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Rapid acting insulins
- Analogs. Bolus p meal tx
- lispro (Humalog)
- aspart (Novolog)
- glulisine (Apidra)
- Onset:
15-30 min - Peak: 1-3 hr
- Duration: 3-4 hr
-
Short acting insulin
- Regular insulin (Humulin R, Novolin R)
- Onset: 0.5-1 hr
- Peak: 2-4 hr
- neutral pH
-
Intermediate acting insulin
- NPH (neutral protamine Hagedorn)
- Humulin N, Novolin NOnset: 1-2 hr
- Peak: 6-10 hr
- Duration: 16-20 hr
- cloudy
-
Long acting insulins
- Analogs. no peaks, basal tx, forms depot
- glargine (Lantus) - pH 4, precipitates at phys pH
- detemir (Levemir) - 98% binds to plasma albumin
- Onset: 1-2 hr
- Peak: no peak
- Duration: 20-24 hr
- Don't mix with other insulin
-
SE of exogenous insulin
- hypoglycemia
- weight gain
- lipohypertrophy (enlargement of SQ fat depot)
- lipoatrophy (destruction of SQ fat @ site)
-
Sulfonylureas
1st gen: acetohexamide, chlorpropamide - longest t1/2 36h, tolazamide, tolbutamide
2nd gen: glimepiride, glipizide (GITS), glyburide
- MOA: stim phase 2 ins release from b-cells (bind, close K, open Ca --> translocation of granules)
- bioavailability ~90%, protein bound
- Hepatic metabolism (CYP2C9) - rifampin is inducer, amiodarone is inhibitorSE: hypoglycemia (risk ^w/longer t1/2), weight gain, disulfiram like w/tolbutamide or chlorpropamide
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Short-Acting insulin secretagogues (Meglitinides)
repaglinide (Prandin)
nateglinide (Starlix)
- MOA stimulate insulin secretion from b-cells (phase1)
- given before each meal
- regaglinide 2C8/3A4
- nateglinide 2C9/3A4
- rifampin inducer of all 3, grapefruit inhibitor 3A4, gemfibrozil inhibitor 2C8
- SE hypoglycemia, weight gain
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Biguanides
metformin
- MOA decrease hepatic glucose production by decreasing gluconeogenesis
- Renally eliminated
- Drugs renal tubule secretion (cimet, dig, triamt) may increase met levels.
- SE GI, maybe weight loss, LACTIC ACIDOSIS -->metabolic acidosis.
- CI- renal insuff, liver impari, CHF, ETOHic, metabolic acidosis, hypoxic lung disease
-
Thiazolidinediones (TZDs)
PPARy agonists
rosiglitazone (Avandia)
pioglitazone (Actos)
- MOA stim PPARy (reg gene transcription)
- increases insulin sensitivity in muscle, liver, fat
- rosi 2C8>2C9 - gemfib is 2C8 inhibitor
- pio 2C8>3A4 - rifampin is 2C8 inducer
- SE weight gain, CHF (bbw), anemia
-
a-Glucosidase inhibitors
acarbose (Precose)
miglitol (Glyset)
- MOA inhibit glucosidases in small intestine (prevent breakdwn of polysaccharides to glucose)
- Best for post-prandial glucose concentrations
- SE GI (low dose then titrate), increase in LFT
-
pramlintide acetate (Symlin)
- MOA amylin agonist - dec postpran glucose, dec amt short acting insulin req postpran, delays gastric empty, improves satiety.
- Metabolized by kidneys
- SE hypoglycemia, N/V, loss of appetite, HA
- may delay abs of other drugs (delay gastric empty)
- Don't use w/GI motility moderators
-
Incretin Mimetic Drugs
exendin-4
exenatide (Byetta)
- MOA mimic incretins - binds to /stim GLP-1 receptor
- net result - decrease fasting/postpran glucose levels.
- Renally eliminated - CL reduced w/ESRD
- SE decreased appetite, N/V, hypoglycemia
- may delay absorption of oral drugs (pain, antibiotics)
-
liraglutide (Victoza)
- MOA-GLP-1 receptor agonist, activates GLP-1 receptors on b-cells
- Delays gastric empty time, may dec abs of oral drugs
- SE - HA, N, diarrhea, inj site rxns, hypoglycemia, pancreatits, thyroid tumor (bbw)
- CI - hx of medullary thryoid carcinoma
-
DPP-4 inhibitors
sitagliptin (Januvia)
saxagliptin (Onglyza)
- MOA slows inactivation of incretin-->increase in GLP-1
- net result- decreased fast/postpran glucose
- Renal elim - dose red w/renal impair
- sax -3A4/5 - dec dose w/strong inh (grapefruit, azoles)
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