Quiz 8

  1. MoA: Stimulate insulin release from pancreatic beta-islet cells by binding to and blocking an ATP-ase sensitive K+ channel. Causing depolarization and an increase in intracellular Ca2+ which leads to the release of the hormone. Could also decrease the hepatic clearance of insulin.
    Hepaticially metabolized.
    Adverse effects: (Very low) Hypoglycemia, many drug interactions, possible disulfiram-like reaction with ethanol.
    Individual dosing, used in combination with insulin
    5-10% resistent
    Contraindicated in Type 1 DM, pregnancy, lactation, hepatic and renal failure
  2. Sulfonylureas, First Generation Agents
    • Tolazamide (Tolinase)
    • Tolbutamide (Orinase)
    • Chlorproamide (Diabinese)
    • Acetohexaminde (Dymelor)
  3. First Generation Sulfonylurea
    Serum half life of 7 hours
    Active Metabolites
    Tolazamide (Tolinase)
  4. First Generation Sulfonylurea
    Serum half life 4.5-6.5 hours
    NO Active Metabolites
    Tolbutamide (Orinase)
  5. First Generation Sulfonylurea
    Serum half life 36 hours
    Active Metabolites
    Chlorpropamide (Diabinese)
  6. First Generation Sulfonylurea
    Serum half life 6-8 hours
    Active Metabolites
    Acetohexamide (Dymelor)
  7. Second Generation Sulfonylurea
    Serum half life 2-4 hours
    NO Active Metabolites
    Glipizide (Glucotrol)
  8. Second Generation Sulfonylurea
    Nonmicronized Serum half life 10 hours
    Micronized Serum half life 4 hours
    Weakly active metabolites
    Glyburide (Glibenclamide) (DiaBeta, Micronase, Glynase Pres Tab)
  9. Third Generation Sulfonylurea
    Serum half life 9 hours
    Active Metabolites
    MoA: Appears to cause translocation of GLUT-4 glucose transporter to the cell surface from the cytoplasm, insulin like activity. May bind to a different protein than the usual sulfonylurea receptor on the beta-islet cell.
    Glimepiride (Amaryl)
  10. Second Generation Sulfonylurea agents
    • Glipizide (Glucotrol)
    • Glyburide (DiaBeta, Micronase, Glynase PresTab)
  11. Thiazolidinedione oral agents
    • Rosiglitzaone maleate (Avandia)
    • Piogliazone HCl (Actos)
  12. MoA: Increase the activity of the nuclear receptor PPAR-gama that regulate genes responsible for the control of glucose and insulin metabolism in adipose, liver and skeletal muscle tissues (Increase tissue sensitivity)
    Indicated for Type 2 DM, often in combination
    Work only in the presence of insulin
    Watch for hepatic failure
    taken without regards to food
    Contraindicated in patients at risk for heart failure
    Edema, weight gain of 6 lbs, increase plasma volume, and fatigue common side effects
  13. Thiazolidinedione
    Tightly controlled dispensing
    Metabolized by CYP2C8 lesser extend by 2C9
    Rosiglitazone maleate (Avandia)
  14. Thiazolidinedione
    Metaboliced by CYP3A4
    Decreases the efficacy of OC, additional birth control needed, monitor ALT for hepatotoxicity
    Pioglitazone HCl (Actos)
  15. Indications: Type 2 diabetes with diet and exercise, can be used in combination with a thiazolidinedione
    NON-sulfonylurea analog of glyburide
    MoA: Stimulate insulin release for pancreatic Beta-islet cells by binding to and blocking an ATP-ase sensitive K+ channel. This causes depolarization and an increase in intracellular Ca+2 which leads to the release of the hormone. May also decrease the hepatic clearnace of insulin.
    Metabolized by CYP3A4
    Takes 15-30 minutes preprandially, skip (add) a meal then skip (add) a dose
    Repaglinide (Prandin)
  16. Indication: Type 2 DM with diet and exercise or in combination with a sulfonylurea
    MoA: Decrease heaptic gluconeogenesis and intesintal glucose absorption, increase peripheral tissue and insulin sensitivity, does NOT cause insulin release in the the pancreas
    Half-life is 1.3-4.5 hours, can cause decrease in B12 and folate absorption
    Contraindicated in hepatic and renal failure or a history of lactic acidosis, stop taking if MI occurs of septicemica
    NO PROTEIN BINDSING, NO METABOLISM with rapid renal excretion
    Metformin HCl (Glucophage)
  17. Indications: Type 2 DM
    Unreleated to sulfonylureas, D-phenylglycine analog
    MoA: Stimulates insulin release in the pancreas by interacting with a ATP-sensitive K+ channel on intact pancreatic beta-cells, leads to beta cell depolarization that opens a Ca2+ channel causing insulin secretion.
    Highly slective with low affinity for heart ad skeltal muscle K+ channels, 98% albumin binding, CYP2C9 (70%) and 3A4 (30%) metabolism
    Natglinide (Starlix)
  18. Alpha-glucosidase inhibitors
    Type 2 diabetes adjunct to sulfonylureas, insulin or agents
    MoA: decrease carbohydrate absorption by competitively inhibiting the intestinal enzyme alpha-glucosidase, amino group prevents protonation of glycosidic bond in the saccharides by an essential carboxylic acid group in the enzyme active site
    Take drug with first bite of meals 3 times a day
    Adverse: Diarrhea, flatulence, GI issues that resolve after 2 weeks
    • Acarbose (Precose)
    • Miglitol (Glyset)
  19. Alpha-glucosidase inhibitor
    Minimal systemic absorption
    Increase in serum transaminase at dose higher than 100 mg
    Acarbose (Precose)
  20. Alpha-glucosidase inhbitor
    Rapid and complete systemic absorption
    Miglitol (Glyset)
  21. Combination products for type 2 diabetes?
    • glipizide and metformin HCl (Metaglip)
    • rosiglitazone maleate and metformin HCl (Avandamet)
    • Glyburide and metformin HCl (Glucovance)
    • Rosiglitazone maleate and glimepiride (Avandaryl)
    • Pioglitazone and metformin HCl (ACTOplus met)
    • Repaglinide and metformin (PrandiMet)
  22. Recombinant modified insulins
    • Insulin glulisine (Apidra)
    • Insulin Detemir (Levemir)
    • Insulin glargine (Lantus)
    • Insulin aspart (Novolog)
    • Insulin lispro (Humalog)
  23. Recombinant modified insulin
    Rapid acting product recombinant site directed mutation human insulin produced by E. coli
    Lysine replaces asparagine at position 3 and glutamic acid replaces lysine at postion 29
    Insuline glulisine (Apidra)
  24. Recombinant modified insulin
    Threonine at B30 position has been deleted and a C14-fatty acid chain has been attached to the B29 amino acid lysine
    Long acting 24 hour product recombinant site directed mutation human insulin produced in Saccharomyces cerevisiae followed by chemical modification with a fatty acid
    98% bound to plasma albumin
    Insulin Detemir (Levemir)
  25. Recombinant modified insulin
    Forms microprecipitaes in subcutaneous tissue prolonging duration from 18-26 hours
    Possible cancer risks
    Insulin glargine (Lantus)
  26. Recombinant modified insulin
    Rapid acting, 3-5 hour duration, take 5-10 minutes before meals
    Insulin aspart (Novolog)
  27. Recombinant modified insulin
    Rapid actinging, 3-5 hour duration, take 15 minutes before meals or immediately after eating
    Insulin lispro (Humalog)
  28. Recombiant/chemically modified/synthetic polypeptides
    • Exenatide (Byetta)
    • Pramlintide acetate (Symlin)
  29. Recombiant/chemically modified/synthetic polypeptide
    Incretin mimetic or glucagon-like peptide-1 receptor agonist that binds the GLP-1 receptor on the beta-islet cells causing insulin synthesis and excretion
    Exenatide (Byetta)
  30. Recombiant/chemically modified/synthetic polypeptide
    Synthetic analog of human amylin a neuroendocrine hormone made by beta-islet cells that contributes to glucose control postprandial
    Pramlintide acetate (Symlin)
  31. DNA inhalation insulin product
    financila failure
    Rapid actiing insulin product
    Exubera inhaler
  32. Incretic mimetic or glucagon-like peptide-1 receptor agonist
    Peptide analog not substrates for DPP-IV
    Exenatide (Byetta)
  33. rDNA origin injection
    Solution for subcutaneous use
    MoA: incretin mimetic or glucagon-like peptide 1 receptor agonist as an adjunct to diet and exercise
    Inject independent of meals
    Risk of Thyroid C-Cell tumors
    Victoza (Liraglutide)
  34. Small molecule inhbitors of DPP-IV
    Monotherapy for type 2 DM or combination with metformin or thiazolidinediones
    MoA: Dipeptidyl protease IV inhbitor prolongs the biological levels of the natural incretins GLP-1 and GIP thereby increasing insulin rleaseing and decreasing release of glucagon
    Substrate for p-glycoprotein
    take with or without food
    Stagliptin phosphate (Januvia)
  35. Indications: adjunct to diet and exercise to improve glycemic control in type 2 diabetes only
    MoA: dopamine receptor agonist increasing dopamine levels early in the day seems to "reset" the biological clock and improves metabolism problems that are related to diabetes
    Side effects: Nausea?Vomiting, fatigue, headache, dizziness
    Taken orally within 2 hours of awakening with food
    also marketed as Parlodel for hyperprolactinemia, parkinsons et al (old drug but new indications)
    Bromocriptine mesylate (Cycloset)
  36. MoA: DPP-4 inhibitor
    Metabolism by CYP3A4/5 to an active metaboite
    Advers effects include decrease lymphocyte count (URI, UTI), hypoglycemia, uticaria, acute pacreatitis, headaches
    Inhibition of other peptides, cytokine degradation
    Combination with metformin in Kombiglyze XR
    Saxagliptin (Onglyza)
  37. DPP-IV inhibitor
    Limitations of use: Should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, has not been studied in combination with insulin
    Metabolism: 90% excreted unchanged with 80% via hepatobiliary rout
    Drug ineractions: Substrate for P-glycoprotein, CYP3A4 inducer and mild inhibitor
    Adverse effects: When used with an insulin secretagogue consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia
    Can be taken with or without food
    5 mg daily
    Linagliptin (Tradjenta)
  38. Recombinant biotechnology product, human derived platelet growth factor
    Indication: 0.1% gell topical agent used for treatment of lower extremity diabetic neuropathic ulcers assuming adequate blood supply is present (Not a substitute for good ulcer care practices, dosage calculated on ulcer size)
    Contraindicated if known neoplams at site of administration
    Use extreme caution in patients with known malignancy patients with 3 or more tubes have an increased risk of mortaility secondary to malignancy
    Becaplermin (Regranex)
  39. Adjunct agent
    Bile acid sequestrant indicated as an anjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
    Also for hyperlipidemia
    Welchol (colesevelam hydrochloride)
Card Set
Quiz 8
Quiz 8 Drugs for Diabetes