Endocrine: Drugs for Diabetes Flashcards
Which cell receptor does insulin activate to cause cell growth, proliferation, and gene expression?
MAP kinase
Which cell receptor does insulin activate to cause increased GLUT4 expression and synthesis of lipids, proteins, and glycogen?
PI-3K
How does insulin decrease glucose in the blood? (5)
GLUT4 translocation in skeletal/cardiac muscle and adipocytes
Activation of glycolysis
Activation of glycogen synthesis
Inhibition of gluconeogenesis
Inhibition of glycogenolysis
What are the rapid acting insulins?
Lispro
Aspart
Glulisine
What are the short acting insulins?
Regular insulin
Which are the intermediate acting insulins?
NPH insulin
-not used much anymore
What are the longer acting insulins?
Detemir
Glargine
-longest acting
Clinical use of lispro, aspart, or glulisine?
Decrease the post prandial hyperglycemia seen after meals
Which insulin is used for IV?
Regular insulin
-can use in emergency situations like DKA, HHS, or hyperkalemia
So say you wanted to cover someone with diabetes both after meals and all day, which combo of insulins would be best?
A rapid acting + a long
So: lispro, aspart, or glulisine + detemir/glargine
What are some adverse effects of insulin?
Hypoglycemia, lipodystrophy
Weight gain
Resistance
Hypokalemia
MOA of pramlintide? (3)
Amylin analog
- blocks glucagon secretion
- slows gastric emptying
- increases satiety
What type of DM does pramlintide treat?
Type 1 or 2
The rest, besides insulin, only treat type 2
What are the adverse effects of pramlintide?
Nausea, vomiting, diarrhea
Severe hypoglycemia if used with insulin
MOA of Exenatide or Liraglutide?
GLP-1 agonists
-activates Gs, increases cAMP and PKA, which causes exocytosis of insulin
Adverse effects of the GLP-1 agonists (exenatide and liraglutide)
N/V, diarrhea, anorexia
Hypoglycemia
What is the suffix of all the DPP-4 inhibitors
Gliptin!
Sitagliptin, linagliptin, saxagliptin, alogliptin
MOA of the DPP-4 inhibitors (gliptins)
Decrease breakdown of GLP-1
-ultimately increases insulin release
Adverse effects of the DPP-4 inhibitors?
Hypoglycemia
What is the MOA of Sulfonylureas/meglitinides?
block K-ATPase channels (via SUR1), Ca++ rushes in and Insulin is released
What are the first gen sulfonyureas
Amides
Chlorpropamide, tolbutamide, tolazamide
What are the second generation sulfonylureas?
Glipizide
Glyburide
Glimepiride
What are the meglitinides?
Nateglinide
Repaglinide
-glinides
What are the adverse effects of the sulfonyureas/meglitinides?
Hypoglycemia
Weight gain
Secondary failure
What drugs can enhance the effect of sulfonylureas?
sulfonamides, clofibrates, aspirin/NSAIDs
Ethanol
CYP inhibitors: azoles, gemfibrozil. cimetidine
What drugs can decrease the glucose lowering effect of sulfonylureas?
Drugs that inhibit insulin secretion: B-blockers, CCBs
CYP inducers: phenytoin, griseofluvin, rifampin
Clinical use for the meglitinides?
Control of postprandial hyperglycemia in T2DM
-shorter acting than the sulfonylureas
MOA of metformin?
activation of AMP kinase
-decreases gluconeogenesis, increases insulin sensitivity
Which diabetic agent is usually first line in those w T2DM?
Metformin
- no real issue w hypoglycemia
- promotes weight loss
- taken orally (instead of injection)
- Can be combined
How is metformin excreted?
Unmetabolized
-watch in those w renal failure!!
Adverse effects of metformin?
GI upset
Lactic acidosis
What conditions is metformin contraindicated in?
Renal or liver issues
What are the thiazolidinediones (TZDs)?
-glitazones
Pioglitazone
Rosiglitazone
MOA of the TZDs?
ligands for PPARy
-increase adiponectin and GLUT4
Whare TZDs safe for those with renal issues?
Yes
Adverse effects of TZDs?
Weight gain
Edema
-increases ENaC channels
Exacerbate HF
-increased water retention
Osteoporosis
-suppress osteoblasts
MOA of canagliflozin, dapagliflozin, empagliflozin?
SGLT2 inhibitors
-work at PCT to block reabsorption of glucose
Adverse effects of the SGLT2 inhibitors (flozins)
Osmotic Diuresis and Orthostatics
Genital and UTIs (candidiasis)
Benefitial effects of SGLT2 inhibitors?
Reduces plasma uric acid levels
Weight loss
improves overall cardiovascular and renal outcomes
MOA of acarbose and Miglitol?
competitive inhibition of a-glycosidases
-block resorption of disaccharides in intestines
Effect of acarbose and miglitol on glucose levels?
Lower postprandial hyperglycemia to create insulin sparing effect
Adverse effects of acarbose and miglitol?
GI Upset: malabsorption and flatulence
