Lispro, Aspart, Glulisine Action
-bind insulin receptor (tyrosine kinase activity) -increase glucose stored as glycogen in the liver -increase glyocgen, protein synthesis, and K+ uptake in muscle -increase TG storage in fat (rapid-acting)
Clinical use of lispro, aspart and glulisine
-DM1 -DM2 -GDM (postprandial glucose control)
Use of Inuslin, Regular
-DM1, DM2 -GDM -DKA -hyperkalemia -stress hyperglycemia (short acting)
intermediate acting insulin -DM1, DM2, GDM
Glargine and Detemir are…
long acting insulins for DM1, DM2, GDM (basal glucose control)
Metformin (a biguanide) acts to…
-decrease gluconeogenesis -increase glycolysis -increase peripheral glucose uptake (insulin sensitivity)
Use of Metformin
-first line therapy in type 2 DM
Toxicities of Metformin
lactic acidosis (thus contraindicated in renal failure)
First generation sulfonylureas
Second generation sulfonylureas
Glyburide Glimepiride Glipizide
MOA of Sulfonylureas
close K+ channel in beta-cell membrane so the cell depolarizes triggering insulin release via calcium influx
Use of sulfonylureas
type 2 DM (requires some islet function so useless in T1)
Toxicities of sufonlyureas
-1st gen: disulfiram-like effects -2nd gen: hypoglycemia (esp. in renal failure)
Pioglitazone and Rosiglitazone (glitazones/thiazolidinediones) MOA
increase insulin sensitivity in the peripheral tissues; binds PPAR-gamma nuclear transcription regulator
Use of Pioglitazone and Rosiglitazone
type 2 DM
Toxicities of Pioglitazone and Rosiglitazone
-weight gain -edema -hepatotoxicity -HEART FAILURE
Acarbose and Miglitol (alpha-glucosidase inhibitors) MOA
-inhibit intestinal brush-border alpha-glucosidases -delayed sugar hydrolysis and glucose absorption leading to decreased postprandial hyperglycemia
Acarbose and Miglitol uses
type 2 DM
Pramlintide is an amylin analog that…
decreases gastric emptying and decreases glucagon. Used in T1 and T2 DM.
Exenatide and Liraglutide are…
GLP-1 analogs that increase insulin and decrease glucagon release. Used in T2 diabetes.
Toxicity of exenatide and liraglutide
Linagliptin, Saxagliptin and Sitagliptin are..
DPP-4 inhibitors that increase insulin and decrease glucagon release used in T2DM.
Genes activated by PPAR-gamma regulate…
fatty acid storage and glucose metabolism. Activation of PPAR-gamma increase insulin sensitivty and levels of adiponectin.
Propylthiouracil and Methimazole MOA
block thyroid peroxidase, inhibiting the oxidation of iodide and organification of iodine leading to inhibition of thyroid hormone synthesis.
PTU also blocks…
5’-deiodinase which decreases peripheral conversion of T4 to T3. (used in pregnancy)
Use of Methimazole and PTU
Toxicity of PTU and Methimazole
-skin rash -agranulocytosis -aplastic anemia -teratogen (Methimazole can cause aplasia cutis)
Levothryoxine and Triiodothyronine are used for…
hypothyroidism and myxedema.
GH is used in…
GH deficiency and Turner syndrome.
Somatostatin (octreotide) is used in…
acromegaly, carcinoid, gastinoma, glucagonoma and esophageal varices.
labor, uterine contractions and milk letdown; it controls uterine hemorrhage too.
ADH (DDAVP) is used for…
- hydrocortisone 2. prednisone 3. triamcinolone 4. dexamethasone 5. beclomethasone 6. fludrocortisone
Mechanism of glucocorticoids
metabolic, catabolic, anti-inflammatory, and immmunosuppressive effects are mediated by interactions with the glucocorticoid response elements and inhibition of transcription factors such as NF-kappaB.
Use of glucocorticoids
-addison disease -inflammation -immune suppression -asthma
Toxicity of Glucocorticoids
-iatrogenic Cushings -adrenal insufficiency when drugs are stopped abruptly after chronic use