Centrally-Acting Anti-Obesity Agents

Question 1

What BMI ranges define overweight and obesity? (4)

Answer 1

• Overweight: 25-29.9
• Obesity Class I: 30-34.9
• Obesity Class II: 35-39.9
• Severe Obesity (Class III): ≥40.

Question 2

What waist circumference thresholds indicate increased health risks? (4)

Answer 2

Men: 94-102 cm (high risk) . 102 cm (very high risk).

Women: 80-88 cm (high risk), >88 cm (very high risk).

Question 3

What is energy homeostasis?

Answer 3

The balance between energy intake and expenditure, regulated by the brain in response to signals like glucose, FFAs, and gut peptides.

Question 4

Name the key brain circuits involved in feeding behaviour. (4)

Answer 4

• Arcuate Nucleus (ARC): Contains orexigenic (NPY, AgRP) and anorexigenic (POMC, α-MSH) neurons.
• Paraventricular Nucleus (PVN): Integrates feeding signals.
• Nucleus of Solitary Tract (NTS): Processes satiety signals.
• Reward Circuitry: Ventral Tegmental Area (VTA), Nucleus Accumbens (NAcc).

Question 5

How do gut peptides like GLP-1 and CCK regulate feeding?

Answer 5

They signal satiety by terminating meals and reducing food intake.

Question 6

What are the genetic factors associated with obesity?

Answer 6

Rare mutations affecting leptin (LEPR) and melanocortin pathways (e.g., POMC deficiency).

Question 7

What is the role of seratonin (5HT) in feeding behaviour? (2)

Answer 7

• Increases in synaptic 5HT decrease food intake
• Acts via 5HT1B, 5HT2C, and 5HT6 receptors in feeding circuits.

Question 8

What is Setmelanotide, and how does it work?

Answer 8

• Mechanism: Melanocotrin-4 receptor (MC4R) agonist that stimulates anorexigenic pathways.
• Approved for POMC and LEPR deficiency

Question 9

How does Orlistat aid in weight loss?

Answer 9

• Mechanism: Lipase inhibitor blocks fat digestion and absorption.
• Side Effects include oily stools and flatulence

Question 10

What are GLP-1 analogues, and how do they work?

Answer 10

Examples: Liraglutide (daily), Semaglutide (weekly).

Mechanism: Mimic GLP-1 to enhance satiety and delay gastric emptying.

Question 11

Why was Fenfluramine/Phentermine (“Fen-Phen”) withdrawn from the market?

Answer 11

Linked to cardiac valvulopathy and pulmonary hypertension.

Question 12

What are the components of the drug Contrave?

Answer 12

• Bupropion: DA/NA
• Naltrexone: Opioid receptor antagonist
• Targets reward-related eating.

Question 13

Why was Lorcaserin withdrawn in 2020?

Answer 13

Due to a slightly increased occurrence of cancer.

Question 14

How does Rimonabant work, and why was it withdrawn?

Answer 14

• Mechanism: CB1 receptor inverse agonist that supressed appetite.
• Withdrawn due to psychiatric effects.

Question 15

What is the NHS-recommended approach for obesity management? (3)

Answer 15

1. Lifestyle changes (diets, exercise).
2. Medications (e.g. Orlistat, GLP-1 analogues).
3. Surgery (BMI ≥ 40 or BMI ≥ 35 with comorbidities like T2DM).

Question 16

What is the primary mechanism of action of Phentermine/Topiramate?

Answer 16

Appetite suppression and enhance satiety through effects on multiple neurotransmitter systems.

Question 17

What are the common side effects of centrally acting anti-obesity agents?

Answer 17

Cardiovascular risks, psychiatric side effects, and gastrointestinal disturbances,

Question 18

How does Bupropion in Contrave assist in weight loss?

Answer 18

Acts as a DA/NA reuptake inhibitor, modulating the reward system.