Pharmacology: Endocrine Pancreas (29)

Mechanism: carbohydrate analogues that bind avidly to intestinal brush border z-glucosidase enzymes, slowing breakdown and absorption of dietary carbohydrates such as starch, dextrin, and disaccharides Clinical Apps: type 2 diabetes Adverse Effects: abdominal pain, diarrhea, flatulence, elevated serum aminotransferase levels, elevated plasma triglycerides Contra: cirrhosis, diabetic ketoacidosis, severe digestive problems, inflammatory bowel disease, bowel obstruction

Mechanism: exogenous insulin promotes carbohydrate metabolism and facilitates glucose, amino acid, and triglyceride uptake and storage in liver, cardiac and skeletal muscle, and adipose tissue Clinical Apps: diabetes mellitus Adverse Effects: hypoglycemia, injection-site reaction, lipodystrophy Contra: hypoglycemia

Mechansim: 1st generation sulfonylureas inhibit b cell K+/ATP channel at the SUR1 subunit, stimulating insulin release from pancreatic b cells and increasing circulating insulin to levels sufficient to ovecome insulin resistance Clinical Apps: type 2 diabetes mellitus Adverse Effects: hypoglycemia, rash, diarrhea, nausea, dizziness Contra: diabetic ketoacidosis

Mechansim: 2nd generation sulfonylureas inhibit b cell K+/ATP channel at the SUR1 subunit, stimulating insulin release from pancreatic b cells and increasing circulating insulin to levels sufficient to ovecome insulin resistance Clinical Apps: type 2 diabetes mellitus Adverse Effects: hypoglycemia, rash, diarrhea, nausea, dizziness Contra: diabetic ketoacidosis

Mechansim: meglitinides inhibit b cell K+/ATP channel at the SUR1 subunit, stimulating insulin release from pancreatic b cells and increasing circulating insulin to levels sufficient to ovecome insulin resistance Clinical Apps: type 2 diabetes mellitus Adverse Effects: hypoglycemia, diarrhea, nausea, upper respiratory infection Contra: diabetic ketoacidosis, type I diabetes mellitus

Mechanism: activates AMP-dependent protein kinase (AMPPK) to block breakdown of fatty acids and to inhibit hepatic gluconeogenesis and glycogenolysis; increases insulin receptor activity and metabolic responsiveness in liver and skeletal muscle Clinical Apps: type 2 DM, polycystic ovarian syndrome Adverse Effects: lactic acidosis, diarrhea, dyspepsia, flatulence, nausea, vomiting, cobalamin deficiency Contra: heart failure, septicemia, alcohol abuse, respiratory disease, renal impairement, iodinated contrast media in renal dysfunction, metabolic acidosis

Mechanism: thiazolidinediones bind and stimulate the nuclear hormone receptor peroxisome proliferator activated receptor-y (PPARy), thereby increasing insulin sensitivity in adipose tissue, liver, and muscle Clinical Apps: type 2 DM, polycystic ovarian syndrome Adverse Effects: heart failure, cholestatic hepatitis, hepatotoxicity, diabetic macular edema, edema, weight gain, increased HDL and LDL, decreasing circulating triglycerides and free fatty acids Contra: hypersensitivity

Mechanism: glucagon-like peptide-1 (GLP-1) receptor agonist that enhances glucose-dependent insulin secretion, inhibits glucagon secretion, delays gastric emptying, and decreases appetite Clinical Apps: type 2 DM Adverse Effects: hypoglycemia, nausea, vomiting, diarrhea, nervousness, dizziness, headache Contra: type 1 DM, diabetic ketoacidosis

Mechanism: dipeptidyl peptidase-IV (DPP-IV) inhibitor that slows proteolytic inactivation of GLP-1 and other incretin hormones Clinical Apps: type 2 DM Adverse Effects: URI, nasopharyngitis, nausea, mild increased in serum creatinine level, diarrhea, headache Contra: type 1 DM, diabetic ketoacidosis

Mechanism: binds to SUR1 subunit of K+/ATP channels in pancreatic b cells and stbilizes ATP-bound state of channel to that b cells remain hyperpolarized, decreasing insulin secretion; hyperpolarizes SUR2-containing channels in cardiac and smooth muscle cells Clinical Apps: hypoglycemia due to hyperinsulinism, malignant hypertension Adverse Effects: heart failure, fluid retention, diabetic ketoacidosis, hypernatremia, bowel obstruction, pancreatitis, neutropenia, thrombocytopenia, extrapyramidal disease, angina, hypotension, tachyarrhythmia, hirsutism, hyperglycemia, dyspepsia, dizziness, glucosuria Contra: hypersensitivity

Mechanism: polypeptide hormone produced by pancreatic a cells that stimulates gluconeogenesis and glycogenolysis in liver, resulting in an increase in blood sugar Clinical Apps: hypoglycemia, intestinal relaxant before radiography of GI tract Adverse Effects: rash, nausea, vomiting Contra: pheochromocytoma