Obesity

Question 1

How can obesity develop?

Answer 1

Only when energy intake is greater than energy expenditure

Question 2

What is PubMed’s definition of obesity?

Answer 2

Too much body fat. NOT overweight

Question 3

What is Obesity Society Position White Paper’s definition of obesity?

Answer 3

Complex condition with many contributors such as genetic and environmental factors beyond patient control

Question 4

What is a commonly used diagnostic for obesity? Give classes for this diagnostic test

Answer 4

BMI Normal: 19-24.9 kg/m2 Overweight 25-29.9 kg/m2 Obese > 30 kg/m2

Question 5

What is the physiology of energy homeostasis?

Answer 5

1) Afferent system generates signal from fat, pancreas, and stomach 2) HP processes signal either thru orexigenic or anorexigenic neurons 3) Efferent system perform anabolism or catabolism by changing feeding behaviors and energy expenditure

Question 6

What is orexigenic? What is anorexigenic? Which one do we want more of for obese patients?

Answer 6

Orexigenic –> anabolic reactions –Makes you hungry and leads to lower energy consumption– Anorexigenic –> catabolism reactions (want this one to perform more in obese patients) –Makes you full and consume more energy–

Question 7

Why was thyroid hormone used as an obesity drug? Why did it fail?

Answer 7

Increased BMR –> more lipolysis It failed bc it could lead to hyperthyroidism

Question 8

Why was 2,4-dinitrophenol used as an obesity drug? Why did it fail?

Answer 8

It inhibited ATP production within the mitochondria and uncoupled phosphorylation leading to more energy consumption w/o ATP production –> creates a pore that leaked protons and disrupts ETC from creating potential It failed bc it could lead to cataracts, agranulocytosis (low WBC), and lethal hyperthermia

Question 9

What does 2,4-dinitrophenol structure look like?

Answer 9

Question 10

Why was amphetamine used as an obesity drug? Why did it fail?

Answer 10

It increased BMR, lipolysis, and activated alpha 1 and beta 2 in HP to decrease appetite.

(preferential monoamine release –> NE and DA)

Itdidn’t worktoo well because of potential for addition and signs of insomnia

Question 11

What is the structure of amphetamine look like?

Answer 11

Question 12

Why is Fenfluramine used to treat obesity? Why did it fail?

Answer 12

Same as amphetamine but preferentially releases 5HT (serotonin)

Which activates POMC/CART –> leads to anorexigenic

Caused pulmonary hypertensionand valvular heart disease by activity of 5HT2B receptors

Question 13

What is the MOA of phentermine? Short term or long term drug? What are CIs with this drug?

Answer 13

Induce NE and DA release (similar to amphetamine)

Used for short term treatment of obesity

CI: Hyperthyroidism, glaucoma, pregnant women

Question 14

What is Phentermine with Topiramate used for? What is the best hypothesis forTopiramate’s MOA?

Answer 14

CHRONIC weight management

• Topiramate decrease the activity of voltage-gated channels and AMP receptors in orexigenic neurons

Question 15

What is the MOA of Bupropion? Naltrexone?

What is the combination product used for?

Answer 15

Bupropion blocks reuptake of DA, NE, and 5HT

Naltrexone is mu-opiod receptor antagonist

The combination is used for long-term use for obesity

Question 16

What is Lorcaserin (drug class)? Which receptor is it selective for and what is its MOA? What is it used for?

Answer 16

Selective-serotonergic agent that is selective for the 5-HT2C agonist

Stimulates neurons with POMC/CART of HP which leads to increase of alpha MSH –> anorexigenic

Approved for long-term use management of obesity

Question 17

What is the structure of Lorcaserin look like?

Answer 17

Question 18

What is Orlistat (drug class)? Where is it derived from? What is its MOA? What is it used for?

Answer 18

Lipase inhibitor that is derived from Strep. Toxytricini

Orlistat decreases lipid absorption by attenuating gastric emptying and secretion of pancreaticabilliary substances