ANTI-DIABETICS Insulin preparations:

Rapid-acting (IV)- lispro, aspart, glulisine Short-acting (IV)- regular insulin (tx DKA coma) Intermediate-acting (NO IV- unstable enough)-NPH, isophane insulin (protamine in phosphate buffer) Long-acting (NO IV- unstable enough)- insulin glargine (at pH 4.0 in solution) insulin detemir (myristoylated, increasing its t1/2) -----------------------Following drugs are only effective in IIDM! Sulfonylureas: Binds and blocks ATP-sensitive K+ channel membrane depol Ca2+ influx on cells Overall effect: stimulate insulin release from cells; indirectly potentiate action of insulin on target issues Side effects: Hypoglycemia (less with 2nd gen) Wt gain Caution with sulfa allergies! Class 1st gen 2nd gen (long t1/2; less S.E.) Drug Tolbutamide Chlorpropamide Glyburide Glipizide Glimepiride Effect Safest in elderly t1/2: 32 hours Toxicity Disulfiram-like effect Contraind: Hepatic impairment, renal insufficiency Little hypoglycemic effect

cardioprotective

Meglitinidies: Not sulfonamids = can be used in sulfa allergy! Mechanism just like sulfonylureas Drug Repaglinide Effect postprandial serum glucose Mimics insulin better HbA1c No weight changes Toxicity Liver metabolism- CYP3A4 Contraind: Not be used in combo with sulfonylureas Caution- liver probs Hypoglycemia (comparable to 2nd gen sulfonylureas)

Nateglinide

Biguanides: Drug

Metformin

Effect DOC for newly dx DM with lifestyle changes! mainly b/c NO wt gain macrovascular events Does NOT release insulin (independent!!!) glucose removal from blood (insulin action in muscle/fat) glucose GI absorption (postprandial), plasma glucagon, gluconeogenesis glucose levels euglycemia! (not in normal subjects) SAFE children > 10 y/o

Toxicity Lactic acidosis Diarrhea Contraind: Lactic acidosis condns Renal or hepatic dz Alcoholism Dz predisposing to tissue hypoxia (CHF, COPD) Pregnancy

Thiazolidinedione: Drug Effect Insulin sensitizers Rosiglitazone Ligands of nuclear PPAR R = post-R insulin-mimetic action! Do NOT stimulate insulin secretion insulin resistance Pioglitazone Prophylactic use- dvlp IIDM fasting glucose, HbA1c Wt gain Alpha-glucosidase inhibitors: Drug Effect glucose absorption, carbohydrate digestion Acarbose -glucosidase present in SI enterocytes Minimal effects on fasting glucose Miglitol No weight changes

Toxicity Edema risk heart failure in CHF pts Rosiglitazone: Black label warning (MI, angina) Contraind: CHF Hepatic disease

Toxicity Flatulence Metabolism via GI digestive enzymes, microorganisms

Glucagon-like Peptide 1 (GLP-1): Drug Effect Synthetic version of GLP-1 Exenatide Resistant to degradation by DPP-IV postprandial, fasting glucose Liraglutide HbA1c, gastric emptying Wt loss Potential cell number/function Dipeptidyl-peptidase-IV inhibitors (DPP-IV): Drug Effect Potentiate effects of incretiin hormones Sitagliptin postprandial, fasting glucose No weight changes

Toxicity SubQ injections- 1h before 2 main meals Single daily subQ injection Contraind: Thyroid CA (black box warning)

Toxicity Oral ok (better than GLP-1) because avoids subQ

Amylin-like peptide: Drug Effect Adjunct to insulin therapy for IDDM, IIDM Synthetic analog of amylin (hormone co-secreted with insulin) Pramlintide Regulate postprandial glucose concentrations Wt loss: gastric empty, centrally-mediate appetite modulation Hyperglycemic agents: Drug Effect blood glucose when glycogen available Not as favorable in juveniles Glucagon Inotropic, chromotropic Profound relaxation of the intestine Non-diuretic thiazide, vasodilate, hyperglycemic Diazoxide Directly inhibit insulin secretion Tx insulinoma

Toxicity SubQ, 3x/d Hypoglycemia Contraind: Slow GI problems

Toxicity Parenteral admin

Fairly long duration of action