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49 Cards in this Set
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How can you treat type I DM?
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Insulin, chronic hyperglycemia caused by autoimmune destruction of pancreatic beta cells (insulin-producing).
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How can you treat Type II DM?
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Non-insulin antidiabetic drugs, chronic hyperglycemia initially caused by insulin resistance, can progress to insulin deficiency.
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What are the major target organs where insulin has an effect and what are these effects?
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Insulin receptor autophosphorylates (tyrosine kinase).
Liver: increases storage of glucose as glycogen in liver, inserts GLUT2 in membranes, increases synthesis of pyruvate kinase, phosphofructokinase and glucokinase, decreases protein catabolism Skeletal muscle: stimulates glycogen synthesis and protein synthesis, inserts GLUT4, potassium uptake Adipose tissue: triglyceride storage by activating lipoprotein lipase (in plasma), GLUT4, decrease intracellular lipolysis |
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What are the 3 rapid-acting insulin analogs? What are their advantages and uses?
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Injected: Insulin Lispro, Aspart, Glulisine
(also inhaled form) Rapid onset, early peak -- postprandial glucose control Preferred for continuous subQ infusion devices Also emergency tx of uncomplicated diabetic ketoacidosis |
Also life-threatening hyperkalemia and stress-induced hyperglycemia
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How are the rapid acting analogs lispro, aspart and glulisine able to be fast-acting? What are we concerned about with the faster onset of action?
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Small changes to insulin allows molecules to repel each other, dissociate more rapidly
May cause late postprandial hyperglycemia |
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What is the short-acting insulin and its uses?
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Regular insulin
IV for emergencies SubQ for ordinary maintenance, alone or mixed with longer-acting |
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What is the intermediate-acting insulin and its uses?
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NPH insulin, combined with regular and rapid-acting insulins
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What is the disadvantage of NPH? What is the advantage of NPH?
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10-16 hours DOA
Unpredictable hypoglycemia, more nocturnal hypoglycemia, more weight gain Can be combined with other insulins in same syringe (not Glargine and Detemir) |
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What are the 2 long-acting insulins and their uses?
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Insulin GLARGINE and insulin DETEMIR
Peakless basal insulin level lasting more than 20 hours, help control basal glucose levels without producing hypoglycemia |
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How is the long-acting insulin analog glargine able to have an extended DOA? What does it lower compared to NPH?
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Injected as acidic solution, precipitates/dissociates slowly
Peakless, long-lasting insulin profule gives LOWER incidences of symptomatic hypoglycemia compared to NPH |
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How is the long-acting insulin analog detemir able to have and extended DOA? What is its advantage?
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Detemir (MYRistic acid --> allows binding to albumin, absorption and dissociation longer)
Minor peak is dependent on dose -- not peakless Most CONSISTENT response with each dose |
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What are the AEs of insulin use?
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Hypoglycemia from excessive insulin
Most susceptible: advanced renal dz, elderly, children < 7yo Avoid brain damage, give glucose (PO, IV) or glucagon (IM) Also, insulin-induced immunologic complication: formation of ab's to insulin or contaminants (resistance or allergies), hypersensitivity rxn is v. rare |
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What is pramlitide and its MOA?
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Short-acting injectable AMYLIN analog
Suppresses glucagon release Slows gastric emptying Reduces appetite in CNS |
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What is the use of pramlitide and its AEs?
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SubQ, used with insulin to control postprandial glucose levels
Hypoglycemia, GI disturbances (N/V) |
Recommended for ALL severe Type I and Type II
(reduce A1C and reduce weight) with insulin |
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In which patients are the AEs of pramlintide more severe?
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Type I DM (GI, hypoglycemia) because don't make endogenous amylin
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What is the advantage of pramlintide and how should you dose it?
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Greater reduction in A1C, reduction in weight
Titrate up |
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What is the tx for Type 1 DM?
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Dietary instruction, parenteral insulin, possibly pramlintide for postprandial glucose control
TIGHT CONTROL reduces incidence of vascular complication including renal and retinal damage |
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What are the four oral antidiabetic drug groups for Type 2 DM? What are the 3 new agents that target endogenous regulators of glucose homeostasis?
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Insulin secretagogues (sulfonylureas and glinides), Biguanide metformin, Thiazolidinediones, alpha-glucosidase inhibitors
Pramlintide, exenatide, sitagliptin |
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What are the insulin secretagogues?
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Older agents (sulfonylureas): Tolbutamide, Chlorpropamide
Second-gen, more potent!! (sulfonylureas): GLYBURIDE, GLIPIZIDE, GLIMEPIRIDE (DOC) (glinides): Repaglinide, Nateglinide |
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What is the MOA of insulin secretagogues?
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Close K channels in pancreatic beta cell membrane, depolarize and trigger insulin release by Ca influx
NEED functional beta cells (useless in type 1 or severe type 2...) |
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What are the toxicities of insulin secretagogues?
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Hypoglycemia
Rash, allergy occasionally Weight gain |
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What are the AEs of sufonylureas (glyburide, glipizide, glimiperide)? When is glyburide CI?
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Hypoglycemia (esp eldery, liver/kidney dysfcn)
Weight gain CV disease Sulfa allergy Glyburide: CI in CVD |
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How are repaglinide and nateglinide useful?
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Rapid onset, short DOA, before a meal for postprandial glucose levels
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When should you be cautious with repaglinide?
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Repaglinide and Gemfibrozil
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Which insulin secretagogues are used more often?
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Sulfonylureas, especially glimiperide
Meglitinides only if hypoglycemia or allergy |
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What is the biguanide and its MOA?
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Metformin, ENHANCES insulin sensitivity, reduces endogenous insulin production (insulin-sparing effect)
Inhibit hepatic and renal gluconeogenesis Stimulate glucose uptake and glycolysis in peripheral tissues Slow glucose absorption from GIT Reduce plasma glucagon levels |
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What is the toxicity of the biguanide (metformin)?
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NOT hypoglycemia
GI distress (N/D) Lactic acidosis (esp renal/liver dz, alcoholism, predisposed to tissue anoxia or lactic acid production, CI renal failure) |
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What are the uses of the biguanide (metformin)?
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DOC in overweight pts with type II DM (no weight gain)
Also restores fertility in anovulatory women with PCOD (polycystic ovary disease) |
Can be used in pts without beta-cell islet function
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What does the biguanide metformin require for it to work? What are its advantages?
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Insulin presence bc insulin sensitizer
Low risk hypoglycemia May promote weight loss Protection from CHD Decrease A1C |
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When is the biguanide metformin CI?
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Renal failure, liver failure, CHF -- all can lead to lactic acidosis (rare major risk with metformin)
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What are the alpha-glucosidase inhibitors? What is their MOA?
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Acarbose, Miglitol
Carbohydrate analogs, inhibit intestinal brush border alpha-glucosidases, needed for conversion of complex starches, oligosacc's and disacc's to monosacc's Slowed sugar hydrolysis and glucose absorption reduces postprandial hyperglycemia (no effect on fasting blood sugar) |
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What is the use of acarbose and miglitol?
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Monotx or combination
Taken just before a meal |
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What is the toxicity of acarbose and miglitol?
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Flatulence, diarrhea, abd pain from increased fermentation by bacteria in colon
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When are the alpha-glucosidase inhibitors CI?
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Intestinal disease or liver disease bc work on intestinal enzymes
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What are the thiazolidinediones/glitazones? What is their MOA?
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Rosiglitazone, Pioglitazone
INC insulin sensitivity in target tissues by activating PPAR-gamma nuclear receptor (regulates transcription of genes encoding proteins for carb and lipid metabolism) Increase gluc uptake in muscle and adipose tissue Inhibit hepatic gluconeogenesis, lipid metabolism and fat distribution Reduce fasting and postprandial hyperglycemia |
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What is the toxicitiy of rosiglitazone and pioglitazone?
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Fluid retention/weight gain (as anemia and edema), can increase risk of heart failure
Hepatotoxicity, routine monitoring of liver function CV toxicity Females: increased risk of bone fractures Pioglitazone: induce cytP450 (3A4), can reduce serum concentrations of drugs |
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What is the use of rosiglitazone and pioglitazone?
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Monotx or combination
Also restore fertility in anovulatory women with PCOD and evidence of insulin resistance |
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What do the thiazolidinediones (glitazones) depend on?
When is it CI and why? |
Presence of insulin and resistance to insulin bc insulin sensitizer of peripheral tissues
CI in liver failure CI in Class III/IV CHF bc risk of worsening CHF (pulmonary edema AE) |
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What is exenatide/liraglutide and its MOA?
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Long-acting injectable GLP-1 analog
Glucagon-like peptide-1 (GLP-1): member of incretin family of peptide hormones, released from bowel endrocine cells in response to food Reduce postprandial and fasting glucose |
Augment glucose-stimulated insulin release from beta cells
Retard gastric emptying Inhibit glucagon secretion Produce feeling of satiety |
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What is the use of exenatide and its AEs?
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Combination with metformin or a sulfonylurea for type 2 DM
GI disturbances (nausea during initial tx, N/V) Hypoglycemia (when combined with sulfonylurea) |
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What long-term effect do exenatide, and liraglutide (injections) have? What is their advantage to GLP-1?
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Work to increase GLP-1 activity, promotes beta-cell proliferation (reduces A1C) and promotes weight loss
Also resistant to DPP-4, breaks down GLP-1 |
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What is the difference between exenatide and liraglutide?
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Liraglutide is long-acting GLP-1 analog, extends duration with albumin-binding
Less AE, similar effects Both offer dosing covenience |
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What is sitagliptin/vildagliptin/saxagliptin and its MOA?
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Oral inhibitor of DPP-4, enzyme that degrades GLP-1 and other incretins
Reduce postprandial glucose > fasting glucose |
Promotes insulin release
Inhibits glucagon secretion Delays gastric emptying Anorexic affect |
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What is the use of sitagliptin and its AEs?
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Monotx or combination with metformin or a thiazolidinedione (sig reductions when combined)
HA, nasopharyngitis, upper RTI |
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What are the advantages and disadvantages of the DPP-4 inhibitors vildagliptin and sitagliptin over the GLP-1 analogs?
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Adv: oral
Disadv: less potent, weight neutral |
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What is saxagliptin and where must you be careful with its use?
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DPP-4 inhibitor, used as adjunct
CYP3A4 inhibitor, lower dose of secretagoguges due to increased risk of hypoglycemia Caution in pregnancy and children |
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What is colesevelam and when is it used for DM? AEs?
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Bile-acid binding drug, improves lipid profile (modest reduction in A1C)
AE: bloating/gas/constipation |
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What is the tx for Type 2 DM?
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Weight reduction, dietary control, exercise
Oral monotx with metformin, sulfonylurea (glyburide, glipizide, glimepiride) or thiazolidinedione initially Long-acting (sulfonylureas, metformin, thiazolidinediones, exenatide, sitagliptin, some insulins) help fasting and postprandial Short-acting (alpha-glucosidase inhibitors, repaglinide, pramlintide, rapid-acting insulins) target postprandial |
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What are the 3 drugs that have been shown to prevent Type 2 DM in high risk individuals?
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Metformin
Thiazolidinediones (rosiglitazone, pioglitazone) alpha-glucosidase inhibitors (acarbose, miglitol) |
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