Diabetes Medications Flashcards
Mechanism/Target of Metformin
Activates AMP-Kinase (exact mechanism unknown)
↓ Hepatic gluconeogenesis, glycogenolysis, FFA breakdown
↑ glycolysis
↑ insulin sensitivity in the peripheral tissues
First-line therapy in Type 2 DM
Mechanism/Target Sulfonylureas
Closes SUR1 KATP channel on B-cells: inhibits the channel; deplorizes the cell, leads to Ca influx, insulin release. This mimics fed-state
↑ insulin secretion
Mechanism/Target Meglitinides
Closes SUR1 KATP channel on B-cells: inhibits the channel; deplorizes the cell, leads to Ca influx, insulin release. This mimics fed-state
↑ insulin secretion
“fast acting sulfonylureas” - target post-prandial glucose
Mechanism/Target Thiazolidinediones (TZD)
Activates nuclear factor PPAR-gamma
↑ insulin sensitivity
Mechanism/Target of Acarbose/Miglitol
Inhibits intestinal alpha-glucosidase; glucosidases found in intestinal brush borders include: maltase, isomaltase, sucrose, and glucoamylase
decrease CHO absorption
Mechanism/Target of GLP-1 Agonists
Actives GLP-1 receptor; GLP-1 secreted after ingestion of food (e.g., incretins)
↓ gastric emptying ↑ satiety ↑insulin secretion (BG dependent) ↓ glucagon secretion (BG dependent)
*SQ administration
Mechanism/Target of DPP-IV (dipeptidyl peptidase) inhibitor
Inhibits DPP-IV activity and therefore ↑ GLP-1 level; DPP-IV normally inactivates GLP-1
↑ insulin secretions (BG dependent)
↓ glucagon secretion
Metformin - Class
Biguanide
Tolbutamide - Class
First generation Sulfanylurea
Chlorpropamide - Class
First generation Sulfanylurea
Glyburide - Class
Second generation Sulfanylurea
Glimepiride - Class
Second generation Sulfanylurea
Glipizide - Class
Second generation Sulfanylurea
Advantages/Disadvantages of Metformin
A
Low cost No hypoglycemia ↓ macrovascular (UKPDS) Neutral weight effect Can be used in patients without islet function
D
GI upset (nausea/diarrhea) Lactic acidosis Vit B12 deficiency Contraindicated SCr > 1.4
Advantages/Disadvantages of Sulfonylureas
A
Low Cost
↓ microvascular
(UKPDS)
D
hypoglycemia (second generation)
disulfuram effects (first generation)
Weight gain
Require some islet function
Advantages/Disadvantages of Meglitinides
A
Dosing flexibility
D
Hypoglycemia
? CV effects
$$$
Weight gain
Advantages/Disadvantages of TZDs
A
No hypoglycemia
↑ HDL
D
Edema/fluid retention/CHF/hepatotoxic
↑ MI (rosiglitazone)
↑ bladder CA (pioglitazone)
Weight gain
Advantages/Disadvantages of Acarbose/Miglitol
A
↓ post-prandial excursion
? ↓ macroevents (STOP-NIDDM)
Neutral/Lose Weight
D
GI; flatulence, diarrhea
Advantages/Disadvantages of GLP-1 agonists
A
No hypoglycemia events
Weight reduction
? CV protection effects
D
\$\$$ GI side effects (n/v) Injection ? acute pancreatitis ? medullary thyroid CA in animals
Advantages/Disadvantages of DPP IV inhibitors
A
No hypoglycemia
Well tolerated
Neutral weight effect
D
$$$
urticarial/angioedema
? pancreatitis
mild urinary or respiratory infections
Glargine
Long-acting insulin
Detemir
Long-acting insulin
NPH
Medium-acting insulin
Aspart
Rapid-acting insulin
