Non-Insulin Drugs to Treat Diabetes Flashcards
Sulfonylureas are used in the treatment of diabetes?
• 1st generation?
• 2nd Generation?
Sulfonylureas:
- *1st Chlorpropamide, tolbutamide**
- *2nd Glyburide, glipizide, glimepiride – the “G-ides”**
Chorapropamide
MOA
T1DM/T2DM?
Metabolism
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
Metabolism:
These are extensively protein bound, metabolized by the liver and excreted by the kidney
Chlorapropamide
Side Effects
Contraindications
Administration
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
Side Effects:
Hypoglycemia, Renal failure, first generations (chloropropamide, and tolbutamide) have disulfram-like effects.
Contraindications:
NSAIDs cause increased likelihood of hypoglycemic events
Administration:
Oral
Tolbutamide
MOA
T1DM/T2DM?
Metabolism
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
Metabolism:
These are extensively protein bound, metabolized by the liver and excreted by the kidney
Tolbutamide
Side Effects
Contraindications
Administration
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
Side Effects:
Hypoglycemia, Renal failure, first generations (chloropropamide, and tolbutamide) have disulfram-like effects.
Contraindications:
NSAIDs cause increased likelihood of hypoglycemic events
Administration:
Oral
Glyburide
MOA
T1DM/T2DM?
Metabolism
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
Metabolism:
These are extensively protein bound, metabolized by the liver and excreted by the kidney
Glyburide
Side Effects
Contraindications
Administration
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
Side Effects:
Hypoglycemia, Renal failure, first generations (chloropropamide, and tolbutamide) have disulfram-like effects.
Contraindications:
NSAIDs cause increased likelihood of hypoglycemic events
Administration:
Oral
Glipizide
MOA
T1DM/T2DM?
Metabolism
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
Metabolism:
These are extensively protein bound, metabolized by the liver and excreted by the kidney
Glipizide
Side Effects
Contraindications
Administration
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
Side Effects:
Hypoglycemia, Renal failure, first generations (chloropropamide, and tolbutamide) have disulfram-like effects.
Contraindications:
NSAIDs cause increased likelihood of hypoglycemic events
Administration:
Oral
Glimpiride
MOA
T1DM/T2DM?
Metabolism
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
Metabolism:
These are extensively protein bound, metabolized by the liver and excreted by the kidney
Glimepiride
Side Effects
Contraindications
Administration
Sulfonylureas: 1st Chlorpropamide, tolbutamide; 2nd Glyburide, glipizide, glimepiride – the “G-ides”
**TD2M tx only…Requires Islet cell function**
Side Effects:
Hypoglycemia, Renal failure, first generations (chloropropamide, and tolbutamide) have disulfram-like effects.
Contraindications:
NSAIDs cause increased likelihood of hypoglycemic events
Administration:
Oral
What Meglintinides are used in the treatment of Diabetes?
Meglitinides: repaglinide, nateglinide – the “glinides”
*Similar function to sulfonureas, but different structure
Repaglinide
MOA
Metabolism
T1DM/T2DM?
- *Meglitinides** repaglinide, nateglinide – the “glinides”
- **TD2M tx only…Requires Islet cell function***
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
***Structurally unrelated to sulfonureas***
Metabolism:
Taken before meals; metabolized by the liver; Short half-life
Repgalinide
Side Effects
Contraindications
Administration
Meglitinides repaglinide, nateglinide – the “glinides”
Side Effects:
Hypoglycemia – more likely to see this with meglitinides than with sulfonureas
Containdications:
None mentioned
Administration:
Oral
Nateglinide
MOA
Metabolism
T1DM/T2DM?
Meglitinides repaglinide, nateglinide – the “glinides”
**TD2M tx only…Requires Islet cell function**
MOA:
These block the ATP-dependent potassium channel in ß-cells leading to depolarization, opening of Ca2+ channels, and release of insulin vesicles.
***Structurally unrelated to sulfonureas***
Metabolism:
Taken before meals; metabolized by the liver; Short half-life
Nateglinide
Side Effects
Contraindications
Meglitinides repaglinide, nateglinide – the “glinides”
Side Effects:
Hypoglycemia – more likely to see this with meglitinides than with sulfonureas
Containdications:
None mentioned
Administration:
Oral
What biguanides are used in the treatment of DM?
Biguanides: Phenformin (no longer used), Metformin – the “formins”
Metformin
MOA
Metabolism
Biguanides: Phenformin (no longer used), Metformin – the “formins”
****First-line therapy in T2DM*****CAN be used in T1DM
MOA:
These work by increasing AMP kinase activity that is typically activated in times of low ATP so it phosphorylates enzymes used in glycolysis an others that leads to lowering of blood glucose. (decreases gluconeogenesis, increases glycolysis, and increases peripheral glucose uptake.
Metabolism:
not mentioned
Metformin
Side Effects
Contraindications
Administration
- *Biguanides:** Phenformin (no longer used), Metformin – the “formins”
- ****First-line therapy in T2DM*****CAN be used in T1DM*
Side Effects:
LACTIC ACIDOSIS, GI upset
Lactic acidosis makes sense because metformin increases glycolysis and may overwhelm the ox-phos pathway
Containdications:
Renal Insufficiency – because of the risk of lactic acidosis
Administration:
Oral
That thiazolidindiones are used in the treatment of DM?
• how do they work?
Thiazolidindiones: troglitazone, rosiglitazone, pioglitazone, rosiglitazone + metformin – the “azones”
MOA:
Binds to Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) – a nuclear transcription regulator. This leads to increased insulin sensitivity peripherally. Ultimately this leads to increased glucose transport into muscles and adipose tissue.
Troglitazone
MOA
Metabolism
Thiazolidindiones: troglitazone, rosiglitazone, pioglitazone, rosiglitazone + metformin – the “azones”
MOA:
Binds to Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) – a nuclear transcription regulator. This leads to increased insulin sensitivity peripherally. Ultimately this leads to increased glucose transport into muscles and adipose tissue.
Metabolism:
Absorbed from GI tract, little metabolism
Troglitazone
Side Effects
Contraindications
Administration
Thiazolidindiones: troglitazone, rosiglitazone, pioglitazone, rosiglitazone + metformin – the “azones”
Side Effects:
Increased risk of fractures, Hepatotoxicity, weight gain, edema
Containdications:
safe even with renal impairment
Administration:
Oral
Rosaglitazone
MOA
Metabolism
Thiazolidindiones: troglitazone, rosiglitazone, pioglitazone, rosiglitazone + metformin – the “azones”
MOA:
Binds to Peroxisome Proliferator-Activated Receptor-gamma (PPAR-gamma) – a nuclear transcription regulator. This leads to increased insulin sensitivity peripherally. Ultimately this leads to increased glucose transport into muscles and adipose tissue.
Metabolism:
Absorbed from GI tract, little metabolism