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1 - PBS2 > 87 - Drugs Used in Obesity > Flashcards

87 - Drugs Used in Obesity Flashcards

1
Q

Examples of peptides that increase feeding (central)

1-5

A 
Neuropeptide Y 
Melanin concentrating hormone 
Agouti-related peptide 
Orexin A and B 
Endocannabinoids
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2
Q

Examples of peptides that promote satiety (central)

1-5

A 
Alpha-melanocyte stimulating hormone
Urocortin
Corticotrophin releasing hormone
Serotonin
Noradrenaline
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3
Q

Examples of peptides that increase feeding (peripheral)

A

Ghrelin

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4
Q

Examples of peripheral peptides that promote satiety

1-3

A

Leptin
Insulin
Cholecystokinin

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5
Q

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

A

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

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6
Q

How do satiety signals reach the brain?

A

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.

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7
Q

Rhythm of leptin release

A

Circadian rhythm (highest at midnight, reduce until noon)

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8
Q

How does leptin cross BBB?

A

Via a saturable process (transporter)

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9
Q

Where are leptin receptors located?

A

Hypothalamus

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10
Q

What secrete leptin?

A

Predominantly adipocytes.

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

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11
Q

Three ways in which leptin resistance can arise

A

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

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12
Q

Three targets for possible obesity treatments

A

Food intake
Fat
Thermogenesis

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13
Q

Way in which thermogenesis might be targeted for obesity treatment

A

Beta3 adrenoceptor agonists

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14
Q

Why in which fat absorption might be targeted for obesity treatment

A

Lipase inhibitors

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15
Q

TGA-approved anti-obesity drugs

A

1) Phentermine

2) Orlistat

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16
Q

Phentermine

A

Sympathomimetic amine
TGA approved
Can only be used short term

17
Q

Orlistat

A

Decrease dietary fat absorption
TGA approved
Can be used long term

18
Q

Sibutramine

A

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

19
Q

Rimonabant

A

CB1 antagonist.

No TGA approval, as increases risk of suicide

20
Q

Uses of phentermine

A

BMI over 30.

Can only be used short term (amphetamine derivative).

21
Q

Effect of phentermine

A

Non Ca2+-dependent NA release from neurons.

This suppresses appetite

22
Q

Adverse effects of phentermine

A 
Increased BP
Increased HR
Insomnia
Nervousness
Headache
Dry mouth
Addictive, induces tolerance
23
Q

Contraindications of phentermine

A

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

24
Q

When is orlistat prescribed?

A

BMI over 30kg/m^2

25
Q

Dosing of orlistat

A

Three times per day with meal (120mg)

26
Q

Mechanism of orlistat action

A

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.

27
Q

Effect of orlistat

A

Decreases dietary fat absorption by ~30%

28
Q

Clinical effects of orlistat

A

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

29
Q

Side effects of orlistat

A

Limited to GIT, because not absorbed systemically.

If eat fatty meals, can have explosive diarrhoea, faecal fat leakage.

30
Q

What must be combined with orlistat treatment?

A 
Low fat diet
Vitamin supplementation (D and E)
31
Q

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

A

Topiramate

32
Q

Mechanism of topiramate

A

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

33
Q

Adverse affects of topiramate

A

Dizziness
Taste alteration
Teratogenic

34
Q

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

A

Glucagon-like peptide-1 receptor agonist.

35
Q

Administration of glucagon-like peptide-1 receptor agonist

A

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

36
Q

Actions of GLP-1 receptor agonists

A 
Increased insulin secretion and synthesis
Decreased glucagon secretion.
Reduces gastric emptying 
Liver decreases glucose production
Increased glucose uptake into muscles
37
Q

Mechanism of GLP-1 agonist

1-4

A

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

38
Q

Adverse effects of GLP-1 agonist

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

1 - PBS2 (96 decks)

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