dr. AKHTAR ALI
Resident first year
department of
pharmacology
Dr. S. N. Medical college
Jodhpur (raj.)

Obesity represents a state of excess
storage of body fat.
Overweight puristically is defined as an
excess body weight for height.
While adult men have a body fat
percentage of 15-20%, women have a
higher proportion (approximately 25-
30%).
Monday, June 12, 2017
2

Now with the (BMI) you
can diagnose yourself as
an obese or not, but still
one problem. Some
people like the muscular
athletes find their (BMI)
higher than normal, when
they most likely have a
normal amounts of fat in
their bodies, and the
answer is that, they
weight more not because
of fat, but because of
muscles.

 Genetic – familial tendency.
 Sex – women more susceptible .
 Activity – lack of physical activity.
 Psychogenic – emotional deprivation,
depression .
 Social class – poorer classes.
 Alcohol – problem drinking.
 Smoking – cessation smoking.
 Prescribed drugs – tricyclic derivatives.
4

•Inactivity:
without activity you don’t
burn as much calories. and
you need to have more
exercise to burn the
excessive calories.

•Diets: some bad eating habits
like high calories diets epically in
the night, or skipping a healthy
breakfast, and replace it by junk
fast food, all of that increase the
body fat .
•Pregnancy: some women after
the baby is born have an
increasing in their weight, and if
they don’t lose that weight, with
many pregnancies after that,
they may become obese.

•Lack of sleep: this cause disturbances
in the body hormones, and increase the
appetite. you also may crave to height
calories food.
•Drugs: some medications lead the
body to gain more weight, these drugs
include, diabetes medications, steroids
and beta blockers, anti-seizure
medications, antipsychotic medications
and antidepressants drugs.

•Medical conditions: some diseases and syndromes lead the
body to store more fat and gain weight like Cushing syndrome.
some disease low the metabolic rate in the body and low the
amount of burned calories every day such as the
hypothyroidism. And some diseases lead the patient to low his
activity, such as the arthritis or maybe the patients with
paraplegia
•Genetics: genes affect the amount of body fat we store and
where to store,
•Family lifestyle: not because of the genes we find the obesity
runs in the families, it also because of their life style and the food
they eat. We can notice that some countries such as USA, have
more obese people than others countries like Japan and this is
because the culture and the life style.

•Age: obesity could occur at any age, but when we get age
we lose more amount of muscles built. more amount of
muscles give higher rate of metabolism and calories burning.
When we lose them we reduce the calories burning and tend
to fill the body with fat.
9

Because differences in weight
among individuals are only
partly due to body fat
variations, body weight is a
rather limited, although easily
obtained, index of obesity.
10

 Body mass index (BMI), also known as
the Quetelet index, is far more
commonly used to define obesity and
has been found to closely correlate
with the degree of body fat in most
settings.

11

 BMI = (weight [kg]) / (height [m])2.
 Body fat percentage can be estimated
using the Deurenberg equation.
 Body fat percentage = 1.2(BMI) +
0.23(age [y]) – 10.8(sex) – 5.4, with
males coded as 1 and females as 0.
 This formula has a standard error of
4% and explains approximately 80% of
the variation in body fat.
12

 Other indices used to estimate the
degree and distribution of obesity
include the 4 standard skin thicknesses
(ie, subscapular, triceps, biceps,
suprailiac) and various anthropometric
measures, of which waist and hip
circumferences are the most important.
13

 World Health Organization (WHO)
criteria based on BMI. for adults:
 grade 1 (overweight ) BMI of 25-
29.9 kg/m2.
 Grade 2 overweight (obesity) BMI of
30-39.9 kg/m2.
 Grade 3 overweight (severe or
morbid obesity) BMI greater than or
equal to 40 kg/m2.
14

 Surgical literature ( different
classification) for recognize severe
obesity.
 BMI greater than 40 kg/m2 (severe
obesity)
 BMI of 40-50 kg/m2 (morbid obesity)
 BMI greater than 50 kg/m2 ( super
obese)
15

 Adipocyte: is the cellular basis for
obesity, is being found to be an
increasingly complex and metabolically
active cell.
 the adipocyte is being perceived more
frequently as an endocrine gland with
several peptides and metabolites that
may have relevance to the control of
body weight.
16

 products of the adipocyte involved in the complex intermediary
metabolism:
 cytokines
 tumor necrosis factor-alpha
 interleukin-6
 lipotransin,
 adipocyte lipid-binding protein
 acyl stimulation protein
 prostaglandins
 adipsin
 perilipins
 lactate
 adiponectin
 monobutyrin
 phospholipid transfer protein
17

 critical enzymes involved in adipocyte
metabolism:
 endothelial lipoprotein lipase (involved in lipid
storage)
 hormone-sensitive lipase (involved in lipid
elaboration and release from adipocyte depots)
 acylcoenzyme A (acyl-CoA) synthetases
(involved in fatty acid synthesis),
 and a cascade of enzymes (involved in beta
oxidation and fatty acid metabolism)
18

 The pathogenesis of obesity is far more
complex than the simple paradigm of
an imbalance between energy intake
and energy output.
20

 The high prevalence of obesity in the
children of parents who are obese and
the high concordance of obesity in
identical twins suggest a significant
genetic component to the pathogenesis
of obesity, the secular trends of the last
few decades, which are coincident with
recent changes in dietary habits and
activity, also suggest a significant role
for environmental factors.
21

 Leptin was discovered in 1994 by
Friedman et al and ushered in an
explosion of research and a great
increase in knowledge about regulation
of the human feeding and eating cycle.
22

 The major role of leptin in body weight
regulation is to signal satiety to the
hypothalamus and, thus, reduce
dietary intake and fat storage while
modulating energy expenditure and
carbohydrate metabolism to prevent
further weight gain.
23

 Unfortunately, unlike the Ob/Ob mouse
model in which this peptide was first
characterized, most humans who are
obese are not leptin-deficient but
rather leptin-resistant and, thus, have
elevated circulating leptin levels.
24

Disease Examples
Depression Tricyclics
Seizures Valproic acid, Tegretol
Hypertension Clonidine, α-blockers, β-blockers
Hormones Progesterone
25

 Energy imbalance
 calories consumed not equal to
calories used
 Over a long period of time
 Due to a combination of several
factors
 Individual behaviors
 Social interactions
 Environmental factors
 Genetics
32

3500 calories = 1 pound
 100 calories extra per day
 = 36,500 extra per year
 = 10.4 lbs weight gain
 Question: How much is 100 calories?
 Answer: Not very much!
 1 glass skim milk, or
 1 banana, or
 1 slice cheese, or
 1 tablespoon butter
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 More in and less out = weight gain
 More out and less in = weight loss
 Hypothalamus
 control center for hunger and satiety
 Endocrine disorder
 where are the hormones?
34

 Hormone secreted in the stomach
 Acts on the hypothalamus to stimulate
appetite
 Levels peak just before meals and drop
afterward
35

•Naturally occurring hormone that plays a role in satiety
and weight maintenance.
•Produced in adipocytes
•Its role in weight regulation is related to its effects on the
hypothalamus, where it leads to:
• satiety
•decreased food intake
•increased energy expenditure in the periphery
36

 Leptin
 Dieting decreases leptin levels
 Reducing metabolism, stimulating
appetite
 Ghrelin
 Levels in dieters are higher after weight
loss
 The body steps up ghrelin production in
response to weight loss
 The higher the weight loss, the higher the
ghrelin levels
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 Contributes to approximately 300,000 deaths a year,
making it 2nd
only to smoking as a cause of death
 Contributes or causes to many other health problems
including:
 Type 2 Diabetes Mellitus
 Coronary Artery Disease
 Degenerative Joint Disease
 Certain Types of Cancer
 Nonalcoholic Steatohepatitis
40

 Major cause of
preventable death
 Increase in
mortality from all
causes
 Increase in risk for
these cancers
 Endometrium
 Breast
 Prostate
 Colon
 Increase in risk of:
 Hypertension
 Dyslipidemia
 Diabetes type 2
 Coronary artery
disease
 Stroke
 Gallbladder disease
 Osteoarthritis
 Sleep apnea &
respiratory
problems
43

 Assess the patient's readiness and willingness
to lose weight :
 Unfortunately those who are most concerned
about their weights are not necessarily those
who are at the highest health risk.
 Those who are unable or unwilling to embark
on a weight reduction program, but they are
willing to take steps to avoid further weight
gain or perhaps to work on other risk factors
such as cigarette smoking, and they should
be encouraged to do so.
 For those not ready to act, the issue should
be deferred and brought up at the next visit
44

 Assess for other risk factors
 Existing high risk disease:
 coronary heart disease; other atherosclerotic
diseases; type 2 diabetes; sleep apnea
 Diseases associated with obesity
 Gynecological problems; osteoarthritis; gallstones;
stress incontinence
 Cardiovascular risk factors (3 or more = high risk)
 Cigarette smoking; Hypertension; LDL >130; HDL
<35; fasting glucose = 110 to 125; family history
of premature CHD; men age > 45; women age >
55
 Other risk factors
 Physical inactivity; elevated serum triglycerides
 Medications associated with obesity
45

 A multi-faceted
approach is best
 Diet
 Physical activity
 Behavior change
 “A”
Recommendation
46

 Initial goal: 10% weight loss
 Significantly decreases risk factors
 Rate of weight loss
 1 to 2 pounds per week
 Reduction of caloric intake 500-1000 per day
 Slow weight loss is more stable
 Rapid weight loss is almost always followed
by weight gain
 Rapid weight loss increases risk for
gallstones & electrolyte abnormalities
47

 Aim for 4 - 6 months of weight loss effort
 Most people will lose 20 to 25 pounds
 After 6 months, weight loss is more difficult
 Ghrelin & Leptin are at work!
 Changes in resting metabolic rate
 Energy requirements decrease as weight
decreases
 Diet adherence wavers
 Set goals for weight maintenance for next 6
months, then reassess.
48

 Weight reduction with dietary treatment
is in order for virtually all patients with a
BMI 25-30 who have comorbidities and
for all patients over BMI 30.
 Strategies of dietary therapy include
teaching about calorie content of different
foods, food composition (fats,
carbohydrates, and proteins), reading
nutrition labels, types of foods to buy,
and how to prepare foods.
49

 1000 to 1200
kcal/day for women
 1200 to 1600
kcal/day for men
 Adjust for current
weight & activity
 Too hungry?
 increase kcal by
100 - 200/day
 Not losing?
 decrease kcal by
100 - 200/day
50

Nutrient Recommended intake
Calories 500 to 1000 kcal/day reduction from
usual
Total fat <30% of total calories
Cholesterol <300 mg per day
Protein <15% of total calories
Carbohydrate >55% of total calories
Sodium
Chloride
<2.4 g sodium, or <6 g sodium chloride
Calcium 1000 to 1500 mg/day
Fiber 20 to 30 g/day
51

 Physical activity should be an integral part of
weight loss
 Physical activity alone is less successful than
a combined diet & exercise program
 Increased activity alone
does not decrease weight
 Sustained activity does
prevent weight regain
 Reduces risk for heart disease & diabetes
52

 Start slowly
 Many obese people live sedentary lives
 Avoid injury
 Early changes can be activities of daily living
 Increase intensity & duration gradually
 Long-term goal
 30 to 45 minutes or more of physical activity
 5 or more days per week
 Burn 1000+ calories per week
53

 What does it take to burn
1000 calories per week?
Running
11 miles
Walking
12 miles
Dancing 3 hours
Gardening
5 hours
Cycling 22 miles
54

 Keep a journal of diet & activity
 Very powerful intervention!
 Set specific goals re: behaviors
 Eating
 Activity
 Related behaviors
 Track improvement
 Weigh & measure on a regular basis
55

 Focus on the goals
 Plan meals & activity
 Develop reminder systems
 Anticipate temptations & plan resistance
 Reward yourself
 Limit quantities, but do not deprive
yourself
 Have confidence in your ability to
succeed
 Do positive self-talk
56

•A combined intervention of behavior therapy, dietary
changes and increased physical activity should be
maintained for at least 6 months before considering
pharmacotherapy.
NHLBI Obesity Education Initiative, Expert Panel on the Identification, Evaluation, and Treatment of
Overweight and Obesity in Adults
57

 BMI of 30 kg/m² or more or a BMI of 27
kg/m² or more with comorbid condition
 Understand that drug therapy is adjunctive
to lifestyle intervention
 Have realistic expectations about weight
loss goals and outcomes
 Demonstrate readiness for change
 Are unable to lose/maintain weight with
lifestyle change alone
 Comply with medication use
 Have no medical or psychiatric
contraindications
58

•Weight loss drugs should never be used without continued
concomitant lifestyle modifications and as part of a
comprehensive weight loss program.
•Continual assessment of drug therapy for efficacy and safety is
necessary.
•If the drug is efficacious in helping the patient to lose and/or
maintain weight loss and there are no serious adverse effects, it
can be continued.
•If not, it should be discontinued.
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 Pregnancy or lactation
 Unstable cardiac disease
 Uncontrolled hypertension (SBP >180, DBP > 110 mmHg)
 Unstable severe systemic illness
 Unstable psychiatric disorder or history of anorexia
 Other drug therapy, if incompatible (eg MAO inhibitors,
migraine drugs, adrenergic agents, arrhythmic potential)
 Closed angle glaucoma (caution)
 General anesthesia
60

 These drugs are only modestly effective
 2 to 10 kilogram loss
 Most occurs in the first 6 months
 If patient does not lose 2 kilograms in
the first 4 weeks, success is unlikely
 If the first 6 months is successful,
continue medication as long as…
 It is effective in maintaining weight, and
 Adverse effects are not serious
61

 Reducing food intake. Either amplify effects of signals/factors
that inhibit food intake or block signals/factors that augment food intake
 Blocking nutrient absorption (especially fat or
carbohydrates) in the intestine.
 Increasing thermogenesis. Either increase metabolism and
dissipate food energy as heat or increase energy expenditure through the
enhancement of physical activity.
 Modulating fat metabolism/storage. Regulate fat
synthesis/breakdown by making appropriate adjustments to food intake or
energy expenditure.
 Modulating the central regulation of body
weight. Either alter the internal set point or modulate the signals
presented regarding fat stores.
63

Generic/Brand Name Usual Dose Mechanism of Action Side Effects
•Orlistat/Xenical
•Sibutramine/Meridia
•Phentermine/
Adipex, Fastin,
Ionamin and others
•rimonabant
120 mg with each
meal
5-15 mg/d
15-37.5 mg per
day as a single or
split dose
withdrawal
Peripheral: Blocks
absorption of about
30% of consumed fat
Central: Inhibits
synaptic reuptake of
norepinephrine and
serotonin
Central: Stimulates
release of
norepinephrine
Antagonist og CB1
receptor
GI symptoms (oily
spotting, flatus with
discharge, fecal urgency,
oily stools, incontinence)
Dry mouth,
constipation,
headache, insomnia,
increased blood
pressure, tachycardia
CNS stimulation,
tachycardia, dry
mouth, insomnia,
palpitations
Suicidal tendency
64

Generic/Brand Name Usual Dose Mechanism of Action Side Effects
•ephedrine+/-caffeine
"Elsinore"pill
•Bupropion/Wellbutrin
•Topiramate/Topamax
Varies: usually
75-150 mg
ephedrine and
100-150 mg
caffeine
100-300 mg/d
96-192 mg/d
Central: Stimulates
adrenergic receptors
Central: Inhibits
reuptake of
dopamine
norepinephrine and
serotonin
Uncertain: Central ?
CNS stimulation,
tachycardia, dry
mouth, insomnia,
palpitations
CNS stimulation,
dry mouth,
headache, GI
effects
CNS: paresthesia,
fatigue, dizziness,
memory difficulty,
concentration
difficulty, and
depression
65

 Appetite suppressant that works by blocking
reuptake of serotonin and norepinephrine.
 Some experts have postulated that this agent
may be the most effective in helping maintain
weight loss.
 Maintaining weight loss has long been the major
downfall to most diet programs.
 Until recently, the longest clinical trials with this
agent have lasted 1 year.
66

Among obese patients who should undergo drug therapy,
sibutramine works best for those who:
 Experience difficulty controlling food intake
 Do not feel full
 Think about food a lot
 Do not have increased cardiovascular disease risk or
multiple risk factors
 Are younger
Sibutramine is taken once daily with or without food.
67

The use of sibutramine is
contraindicated in patients:
 Taking concomitant monoamine
oxidase inhibitor (MAOI) therapy
 With anorexia nervosa
 Using any other centrally-acting
appetite suppressant
 With hypersensitivity to ingredients
of sibutramine
68

 In addition, sibutramine should not be
used by patients who have:
 uncontrolled hypertension
 coronary heart disease
 congestive heart failure
 Arrhythmias
 stroke
 severe renal or liver dysfunction
 Sibutramine should be used with
caution in patients with narrow-angle
glaucoma.
69

 Can result in dry mouth, constipation,
headache, insomnia, increased blood
pressure, tachycardia.
 Should monitor all patients once a
month for hypertension and side effects
 Should take in the morning to avoid
insomnia
70

 Pancreatic lipase inhibitor that blocks the
absorption of up to one third of ingested fat.
 In addition to helping reduce weight, orlistat has
been shown to also:
 lower plasma low-density lipoprotein cholesterol (LDL)
cholesterol levels.
 The decline in LDL cholesterol is greater than that
expected due to weight loss alone.
 Lower HgbA1C in diabetic patients
71

Among obese patients who meet the criteria for
anti-obesity drug therapy, orlistat is most likely
to benefit those who:
 Do not feel hungry
 Are not preoccupied with food
 Eat out or order-in often
 Have increased cardiovascular disease risk or
multiple cardiovascular risk factors
 Are older
 Take multiple medications
Orlistat is taken 3 times daily with meals
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 Because it blocks intestinal absorption of fat it
can result in diarrhea and steatorrhea
 This is minimized by maintaining a strict low fat
diet (<30% of diet)
 Another concern is the loss of fat soluble vitamins
with a potential for malnutrition.
 To prevent this, recommend a daily multivitamin
for all patients on this therapy
73

 Topiramate is a novel antiepileptic drug approved
by the FDA as an antiseizure medication.
 When reports surfaced that patients enrolled in
initial trials of the drug and also in clinical practice
were experiencing unexpected weight loss, the
effects of the drug on weight began to be studied.
 Mechanism for weight loss is still poorly
understood
74

 47,000 in 2001; 98,000 in 2003
 Types of Obesity Surgery:
 1. Restrictive Surgery - uses bands or staples to
create food intake restriction:
 Vertical Banded Gastroplasty (VBG) - is a “pure”
restrictive surgery since it only involves surgically
creating a stomach pouch. VBG uses bands and
staples and is the most frequently performed
procedure for obesity surgery.
 Gastric Banding – involves the use of a band to
create the stomach pouch.
 Laparoscopic Gastric Banding (Lap-Band),
approved by the FDA in June 2001, is a less invasive
procedure in which smaller incisions are made to
apply the band. The band is inflatable and can be
adjusted over time
76

 2. Combined Restrictive and Malabsorptive
Surgery - is a combination of restrictive surgery
(stomach pouch) with bypass (malabsorptive
surgery), in which the stomach is connected to the
jejunum or ileum of the small intestine, bypassing the
duodenum.
 Roux-en-Y Gastric Bypass (RGB) - is the most commonly
performed gastric bypass procedure, and the second most
frequently performed surgery for obesity after VBG. RGB
involves a stomach pouch for food intake restriction. A direct
connection, which is Y-shaped, is made from the ileum or
jejunum to the stomach pouch for malabsorption.
 Biliopancreatic Diversion (BPD) - is one of the most
complicated obesity surgery, sometimes involving the
removal of a portion of the stomach. The remaining section
of the stomach is connected to the ileum. BPD successfully
promotes weight loss, but this procedure is typically used for
persons with severe obesity who have a BMI of 50 or more
77

 Indications
 100 pounds overweight or more
 Or, BMI > 40
 Or, BMI > 35 and 2 significant
comorbidities
 Age 18 to 60
 Documented failure at nonsurgical
efforts
 Psychological stability
78

 Roux-en-Y gastric bypass
 Limits food intake
 Alters digestion
Figure from NIDDK website
79

 Complications of surgery
 Mortality
 <1% mortality in healthy young adults BMI < 50
 2-4% mortality in patients with disease and BMI >
60
 Operative complications
 < 10%
 Late complications are uncommon
 Incisional hernias
 Gallstones
 Vitamin B12 & iron deficiency
 Weight loss failure
 Neurologic symptoms in unusual cases
80

 Durable weight loss
 One study followed pts for 14 years
 Average excess weight loss =
61.2%
 77% with diabetes no longer
require meds
 From Wald meta-analysis in JAMA 2004)
81

 Schedule a return visit in 2 to 4 weeks after
starting weight loss plan
 Monitor treatment effectiveness & side
effects
 Schedule monthly visits for first 3 months
 If making favorable progress
 See more frequently if monitoring medical
complications or chronic disease
 Reduce frequency of visits after 6 months
82

 Monitor weight, BP, pulse at each visit
 Monitor waist size intermittently
 Share progress with patient; praise efforts
 Share lab results with patient
 Emphasize findings associated with weight
reduction
 Focus on medical benefits
 Most weight loss doesn’t reach individual’s
‘ideal’ (cosmetic) goal
83

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