Obesity

Question 1

Non-Pharmacological Treatments of Obesity

Answer 1

Exercise

Diet
- Calorie Restrictions
- Ketogenic Diet

Surgical/Medical Devices
- Gastric Bypass

Question 2

NPY Neurons

Answer 2

Oxygenic

Question 3

AgRP Neurons

Answer 3

Oxygenic

Question 4

POMC Neurons

Answer 4

Anorexigenic

Question 5

CART Neurons

Answer 5

Anorexigenic

Question 6

Oxygenic

Answer 6

• Promote Food Intake
• Decrease Energy Expenditure

Question 7

Anorexigenic

Answer 7

• Inhibit Food Intake
• Increase Energy Expenditure

Question 8

POMC/CART
- Leptin

Answer 8

Leptin stimulates POMC/CART
- Increases Energy Expenditure
- Decreases Feeding

Question 9

POMC/CART
- GLP-1

Answer 9

GLP-1 stimulates POMC/CART
- Increases Energy Expenditure
- Decreases Feeding

Question 10

POMC/CART
- Insulin

Answer 10

Insulin stimulates POMC/CART
- Increases Energy Expenditure
- Decreases Feeding

Question 11

POMC/CART
- 5-HT

Answer 11

5-HT stimulates POMC/CART
- Increases Energy Expenditure
- Decreases Feeding

Question 12

POMC/CART
- Opioids

Answer 12

Opioids inhibits
POMC/CART
- Decreases Energy Expenditure
- Increases Feeding

Question 13

POMC/CART
- NPY

Answer 13

NPY inhibits POMC/CART
- Decreases Energy Expenditure
- Increases Feeding

Question 14

POMC/CART
- Orexin

Answer 14

Orexin inhibits
POMC/CART
- Decreases Energy Expenditure
- Increases Feeding

Question 15

Leptin
- MOA

Answer 15

Adipokine
- Peptide Hormone from Adipose Tissue
- Doesn’t treat obesity, decreases appetite, only really works on people with Leptin deficiency

Acts on Leptin Receptors in the Hypothalamus
- Reduces AMPK Signals
–> Less Protein Kinase leading to suppression of appetite

Question 16

AMPK Signaling

Answer 16

High AMPK Signals
- Happens when Low Energy/Hungry
- Increases Appetite

Low AMPK Signals
- Happens when High Energy/Well Fed
- Decrease Appetite

Question 17

Liraglutide
- MOA
- Adverse

Answer 17

GLP-1R Agonist
- GPCR (Gs)

Activates GLP-1R in the Hypothalamus
- Increases cAMP
–> Reduced appetite

Adverse:
- Increases Heart Rate
- Pancreatitis

Question 18

Liraglutide
- Dose

Answer 18

1.8 mg for Type 2 Diabetes
3.0 mg for Obesity

Question 19

Semaglutide
- MOA
- Adverse

Answer 19

Newer Treatment
GLP-1R Agonist
- GPCR (Gs)

Activates GLP-1R in the Hypothalamus
- Increases cAMP
–> Reduced appetite

Adverse:
- Increases Heart Rate
- Pancreatitis

Question 20

Semaglutide
- Dose

Answer 20

1.0 mg once weekly for type 2 diabetes
2.4 mg once weekly for obesity

Question 21

Liraglutide/Semaglutide
- Kinetic

Answer 21

Kinetic:
- Acylation prolongs half life, allows it to bind to albumin

Question 22

Orlistat
- MOA
- Adverse

Answer 22

LIpase Inhibitor
- Targets serine residues on active sites of gastric and pancreatic lipases
–> Reversibly inhibits enzymatic activity of lipases

Lipases can no longer break down fat meaning fat can not be absorbed
- Only therapy that functions peripherally and does not centrally act for diabetes

Adverse:
- Flatulence/Fecal Incontinence
- Intestinal Borborygmic
- Oily Spotting

Question 23

Orlistat
- Kinetic

Answer 23

Kinetic
- Primarily excreted in the feces (~97%) with minimal metabolism (~83% unchanged)
- Half-life of 1-2 hours

Question 24

Lorcaserin
- MOA
- Adverse

Answer 24

Selective 5-HT2C Receptor Agonist
- Increases POMC expression in Hypothalamus
–> Increases satiety (fullness)

Adverse:
Valvular Heart Disease

Question 25

Phentermine/Topiramate - MOA - Dose - Adverse

Answer 25

Phentermine: Sympathomimetic Amine - Amine Receptor Agonist Topiramate: Anticonvulsant Agent - Acts on Na+/Ca2+ --> Inhibits Carbonic Anhydrase Dose: 3.75x / 23y Adverse: - Paresthesia (Tingling) - Insomnia - Heart Rate Elevation --> Do not take with Monoamine Oxidase Inhibitors - Teratogenic Graduated downtitration over 3-5 days due to seizure risk with immediate withdrawal

Question 26

Topiramate

Answer 26

Topiramate: Anticonvulsant Agent - Acts on Na+/Ca2+ --> Inhibits Carbonic Anhydrase Monotherapy can decrease appetite in binge eating Combination Therapy with Phentermine - Reduces Body Weight

Question 27

Bupropion/Naltrexone - MOA - Dose - Adverse

Answer 27

Bupropion: NA/DA Reuptake Inhibitor - Treats depression - Metabolite (Hydroxybupropion) can antagonize nicotinic acetylcholine receptors Naltrexone: Competitive Opioid Receptor Antagonist - Mu and K Opioid Receptor Antagonist Together they modify the reward pathway to reduce appetite Dose: Week 1: 8 mg / 90 mg Week 2: 16 mg / 180 mg Week 3: 24 mg / 270 mg Week 4: 32 mg / 360 mg Adverse: - Increased Heart Rate and Blood Pressure

Question 28

Tirzepatide

Answer 28

Unimolecular Co-Agonist - GLP-1 Receptor Agonist - GIP Receptor Agonist Greater weight loss than just a mono GLP-1 agonist

Question 29

Retatrutide

Answer 29

Triple Agonist - GLP-1 Receptor Agonist - GIP Receptor Agonist - Glucagon Receptor Agonist Makes co-agonist better Glucagon increases energy expenditure

Question 30

Picking a suitable drug for obesity

Answer 30

If 5% weight loss is not achieved in first 3-4 months change medications (Unless risk factors show improvement)