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30 Cards in this Set
- Front
- Back
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What are the major pathophysiologic defects in Type II DM?
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1. Liver/Muscle/Fat - Insulin Resistance
- decreased glucose uptake in muscle and fat 2. Pancreas - Islet Cell Dysfunction - decreased B cells - less insulin released - increased alpha cells - high glucagon release 3. Liver - increased glucose output |
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HbA1c
- what does it mean? - purpose?? |
- HbA1c reflects mean blood glucose levels of the past 6-8 weeks
= GOLD STANDARD for monitoring glycemic control! ***Every 1% increase in HbA1c reflects increase in glucose of 30 mg/dL --> increased risk for: - retinopathy - nephropathy - neuropathy - microalbuminemia ... if lower HbA1c --> decreased risks |
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What are the 2 main principles of Lifestyle Modification Therapy after dx with Type II DM?
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GOAL 1: control glucose and lipid values
- modify fat/carb intake - portion control; space meals throughout day - increase physical activity - education on diabetes self-management - monitor Glu, HbA1c, lipids, BP GOAL 2: moderate, sustained weight loss (7-10%) |
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What is the Progressive Care Approach in Type II DM?
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1. Nutrition tx, exercise, lifestyle changes
2. Add oral agents - monotherapy or easy combo therapy 3. Add basal insulin 4. Intensify insulin tx |
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Thiazolidinediones (TZDs)
- names? - MOA - advantages? - disadvantages? |
- Rosiglitazone and Pioglitazone
MOA - Bind to PPAR- gamma --> effects improve insulin action, glucose metab and vascular function = INSULIN SENSITIZERS Advantages: - not likely to cause hypoglycemia (independent of pancreas, so insulin levels will decrease with improved sensitivity) - fasting and postprandial glucose lowered - reduction in circulating insulin - ameliorate many factors of the metabolic syndrome Disadvantages: **Do NOT work without INSULIN - Slow clinical effect - 2-4 months |
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PPARs
- What are they? - Functions? |
Peroxisome Proliferator Activated Receptors - alpha, gamma, delta isoforms
- Transcription factors to regulate expression of genes involved in modification of lipid and carb metabolism PPAR-alpha: ligand for fibrate drugs; increased HDL, decreases TGs PPAR-gamma: ligand for TZDs and some prostanoid and fatty acid derivatives - promotes differentiation of small, metabolically-active adipocytes - Reduces TNFalpha and FFAs - Increases Adiponectin - Shifts visceral fat to more subcutaneous distribution -----> Net: improved insulin action, glucose metab, vascular function |
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Thiazolidinediones (TZDs)
- metabolism? - side effects/contraindications? |
- metabolized in liver - safe for renal failure patients
Side Effects - FLUID RETENTION - contraindicated in pts with CHF!!!!! - WEIGHT GAIN (must restrict calories) Rosiglitazone - possible CV risks (used less) Pioglitazone - safer |
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What is the MOST IMPORTANT diabetes drug??
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Metformin
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Metformin
- MOA? - extra good benefit? |
MOA
**decrease hepatic glu production - enhances insulin sensitvity - works independently of pancreas/reduces circulating insulin leves - activates AMP kinase - alters glu and lipid metab (not to a signif degree) - Helps limit weight gain- might even lose weight |
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What is "insulin sparing"?
- what drugs do this? |
Reduction in circulating insulin levels
- metformin - TZDs |
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Metformin
- Side Effects/Contraindications?? |
GI SIDE EFFECTS!!!
- diarrhea, bloating, etc. - 30% patients overall - Must slowly titrate - low dose until tolerated and build up over time - Take with food CONTRAINDICATED IN KIDNEY DYSFUNCTION!!!! - cleared by kidney - if renal insufficiency, metformin can accumulate and cause lactic acidosis - potentially Fatal! - DON'T GIVE BEFORE SURGERY OR WITH IODINATED CONTRAST MATERIALS - wait until normal renal function returns |
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Alpha-Glucosidase Inhibitors
- names? - MOA? - clinical effects? - side effects? |
- Acarbose
- Miglitol MOA - slow digestion of complex carbs in gut - delay postprandial spike in glucose and lowers corresponding insulin response - MODEST clinical effect - only 0.5% fall in HbA1c Side Effects - GI!! Flatulence, diarrhea, n/v ***NOT used often bc bad side effects with limited clinical effect |
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Secretagogues
- what is the broad name for this class of drugs? - example of a drug name? - MOA? |
= Sulfonylureas
- ex: Glimepiride, Glipizide, Glyburide MOA - Bind to unique receptor on K-ATP channel on B cells --> increases insulin secretion - Use short-acting agents (meglitinides) for a meal-time insulin increase |
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Explain the biochemical mechanism behind glucose stimulating insulin release
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1. Glucose transported into pancreatic B cells by GLUT2 (for glycolysis)
2. Closure of K-ATP channel on B cell - via ATP from glycolysis 3. Influx of Ca2+ --> DEPOLARIZATION 4. Translocation and exocytosis of preformed insulin granules |
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Secretagogues
- Advantages? - Disadvantages? |
Advantages
- work quickly (over a few days) Disadvantages - 15-20% pts are "non-responders" - ***RISK OF HYPOGLYCEMIA - often weight gain - Flat dose-response relationship -->long-term failure (30%): best results at first, then loss of B-cell responsiveness over time... - no metabolic syndrome improvements |
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What important info about diabetes meds did the UKPDS study find, and what is the suggested response??
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B-cell Failure (burn out over time) --> EARLY USE OF COMBO TX!
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What are Incretins?
- names? - where do they come from? |
= Gut hormones that control post-prandial glucose
- GLP-1: from L cells in ileum and colon - GIP: from K cells in duodenum |
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GLP-1
- MOA? - disadvantage? |
After a meal.....
- stimulates insulin response from B cells (glu-dependent manner) - inhibits gastric emptying - reduces food intake and body weight - inhibits glucagon secretion from a-cells (glu-dependent manner) Disadvantage: degraded quickly by enz DPP-4 |
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GLP-1 Agonist Therapy
- name of drug? - what is? - MOA? - mode of admin? - side-effects? - advantage?? |
= Exenatide
= synthetic version of salivary protein from Gila monster - Binds to GLP-1 receptors on B-cells and other sites - Resistant to degradation by DPP-4!!!!!!! - stimulates insulin secretion and inhibits glucagon secretion; slows gastric emptying; early satiety and gastric actions - reduces food intake and body weight Admin: subcut injection BID Side Effect: nausea! ***Low propensity to cause hypoglycemia! |
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DDP-4 Inhibitors
- name? - mode of admin? - advantage? |
= Gliptins - Sitagliptin (Januvia), Vildagliptin (Galvus)
- ORAL MOA - inhibit DPP-4 that inactivates GLP-1 and GIP in circulation --> get increased effects from your own endogenous incretins - increased 2-fold - insulin secretion, glucagon inhibition, slows gastric emptying *Neutral effect on body weight ***Low propensity to cause hypoglycemia |
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Amylin
- what is? - MOA? |
= normally secreted with insulin from B-cells
- inhibits glucagon secretion from a-cells - helps reduce hepatic glu production - slows gastric emptying and has CNS effects on satiety - reduced food intake and body weight |
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Amylin-Analog Therapy
- name of drug? - mode of admin? - indication? |
= Pramlintide
- injection only - indicated for diabetics ON INSULIN TX only |
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What drug classes MUST be taken with Insulin?
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- Thiazolidinediones
- Amylin Analog Tx (Pramlintide) |
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What drugs are injection only?
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- GLP-1 agonists (Exenatide)
- Amylin agonist tx (Pramlintide) |
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What drugs have bad GI side effects?
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- Metformin - must titrate slowly
- Alpha-Glucosidase Inhibitors - MAJOR GI problems - GLP-1 agonists (exenatide) - nausea |
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What drug might cause lactic acidosis in patients with renal failure?
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Metaformin
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What drug is contraindicated in patients with CHF? Why?
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TZDs - bc major fluid retention
(and metformin if patient has reduced renal excretion due to CHF) |
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Which drugs have worst propensity to cause hypoglycemia?
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Sulfonylureas
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Meglitinites
- what are? - function? |
= class of secretagogues
**Short-acting --> give right before meals to increase insulin secretion |
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What drugs might cause:
- weight gain? - weight loss? |
Weight Gain:
- TZDs - Sulfonylureas Weight Loss: - Metformin - GLP-1 agonist (exenatide) - Amylin agonist (Pramlintide |
