Drugs Used in Obesity

Question 1

What are the limitations of body mass index (BMI)?

Answer 1

Doesn’t take lean muscle mass into account

Age/gender/ethnicity differences

Question 2

What are the weight classifications of BMI?

Answer 2

Underweight 30

Morbid obese >40

Question 3

What are some factors contributing to the increasing incidence of obesity?

Answer 3

Susceptibility genes
Decline in physical activity
Eat more
Energy dense food
Sleep deprivation
Cultural and SE status

Question 4

What causes obesity to be the second most common cause of preventable death?

Answer 4

Co-morbidities

Question 5

What are the co-morbidities of obesity?

Answer 5

Diabetes
Sleep apnoea
Osteoarthritis
Cancer
Non-alcoholic fatty liver disease
Coronary heart disease
Hypertension

Question 6

What are the long-term mechanisms for control of appetite?

Answer 6

Adiposity signals

• Insulin
• Leptin

Question 7

How does leptin affect appetite?

Answer 7

Accesses hypothalamus

Changes expression and release of various neuropeptides

Question 8

What are the short-term mechanisms for control of appetite?

Answer 8

Satiety signals

• Nerve input
• CCK
• Other hormones and neurohormones

Question 9

Where is short-term satiety regulated in the brain?

Answer 9

Medulla

Question 10

Which hormone increases hunger and how?

Answer 10

Ghrelin released from stomach when its empty > goes to medulla > hunger

Question 11

What does it mean for drug therapy design since it’s a complex system of peptides that regulates food intake?

Answer 11

Need cocktail of drugs with multiple targets for successful treatment

Question 12

Which cells predominantly secrete leptin?

Answer 12

Fat cells

Question 13

What are plasma levels of leptin proportional to?

Answer 13

BMI

Fat

Question 14

Where are the receptors for leptin located?

Answer 14

Hypothalamus

Question 15

Are leptin defects relevant to human obesity?

Answer 15

Only in very small number of patients

Question 16

Why may leptin insensitivity develop in obesity?

Answer 16

Trouble crossing BBB

Down-regulation of leptin receptors

Question 17

What do beta3-adrenergi receptor agonists do?

Answer 17

Increase thermogenesis > increase energy expenditure

Question 18

What do all obesity treating drugs need to be combined with?

Answer 18

Very low calorie diet

Increased exercise

Question 19

What is phentermine?

Answer 19

Amphetamine derivative that increase noradrenaline availability to bind to receptors
Suppresses appetite

Question 20

How is phentermine used?

Answer 20

BMI >30
Only useful in short-term
- Usually for 4-6 weeks
- Up to 12 weeks

Question 21

How does phentermine work?

Answer 21

Competes with noradrenaline for neuronal re-uptake receptors > taken up
Displaces noradrenaline from vesicles
Increased noradrenaline intracellularly > Ca-independent release
More noradrenaline binds to post-synaptic receptors

Question 22

What are the adverse effects of phentermine?

Answer 22

Increased BP and HR
Insomnia
Nervousness
Headache
Dry mouth

Question 23

Does tolerance and dependenc develop to phentermine?

Answer 23

Some dependence

Tolerance, yes > why used in short term

Question 24

What are the contra-indications for phentermine?

Answer 24

Other weight loss dugs
MAO inhibitors
Pregnancy

Question 25

What is orlistat?

Answer 25

Gastric and pancreatic lipase inhibitor | Decreases dietary fat absorption

Question 26

When is orlistat used?

Answer 26

BMI >30

Question 27

How does orlistat work?

Answer 27

Covalently binds to lipases in gut to inhibit their activity

Question 28

What does orlistat reduce?

Answer 28

``` Body weight Waist circumference Blood glucose Insulin Dyslipidaemia Blood pressure ```

Question 29

What are the adverse effects of orlistat?

Answer 29

Mainly GI > controlled if adhere to low fat diet - Explosive diarrhoea - Faecal fat leakage

Question 30

What must orlistat be combined with?

Answer 30

Low fat diet | Vitamin E and D supplementation

Question 31

What is liraglutide?

Answer 31

Glucagon-like peptide-1 (GLP-1) receptor agonist

Question 32

What are the adverse effects of liraglutide?

Answer 32

Nausea Diarrhoea Rare: pancreatitis

Question 33

What are the actions of GLP-1 agonists?

Answer 33

``` Increase - Neuroprotection - Insulin - Insulin biosynthesis - Glucose uptake and storag Decrease - Appetite - Gastric emptying - Glucagon secretion - Glucose production ```

Question 34

What is topiramate?

Answer 34

Used for epilepsy and migraine | Off-label use for weight loss

Question 35

What does topimarate do?

Answer 35

Energy expenditure | Appetite suppression

Question 36

What are the adverse effects of topimarate?

Answer 36

Dizziness Taste alteration Teratogenic