pharm endo goshko info.txt

Less gluconeogenesis, possibly via inhibition of AMP kinase (needed for glucose formation). also improves muscle/adipose tissues' sensitivity to insulin. also delayed absorption of glucose from GI tract.

PO

DM type 2, off-label PCOS.

many, including DKA, iodinated contrast, and renal impairment (CrCl < 60).

BBW lactic acidosis. several GI (start low go slow, take after meals). metallic taste, malabsorption of B12/folate. No weight gain.

metformin IR 850-1000mg PO BID

No -- since metformin does not stimulate pancreatic beta cell insulin secretion, the risk of hypoglycemia is low if metformin is used alone.

increase insulin secretion by binding to sulfonylurea receptor on pancreatic beta cells (less K efflux -> depolarization -> insulin release). also decrease glucagon release from pancreatic alpha cells.

PO. second generation agents are 100 times more potent than first generation agents

DM type 2

DKA, prone to hypoglycemia. caution w/ sulfa allergy.

weight gain, rash. only 65% will respond to treatment (of those, 5-10% per year will gradually lose glycemic control)

yes (start low, go slow) -- because we are "squeezing the pancreas"

glyburide 1.25-20mg PO qday

TZDs, glitazones, insulin sensitizers

increase the sensitivity of cells to insulin by agonizing PPARs. These receptors decrease glucose production (liver), increase glucose uptake (muscle/adipose), and increase free fatty acid uptake/storage (adipose tissue).

PO

DM type 2

Heart failure (worsen CHF by fluid retention -- BBW). Rosiglitazone additional BBW for MI.

weight gain, edema, fracture risk, anemia. pioglitazone also bladder cancer.

No -- only messing with insulin sensitivity, not insulin release

rosiglitazone 15-45mg PO qday

Incretins such as GLP-1 (glucagon-like peptide 1) are hormones released after meals that lower blood glucose by stimulating insulin release. Their activity is typically blunted in diabetes. Mimetics mimic incretins (structurally modified to resist degradation) -- DPP-4 inhibitors prevent their breakdown (block incretin inactivation by DPP-4).

SC

DM type 2

liraglutide personal/family hx of thyroid CA (BBW).

NAUSEA. Serious side effects include pancreatitis, anaphylaxis, renal failure.

Yes -- stimulate insulin release

exenatide 5-10mcg SC BID w/i 60min of meal

These drugs are carbohydrate analogues that competitively bind to alpha-glucosidase (enzymes that break down carbs into glucose) with greater affinity than natural dietary carbs. This helps prevent an after-meal glucose spike.

PO

DM type 2

IBD, DKA, GI obstruction, elevated LFTs. acarbose also renal dysfunction.

GI (bloating, flatulence, diarrhea, abdominal pain), elevated LFTs

No -- keeps sugars from being digested, does not spike insulin levels

Bind to a receptor (SUR-1) on pancreatic beta cells that blocks the efflux of potassium. The resultant depolarization eventually results in insulin release. Stimulate only glucose dependent insulin secretion (sulfonylureas are glucose-independent).

PO. Rapid onset, short duration of action. Give up to 30 minutes prior to meal. repaglinide more effective than nateglinide.

DM type 2

DKA. Adjust dose for liver (both) and kidney (only repaglinide) issues.

repaglinide + gemfibrozil (raises repaglinide levels due to inhibition of hepatic metabolism)

GI (diarrhea, flatulence, abdominal cramps, bloating)

Yes -- stimulating insulin release

amylin is a hormone that works with insulin to help regulate glucose levels by inhibiting post-prandial glucagon secretion, slowing gastric emptying, and decreasing appetite.

SC

DM types 1 and 2

when initiating, premeal doses of rapid and short-acting insulins should be reduced by 50% to prevent hypoglycemia (BBW)

avoid other agents that slow GI motility, may delay absorption of PO medications (give 1 hr prior or 3 hrs after).

Yes -- inhibits secretion of glucagon -- BBW FOR HYPOGLYCEMIA

GI (N/V, anorexia), HA.

mimics endogenous glucagon secreted from alpha cells of pancreas -- leads to decreased glycogen synthesis, increased glycogenolysis/glucose, increased glycolysis, and increased ketogenesis. At higher concentrations, also increases ionotropy/chronotropy (via increased cAMP).

available SC, IM, and IV. T1/2 is 3-6min.

Refractory hypoglycemia, Hyperinsulin states (insulinoma), b-blocker/CCB/insulin overdose.

hypokalemia, hyperglycemia

Naturally occurring hormone that reduces blood glucose via increasing glucose uptake in liver, muscle, and adipose tissues. Also decreases glucose production in liver, decreases lypolysis, increases storage of triglycerides, enhances amino acid uptake, and prevents protein breakdown.

Yes -- we're giving insulin

Take rapid acting insulins immediately before eating (w/i 30 min). Take short acting 30 to 60 min prior to meals (peak 2-4hrs). Intermediates onset 1-4h, peak 4-14hrs, duration 10-24 hrs. Long-acting mimics basal insulins. SC, Rapid/short acting are the only ones available IV.

DM type 1. DM type 2 if severe sx, marked hyperglycemia, DKA, oral agents contraindicated/not effective, during pregnancy.

injection site reactions (including lipohypertrophy), weight gain

typical insulin dosing for DM type 1: 0.3-0.6 U/kg/d

once prandial insulins started, sulfonylureas and meglitinides are usually stopped (though sensitizers should be continued in obese, insulin resistant patients).