30. Anti-Obesity & T2 Diabetes Therapies Flashcards
Define
Laproscopic sleeve gastrectomy (LSG)
a weight loss procedure where about 75% of the stomach is removed leaving a narrow gastric “tube” or “sleeve”
Define
Sulfonylureas
a group of medicines used to treat type 2 diabetes. They act by increasing insulin release from the beta cells in the pancreas.
Define
Orlistat
a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake
Define
Lorcaserin
a weight-loss drug developed by Arena Pharmaceuticals. It reduces appetite by activating a type of serotonin receptor known as the 5-HT2C receptor in a region of the brain called the hypothalamus, which is known to control appetite
Define
Contrave
a combination (naltrexone/bupropion) medication for chronic weight management. It is for people with overweight and weight-related complications or obesity. It is meant to be used together with a lifestyle therapy regimen involving a reduced calorie diet and increased physical activity
Define
Laproscopic adjustable gastric band (LAGB)
a type of weight-loss surger where an inflatable silicone device placed around the top portion of the stomach to treat obesity, intended to decrease food consumption
Define
Incretin
a group of metabolic hormones that stimulate a decrease in blood glucose levels
Define
GLP-1 receptor agonists
a type of incretin-based medicine for type 2 diabetes. This type of medicine is based on the action of hormones called incretins, which help control how the pancreas works
Define
Bariatric surgery
surgery that affects your stomach and how you digest food. It’s designed to make your stomach much smaller, which causes you to feel full after eating only a small amount of food
Define
Metformin
marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain.
Definition
a weight loss procedure where about 75% of the stomach is removed leaving a narrow gastric “tube” or “sleeve”
Laproscopic sleeve gastrectomy (LSG)
Definition
a group of medicines used to treat type 2 diabetes. They act by increasing insulin release from the beta cells in the pancreas.
Sulfonylureas
Definition
a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet by acting as a lipase inhibitor, thereby reducing caloric intake
Orlistat
Definition
a weight-loss drug developed by Arena Pharmaceuticals. It reduces appetite by activating a type of serotonin receptor known as the 5-HT2C receptor in a region of the brain called the hypothalamus, which is known to control appetite
Lorcaserin
Definition
a combination (naltrexone/bupropion) medication for chronic weight management. It is for people with overweight and weight-related complications or obesity. It is meant to be used together with a lifestyle therapy regimen involving a reduced calorie diet and increased physical activity
Contrave
Definition
a type of weight-loss surger where an inflatable silicone device placed around the top portion of the stomach to treat obesity, intended to decrease food consumption
Laproscopic adjustable gastric band (LAGB)
Definition
a group of metabolic hormones that stimulate a decrease in blood glucose levels
Incretin
Definition
a type of incretin-based medicine for type 2 diabetes. This type of medicine is based on the action of hormones called incretins, which help control how the pancreas works
GLP-1 receptor agonists
Definition
surgery that affects your stomach and how you digest food. It’s designed to make your stomach much smaller, which causes you to feel full after eating only a small amount of food
Bariatric surgery
Definition
marketed under the trade name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain.
Metformin
What are the complications of diabetes?
Macrovascular disease (heart attack, stroke, angina etc)
Microvascular disease (diabetic retinopathy, end-stage renal disease, neuropathy etc.)
What causes the complications seen in diabetes?
Increased glucose levels cause an increase in glycosylation
What is the most common cause of blindness in industrialised countries?
Diabetic retinopathy
What percentage of diabetics have neuropathy?
50%
What is the first-line treatment for diabetes?
Changing lifestyle habits (diet and exercise)
What therapies are used for diabetes?
- Lifestyle (diet & exercise)
- Metformin (e.g. Glucophage, Glumetza)
- Sulfonyureas (e.g. Diabeta, Glucotrol)
- GLP-1 receptor agonists (e.g. Exenedin/ Liraglutide)
- DPP-4 inhibitors (e.g. Januvia, Onglyza)
- Thiazolidinediones (TZDs; e.g. Avandia, Actos)
- SGLT2 inhibitors new (e.g. Ivokana, Farxiga)
- Insulin
- Bariatric surgery
What is the first-line pharamcological treatment for diabetes?
Metformin
How does Metformin treat diabetes?
Prevents the progression of impaired glucose tolerance to T2DM by mimicing insulin
Increases levels of AMPK which allows GLUT4 translocation
How does Metformin act to improve glucose metabolism in the liver and skeletal muscle?
Why are Sulfonylureas no longer the first-line treatment for diabetes?
Complications include:
- May induce hypoglycemia as a result of excess insulin production and release (high dose, fasting).
- Weight gain.
- Can’t be used in pregnancy (may cause birth defects).
- Can’t be used in renal / liver failure due to high risks of hypoglcemia.
Why are Sulfonylureas not effective in T1D?
It acts to increase levels of insulin but insulin cannot be produced in T1D
What is the mechanism of sulfonylurea action?
Sulfonylureas block ATP-sensitive potassium channels causes K+ to acculmulate in the cell.
This causes cell depolarisation through calcium influx
Increased calcium levels cause insulin to be released from pancreatic beta cells
Where was GLP-1 receptor agonists originally found?
Saliva of the Gila monster
What are GLP-1 receptor agonists?
Incretin mimetics
The cause an increase in the amount of insulin released from the beta cells, even before glucose is is elevated
Works within 10 minutes of administration
What does the GLP-1 receptor do?
Inhibits food intake via GLP1-R
GLP-1 act directly at POMC neurons
Indirectly inhibits NPY/AGRP neurons via GABA
What are the new generation drug development strategies for diabetes?
Monotherapies
Combination Therapy
Personalised Medicine
Targeted Therapy
Which type of new gen drug does not act in the brain?
Orlistat (lipase inhibitor)
Where do the new generation drugs (Orlistat, Contrave, Liraglutide, Lorcaserin and Qsymia) act to treat diabetes?
- Lipase inhibitor
- Orlistat
- Predominant action via the melanocortin pathway
- Contrave
- Liraglutide
- Lorcaserin
- Wise-spectrum pharmacology acts at the brain
- Qsymia
What is the mode of action of Orlistat and what are the side-effects?
Inhibits lipase molecules preventing the breakdown and absorption of fats
Side effects include include cramping, gas, diarrhea, anal leakage and oily underwear stains
What is Lorcaserin and how does it treat diabetes?
Lorcaserin is a monotherapy that acts as a serotonin agonist selectively activates POMC neurons by targeting the 5-HT 2CR receptor specificlly
What two drugs does contrave include?
Bupropion
Naltrexone
How do the two contrave drugs (Naltrexone and Bupropion) cause synergistic effects?
Bupropion stimulates POMC neurons to release α-MSH
Naltrexone prevents the β-endorphin mediated POMC autoregulation
How are POMC cells autoregulated?
POMC cells produce both α-MSH and β-endorphins. The endorphins act on self receptors to repress activity
What is the only effect mechanims of long-term weight loss?
Bariatric surgery
Why is a Roux-en-Y gastric bypass (RYGB) rarely used in Australia?
High rates of malnutrition
At what point does the gastric band improve insulin sensitivity?
Following the weight loss caused by the surgery
What effects does the gastric sleeve have on ghrelin and gut peptides?
↓ ghrelin
↑ GLP-1
At what points does the gastric sleeve have an effect on insulin sensitivity?
Immediately irrespective of weight loss
Rapid nutrient passage into the small intesitine causes increased post-prandial insulin secretion cause glucose uptake
List the bariatric surgeries in order of decreasing effectiveness
- RYGB
- Sleeve (LSG)
- Band (LAGB)
