Diabetes Pharm

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Author:
Uchechi
ID:
30778
Filename:
Diabetes Pharm
Updated:
2010-08-23 22:27:21
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Diabetes
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Diabetes Pharmacology
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  1. Insulin Mechanism of Action
    • Activates insulin receptors
    • Tyrosin Kinase 2ndary messenger
    • increases cellular glucose uptake via GLUT4 in muscle and adipose tissue
  2. Rapid Onset Insulins
    • Lispro (2-4 hr duration)
    • Glulisine (2-5 hr duration)
    • Aspart (4-6 hr duration)

    15min onset for all
  3. Short acting insulin
    - structure
    - onset
    - duration
    • crystalline - identical to human insulin
    • 30-45 min onset SC
    • 5-7 hrs duration
  4. Only insulin available for IV administration?
    Short acting insulin
  5. Short acting insulin approved for pump use
    velosulin
  6. 1st line for Ketoacidosis or severe hyperglycemia?
    • IV regular insulin
    • * may also use rapid onset insulins (lispro, aspart, glulisine) to reduce KA but give SC
  7. Name an intermediate-acting insulin
    - onset
    - peak time
    • NPH - protamine insulin
    • onset - 1-2 hrs
    • peaks at 4-8 hrs
    • * usu mixed with rapid onset insulin to provide postprandial control
  8. long-acting insulins
    - onset
    - duration
    • glargine
    • onset - slow, peakless
    • duration 24hr
  9. What is Pramlitide
    fxn in Type I
    fxn in Type II
    • Injectable analog of amylin - used in conjunction with insulin in type I and II
    • In type I - stabilizes postprandialglucose peaks and valleys
    • In type II - suppresses postprandial glucagon secretion and reduces food intake

    Slows gastric emptying – may alter absorption of other medications/ nausea adverse effect
  10. Tx for hypoglycemia
    • juice, candy or high glucose food if conscious
    • Unconscious or vomiting: IV glucose or IM glucagon as soon as possible
    • * glucagon onset is not immediate
  11. Mechanism of Action of glucagon
    onset
    • Gs-cAMP activation: phosphorylates enzymes that catalyze gluconeogenesis.
    • onset - may take up to 30 mins to increase BG
  12. List some complications of insulin use
    • Hypersensitivity - IgE mediated
    • Immune insulin resistance - anti-insulin IgGs. More common in obese diabetics
    • Lipodystrophy - body fat redistribution. rotate injection site or use highly puriifed preps.
  13. How do you prevent insulin allergy?
    Use recombinant therapy
  14. What is the first line tx for Type II diabetes?
    Metformin
  15. Effects of Metformin?
    • Decreases hyperglycemia w/o hypoglycemia
    • Stimulates glycolysis and inhibits gluconeogenesis
    • reduces plasma glucagon
  16. Benefits of Metformin use?
    • May promote weight loss.
    • PO, inexpensive
    • Lowers A1c 1-2%
  17. Concerns while using metformin?
    • Nausea, diarrhea
    • Renal elimination (contraindicated in pts with renal dysfunction)
    • Potentially fatal lactic acidosis if renal impairment also
  18. Name some conditions that increase the risk of metformin-induced lactic acidosis
    • Kidney dysfuntion
    • alcohol abuse
    • Dehydration
  19. Mechanism of Action of Rosiglitazone? Alt: pioglitazone
    • A TZD. Activates peroxisome proliferator-activated receptor gamma (PPARg).
    • This increases GLUT1 and GLUT4 gene expression
  20. Beneficial effects of Rosiglitazone?
    • Increases muscle glucose uptake and redistributes fat to decrease insulin resistance - "insulin sensitizer"
    • Drops A1c 1%
    • rarely causes hypoglycemia
  21. Concerns while using Rosiglitazone?
    • Increased risk of CHF and MI (esp in combo w/insulin)
    • Increased risk of fractures in postmenopausal women
    • Does not act rapidly - delay in decreasing BG
    • Weight gain and edema
    • metabolized by liver enzymes?? - drug interaction issues.
  22. What is the mechanism of action of exanatide?
    • GLP-1 receptor agonist. Adjunct in metformin/SUR therapy
    • Potentiates insulin release when BG rises
    • Decreases glucagon levels
    • Promotes weight loss in obese
  23. Pharm benefits of Exenatide?
    • hypoglycemia is rare when used w/metformin
    • Potentiates insulin release when BG rises
    • Decreases glucagon levels
    • Promotes weight loss in obese
  24. Concerns with exenatide use
    • expensive, injection
    • nausea, diarrhea
    • Can cause serious renal dysfunction if there's HPN, renal impairment, dehydrated or elderly
  25. What is Sitaglipitin? What is its mechanism of action?
    • Orally available GLP-1 therapeutic. Like exenatide.
    • inhibits DPP-4 to block GLP-1 breakdown increasing its levels
  26. What is the mechanism of action of Glimepiride?
    a 2G SUR. Closes K+ channels and potentiates insulin release in response to glucose uptake
  27. Name other SURs
    glipizide and glyburide
  28. Name some beneficial chx of glimepiride
    • PO, low cost
    • rapid onset
    • long duration
    • drops A1c 1-3%
  29. Some concerns while usuing glimepiride?
    • CYP2C9 metabolism.
    • Some renal elimination - adjust dose.for mild renal impairment.
    • Hemolytic anemia risk in pts with G6PD deficiency - avoid SURs
    • Hypoglycemia
    • Weight gain
  30. Name some insulin secretagogue alternatives for pts with a G6PD deficiency?
    • nateglinide and repaglinide - non-sulfonamide.
    • Also appropriate for pts with sulfur allergies
  31. Nateglinide action?
    • transient, very rapid but short-acting effect to close K+ channel to increase insulin release.
    • appro for postprandial use
  32. Repaglinide action?
    • Closes K+ channels, more similar to sulfonylureas.
    • Also rapid - appropriate for postprandial surge in BG
  33. Benefits of non-sulfonamide insulin secretagogues?
    • ideal for post-prandial BG surges
    • Nateglinide considered OK if renal impairment
    • Drops A1c 0.5-1.5% , >>> A1c drop if given w/ metformin
    • Generally adjunct if post-prandial glucose surges
  34. Concerns with the use of repa~ and nateglinide?
    Hepatic CYP3A4 (also 2C9 for nateglinide) metabolism

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