Diabetes

Type 1 DM is about 9% of diabetes pt s. Juvenile or insulin depedent. -onset before age 40, peak incidence = age 14; most symptoms 2 to hyperglycemia: polyuria, polydipsia, polyphagia -severe form assoc w/ketosis; exogenous insulin req d to prevent ketosis, reduce hyperglycemia, and reverse catabolic state 4 types of insulin preparations: ultra-short (lispro), short, intermediate (lente), and long acting (ultra-lente); the long and intermediate are turbid suspensions that usually have a protamine/phosphate buffer and zinc buffer added Lispro Rapidly absorbed; peak serum values within 1 hr Duration 3-4 hrs Short Onset: 30mins Duration: 5-7 hrs (incr w/dose) IV tx for ketoacidosis Intermediate (lente) 30% semilente; 70% ultralente Delayed onset, prolonged duration Long (ultra-lente) Same as lente

Diabetic nephropathy leading cause of death/disability due to DM (50% end stage renal dz in US), 35% IDDM, 15-60% NIDDM; diabetic neuropathy major cause of morbidity (mainly feet ulcers) Radiculopathy is a sensory syndrome involving pain in chest or abdomen, tx w/codeine if severe pain, alt drugs: phenytoin, amitriptyline/fluphenazine combo Type 2 DM is non-insulin dependent, though 20% pt s may use insulin. Treatment regimen: diet, weight loss, sulfonylurea drugs, and insulin (some pt s); oral meds are sulfonylureas, biguanides, thiazolidinediones, and -glucosidase inhibitors. Sulfonylurea drugs promote release of insulin from cells, reduce serum glucagon, and potentiate insulin action at target tissues. Drug Tobutamide Details Well absorbed Short duration Safe for elderly Rare toxic rxn Chlorpropamide (Diabinese) Slow metabo, DM type 1, DKA, preg near term, hepatic/renal/hrt dz, elderly, malnutrition Same as above Prolonged hypoglyc in elderly Contraindication DKA, hepatic impairment Adverse Hypoglyc, HA, constipation, diarrhea, photosensitivity

NPH (neutral protamine Hagedorn)- Mixed w/regular insulin for bid admin Split-dose injections are mixtures of short and intermediate insulins; the ultra-short/short are taken before meals while the intermediate are taken overnight. Beef insulin is the 1 component in most commercial insulin: 70% beef/30% pork Human insulin is available and is more readily absorbed w/slightly shorter duration of action. Human proinsulins have 4-6X longer life, but 8-12% activity of human insulin. Diabetic Ketoacidosis (DKA)- results from failure to take insulin in estab d pt s, acute stress, or poor sick-day management; treat with insulin at higher than normal dose along with IV fluids and potassium replacement. NOTE: plasma glucose values fall faster than ketone levels, so continue insuli until ketosis clears. Tight glycemic control is good, but caution in pt s w/adv renal dz, elderly, and peds <7 yrs Hypoglycemia is the most common complication of insulin tx For mild hypoglycemia, give OJ, sugar sweetened drink, food; if pt unconscious, IV infusion of 50% glucose over 2-3 min interval; if no IV available, give SC/IM glucagon Common circulatory problems: atheroscleritis, incr platelet adhesion, incr endothelin-1 (vasoconstrict) , decr NO (vasodilate) Diabetic retinopathy is the leading cause of blindness in US Tolazamide

Glyburide

Short life w/prolonged biological effect, no water retention Shortest life, less severe hypoglyc, extensive liver metabo (90%) 1/day w/insulin, most potent, long life (5 hrs),

Blurred vision, photosensitivity, incr liver transaminases Mostly same plus farting

Glipizide (glucotrol)

Same

Glimepriride

Same

Photosensitivity plus most from above

Monotherapy for DM type 1 plus same as above

2 generation glyburide, glipizide, and glimepiride have fewer adverse effects

nd

Biguanide Drug Metformin (fortamet, glucophage, riomat, glumetza) Details Glycolysis stimulation, decr plasma glucagon, decr gluconeogen, decr glucose absorpt in GI Useful in pt s w/refractory obesity and insulin resitance No hypoglyc, no weight gain, can combo w/sulfonylurea Contraindications DKA, metabo acidosis, renal dz, lactic acidosis, surgery, hepatic dz, caution if CHF, elderly, alcohol abuse, may induce ovulation Adverse GI, anorexia, N&V, diarrhea (most upon initiation of tx) Flatulence, ha, rash, metallic taste

Thiazolidinedione Drug Troglitazone (Rezulin) Details Removed from US market; approved for insulin resistant pt s, increases tissue insulin sensitivity, decr resistance, decr insulinemia, decr hyperglyc no liver toxicity, well absorbed po, life 3-4 hrs DM type 1, DKA, CHF, female pt s, edema, acute coronary syndrome, sulfonylurea use, may induce ovulation URI, hA, edema, fluid retent, wgt gain, anemia, dyspnea, hypoglyc CI s Adverse

Rosiglitazone (Avandia)

Alpha-glucosidase inhibitors Drug Miglitol (Glyset) Details Binds intestinal disaccharides; reduces postprandial glucose rise 30-50%; results in delayed carb absorption; starches, dextrins, maltose, sucrose (NOT lactose); systemically absorbed, but not metabolized Same, but not systemically absorbed CI s DKA, IBD, colonic ulcers, Cirrhosis, GI obstruction, renal impair, malabsorption Adverse Flatulence, ab pain, rash, diarrhea

Pioglitazone (Actos)

Incr insulin sensitivity

Same plus sinusitis, myalgia, and pharyngitis

Most combo drugs include Metformin. Other Type 2 DM Treatments: Byetta- 1/2life 2-4 hrs, activates glucagon-like peptide receptor; incr insulin secretion, decr glucagon secretion, and delays gastric emptying. Cycloset- biphasic life 4-4.5 hrs, 15 hrs; stimulates dopamine receptors, inhibits anterior pituitary prolactin secretion, decreases fasting and postprandial hyperglycemia without increasing insulin levels. Glucagon- peptide produced by alpha cells of pancreas; 8-18 minute life; converts glycogen to glucagon; emergency tx in insulin dependent unconscious pts; can cause severe hyperglycemia and allergic rxns. Causes positive inotropic and chronotropic action (incr contractility and HR).

Acarbose (Precose)

Same

Same