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MD1 Metabolism > Drugs Used in Obesity > Flashcards

Drugs Used in Obesity Flashcards

1
Q

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

A

Doesn’t take lean muscle mass into account

Age/gender/ethnicity differences

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2
Q

What are the weight classifications of BMI?

A

Underweight 30

Morbid obese >40

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3
Q

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

A 
Susceptibility genes
Decline in physical activity
Eat more
Energy dense food
Sleep deprivation
Cultural and SE status
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4
Q

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

A

Co-morbidities

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5
Q

What are the co-morbidities of obesity?

A 
Diabetes
Sleep apnoea
Osteoarthritis
Cancer
Non-alcoholic fatty liver disease
Coronary heart disease
Hypertension
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6
Q

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

A

Adiposity signals

  • Insulin
  • Leptin
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7
Q

How does leptin affect appetite?

A

Accesses hypothalamus

Changes expression and release of various neuropeptides

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8
Q

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

A

Satiety signals

  • Nerve input
  • CCK
  • Other hormones and neurohormones
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9
Q

Where is short-term satiety regulated in the brain?

A

Medulla

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10
Q

Which hormone increases hunger and how?

A

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

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11
Q

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

A

Need cocktail of drugs with multiple targets for successful treatment

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12
Q

Which cells predominantly secrete leptin?

A

Fat cells

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13
Q

What are plasma levels of leptin proportional to?

A

BMI

Fat

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14
Q

Where are the receptors for leptin located?

A

Hypothalamus

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15
Q

Are leptin defects relevant to human obesity?

A

Only in very small number of patients

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16
Q

Why may leptin insensitivity develop in obesity?

A

Trouble crossing BBB

Down-regulation of leptin receptors

17
Q

What do beta3-adrenergi receptor agonists do?

A

Increase thermogenesis > increase energy expenditure

18
Q

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

A

Very low calorie diet

Increased exercise

19
Q

What is phentermine?

A

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

20
Q

How is phentermine used?

A

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

21
Q

How does phentermine work?

A

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

22
Q

What are the adverse effects of phentermine?

A 
Increased BP and HR
Insomnia
Nervousness
Headache
Dry mouth
23
Q

Does tolerance and dependenc develop to phentermine?

A

Some dependence

Tolerance, yes > why used in short term

24
Q

What are the contra-indications for phentermine?

A

Other weight loss dugs
MAO inhibitors
Pregnancy

25
Q

What is orlistat?

A

Gastric and pancreatic lipase inhibitor

Decreases dietary fat absorption

26
Q

When is orlistat used?

A

BMI >30

27
Q

How does orlistat work?

A

Covalently binds to lipases in gut to inhibit their activity

28
Q

What does orlistat reduce?

A 
Body weight
Waist circumference
Blood glucose
Insulin
Dyslipidaemia
Blood pressure
29
Q

What are the adverse effects of orlistat?

A

Mainly GI > controlled if adhere to low fat diet

  • Explosive diarrhoea
  • Faecal fat leakage
30
Q

What must orlistat be combined with?

A

Low fat diet

Vitamin E and D supplementation

31
Q

What is liraglutide?

A

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

32
Q

What are the adverse effects of liraglutide?

A

Nausea
Diarrhoea
Rare: pancreatitis

33
Q

What are the actions of GLP-1 agonists?

A 
Increase
- Neuroprotection
- Insulin
- Insulin biosynthesis
- Glucose uptake and storag
Decrease
- Appetite
- Gastric emptying
- Glucagon secretion
- Glucose production
34
Q

What is topiramate?

A

Used for epilepsy and migraine

Off-label use for weight loss

35
Q

What does topimarate do?

A

Energy expenditure

Appetite suppression

36
Q

What are the adverse effects of topimarate?

A

Dizziness
Taste alteration
Teratogenic

MD1 Metabolism (18 decks)

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