Obesity

Question 1

OBESITY DEFINITIONS

Answer 1

 Illness where the health (and hence life
expectancy) is adversely affected by excess
body fat
- BMI ≥ 25kg/m2: Overweight
- BMI ≥30kg/m2: Obese

 Multifactorial disorder of energy balance
- Calorie intake over the long term exceeds energy output

Question 2

Obesity factors

Answer 2

Lifestyle
Genetics
Culture
Diet

Question 3

What does GLP-1 do

Answer 3

• found in stomach
• stimulus to release after feeding
• target: bring stem, hypothalamus
• postpones need for next meal

Question 4

What does Leptin do

Answer 4

• found in Adipose tissue
• signal to release
• target; Brain stem, arcuate nucleus
• Effect: longer term regulation of food intake

‘P.”,
-

Question 5

‘Arcuate nucleus (ARC) of the hypothalamus
Axns

Answer 5

\
 Regulates appetite, feeding behavior and energy
status
 Receives afferent inputs originating from the GI
tract
 Contains receptors for leptin and other hormones
 Extensive reciprocal connections with other parts
of the hypoth

)

Question 6

Two groups of functionally distinct neurons that exert
opposite effects on appetite

Answer 6

1.Anorexigenic (appetite suppressing)

.
2. Orexigenic (appetite promoting) neurons

 Energy homeostasis depends on the balance between these actions
 Final effects realized by the brain stem motor system as changes in feeding behavior

Question 7

Anorexigenic (appetite suppressing)
Exs

Answer 7

 Pro-opiomelanocortin (POMC)-derived peptides (such as α. melanocyte-stimulating hormone; α-MSH)
 Cocaine- and amphetamine-regulated transcript (CART)-derived peptides

Question 8

Orexigenic (appetite promoting) neurons
Exs

Answer 8

 Neuropeptide Y (NPY)
 Agouti-related peptide (AgRP)

Question 9

PHARMACOLOGICAL APPROACHES TO OBESITY

Answer 9

As adjunct to caloric restriction, increased
physical activity and behavioral modification

For T2D: when choosing glucose-lowering
medications for overweight or obese patients
consider their effect on weight

Question 10

CENTRALLY-ACTING MEDICATIONS
Exs

Answer 10

‘Impair dietary intake by promoting satiety

1. Phentermine/
2. topiramate
3. Bupropion
4. Naltrexon
5. GLP-1 mimetics (liraglutide, semaglutide)

Question 11

Phentermine
PK PD

Answer 11

 Sympathomimetic amine: anorectic effects in
hypothalamus and limbic areas of the brain
-Increases the release of norepinephrine and dopamine (DA) —> increased POMC/CART neuron activity

 Can also be used as monotherapy

Question 12

Topiramate

Answer 12

Anti-epileptic drug that possibly suppresses appetite
and enhances satiety

Question 13

Bupropion (typical anti depressant): MoA

Answer 13

Increases DA activity in the brain,
reduction in appetite and increase in energy
expenditure by increased POMC neuron activity

Question 14

Naltrexon MoA

Answer 14

-Blocks opioid receptors on POMC neurons,
preventing feedback inhibition of these neurons with
increased POMC activity

-May regulate activity in the dopamine reward system of the brain that helps control food cravings and
overeating behaviors

Question 15

GLP-1 mimetics (liraglutide, semaglutide)
- glutide

Answer 15

promote weight loss in patients with or without
T2D
• GLP-1 is a regulator of appetite and calorie
intake
• GLP-1 receptor found in many areas of the
brain involved in appetite regulation

Question 16

PERIPHERALLY-ACTING MEDICATION

Answer 16

Orlistat

Question 17

ORLISTAT
MoA + what do they do

Answer 17

 Inhibits irreversibly gastric and pancreatic lipases  Prevents the breakdown of dietary fat to fatty acids and glycerols
 Decreases fat absorption
 Effective in T2D
 Reduces blood pressure
 Delays gastric emptying and gastric secretion
 Does not induce changes in energy expenditure

Question 18

ORLISTAT AE

Answer 18

Abdominal cramps, flatus with discharge, faecal
incontinence, intestinal borborygmi (rumbling), oily spotting

[ Supplementary therapy with fat-soluble
vitamins may be needed
 Absorption of drugs (e.g. contraceptive pills,
ciclosporin) may be decreased ]

Question 19

CHOOSING A DRUG
1st line…

Answer 19

 GLP-1 mimetics recommended as first-line
treatment
 Switch to orlistat if GLP-1 mimetic is not effective
or not well-tolerated
 Phentermine may be used as third-line treatment
 Combination treatment is less preferred

Question 20

DRUGS THAT MAY CAUSE WEIGHT GAIN

Answer 20

 TCAs  MAOIs  Anti-psychotics  SNRIs  Anti-convulsants (phenytoin, carbamazepine)  Anti-diabetics (insulin, sulfonylureas, thiazos)  α-blockers  β-blockers  Steroids

Question 21

DRUGS THAT MAY CAUSE WEIGHT LOSS

Answer 21

 Anti-infective agents  Anti-cancer drugs  Salbutamol  Theophylline  Amiodarone  Hydralazine  Methylphenidate  Fluoxetine  Galantamine  Rivastigmine  Sulfasalazine  Topiramate  Metformin