05 Thera VI Insulin and Injectables Lee Flashcards
How is insulin stored?
Insulin molecules form inactive storage hexamers (2 Zn and 6 insulin molecules). Insulin hexamers dissociate back into monomers (active form) in order to be diffused into the blood stream (results in delay in insulin onset of action). Newer insulin analogs have minimal hexamerization and diffuse faster
What is the physiological action of insulin?
Binds to its receptor. Translocation of Glut-4 transporters to plasma membrane. Influx of glucose into cell (most prominently muscle and adipose tissue)
What are the physiological effects of Insulin?
Increase: glucose uptake, glycogen synthesis, protein synthesis, triglyceride synthesis, potassium uptake. Decrease: gluconeogenesis, glycogenolysis, proteinolysis, lipolysis
What are the pharmacokinetics of insulin?
Cleared primarily by liver and kidneys. Half-life: 3-5 minutes
What is the normal basal insulin release in your body?
About 1 unit/hour
What is the advantage of using insulin therapy?
Decrease microvascular risk. Minimal side effects. No max dose. Unlimited efficacy
What are the disadvantages of insulin therapy?
Frequent monitoring. Injectables only (risk of lipodystrophy with incorrect technique). Weight gain. Hypoglycemia. Requires extensive patient education and dedication
What are the different types of insulin?
Rapid-acting. Short-acting. Intermediate-acting. Long-acting. Premixed
Which types of insulin are bolus/meal insulin?
Rapid- and short-acting
Which types of insulin are basal insulin?
Intermediate- and long-acting
What are the Rapid-Acting insulins?
Aspart (Novolog). Lispro (Humalog). Glulisine (Apidra)
What is the onset time for rapid-acting insulin?
5-15 minutes
What is the peak time for rapid-acting insulin?
30-90 minutes
What is the duration for rapid-acting insulin?
3-5 hours
What are the advantages of Rapid-Acting insulin?
Stimulates physiologic insulin relative to meals. More flexibility in meal timing. Can mix with insulin NPH. Can be given IV (aspart, glulisine)
What are the disadvantages of Rapid-Acting insulin?
High cost. Frequent injections. Provides only prandial coverage, still need basal insulin
What are the Short-Acting insulin drugs?
Regular (Humilin R, Novolin R)
What is the onset time for Short-Acting insulin?
30 minutes
What is the peak time for Short-Acting insulin?
2-4 hours
What is the duration of Short-Acting insulin?
4-8 hours
What are the advantages of Short-Acting insulin?
Cheaper. Can mix with NPH. Can be given IV/IM
What are the disadvantages of Short-Acting insulin?
Requires proper timing of injection relative to meals. Variable PK
What are the Intermediate-Acting Insulins?
NPH (Humulin N, Novolin N). CLOUDY appearance
What is the onset time of Intermediate-Acting Insulin?
2 hours
What is the peak time of Intermediate-Acting Insulin?
4-12 hours
What is the duration of Intermediate-Acting Insulin?
14-24 hours
What are the advantages of Intermediate-Acting Insulin?
Cheaper. Can mix short- or rapid-acting insulin –> fewer # of injections
What are the disadvantages of Intermediate-Acting Insulin?
In most patients, require BID injections for basal coverage. Causes more hypoglycemic events due to peaks (nocturnal hypoglycemia)
How often is Intermediate-Acting Insulin given?
Inject SQ QD-BID (timing of SQ injection depends upon the insulin with which it is administered)
What are the Long-Acting Insulins?
Detemir (Levemir). Glargine (Lantus)
What is the onset time for Long-Acting Insulin?
2-4 hours
What is the peak like for Long-Acting Insulin?
Detemir (Levemir) is relatively flat. Glargine (Lantus) is flat
What is the duration of Long-Acting Insulin?
Detemir (Levemir) is 6-24 hours (depends on dose). Glargine (Lantus) is 24 hours
What are the advantages of Long-Acting Insulin?
Stimulates physiologic basal insulin. Less hypoglycemia compared to NPH. Use with rapid-acting insulin allows for physiological insulin regimen
What are the disadvantages of Long-Acting Insulin?
Cannot mix with other insulins. Cost. Only provides basal coverage, will require PPG coverage
What are the advantages of Pre-Mixed Combinations?
May be better for patients unable to mix/measure insulin. Fewer injections. May be less costly (NPH/Reg)
What are the disadvantages of Pre-Mixed Combinations?
Does not allow for fine tuning. Less flexibility in timing meals
What is the main Pre-Mixed Combination used?
NPH/Regular (Humulin 50/50, 70/30, Novolin 70/30)
What are the acceptable insulin injection sites?
Abdomen (2 inches away from navel). Upper outer thighs. Upper arm. Buttock. Rotate sites to avoid lipohypertrophy (rotate within one injection site)
What are the factors that can alter absorption of insulin?
Injection site (abdomen (fast) > arm > thigh > buttock). Exercise (increase absorption if muscle near injection site used immediately after injection). Temperature (heat increases absorption rate). Massaging (increases absorption, avoid rubbing injection site)
How can you minimize painful injections?
Keep open insulin at room temperature. Remove air bubbles. Allow alcohol to completely evaporate before injecting
What are the available syringe sizes?
1ml, 0.5ml, 0.3ml. Low dose (0.5, 0.3ml) syringes preferred for patients using smaller units and/or are insulin-sensitive
What are some alternate glucose testing sites?
Fingertips vs. forearm, upper arm, palm, thigh, calf. Lag time: 20-39 minutes
When should you NOT use alternative blood glucose testing sites?
BG rapidly changing. Suspect low BG. Hypoglycemic unawareness. Within 1-2 hours after meals (USE fingertips!)
When should you initiate insulin in T2DM according to ADA/EASD 2012?
A1c above goal after 3 months with metformin + lifestyle modifications. Significant hyperglycemic symptoms and/or dramatically elevated glucose level (>300-350) or A1c > 10. High baseline A1c (> 9%( may consider insulin
What is the general approach for Insulin use?
First, target FPG with basal insulin (intermediate or long-acting insulin). Then, target PPG with bolus/meal insulin (rapid- or short-acting)
What is the Treat-To-Target insulin dosing?
Initial dose: 10 units/day (6 units if FPG < 126 or BMI < 26). Increase dose 2 units every 3 months until target levels reached
What is the ADA/EASD 2012 insulin dosing?
Initial dose: 0.2 units/kg/day. Maintenance: 0.7-1.2 units/kg/day. Increase dose 2 units every 3 days until target levels reached
When taking insulin, what should be done if there are signs of hypoglycemia after injecting?
Decrease by 4 units or 10% (whichever is greater)
When should you initiate insulin in T1DM?
Initiate insulin ASAP
What are the ADA/EASD 2012 recommendations for T1DM?
Intensive insulin therapy (multiple-dose insulin injections, continuous SQ insulin infusion). Use of insulin analogs. Matching prandial insulin to carbohydrate intake, premeal blood glucose and anticipated activity
What is the general approach to insulin dosing in T1DM?
Empiric Total Daily Dose (TDD) dosing: 0.5-0.8 units/kg/day. Basal: 50-60% of total insulin requirement. Prandial: 40-50% of total insulin requirement
What is the usual starting dose for bolus/meal doses in T1DM?
4 units/meal. If 2h PPG values are not at goal, increase dose by 2 units every 3 days until PPG in target range
How can patients self-adjust bolus dose by calculating CHO intake for each meal?
> 180 lbs: 1 unit/10 grams of CHO. If < 140lbs: 1 unit/15 grams of CHO
What are the recommended carbs per meal?
45-60g
What is the equation for bolus dose?
Bolus dose = (total carbs in meal) / (carb:insulin ratio)
What is the carbohydrate:insulin ratio?
The amount of carbs that can be covered by one unit of bolus insulin (1 units = 10-15g carbs, varies with individuals, time of day, physical activity)
What is the Rule of “500”?
Carbohydrate:Insulin ratio. 500 / TDD. Example: someone taking 50 units of insulin a day, 500/50 = 10. 1 unit of rapid acting insulin will cover 10g of carbs
What is the “Correction Factor = Rule of 1800”?
Correction dose is the amount of bolus insulin needed to correct episodes of hyperglycemia. Correction dose = (Actual BG - BG target) / CF. Correction Factor = 1800 / TDD. Correction factor estimates how much BG will be lowered with 1 unit of bolus insulin. Varies between individuals
What are common symptoms of hypoglycemia during the night?
Nightmares/crying out. Pajamas/sheets wet from perspiration. Feeling tired, irritable, or confused upon waking
How can being sick affect insulin treatment?
Illness may increase insulin requirements (continue usual insulin dose). Monitor blood glucose every 3-4 hours (administer supplemental doses of bolus insulin if needed, call MD if glucose remains over 240 after three insulin doses). Monitor ketones if SMBG > 240. Maintain fluids and carbohydrate intake
What are the Incretin Mimetics?
Exenatide (Byetta). Exenatide ER (Bydureon). Liraglutide (Victoza)
What is the MOA of Incretin Mimetics?
Increase glucose-dependent insulin secretion. Slow gastric emptying, suppress appetite, decrease glucagon secretion)
Which Incretin Mimetic does not need renal adjustment?
Liraglutide (Victoza)
How often is Exenatide ER (Bydureon) dosed?
2mg SQ every week
What are the ADRs associated with Incretin Mimetics?
GI (N/V). Low risk of hypoglycemia (increase concomitant SFU use). Weight loss (2-3kg). Pancreatitis
What is the Amylin analog drug?
Pramlintide (Symlin). Synthetic analog of amylin
What is the MOA of Amalin analogs?
Slows GI emptying (appetite suppression). Prevents post-prandial rise in glucose
What is Pramlintide (Symlin) indicated?
Adjunct therapy in T1DM and T2DM adults on insulin
What is the efficacy of Pramlintide (Symlin)?
Decrease A1c by 0.2-0.6%, decrease weight by 1.4kg
When is Pramlintide (Symlin) usually administered?
T1DM: 15mc SQ immediately before major meals. T2DM: 60mcg SQ immediately before major meals for 3-7 days
What is important to remember when taking Pramlintide (Symlin)?
DO NOT mix with insulin. Must reduce current insulin dose by 50%
What is the BBW associated with Pramlintide (Symlin)?
Severe hypoglycemia with insulin
What are the ADRs associated with Pramlintide (Symlin)?
Nausea (minimize with slow titration). Anorexia
What are the contraindications for Pramlintide (Symlin) use?
Gastroparesis. Hypoglycemia unawareness
