Flashcards in Pharmacology of Insulin and Oral Hypoglycemics Deck (58)
What is the function of pancreatic polypeptide and from what cell type in the pancreas is it released?
- self-regulates pancreatic secretions and comes from F cells.
What is the function of ghrelin and from what cell type is it secreted?
- stimulates growth hormone release and comes from Epsilon cells.
What is the role of somatostatin and from what cell type is it secreted?
- inhibitor of secretory cells, and comes from delta cells.
What is the normal, prediabetic, and DM levels, respectively for fasting blood glucose?
- normal= less than 100
- prediabetes= 100-125
- DM= greater than 126
What is the normal, prediabetic, and DM levels, respectively for 2-hr postload blood glucose?
- normal= less than 140
- prediabetes= 140-199
- DM= greater than 200
What is the normal, prediabetic, and DM levels, respectively for hemoglobin A1c %?
- normal= less than 5.6
- prediabetes= 5.7-6.4
- DM= greater than 6.5
What type of insulin do you want to give for PRANDIAL situations (after a meal)?
- short and fast acting
How is insulin synthesized?
- in pancreatic Beta cells as proinsulin (A, B, and C chains), which will be packaged into secretory granules with trypsin-like proteolysis, which will cleave proinsulin into C-PEPTIDE and INSULIN (A and B chains connected via 2 disulfide bonds).
Does C-peptide or insulin have a longer half-life?
Does loss of disulfide linkage of insulin result in loss of function?
**** What stimulates insulin release?
- increased blood GLUCOSE (also B-adrenergic stimulation, vagal stimulation, and glucagon-like peptide 1; GLP-1), which is taken into the pancreatic beta cell via GLUT2 transporter, INCREASING ATP and CLOSING K+ channels, thus depolarizing the cell and OPENING CALCIUM channels= exocytosis of INSULIN :)
What drugs will stimulate insulin release?
What will inhibit insulin release?
What drugs will inhibit insulin release?
*** What intracellular enzyme is linked to the extracellular insulin receptor?
- TYROSINE KINASE= phosphorylates insulin receptor substrates (IRS), leading to upregulation of GLUT4 transporters on adipose and skeletal muscle tissue and thus entry of glucose into the tissues. This leads to protein, fat, and glycogen synthesis (as well as growth and gene expression).
What electrolyte must you monitor when giving insulin?
- K+ because it will also be taken into the cells (can lead to hypokalemia).
What are the sources of insulin?
- human and analog insulin (only human used in U.S.)
*** What are the RAPID-acting (less than 4 hrs) insulin agents?
- new= afrezza (inhaled)
*subcutaneously just before a meal.
*** What is the SHORT-acting (5-8 hrs) insulin agent?
- regular insulin
*subcutaneously 1 hr before meal.
*** What is the INTERMEDIATE-acting (4-12 hrs) insulin agent?
- neutral protamine hagedorn (NPH) insulin
*subcutaneously mixed with rapid or short-acting.
*** What are the LONG-acting (12 or 24 hours) insulin agents?
*subcutaneously background insulin replacement.
Can intermediate or long acting agents ever be used intravenously?
For what use is rapid-acting insulin (lispro, aspart, or glulisine) used?
- IV for uncomplicated ketoacidosis
For what use is short-acting insulin (regular insulin) used?
- IV for ketoacidosis, surgery, or acute infections (most common).
What is the goal mean blood glucose for insulin therapy?
- less than 154 mg/dL or HbA1c less than 7%
*standard therapy= twice daily injections.
What are the symptoms of hypoglycemia (ADR of insulin)?
- headache, anxiety, tachycardia, confusion, vertigo, diaphoresis, shaky, blurred vision, fatigue...
What is lipodystrophy?
- abnormal or degenerative conditions of the body's adipose tissue due to hypersensitivity to insulin injections.
**** What are the anti-diabetic type II drugs?
- secretagogues; increased insulin secretion= SULFONYLUREAS, meGLITINIDES, D-phenylalanine derivatives.
- DPP-IV inhibitory; increased insulin secretion= sitaGLIPTIN
- METFORMIN and THIZOLIDINEDIONES= increased insulin sensitivity at peripheral tissues
- alpha-glucosidase inhibitors= reduce glucose absorption from GI system.
- SGLT-2 inhibitor; reduced glucose reabsorption at proximal convoluted tubule of kidney= dapagliFLOZIN
- decreased gastric emptying= AMYLIN (PRAMLINTIDE)
**** What is the mechanism of action for SULFONYLUREAS?
- stimulation of insulin release by blocking ATP-sensitive K+ channels, leading to depolarization, Ca2+ influx, and thus insulin exocytosis.
*given P.O. and metabolized by liver.