Diabetes Drugs

Question 1

Insulin:
 Lispro (rapid-acting)
 Aspart (rapid-acting)
 Glulisine (rapid-acting)
 Regular (short-acting)
 NPH (intermediate)
 Glargine (long-acting)
 Detemir (long-acting)

Answer 1

Action: Bind insulin receptor (tyrosine kinase activity).
Liver: Increased glucose stored as glycogen.
Muscle: Increased glycogen and protein synthesis, K+ uptake.
Fat: aids TG storage.

Clinical use: Type 1 DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stress-induced hyperglycemia.

Toxicities: Hypoglycemia, very rarely hypersensitivity reactions.

Question 2

Biguanides:

Metformin

Answer 2

Action: Exact mechanism is unknown.
Decreased gluconeogenesis, increased glycolysis, increased peripheral glucose uptake (insulin sensitivity).

Clinical use: Oral. First-line therapy in type 2 DM. Can be used in patients without islet function.

Toxicities: GI upset; most serious adverse effects is lactic acidosis (thus contraindicated in renal failure).

Question 3

Sulfonylureas:
 First generation:
   Tolbutamide
   Chlorpropamide
 Second generation:
   Glyburide
   Glimepiride
   Glipizide

Answer 3

Action: Close K+ channel in Beta-cell membrane, so cell depolarizes -> triggering of insulin release via increased Ca2+ influx.

Clinical use: Stimulate release of endogenous insulin in type 2 DM. Require some islet function, so useless in type 1 DM.

Toxicities: First generation: disulfiram-like effects;
Second generation: hypoglycemia.

Question 4

Glitazones/thiazolidinediones:
Pioglitazone
Rosiglitazone

Answer 4

Action: Increased insulin sensitivity in peripheral tissue. Binds to PPAR- nuclear transcription regulator.

Clinical use: Used as monotherapy in type 2 DM or combined with above agents.

Toxicities: Weight gain, edema. Hepatotoxicity, heart failure.

Question 5

Alpha-glucosidase inhibitors:
Acarbose
Miglitol

Answer 5

Action: Inhibit intestinal brush-border alpha-glucosidases. Delayed sugar hydrolysis and glucose absorption -> decreased postprandial hyperglycemia.

Clinical use: Used as monotherapy in type 2 DM or in combination with above agents.

Toxicities: GI disturbances.

Question 6

Amylin analogs:

Pramlintide

Answer 6

Action: Decreased glucagon.

Clinical use: Type 1 and type 2 DM.

Toxicities: Hypoglycemia, nausea, diarrhea.

Question 7

GLP-1 analogs:
Exenatide
Liraglutide

Answer 7

Action: Increased insulin, decreased glucagon release.

Clinical use: Type 2 DM.

Toxicities: Nausea, vomiting; pancreatitis.

Question 8

DPP-4 inhibitors:
Linagliptin
Saxagliptin
Sitagliptin

Answer 8

Action: Increased insulin, decreased glucagon release.

Clinical use: Type 2 DM.

Toxicities: Mild urinary or respiratory infections.