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Drugs Online > Anti-Obesity Drugs > Flashcards

Anti-Obesity Drugs Flashcards

1
Q

What percentage of Australians are overweight or obese?

A

67%

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2
Q

What percentage of overweight or obese account for the total disease burden in Australia?

A

8.4% - the 2nd leading risk factor behind tobacco use

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3
Q

What diseases are reported at higher rates in overweight and obese people?

A 
Arthritis 
Back pain/problems
Cancer
Diabetes
Cardiovascular disease
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4
Q

What socioeconomic groups is overweight/obesity more commonly in?

A
  • Lower socioeconomic
  • Rural populations
  • Some immigrant groups
  • Aboriginal and Torres Strait Islander people
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5
Q

Definition of overweight and obesity?

A

WHO defined them as abnormal or excessive fat accumulation that presents a risk to health

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6
Q

Between 19080 - 2015 how many countries did obesity prevalence double in?

A

73 countries

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7
Q

By the year 2030 what percentage of the worlds population will be overweight or obese?

A

58%

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8
Q

What is the desirable BMI range for young adults?

A

18.5 - 24.9 kg/m2

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9
Q

What BMI range is overweight defined as?

A

25 - 30 kg/m2.5

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10
Q

What waist circumference is classified as a adverse risk?

A

> 94cm in men

>80cm in women

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11
Q

What diseases are associated with overweight and obesity?

A
  • Cardiovascular (CHD, Stroke, CKD, HTN)
  • Respiratory (Asthma)
  • Mechanical (OA, Back pain)
  • Metabolic (DM, Gout)
  • Cancer (Breast, Ovary, Bowel, Esophageal, Liver, Kidney, Pancreatic, Uterine, Leukemia, Thyroid, Gallbladder)
  • Neurological (Dementia)
  • GI (Gallstones)
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12
Q

What stimuli can trigger the eating center?

A 
Tastes
Smells
Low BGL
Marijuana
Low temperatures
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13
Q

What stimuli can inhibit eating?

A

High ambient temps
Gut distention
Malaise
Sympathetic nervous system activity

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14
Q

What hypothalamic peptide is a potent stimulant of feeding?

A 
Neuropeptide Y (NPY)
(produced in the gut and inhibits the satiety center)
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15
Q

What is secreted by the stomach to stimulate appetite?

A

Ghrelin (blood levels of ghrelin fluctuate, decreasing after a meal and increasing prior to eating)

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16
Q

What neurotransmitters inhibit eating?

A

Monoamine neurotransmitters = noradrenaline and serotonin

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17
Q

What hormone stimulates the satiety center in the hypothalamus?

A

Cholecystokinin (CCK) = secreted in the GI system when triglycerides are digested in the small intestine

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18
Q

What tells the brain about body fat levels?

A

Adipose cells provide the brain with information about body fat levels through the secretion of leptin

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19
Q

Where are leptin receptors located?

A

Hypothalamus feeding centers of the brain

leptin increases energy expenditure

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20
Q

What drugs for other illnesses have been identified to promote weight loss?

A
  • Bupropion
  • Fluoxetine
  • Metformin
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21
Q

What is the name of drugs that reduce food intake?

A

Anorectic (anorexic)

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22
Q

How do serotonergic drugs work for weight loss?

A

Causes increased secretion of serotonin and is believed to act mainly in the hypothalamus, the appetite and satiety center of the brain.

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23
Q

What serotonergic drugs were approved in 1973 and 1996 in the USA?

A

Fenfluramine (Pondimin)
Dexfenfluramine (Redux)

It became common practice to prescribe one of two drugs with phentermine (“fen-phen” or dexfen-phen”).

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24
Q

What happened in 1997 from long term Fen-Phen treatment?

A

It was associated with valvular lesion, with incompetence of the aortic and mitral valves

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25
Q

What was also reported to significantly increase from Fen-Phen?

A

Primary Pulmonary Hypertension

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26
Q

How do noradrenergic drugs work? (Phentermine - duromine)

A
  • This group of drugs releases noradrenaline or blocks its re-uptake into the neurons of the hypothalamus.
  • The increase in noradrenaline in the brain areas that control appetite delays the onset of hunger sensation and decreases the drive to eat
  • Phentermine (Duromine) stimulates release of noradrenaline from the presynaptic granules.
  • Drugs in this group include amphetamines. Amphetamines are no longer recommended because of strong stimulatory properties and addictive potential.
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27
Q

Adverse effects of noradrenergic drugs? (Phentermine - duromine)

A
  • The most common side effects are: headache, insomnia, nervousness and irritability.
  • Other side effects include: palpitations, increased heart rate (>100bpm), high blood pressure.
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28
Q

Who should not take Phentermine (duromine - noradrenergic)?

A

Individuals with hyperthyroidism, glaucoma, advanced arteriosclerosis, htn, history of drug abuse.

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29
Q

In what countries is Phentermine (duromine) banned in due to pulmonary htn and valvular problems?

A

Europe and Britain

30
Q

Phentermine (duromine) still available in Australia?

A

Yes, it is still being prescribed in Australia, with more than 144,000 prescriptions for Phentermine (Duromine) issued in 1997.
- This drug is also available in Australia without prescription, online.

31
Q

How does a mixed noradrenergic-serotonergic drug work?

A

Unlike the other appetite suppressant drugs which act primarily by increasing the transmission of catecholamines such as noradrenaline or by stimulating serotonin release, thereby raising concentrations of these substances, Sibutramine only inhibits the re-uptake of these substances. It is also mildly thermogenic by central effects, possibly by activating the beta3-adrenergic system in the brown adipose tissue

32
Q

What is the name of a mixed noradrenergic-serotonergic drug ?

A

Sibutramine hydrochloride (Reductil)

This drug is a serotonin and noradrenaline re-uptake inhibitor and has the effect of reducing appetite and promoting a feeling of satiety after eating a meal. 
Most drugs of this class are prescribed for the treatment of depression.
33
Q

What are the complications associated with taking Reductil (Sibutramine)?

A
  • The drug increased heart rate and blood pressure and was not indicated in obese or overweight patients with a history of cardiovascular disease.
  • In October 2010, following the findings of a comprehensive study examining the potential cardiovascular risks and a split decision of an FDA advisory panel, Abbott Laboratories, the manufacturers of Sibutramine, withdrew Sibutramine from the US, Australia, and other countries.
34
Q

Side effects of Reductil (sibutramine)?

A

Possible adverse reactions include headache, dry mouth, anorexia, constipation, and insomnia. In trials, it also caused a mean increase in blood pressure (BP) and pulse rate

35
Q

What are drugs that increase energy expenditure?

A

Ephedrine & Caffeine

  • Ephedrine increases the release of noradrenaline which alters appetite control in the brain as well as stimulating heart rate and blood pressure to enhance energy expenditure.
  • Ephedrine probably stimulates the beta3-adrenergic receptors and stimulates weight loss in a dose-dependent manner.
  • Caffeine, an adenosine antagonist, reduces the breakdown of noradrenaline in the synaptic junction.
36
Q

Side effects of ephedrine and caffeine?

A
  • Side effects include tremor, insomnia and dizziness.
  • These drugs are not tolerated well in high doses.
  • The adverse effects include an acute increase in blood pressure, increased blood sugar level and severe tremor.
37
Q

What are drugs that interfere with food absorption?

A

Orlistat (Xenical) or Tetrahydrolipstatin is a derivative of lipstatin, an inhibitor of lipases isolated from the Gram-positive bacterium Streptomyces toxytricini.
Orlistat (Xenical), an anti-obesity agent that

38
Q

How does Orlistat (Xenical) work?

A

It interferes with nutrient absorption, is a gastric and pancreatic lipase inhibitor. It inhibits lipase in the gut and reduces the absorption of fat by approximately 30%
This fat is consequently passed in the stool, producing steatorrhea.

39
Q

Side effects of Orlistat?

A
  • Most patients develop adverse effects including fatty stools, loose stools, feacal urgency, flatulence and incontinence.
  • Reduced vitamin K absorption could alter the control of patients taking warfarin
40
Q

Metformin (diabex, diaformin) mechanism of action?

A
  • Reduces hepatic glucose output, improves peripheral sensitivity to insulin, inhibits gastrointestinal absorption of glucose, and reduces food intake
  • This agent also reduces free fatty acids; free fatty acid elevations have been linked to central obesity
41
Q

Side effects for metformin?

A 
Watery diarrhea
nausea
abdominal bloating/cramping
flatulence
anorexia occur in up to 50% of individuals taking this medication
42
Q

Topiramate (topamax) mechanism of action?

A

This antiepileptic drug which enhances the activity of gamma-aminobutyric acid (GABA) is known to promote significant weight loss, including reducing the frequency of binge eating

43
Q

Side effects of topiramate?

A

Central nervous system adverse effects (numbness, drowsiness and memory loss) limit the usefulness of this drug at this time.

44
Q

What is leptin?

A

Leptin (Gk leptos, “thin”) hormone is a protein produced by fat cells as a signal to the body about its energy stores.

45
Q

What happened in laboratory mice with high leptin levels?

A

In laboratory mice, high leptin levels were found to decrease food intake and increase their metabolic rate to become thinner.
When starving, the leptin levels drop and the brain senses a leptin level below personal threshold, i.e. starvation
That promotes the drive to eat by stimulating the vagus nerve.

46
Q

How does high leptin levels work in overweight people?

A

The body adapts to higher leptin levels and becomes resistant to its effects, similar to insulin resistance.
There appears to be no limit to the rise in leptin.
The ratio of leptin concentration in the cerebrospinal fluid (CSF) to leptin concentration in the blood appears to be lower in obese subjects
- The brain seems to be starved while the body is obese. Leptin also relates to eating “reward”.

47
Q

How does leptin relate to reward eating?

A

When low, it stimulates pleasure from eating, but when high the brain reward signal is not effective, so people eat more to try to achieve pleasure.

48
Q

What leptin based drug is used for weight loss?

A

Regeneron (Axokine) is a modified ciliary neurotrophic factor, originally marketed for stimulating the survival of nerve cells of the brain in motor neuron disease.
These patients seemed to lose considerable amounts of weight. It was secondarily discovered that it could activate non-leptin pathways in leptin resistant individuals, reducing appetite.

49
Q

What is the risk of taking Regeneron (Axokine) for weight loss?

A

It is now considered risky as it results in an immune response in 70% of patients, developing antibodies to the drug after 3 months.
This results in drug resistance and decreased effectiveness.
Axokine was subsequently discontinued

50
Q

What is the artificial uncouples?

A
  • This group of potential drugs works by increasing energy utilization by the body.
  • During the conversion of food into useful energy (e.g. ATP), heat is produced and lost.
  • This heat production instead of useful energy is influenced by specific proteins called the uncoupling proteins that were first identified in the brown fat of animals decades ago.
  • In animals, the uncoupling process helps animals stay alive in cold weather.
    Recently, proteins were identified in human cells which catalyze the uncoupling process in humans and became known as uncoupling proteins (UCP2 in brain, muscle, and fat; UCP3 in skeletal muscle).
51
Q

What are incretin mimetics (exenatide - byetta)

A
  • The intake of food stimulates the secretion of the incretin hormone glucagon-like peptide (GLP-1), which stimulates insulin secretion and inhibits glucagon release.
  • The release of GLP-1 also inhibits gastric emptying; additionally, this incretin hormone promotes satiety and reduces food intake by acting on the GLP-1 receptor in the brain
  • Exenatide (Byetta) is an incretin mimetic agent.
  • It increases glucose-dependent insulin secretion from pancreatic beta cells and hence only promotes insulin release in the presence of elevated glucose concentrations.
  • This drug is a synthetic version of exendin-4, a naturally-occurring hormone derived from the Gila monster salivary gland.
  • The amino acid sequence of exenatide partially overlaps that of the human incretin hormone GLP-1, but has a longer half-life than native GLP-1
52
Q

How do cannabinoid receptor antagonists work?

A
  • Cannabinoid receptors belong to the G-protein coupled receptor family.
  • The cannabinoid-1 receptor (CBR1) plays a role in the regulation of appetitive.
  • The cannabinoid antagonist agent suppresses appetite and increases metabolic rate by blocking the cannabinoid receptor-1 (CBR1) in the brain.
53
Q

What is a cannabinoid receptor antagonists drug called?

A

Rimonabant (Acomplia) = works on the premise that if cannabinoids stimulate appetite, blocking cannabinoid receptors in the brain might reduce appetite.
Ongoing Phase III trials of this drug have demonstrated weight loss with this drug is more dramatic than with existing drugs.

54
Q

Side effects of CBRI Rimonabant (Acomplia)?

A
  • Nausea, diarrhea, and adverse psychiatric events including anxiety, depression and suicidal ideation and attempts.
  • In 2008 Acomplia® was withdrawn from the European market after risk benefit analysis saw significant psychiatric depression that outweighed the weight loss benefits.
55
Q

How does a pancreatic hormone drug work for weight loss?

A

Pramlintide (Symlin/Amylin) slows gastric emptying and suppresses glucagon production by the liver during and after meals, which prevents circulating glucose fluctuations after a meal.
- is an analog of the human pancreatic hormone amylin.

56
Q

Ephedrine causes weight loss by stimulating ________ receptors?

A

Beta 3 -adrenergic

57
Q

It has been shown in animal studies that high leptin levels:

A

Increase their energy expenditure

58
Q

Which of the following ant obesity drugs are associated with an increased incidence of primary pulmonary hypertension?

A

Dexfenfluramine (Redux) and Fenfluramine (Pondimin)

59
Q

What is an adverse effect of caffiene?

A

Hypertension

60
Q

A body mass index of 25-29.9kg/m2 is classified as:

A

Overweight

61
Q

Which of the following type of agents slows gastric emptying?

A

Pramlintide (Symlin)

62
Q

The mechanism of action of Sibutramine is?

A

Inhibit both the reuptake of noradrenaline (norepinephrine) and serotonin in the brain

63
Q

The mechanism of action of phentermine (duromine) is?

A

Increases noradrenaline release from the presynaptic membrane

64
Q

Anorectic drugs include?

A

Fenfluramine (Pondimin) and Phentermine (duromine)

65
Q

What is a noradrenergic agent?

A

Phentermine (Duromine)

66
Q

Appetite is simulated by?

A

Cannabinoids

67
Q

Obese individuals are more prone to?

A

Depression and blood clots

68
Q

What anti-obesity drug is poorly absorbed when administered orally?

A

Orlistat (Xenical)

69
Q

What neurotransmitter is strongly implicated in appetite control?

A

Serotonin

70
Q

A cannabinoid antagonist promotes weight loss by?

A

Diminishing appetite

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