2. Obesity
• All of us love to have a well-built bodies, or at least
not to be obese, and we have the right to think like
that, because obesity is not just a cosmetic concern,
it's also a risk for some health problems, such as
heart disease, diabetes and the high blood pressure
and plenty of others.
3. • Now you want to know if you are obese or not, all you
want is to measure your weight in Kilograms (kg) and
your height in meters (m), and then use this formula
to calculate BMI.
4. • This formula will give you your body mass index (BMI).
• The obesity is diagnosed when the (BMI) is 30 or more.
BMI Result
Less than 18.5 Underweight
18.8-24.9 Normal
25-29.9 Overweight
30-34.5 Obese I
34.5-39.9 Obese II
>40 Morbid obesity
5. • In simple terms , obesity is an illness where the
quality as well as the life expectancy is adversely
affected by an excess body fat.
• Since Body Mass Index (BMI) depends on an
overall energy balance, obesity is defined as a
multifactorial disorder of energy balance in which
long term calorie intake exceeds energy output
which results in higher BMI.
6. ETIOLOGY OF OBESITY
• A heterogeneous group of disorders are associated with
obesity.
• Complexity of neuroendocrine and metabolic syndromes
regulate energy intake, storage and expenditure.
• Obesity is caused by imbalance between energy intake
and expenditure.
• Obesity is inherited in families
• Inheritance is not mendelian.
7. Regulation of appetite
• Appetite – lateral hypothalamus
• Satiety – ventromedial hypothalamus
Destruction of LHA leads to starvation and death.
Destruction of VMA leads to obesity.
8. HOMEOSTATIC CONTROL OF ENERGY
BALANCEAND FAT STORES
• LEPTIN is a peptide secreted by adipose tissue and acts
through the hypothalamus.
• It acts on two sets of neurons in the arcuate nucleus of
the hypothalamus with opposing actions
• Both group of neurons express leptin as well as insulin
receptors
• Leptin is called as thinning hormone.
9. LEPTIN
• Leptin acts on receptors in the hypothalamus of the brain
where it:
1. counteracts the effects of neuropeptide Y (NPY) /
agouti related peptide (AGRP) [a potent feeding
stimulant secreted by cells in the gut and in the
hypothalamus]
2. Activates neurons of preproopiomelanocortin (POMC)
to increase synthesis of α-MSH, an appetite
suppressant;
RESULT- inhibition of food intake.
10. STARVATION (↓ed fat stores OVERFED STATE (↑ed fat
or weight loss) store or weight gain)
↓ ↓
↓ed leptin from adipocytes ↑ed leptin from adipocytes
arcuate nucleus of hypothalamus
↓ ↓ ↓ ↓
↑ed NYP/ AGRP ↓ α-MSH ↓ NPY/ AGRP ↑ed α-MSH
↑ food intake ↓ food intake
↓ energy expenditure ↑ energy expenditure
↓ ↓
WEIGHT GAIN WEIGHT LOSS
NPY/AGRP POMC
neurons neurons
NPY/AGRP POMC
neurons neurons
11. LEPTIN
In addition to its effect on the hypothalamus, leptin acts
directly on:
• the cells of the liver and skeletal muscle where it
stimulates the oxidation of fatty acids in the mitochondria.
This reduces the storage of fat in those tissues (but not in
adipose tissue).
• T cells where it enhances the production of Th1 cells
promoting inflammation.
12.
13. • Common orexigenic factors (which stimulate feeding
behaviour) are :
Melanin concentrating hormone (MCH)
GABA
Growth hormone releasing hormone
Ghrelin
• Common anorexigenic factors (which inhibit feeding behaviour)
are :
Corticotropin releasing hormone
TNF-α
Glucagon like peptide (GLP)
Cholecystokinin
serotonin
14. GUT HORMONES
• PYY (Peptide YY)
1. Secreted from L cells of GI tract
2. Reduces food intake
• Ghrelin-
1. mainly secreted from stomach
2. A potent Orexigenic
• Cholecystokinin
1. Mainly secreted in duodenum
2. Decreasing meal size and duration both.
15. COMPLICATIONS OF OBESITY?
If you are obese you are at risk to have one or more of a great number
of obesity health problems. including:
•Type 2 diabetes.
•High blood pressure.
•Stroke.
•Heart disease.
•Gallbladder disease.
•Osteoarthritis.
•poor wound healing.
•Sleep apnea,( dangerous sleep disorder in which breathing repeatedly
stops and starts).
•High cholesterol and triglycerides.
•Metabolic syndrome.
•Cancer.
•Depression.
16. TREATMENT
The healthy weight is the main goal for obesity treatment and
you can reach that by making a good treatment plan with your
doctor and may be a big team of nutritionist, dietitian, obesity
specialist and nurse.
This plan include:
Dietary changes.
Exercise and activity.
Behavior change.
Prescription medication.
Weight-loss surgery.
17. DRUG TREATMENT
• Three mechanism mainly forms the basis for all currently
prescribed antiobesity drugs :
1) Supression of apetite via centrally active drugs that
alter monoamine neurotransmitters.
2) By reducing the absorption of lipids or fat from GIT.
3) by selectively blocking the central endocannabinoid
receptors (CB1)
18. CENTRALLYACTING ANOREXIANT
DRUGS
• All of them act by inhibiting the reuptake of NE or 5-HT
enhancing their neurotransmission.
Noradrenergic agents : phentermine, benzamphetamine,
diethylpropion, mazindol
( not used now bcoz of CNS stimulation, insomnia, tremors,
addiction liability and hypertension and tolerance)
• Serotonergic agents : fenfluramine, dexfenluramine
(obsolete due to cardiotoxicity, PHT and sudden deaths)
• Sibutramine : 5-HT and NE reuptake inhibitor. It is banned
by FDA in Oct 2010 due to cardiotoxicity
19. GI Lipase Inhibitor (ORLISTAT)
• Synthetic ester that inhibits gastric and pancreatic lipases
which are required for hydrolysis of dietary fat into fatty
acids that is the step prior to their absorption
• Also suitable for obese persons with additional risk factors
like diabetes and hypertension
• Dose 120mg Thrice daily per orally
• ADR : flatulence,
oily spotting
faecal urgency
Deficiency of vit A D E K
steatorrhea
20. • Contraindications : malabsorption of fat
cholestasis
pregnancy n lactating mother
• Metabolism – In GI Tract to inactive metabolites.
• Excretion – Faeces ( 97 % ). 83 % is unchanged.
• Half Life – 14 – 19 hrs
• FDA Approval – for adults and adolescents as well as
children in 2007
21. • Precautions –
1. Patient should take 3 main meals into which dietary
constituents are equally divided.
2. Multivitamins are to be added
3. High fat diet should be avoided as it will lead to fatty
large stools.
• Overdose – it is safe as significant overdoses are seen
without any harmful effects.
• Pellets – pelletized formulations increasing surface area
of the drugs are also available.
22. • Advantages –
1. Weight loss observed within 2 weeks of starting therapy
2. 6 kg weight loss in a year
3. Decrease LDL cholesterol, and raises HDL cholesterol.
4. Reduces Systolic and Diastolic blood pressure.
5. Reduces waist and hip circumferance
6. Weight regain is also less significant.
23. CANNABINOID RECEPTOR
ANTAGONIST
• Two types : CB1 and CB2
• CB1 are abundant in brain and CB2 are predominantly
present on immune cells
• CB1 thought to control food intake by reinforcing
motivation to consume food
• RIMONABANT : selective CB1 antagonist
dose : 20 mg OD p.o.
ADR : CNS depression with suicidal tendencies, anxiety,
nausea
It is also banned now due to increasing suicidal tendencies.
24. LORCACERIN
• Approved by FDA in 2012 for chronic weight management
• Mechanism : 5-HT2c receptor agonist
• Dose : 10 mg twice daily
• Adverse effects : Headache, nausea, dry mouth,
dizziness, fatigue, constipation
• Contraindication : Pregnancy and breastfeeding
Use with caution with : SSRI, SNRI/MAOI,
St John’s wort, triptans, buproprion,dextromethorphan
25. QNEXA
• It is combination drug of phentermine and topiramate
• FDA approved the combination in 2012 for chronic weight
loss
• Mechanism : GABA receptor modulation (T) plus
Norepinephrine releasing agent (P)
• Dose : 7.5 mg P/46 mg T daily (recommended dose)
• Adverse reaction: Insomnia, dry mouth, constipation,
paraesthesia, dizziness, dysgeusia
• Contraindication : Pregnancy and breastfeeding,
hyperthyroidism, glaucoma, MAO inhibitor,
sympathomimetic amines
26. Naltrexone / bupropion
• FDA approved the combination in 2014 for chronic weight
loss
• Mechanism : Reuptake inhibitor of dopamine and
norepinephrine (bupropion) and opioid antagonist
(naltrexone)
• Dose : 32 mg/360 mg 2 tablets QID (high dose)
• Adverse reaction : Nausea, constipation, headache,
vomiting, dizziness
• Contraindication : Uncontrolled hypertension, seizure
disorders, anorexia nervosa or bulimia, drug or alcohol
withdrawal, MAO inhibitors
27. LIRAGLUTIDE
• FDA approved the combination in 2014 for chronic weight
loss
• Mechanism : GLP-1 agonist
• Dose : 3.0 mg injectable
• Adverse reaction : Nausea, vomiting, pancreatitis
• Contraindication : Medullary thyroid cancer history,
multiple endocrine neoplasia type 2 history
28. AMYLIN PRAMLINTIDE
• Part of the endocrine pancreas and contributes to
glycemic control
• Functions as a synergistic partner to insulin
• It is co secreted from pancreatic beta cells in response to
meals
• MOA : Reduction of food intake, slowing of gastric
emptying, inhibition of digestive secretion
• It was recently approved for adult use in patients with both
diabetes mellitus type 1 and diabetes mellitus type 2
• Insulin and pramlintide, injected separately but both
before a meal,
