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PHARM 243 (Midterm 2) > Endocrine 2 (Type 2 Diabetes | Cardio Risk ) > Flashcards

Endocrine 2 (Type 2 Diabetes | Cardio Risk ) Flashcards

1
Q

What is Type 2 Diabetes

A

Insulin Resistance
Hyperinsulinemia
Hyperglycemia

  • Later stages beta-cell destruction
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2
Q

Type 1 vs Type 2 Diabetes

A

Type 1 can be treated with insulin therapy

Type 2 can only be treated with insulin therapy at later stages

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3
Q

Methods to lower glucose in Type 2 Diabetes

A

Overcome Insulin Resistance

Insulin Independent Methods of Glucose-Lowering

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4
Q

Overcome Insulin Resistance
- Methods?

A
  • Insulin Secretagogues
  • Thiazolidinedione
  • Metformin?
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5
Q

Insulin Independent Methods of Glucose-Lowering
- Methods?

A

Decrease Hepatic Glucose Production
- Metformin

Prevent Dietary Glucose Absorption
- Alpha-Glucosidase Inhibitors

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6
Q

Secretagogues
- Examples

A

1st Generation Sulfonylureas
- Tolbutamide, Chlorpropamide, Acetohexamide

2nd Generation Sulfonylureas
- Glyburide, Glipizide, Glimepiride

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7
Q

Secretagogues
- 1st vs 2nd Generation

A

2nd Generation Sulfonylureas:
- More potent
- Shorter half life
- Fewer side effects

Less dose needed to get insulin secretion

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8
Q

Secretagogues
- MOA

A
  1. Sulfonylurea binds the sulfonylurea receptor/subunit of the K(ATP) channel
  2. Inhibits K(ATP) channel
  3. Prevents K+ efflux causing depolarization
  4. Activates Ca2+ channels causing Ca2+ influx
  5. Exocytosis of insulin from insulin granules

Result: Increased Insulin Secretion to overcome Insulin resistance

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9
Q

Secretagogues
- Adverse Effects

A
  • Hypoglycemia
  • Weight Gain
  • Cardiovascular Complications (KATP channels are important in preventing ischemic events)
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10
Q

Non-Sulfonylurea Secretagogues
- Example

A
  • Repaglinide
  • Nateglinide
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11
Q

Non-Sulfonylurea Secretagogues
- MOA

A
  1. Binds to a different site on K(ATP) Channel
  2. Inhibits K(ATP) channel
  3. Prevents K+ efflux causing depolarization
  4. Activates Ca2+ channels causing Ca2+ influx
  5. Exocytosis of insulin from insulin granules

More selective for beta cell K(ATP) channels than cardiac cell K(ATP) channels

Rapid onset and Short duration
- Lower risk of hypoglycemia

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12
Q

Alpha-Glucosidase Inhibitors
- Examples

A
  • Acarbose
  • Miglitol
  • Voglibose
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13
Q

Alpha-Glucosidase Inhibitors
- MOA

A
  1. Competitive inhibitor of intestinal alpha-glucosidase enzyme.
  2. Preventing the breakdown disaccharides
  3. Delays/Decreases absorption of monosaccharides
  4. Reduces postprandial glucose rise

Result: Preventing dietary glucose absorption, thus, lowering glucose

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14
Q

Alpha-Glucosidase Inhibitors
- Adverse Effects

A
  • Least effective oral antidiabetic drug
  • Does not influence insulin = No Hypoglycemia
  • Unbroken sugars cause issues GI issues
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15
Q

Thiazolidinediones
- Examples

A

Rosiglitazone, Pioglitazone, Troglitazone

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16
Q

Thiazolidinediones
- MOA

A

Insulin Sensitizer
1. Peroxisome Proliferator Activated Receptor Gamma Agonist (PPAR Gamma)
- Nuclear Receptor in Adipose Tissue
2. Manages gene expression to promote uptake and storage of fatty acids into adipose tissue
3. Improves muscle insulin sensitivity as excess fat is not stored in organs

Takes 6-12 Weeks to reach full effect

17
Q

Thiazolidinediones
- Adverse Effects

A
  • Weight Gain
  • Cardiovascular (Rosiglitazone does not actually increase risk of heart attacks, however, its reputation is already ruined)
  • Cancer
18
Q

Biguanides
- Examples

A

Metformin

19
Q

Biguanides
- MOA

A

First Line Therapy
- Increases AMPK, an important regulator in energy metabolism
- Inhibits Glucagon Signaling in Liver
- Decreases hepatic gluconeogenesis
- Promotes glucose uptake skeletal muscle

20
Q

Biguanides
- AMPK

A
  1. Metformin increases AMPK
  2. AMPK inhibits Acetyl CoA Carboxylase (ACC)
  3. Increased fatty acid oxidation (Breakdown of Fat)
  4. Decreased Hepatic Glucose Production
    (Less Fatty Liver = Less Glucose Production)

Result: Lower Blood Glucose Levels

21
Q

Biguanides
- Glucagon

A
  1. Metformin inhibits Glucagon signaling
  2. Prevents Glucagon from activating Hepatic Gluconeogenesis
  3. Decreased Hepatic Glucose Production

Result: Lower Blood Glucose Levels

22
Q

Biguanides
- Adverse Effects

A
  • Independent from Insulin = No Hypoglycemia
  • GI Symptoms
  • Lactic Acidosis (Phenformin)
    –> Build up of lactic acid does acidifies the blood

PHARM 243 (Midterm 2) (11 decks)

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