FA USMLE COMLEX Diabetes Pharm

nonspecificstchanges's version from 2017-03-01 14:43

Diabetes Drug Pharmacology

Tx for DM
Type I DM: Low carb diet; insulin replacement
Type II DM: Diet modification & exercise for weight loss; Oral agents, non-insulin injectables, insulin replacement
Gestational DM (GDM): Diet modification, exercise, insulin replacement if lifestyle modifications fail

Insulin Preparations

Drug ClassDrug(s)ActionClinical UseRisk/Concern
Insulin, Rapid actingLispro, Aspart, GlulisineBinds Insulin receptor (tyrosine kinase) rapidly, no LAG; Liver: Increase glucose stored as glycogen. Muscle: Increases glycogen & protein synthesis, Increases K+ uptake. Fat: Increases Triglyceride StorageType I DM, Type II DM, GDM (Post prandial Glucose controlHypoglycemia, lipodystrophy, rare hypersensitivity rxns
Insulin, Short actingRegular Insulin, Crystalline ZincSame as RapidType I DM, Type II DM, GDM, DKA (IV), Hyperkalemia (+glucose), Stress hyperglycemiasame as rapid
Insulin, IntermediateNPHSame as RapidType I DM, Type II DM, GDMsame as rapid
Insulin, Long actingDetemir, GlargineSame as RapidType I DM, Type II DM, GDM (basal glucose control)same as rapid

Oral Diabetes Drugs

Drug ClassDrug(s)ActionClinical UseRisk/Concern
BiguanidesMetforminExact mechanism unknown. Decrease Gluconeogenesis, Increase Glycolysis, Increase Peripheral Glucose Uptake (Increase Insulin Sensitivity)Oral. 1st Line use Type II DM, Causes modest Weight Loss. Can be used in patients w/o islet function.GI upset; most serious is Lactic Acidosis (CI in Renal Insuffiency)
Sulfonylureas"-ids" 1st gen: Chlorpropamide, Tolbutamide. 2nd gen: Glimepiride, Glipizide, GlyburideClose K+ channels in Beta-Cell membrane-> Cell depolarizes-> Insulin release via increased Ca2+ influx. Hyperinsulinemia eventually can make DM worse.Stimulates Release of Endogenous insulin in Type II DM. Require so islet function, useless in Type I DMRisk of Hypoglycemia in Renal failure, Weight gain. 1st gen: Disulfram like effects. 2nd gen: hypoglycemia
Glitazones/Thiazolidinediones"-glitazone"; Pioglitazone, RosiglitazoneIncreases Insulin sensitivity in peripheral tissue. Binds PPAR-gamma nuclear transcription regulator. PPAR-gamma increases adiponectin.Used as Monotherapy in Type II DM or combined with other oral diabetic rx. Safe to use with Renal ImpairmentWeight gain, Edema, Hepatotoxicity, HF, Increased risk of fractures.
Meglitinides"-glinide"; Nateglinide, RepaglinideStimulates postprandial insulin by binding to K+ channels on Beta-cell membranes (site different from sulfonylureas)Used as monotherapy in Type II DM or combined with metformin.Hypoglycemia (Increased risk of Renal Failure) Weight gain
GLP-1 Analogs"-tide", Exenatide, Liraglutide (sc inj)Increases Glucose-dependent insulin release, Decrease Glucagon release, Decrease gastric emptying, Increase satiety.Type II DMN/V, Pancreatitis , modest weight loss.
DDP-4 Inhibitors"-gliptin", Linaglipton, Saxagliptin, SitagliptinInhibits DDP-4 enzyme that deactivates GLP-1 (GLP-1 not degraded as much). Increases Glucose-dependent insulin release, Decreases glucagon release, Decrease gastric emptying, Increases Satiety.Type II DMMild urinary or respiratory infections, weight neutral, Increased Risk of Angioendema with ACE-Inhibitors
Amylin analogsPramlintide (sc inj)Decreases gastric emptying, Decreased Glucagon.Type I DM, Type II DMHypoglycemia (mistimed prandial insulin), nausea
SGLT-2 Inhibitors (Sodium-Glucose co-transporter 2)"-agliflozin", Canagliflozin, Dapagliflozin, EmpagliflozinBlocks Absorption of Glucose in PCTType II DMGlucosuria, UTIs, Vaginal Yeast infections, Hyperkalemia, dehydration (orthostatic hypotension), EUGLYCEMIC ketoacidosis (increased FA oxidation)
a-glucosidase inhibitorsAcarbose, MiglitolInhibit intestinal brush-boarder a-glucosidases. Delayed carbohydrate hydrolysis & glucose absorption -> Decreased postprandial hyperglycemiaType II DMGI disturbances. Sucrose/disaccarides will NOT help relieve symptoms of Hypoglycemia