Diabetes Mellitus

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Diabetes Mellitus
2012-12-06 15:07:21
Diabetes Mellitus Drugs

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  1. What are the insulin agonists?
    Which ones are:
    short acting?
    rapid acting?
    intermediate acting?
    long acting?
    • Regular insulin aka crystaline insulin is short acting.
    • Lispro
    • Aspart                Are rapid acting
    • Glusine
    • NPH (isophane) is intermediate
    • Glargine
    • Detemir              Are long-acting
    • Ultralente

  2. Why do we take different time acting insulin subcutaneously?
    To mimic both postprandial levels of insulin secretion and the basal insulin levels in between meals as close as possible. (Maintain the circadian balance of insulin levels)
  3. Which drug is the best option for controlling DM in pregnancy and why?
    Regular insulin is the best option in controlling DM in pregnancy because insulin does NOT cross the placenta.
  4. Name the 2nd gen sulfonylureas and meglitinide.  What is the general mechanism of these drugs?
    • 2nd gen sulfonylureas:
    • Glipizide
    • Glipizide
    • Glyburide
    • Glimiperide
    • Meglitinide:
    • Rapaglinide
    • Nateglinide

    These drugs are oral anti-diabetic drugs that release insulin (stimulates the pancreas).
  5. Specifically, what do the sulfonureas and meglitinides in a cellular level?
    Glipizide, glyburide, glimiperide, rapaglinide, nateglinide

    They inhibit B-cell K-ATP channels by binding to the SUR sites.  When you inhibit these channels, you depolarization of the B-cell, depolarization leads to insulin release, thus you release insulin.
  6. Metformin.
    also known as Biguanides block gluconeogenesis in the liver, thuse reducing glucose.  This is the most commonly used drug in DM as it is the first line of therapy.  It is also used in polycistic ovarian disease.
  7. What are adverse effects of metformin?
    (Hint think alcohol.  formin sounds kind of like formalin, they're both chemicals, idk man)
    Lactic acidosis is common, and especially risky for patients with kidney disease (drug is excreted via kidneys, do not use contrast dyes when on metformin) and alcohol consumption.  This drug blocks gluconeogenesis via glycolosis so the precursors (pyruvate) will increase.  Pyruvate turns into lactic acid.  It is relatively rare though.
  8. Glitazones:
    • Aka thiazolidinediones increase the sensitivity of target cells to insulin in muscle and fat.
    • These drugs are the best insulin sensitizers.  They act on PPAR gamma (related to glucose metabolism).
    • Pio is better than Rosi because Rosi increases risk of cardiovascular diseases.
  9. Which glitazone acts on gamma and alpha receptors on lipids?
    Which gltazone acts only on gamma?
    • Pioglitazone acts on both
    • Riso acts on only gamma.
  10. Adverse effects of the insulin sensitizers?
    • Increased incidence of bone fracture in women (especially in the hips)
    • Fluid retention and weight gain (most common)
    • heart failure
    • Macular edema (can cause blindness)
    • Bladder cancer
  11. Do glitazones cause hypoglycemia?
    NO because it does not release insulin, it just sensitizes the muscles and adipose tissue to the regular physiologic insulin release.
  12. Acarbose
    Are alpha glucosidase inhibitors.  They reduce the absorption of sugars from the GIT by blocking alpha glucosidase enzyme (this enzyme converts dietary starch and complex carbs into simple sugars and ultimately glucose).
  13. Adverse effects of acarbos and miglitol?
    Flatulence, bloating and diarrhea.
  14. Why do acarbose and miglitol cause flatulence, bloating and diarrhea?
    It blunts the postprandial plasma sugars and foot gets absorbed by bacteria in the lower portions of the GIT.  Bacteria get a big feast and cause flatulence and bloating.
  15. What are the GLP1 agonists?
    • Exenatide
    • Liraglutide
  16. What is mechanism of GLP1 agonists?
    • GLP1 is an incretin and it has 4 major functions:
    • 1. inhibits gastric emptying
    • 2. promotes insulin release
    • 3. inhibits glucagon release
    • 4. suppresses appetite.
    • We use this as a subcutaneous injection.
  17. Which anti-diabetic drugs cause hemorrhagic pancreatitis?
    The GLP1 (incretin) agonists, exenatide and liraglutide (-tides) may cause (but is rare) hemorrhagic pancreatitis because they are constantly stimulating the pancreas.  One of the functions of incretins is to promote insulin release when there is glucose (food) in the system.
  18. Sitagliptin, Saxagliptin (-gliptins)
    • Inhibits DPP4
    • DPP4 inhibits GLP and GIP (incretins)
    • Therefore, by inhibiting incretins, you potentiate insulin secretion and suppress glucagon release from the pancreas.  Use this with metformin to treat DM T2.
  19. What are the amylin analogs?
    Pramlintide improves blood sugar levels by reducing appetite, reducing glucagon, and slowing gastric emptying. (very similar to incretins)
  20. What is glucagon?
    • Glucagon is the opposite of insulin.
    • It increases blood sugar levels.  Glucagon, GH, cortisol, and catecholamines all increase blood sugar levels and are therefore contraindicated for DM.