87 - Drugs Used in Obesity

Question 1

Examples of peptides that increase feeding (central)

1-5

Answer 1

Neuropeptide Y 
Melanin concentrating hormone 
Agouti-related peptide 
Orexin A and B 
Endocannabinoids

Question 2

Examples of peptides that promote satiety (central)

1-5

Answer 2

Alpha-melanocyte stimulating hormone
Urocortin
Corticotrophin releasing hormone
Serotonin
Noradrenaline

Question 3

Examples of peptides that increase feeding (peripheral)

Answer 3

Ghrelin

Question 4

Examples of peripheral peptides that promote satiety

1-3

Answer 4

Leptin
Insulin
Cholecystokinin

Question 5

How do leptin and insulin reach the hypothalamus to modulate hunger?

Answer 5

Are transported across the BBB, because they are large peptides.

Question 6

How do satiety signals reach the brain?

Answer 6

CCK released from GIT following fatty meals.
CCK binds vagus nerve receptors, signal sent along vagus to nucleus tractus solitarius, which signals to hypothalamus to decrease appetite.

Liver also sends sympathetic signals to NTS.

Question 7

Rhythm of leptin release

Answer 7

Circadian rhythm (highest at midnight, reduce until noon)

Question 8

How does leptin cross BBB?

Answer 8

Via a saturable process (transporter)

Question 9

Where are leptin receptors located?

Answer 9

Hypothalamus

Question 10

What secrete leptin?

Answer 10

Predominantly adipocytes.

Also released by lung cells, immune cells, albeit at much lesser levels.

Question 11

Three ways in which leptin resistance can arise

Answer 11

Saturation of leptin transporters.
Hypothalamic leptin receptors become desensitised
Leptin receptor 2nd messenger systems become less sensitive

Question 12

Three targets for possible obesity treatments

Answer 12

Food intake
Fat
Thermogenesis

Question 13

Way in which thermogenesis might be targeted for obesity treatment

Answer 13

Beta3 adrenoceptor agonists

Question 14

Why in which fat absorption might be targeted for obesity treatment

Answer 14

Lipase inhibitors

Question 15

TGA-approved anti-obesity drugs

Answer 15

1) Phentermine

2) Orlistat

Question 16

Phentermine

Answer 16

Sympathomimetic amine
TGA approved
Can only be used short term

Question 17

Orlistat

Answer 17

Decrease dietary fat absorption
TGA approved
Can be used long term

Question 18

Sibutramine

Answer 18

Decrease NA and 5-HT uptake
Anti-obesity drug
TGA approval has been withdrawn (increases MI risk)

Question 19

Rimonabant

Answer 19

CB1 antagonist.

No TGA approval, as increases risk of suicide

Question 20

Uses of phentermine

Answer 20

BMI over 30.

Can only be used short term (amphetamine derivative).

Question 21

Effect of phentermine

Answer 21

Non Ca2+-dependent NA release from neurons.

This suppresses appetite

Question 22

Adverse effects of phentermine

Answer 22

Increased BP
Increased HR
Insomnia
Nervousness
Headache
Dry mouth
Addictive, induces tolerance

Question 23

Contraindications of phentermine

Answer 23

Other weight loss drugs
MAO inhibitors (and other antidepressants)
Not safe in pregnancy

Question 24

When is orlistat prescribed?

Answer 24

BMI over 30kg/m^2

Question 25

Dosing of orlistat

Answer 25

Three times per day with meal (120mg)

Question 26

Mechanism of orlistat action

Answer 26

Inhibits gastric and pancreatic lipases. Triglycerides need to be broken down into free fatty acids and monoglycerides to be absorbed by gut wall. This cannot occur if lipases are inhibited.

Question 27

Effect of orlistat

Answer 27

Decreases dietary fat absorption by ~30%

Question 28

Clinical effects of orlistat

Answer 28

Decrease body weight, waist circumference Restoration of insulin sensitivity Help resolve dislipidaemia, blood pressure

Question 29

Side effects of orlistat

Answer 29

Limited to GIT, because not absorbed systemically. | If eat fatty meals, can have explosive diarrhoea, faecal fat leakage.

Question 30

What must be combined with orlistat treatment?

Answer 30

``` Low fat diet Vitamin supplementation (D and E) ```

Question 31

Anti-epilepsy drug that is FDA approved for anti-obesity, in combination with phentermine

Answer 31

Topiramate

Question 32

Mechanism of topiramate

Answer 32

Unknown. Maybe increases energy expenditure, suppresses appetite, but the mechanism for these is unknown. Increases half-life of phentermine.

Question 33

Adverse affects of topiramate

Answer 33

Dizziness Taste alteration Teratogenic

Question 34

Anti-diabetes drug that is FDA approved for anti-obesity

Answer 34

Glucagon-like peptide-1 receptor agonist.

Question 35

Administration of glucagon-like peptide-1 receptor agonist

Answer 35

Injection (a peptide, so can't be digested without hydrolysis)

Question 36

Actions of GLP-1 receptor agonists

Answer 36

``` Increased insulin secretion and synthesis Decreased glucagon secretion. Reduces gastric emptying Liver decreases glucose production Increased glucose uptake into muscles ```

Question 37

Mechanism of GLP-1 agonist | 1-4

Answer 37

–Potentiates glucose mediated insulin secretion –Suppress glucagon secretion –Slows gastric emptying –Loss of appetite (central action)

Question 38

Adverse effects of GLP-1 agonist

Answer 38

``` Nausea Vomiting Diarrhoea Pancreatitis Hypoglycaemia (if patient doesn't have hyperglycaemia) ```