Endo Pharm

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Endo Pharm
2012-10-22 18:52:47
Endo Pharm

Pharm for endo block
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  1. Biguanide
    • Oral therapy
    • Prototype: Metformin
    • Mechanism of action: Exact mechanism unknown, but it works by decreasing hepatic production of glucose and intestinal glucose absorption, and by increasing insulin sensitivity
    • SE: primarily GI (diarrhea, abdominal bloating, nausea), vitamin B12 deficiency with long term use, and lactic acidosis (the most severe but rare)
    • Effect on plasma insulin: decreased
    • Risk of hypoglycemia: not as monotherapy (because does not increase insulin secretion)
    • Contraindicated in: renal impairement and acute/chronic metabolic acidosis
    • Benefits: No weight gain (patient may actually have weight loss)
  2. Secretagogue
    • Oral therapy
    • Includes insulin secretagogues (sulfonylureas)  and the glinides (repaglinide and nateglinide)
    • MoA: Sulfonylureas block the potassium channel in beta cells (stimulating extra insulin release); glinides bind distinct sites on the potassium channel and also stimulate insulin release (these have rapid onset and short duration of action)
  3. Sulfonylurea
    • Oral therapy
    • First generation prototypes: tolbutamide and chlorpropamide
    • Second generation prototypes: glyburide, glipizide/glipizide XL, glimepiride
    • MoA: close potassium channel in beta cell membrane, causing the cell to depolarize and release insulin
    • SE: Hypoglycemia (esp in elderly patients, those with hepatic/renal impairment, and when used as combo therapy), weight gain, decreased efficacy over time
    • First generation SE: disulfiram-like effects (headache, drowsiness, tiredness, nausea, vomiting, etc)
    • Useless in type 1 because they require some islet cell function
    • Glyburide may be a safe alternative for pregnant diabetic patients
    • Second generation SE: hypoglycemia
    • Efficacy: has more rapid effect and decreases A1C 1.5%
    • Effect on plasma insulin: increased for both generations
  4. Glinides
    • Oral therapy
    • Prototypes: repaglinide, nateglinide
    • Short acting secretagogues that stimulate insulin release from pancreatic beta cells that have a shorter half life than sulfonylureas (insulin release is rapid and lasts only 1-2 hours)
    • Targets postprandial glucose levels
    • SE: Hypoglycemia (smaller risk than sulfonylureas), weight gain
    • Effect on plasma insulin: increases it
  5. Thiazolidineodiones (TZDs)
    • Oral therapy
    • Prototype: Rosiglitazone and pioglitazone
    • MoA: Insulin sensitizers that are PPAR-gamma receptor activators in muscle, fat, and liver to decrease insulin resistance (increases insulin, primarily in peripheral tissue)
    • SE: Peripheral edema, weight gain (due to fluid retention), heart failure (greater risk if used in conjunction with insulin), increased fracture risk, potential bladder cancer risk, hepatotoxicity
    • Contraindications: ATL > 2.5x ULN, pt with heart failure NYHA class III or IV (class I and II are okay so long as you monitor pt), alcohol abuse
    • Effect on plasma insulin: decreased
    • Risk of hypoglycemia: no
    • Notes: effective in highly insulin-resistant pt; must monitor liver functions
  6. Alpha-glucosidase inhibitors
    • Oral therapy
    • Prototypes: acarbose, miglitol
    • MoA: Inhibits alpha-glucosidase, a small intestinal brush border enzyme that cleaves oligosaccharides, thus preventing glucose absorption and decreasing post-prandial glucose levels
    • SE: diarrhea, abdominal pain, flatulence (all not well tolerated)
    • Contraindicated: chronic intestinal disease, cirrhosis
    • Note: if tx someone on this who is hypoglycemic, it is important to use glucose and not sucrose, as these also inhibit sucrase
    • Risk of hypoglycemia: no (not as monotherapy)
    • Effect on plasma insulin: little or no change
  7. DDP-IV inhibitors
    • Oral therapy
    • Prototype: sitagliptin, saxagliptin, lingliptin
    • MoA: inhibits DDP-IV, the enzyme that inactivates GLP-1; prolonged incretin activity increases insulin release in response to meals and reduces inappropriate glucagon secretion
    • SE: well tolerated with few post-marketing reports of hypersensitivity rxns
    • Contraindications: None yet known
    • Effect on plasma insulin: increases
    • Risk of hypoglycemia: No
  8. Glucagon-like peptide 1 (GLP-1) agonists
    • Non-Oral therapy: given subcutaneously
    • Prototypes: exenatide, exenatide LAR, liraglutide, bydureon (extended release exenatide)
    • MoA: GLP-1 analog that mimics incretin to increase glucose-dependent insulin release, suppress high glucagon levels and delay gastric emptying
    • SE: nausea, vomiting, weight loss, acute pancreatitis, hypoglycemia (if used in conjunction with sulfonylureas)
    • Effect on plasma insulin: increases
    • Risk of hypoglycemia: no
    • Note: Because of the gastric emptying delay, this can affect absorption of other medications
    • Contraindications: Type I DM, gastroparesis, hx of medullary thyroid cancer and MEN type II
  9. Major differences between DDP-4 inhibitors and GLP-1 receptor agonists
    • Slows gastric emptying: DPP-4 inhibitors don't, GLP-1 agonists do
    • Body weight effects: DDP-4 are neutral; GLP-1 cause weight loss
    • SE: DDP-4 are well tolerated; GLP-1 has nausea/vomiting
    • Administration: DDP-4 is oral once daily; GLP-1 is subcutaneous one or twice daily or once a week
  10. Pramlintide
    • Synthetic analog of human amylin
    • MoA: suppresses postprandial glucagon secretion, regulates rate of gastric emptying, and reduces food intake
    • Amylin is co-secreted with insulin in response to a meal and is deficient in both type 1 and type 2 diabetes
    • Note: should be given immediately prior to a meal; if used in conjunction with insulin, should lower the dose of insulin
  11. Types of Insulin
    • Rapid acting (for pre-meal): Humalog (lispro), Novolog (aspart), and apidra (glulisine)
    • Short acting (for pre-meal): Novolin R, Humulin R
    • Intermediate acting: Novolin N, Humulin N
    • Long acting (for basal insulin): Levemir (detemir), and lantus (glargine)
    • Action: Bind insulin receptor
    • In liver: causes increased glucose stored as glycogen
    • In muscle: causes increased glycogen and protein synthesis and potassium uptake
    • In fats: aids triglyceride storage
    • Use: Type I DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stressed-induced hyperglycemia
    • Tox: hypoglycemia and hypersensitivity rxn (very rare)
  12. Detemir (levemir)
    • MoA: An attached fatty acid side chain that binds interstitial albumin at the subcutaneous injection site (prolongs absorption)
    • Must dissociate from albumin to bind insulin receptors
    • Onset: 2 hrs
    • Peak: 6-9 hrs
    • Duration: 24 hrs
  13. Glargine (lantus)
    • MoA: Forms microprecipitates when injected into the body that slowly dissolves into monomers that are absorbed
    • Is soluble at pH 4
    • Onset: 4-5 hr
    • Peak: none or blunted
    • Duration: 24 hrs
  14. Neutral Protamine Hagedorn (NPH)
    • Intermediate acting insulin
    • Onset: 1 to 2 hr
    • Peak: 6 to 10 hr
    • Duration: 12-18 hr
    • It an alternative basal insulin
    • Novolin N and Humulin N work similarly
  15. Novolin R and Humulin R
    • Short acting insulin
    • Onset: 30 min
    • Peak: 2 to 5 hr
    • Duration: 4-6 hr
  16. Lispro (Humalog), Aspart (Novolog), Glulisine (Apidra)
    • Rapid acting insulin
    • Onset: 5-15 min
    • Peak: 1-3 hr
    • Duration: 3-5 hr