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90 Cards in this Set
- Front
- Back
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2 phases of insulin secretion?
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Rapid (from stored insulin, impaired in type 2)
Delayed (from newly synthesized) |
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What's up with insulin complexes?
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Monomer
Dimer Hexamer (requires zinc) Hexamer = better storage Monomer = circulating insulin |
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Daily Insulin Needs?
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Fasting Level = 5-15 microU/mL to keep stuff from being broken down
Postprandial = 60-90 microU's |
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what do the differing levels of insulin mean for therapy?
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we need to mimic those levels
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What's up with insulin degradation?
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50-60% never reaches circulation thanks to the liver
35% excreted by kidney half life = 3-5 minutes |
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what is the DM paradox?
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there's tons of glucose out there, but the cells can't take it up
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Sx's of Type 1 DM?
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Polydipsia
Polyphagia Polyuria w/o Insulin: ketoacidosis, coma, and death |
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how does ketoacidosis occur?
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without insulin, proteins get broken down into AA's that get converted to glucose. But the breakdown of proteins also realeases ketone bodies...
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Ketoacidosis and Type 2?
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RARE
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who are the rapid acting insulins?
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Regular Insulin
Insulin Lispro Insulin Aspart/glulisine |
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Who are the intermediate acting insulins?
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Neutral Protamine Hagedorn (precipitated)
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Long acting Insulins?
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Insulin Glargine
Insulin Detemir |
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How can you give regular insulin?
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IV
IM SC 45 minutes before meals... |
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Indications for regular insulin?
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Emergencies (ketoacidosis)
Changing insulin needs (surgery) Prandial needs? |
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Types of Insulin Lispro?
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Hexamer (injectable)
Monomer |
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Benefit of Lispro monomer?
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absorbed faster
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Administration of Lispro?
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Usually SC, 15' before meal
can give after meal IV is possible but not common |
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Usefulness of Aspart/Glulisine?
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Can be used in CSII pumps
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Benefit of Glulisine?
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Dissociates into monomers faster than aspart or lispro
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how does Insulin Glargine work?
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It starts off as a solution w/ pH 4 and precipitates at physiological pH after SC injection
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other kickers for Glargine?
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once a day
not good for preggers can't be mixed with other insulins |
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What's up with Insulin Detemir?
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Its got a FA thrown in that promotes self-association/albumin binding
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administration of Detemir?
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1-2 times a day SC
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As far as insulin goes, what does type 1 need?
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Mix of rapid and prolonged acting insulins
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what mixes are available?
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Regular + NPH
Lispro + intermediate + protamine (NPL) |
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Insulin delivery systems?
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mostly SC
Pen injectors Continous infusion pumps Inhalers (exubera) |
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Goals of Insulin Therapy?
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Fasting Glucose <126
2 hr postprandial glucose < 200 HbA1c <7% |
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Why do you need a basal insulin level?
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Suppress hepatic glucose production (gluconeogenesis, glycogenolysis)
Suppress lipolysis and proteolysis |
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how much of your daily insulin dose goes to the basal needs?
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40-60%
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Typical Therapy for Type 1 after puberty?
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Multiple injections/CSII pump
few complications and tighter control |
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Contraindications for multiple shots/pump?
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Hepatic/renal disease
Elderly < 7 yo |
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most common complication w/ insulin therapy?
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Hypoglycemia (< 70)
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Reasons for hypoglycemia?
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Changes in diet/eating pattern
Physical exertion Too high dose of insulin Mismatch between peak insulin and food intake Inc SC blood flow (hut tob) |
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Rx for Hypoglycemia?
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Glucose (15-20g)
Mild: OJ, gel, candy bar Severe: Glucose IV or glucagon SC/IM |
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Rx for Ketoacidosis?
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Regular Insulin IV
--->10% fall in glucose per hr Ketone body clearance takes longer Electrolyte replacement as needed Give SC insulin 30' before stopping IV |
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Other complications w/ insulin therapy?
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Allergy: IgG = mild, IgE = life threatening
Immune Insulin Resistance (anti-insulin Abs) Hypertrophy/Atrophy of injection site Insulin Edema |
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What are other drugs that can have hypoglycemic interactions?
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Beta Blockers
ACE-I Antipyretics/Anti-Infl Ethanol |
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What are other drugs that can have hyperglycemic interactions?
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Diuretics
Beta agonists CCB's H2 Receptor Blockers |
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Who is the main Biguanide?
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Metformin
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Benefits of Metformin
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Anti-hyperglycemic (so no hypoglycemia)
No effect on Insulin Release 20% dec in TG's Inc sensitivity to insulin Dec gluconeogenesis in Liver |
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Metformin MOA to inc sensitivity to insulin?
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AMP-dependent protein kinase activation
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Pharmacokinetics of Metformin?
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2-3 times a day w/ meals
for type 2 only Combo it |
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Contraindications of Metformin?
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Renal/Hepatic Failure
Lactic Acidosis HF/MI Chronic Hypoxic Lung disease Prolonged fast/low calorie diet Severe GI SE's Septicemia Alcoholism |
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SE's of Metformin?
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Uncommon
GI-related, Metallic Taste, Anorexia Chronic: b12/folate malabsorption, Ca supplements |
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When should you stop metformin?
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plasma lactate > 3mM
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what are TZD's?
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Thiazolidinediones
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Examples and current use of each TZD
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Troglitazone--Hepatotoxic
Rosiglitazone: CHF risk Pioglitazone: ok...maybe liver tests required |
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MOA for TZD's?
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agonist for PPAR-gamma
PPARy activates genes-->inc tissue sensitivity |
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Pro's of TZD's?
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inc sensitivity
no hypoglycemia may dec hepatic glucose production only Type 2 |
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Kicker for pharmacokinetics of TZD's?
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hepatic metabolism only, so its ok for compromised kidneys
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SE's of Pioglitazone?
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messes w/ CYP28/CYP3A4 which alters metabolism of OCP's
Anemia, Wt. Gain, Edema |
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Contraindications of Pioglitazone?
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preggers
CHF (class 3-4) Liver disease |
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First Generation Sulfonylureas
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Tolbutamide
Tolazamide Acetohexamide Chlorpropamide |
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Second Gen Sulfonylureas
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Glyburide
Glipizide Gliclazide Glimepiride |
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Difference between 1st and 2nd gen sulfonylureas?
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First Gen required GRAMS each day
Second Gen requires much much less more or less have same 24ish duration |
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Indications for Sulfonylureas?
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For Hyperglycemia when diet/lifestyle changes fail
Many type 2's do better on sulfonylureas than insulin |
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Mech for Sulfonylureas?
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Inhibit beta cell ATP-sensitive K channels
Inc beta cell sensitivity to insulin/glucose minor Inc tissue sensitivity to insulin minor dec in hepatic degradation of insulin |
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When to take sulfonylureas?
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30' before meal
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SE's for Sulfonylureas?
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Uncommon w/ 1st gen, very uncommon w/ 2nd
Hypoglycemia is most common GI issues Jaundice Allergic rxn Dermatologic Anemias Wt Gain |
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Drug interactions of Sulfonylureas?
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Ethanol enhances hypoglycemic actions
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Contraindications for Sulfonylureas?
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Type 1 DM
Pregnancy/Lactation Hepatic/Renal disease Caution w/ elderly and CV disease |
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Who are the Meglitinides and who are they for?
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Repaglinide
Nateglinide Type 2! |
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Overall character of Meglitinides?
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Same mech, utility, and SE's as sulfonylureas
Combo w/ Biguanides No Sulfur so good for allergies |
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Who are the alpha-Glucosidase Inhibitors?
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Acarbose
Miglitol |
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Mech of alpha-glucosidase inhibitors?
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Inhibit intestinal BB a-glucosidases (and other carb digesting enzymes)
Dec absorption of starch, complex sugars Dec prandial glucose levels No hypoglycemia |
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Indications for alpha-glucosidase inhibitors?
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Type 1 and Type 2
Marginal pts (since it dec HbA1C by 1% and fasting glucose by 25mg/dL) |
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Pharmacokinetics of alpha glucosidase inhibitors?
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Miglitol 6 times as potent as acarbose
Titrate dose up Best w/ starchy, high fiber diet w/ low simple sugars Combo w/ insulin, biguanides, sulfonylureas |
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Utility of Alpha-Glucosidase Inhibitors?
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Elderly w/ postprandial hyperglycemia
Pt at risk for hypoglycemia/lactic acidosis Type 2 w/ severe hyperglycemia Type 1 w/ delayed SC insulin absorption |
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SE's for alpha-glucosidas inhibitors
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Malabsorption
Flatulence Bloating Diarrhea improve w/ time hypoglycemia if combo'd w/ sulfonylureas |
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Contraindications of alpha-glucosidas inhibitors
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IBS and other intestinal issues
Renal Disease and Hepatic disease |
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Who are the new kids on the block?
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Incretins
Sitagliptin Pramlintide |
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Ex. of Incretin?
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Exenatide
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What is exenatide?
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glucagon like peptide 1 (GLP1) from gila
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Benefits of Exentide?
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Resistant to DPP IV
Inc Insulin Dec Glucagon Prevents islet apoptosis Delays gastric emptying Lower hypoglycemic risk |
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Who is exentide for?
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Type 2
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Admin of Exentide
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SC
expensive combos |
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SE's of Exenatide?
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Nausea (40%)
Hypoglycemia when combo'd w/ sulfonylureas |
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What is Sitagliptin?
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DPP IV inhibitor
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Benefits of Sitagliptin
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Less nausea than exentide
Combos No wt loss |
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SE's of sitagliptin?
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Nasopharyngitis
Upper Resp Infections |
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What is Pramlintide?
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Islet Amyloid Polypeptide Analog
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Role of Pramlintide?
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Delays Gastric Emptying
Inhibits Glucagon Secretion Suppress Appetite |
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Admin of Pramlintide?
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SC for type 1 and insulin-rx type 2
Before meals |
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SE's of pramlintide?
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Hypoglycemia (reduce insulin rx in type 1)
Nausea (improves w/ time |
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Glucagon uses?
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Emergency Insulin Overdose
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Pharmacokinetics of Glucagon?
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1mg IM or IV
works fast and is gone fast |
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MOA of glucagon
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binds cell surface receptors
elevates cellular cAMP LIVER activates glycogenolysis Inc gluconeogenesis and KB's PANCREATIC Beta Cells normally would inc insulin, but blunted in diabetics HEART inc chrono and ino-tropy SMOOTH MUSC High dose increases relaxation cAMP independent |
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Clinical uses of Glucagon?
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-Severe Hypoglycemia in Type 1 (i.e. when unconscious)
-Endocrine Diagnostics (tests pancreatic beta cell reserve) -Beta Blocker Poisoning (elevates cAMP and reverses cardiac OD effects) Radiology of Bowel (relaxes smooth musc) |
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SE's of Glucagon?
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Mild, not severe
N&V |
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Contraindications of Glucagon?
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pheochromocytoma
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