Insulin Properties and Types PDF

44 I DI AB ETE S INSULIN In an individual without diabetes, the pancreas controls the release of insulin in the body. It provides a consistent level (or basal amount) of insulin at all times, then releases more insulin when the BG is elevated postprandially (after meals). In a patient with diabete...

44 I DI AB ETE S INSULIN In an individual without diabetes, the pancreas controls the release of insulin in the body. It provides a consistent level (or basal amount) of insulin at all times, then releases more insulin when the BG is elevated postprandially (after meals). In a patient with diabetes, insulin can be administered to mimic the normal physiologic process. Insulin cannot be given orally; it is given as a subcutaneous injection (most common), intravenously (less often, usually for acutely high BG) or inhaled (uncommon). Insulin is a h igb-ale1t medication, which means it has a high risk of causing patient harm and requires extra care during handling and administration. Insulin is high-alert primarily due to human errors, such as misreading measurements, using the wrong insulin type, strength, dose or frequency and skipping meals. INSULIN PROPERTIES AND TYPES The graph below shows the onset, peak and duration of action of the common insulin types, which must be understood in order to design an insulin regimen and to make adjustments when the BG trends too high or too low. The table that follows describes how the different types of insulins are used and their major safety issues. Basal and rapid-acting insulins are called insulin analogs; when basal insulin is used with mealtime rapid-acting insulin, the profile is analogous (similar) to the natural pattern of insulin secretion from the pancreas. Basal Insulin Basal insulin includes glargine (red line), detemir (blue line) and ultra-long acting degludec (pink line). These insulins are "peakless" with an onset of 3 - 4 hours and duration~ 24 hours. They mainly impact fasting glucose. Intermediate-Acting Insulin Inst, 1 l (yellow line) is intermediate-acting but it can be used as a basal insulin. NPH has an onset of 1- 2 hours, and it peaks at 4 -12 hours, which can cause hypoglycemia. BG control is further complicated by the variable, unpredictable duration of action (14- 24 hours). The P in NPH is for rotamine, which helps to delay absorption/extend the duration of effect. Protamine also comes in lispro-protamine and aspart-protamine, which have the same onset, peak and duration as NPH. These come in premixed solutions only and are combined with standard rapid-acting insulin (aspart and lispro) . Rapid-Acting and Short-Acting Insulin • Rapid-acting insulin (purple line) includes aspart, lispro and glulisine. These provide a bolus dose, similar to the pancreas releasing a burst of insulin in response to food. They have a fast onset (- 15 min), peak 1n 1 - 2 hours and a dura tion of 3 - 5 hours (gone by the next meal). Regular insulin U-100 (green line) is considered a shortacting insulin; it can be given as a bolus at mealtimes like rapid-acting insulin, but has a slower onset and lasts longer than needed for a meal. Regular insulin has an onset of 30 minutes, peaks at - 2 hours and lasts 6 -10 hours. Other Insulins (Not Included in Graph) • Regular U-500 is a very concentrated insulin. The onset is the same as regular insulin U-100, but the duration is closer to NPH; it can last up to 24 hours. It is often dosed twice daily or TIO, before meals. • Inhaled insulin is not used commonly. It is a mealtime insulin with fast absorption through the lungs. Aspart, lispro, glullsine UI ] .5 "S UI to 42+ how·s .5 0 2 4 6 8 10 12 Hours 622 14 16 18 20 22 24 r~ © RxPrep RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 INSULIN SAFETY ISSUES AND NOTES; APPLIES TO ALL INJECTABLE INSULIN, EXCEPT WHERE NOTED CONTRAINDICATIONS • Do not administer during episodes of hypoglycemia. WARNINGS • Hypoglycemia, hypokalemia (insulin facilitates K+ entry into cells, and is used to treat hyperkalemia). SIDE EFFECTS • Weight gain: insulin causes excess glucose to move into adipose cells. • Lipoatrophy: loss of SC fat at the injection site (which disfigures skin) and lipohypertrophy: accumulation of fat lumps under injection site. Avoid both by rotating Injection sites and using analog insulins (lower risk than with older insulins). STORAGE AND ADMINISTRATION NOTES Most vials are 10 ml and most pens are 3 ml. Insulin concentrations are 100 units/ml, unless noted otherwise (discussed later in the chapter). Do not shake; turn suspensions (NPH, protamine mixes) up and down slowly or roll between hands. Do not freeze or expose to extreme heat. Unopened insulin vials and pens are stored in the refrigerator. Open vials and pens can be kept at room temperature (see Room Temperature Stability of Insulin chart later in the chapter). It is more painful/uncomfortable to inject cold insulin. Pen devices should~ be shared (even if the needle is changed) due to the risk for transmission of blood -borne pathogens. Any percentage mixture of NPH and regular (or rapid-acting) insulins can be made by mixing the two insulins in the same syringe; regular insulin (or rapid-acting) is clear and is drawn up (into the syringe) first, before the NPH, which is cloudy. Rapid-Acting (Bolus) Insulin Aspart (Novolog, Fiasp) Llspro (Humalog, Admelog, Lyumjev) Lispro U-200 (Humalog U-200) Insulin glulisine (Apidra} Clear and colorless Inject SC 5-15 minutes before meals to have insulin available when glucose from the meal is absorbed. can also be administered right after eating. Fiasp and Lyumjev can be injected with the first bite or within 20 minutes of starting a meal. Used as prandlal lnsulln (to prevent high BG from a meal) and for correction doses when BG is high (often by sliding scale). Preferred insulin type for insulin pumps (discussed later in the chapter}. Apidra SoloStar pens contain glulisine Humalog KwikPens contain lispro Novolog FlexPens contain aspart Aspart and lispro insulins come in premixed insulins with intermediate-acting protamine insulin. Inhaled insulin (Afrezza) Contraindicated in any~ disease, including asthma and COPD; do not use Afrezza in smokers. Co-formulations with faster absorption: Fiasp is formulated with niacinamide (vitamin B3} and Lyumjev is a newer form of lispro, formulated with treprostinil and citrate. Can cause acute bronchospasm, cough and throat pain. Requires lung monitoring with pulmonary function tests (FEV1). Replace inhaler every 15 days. Short-Acting (Bolus) Insulin Regular (Humulin R, Novolin R) Inject SC 30 minutes before meals to have insulin available when the glucose from the next meal is absorbed. Clear and colorless Used as prandiaf insulin and for correction doses when BG is high (often by sliding scale}. Rx and OTC Myxredlin is a ready-to-use (RTU) regular insulin IV solution (100 ml bag) Concentrated Regular (Humulin R U-500) Regular insulin is preferred for IV infusions, including in parenteral nutrition; it is less expensive than other insulins and when administered as a continuous IV infusion, the onset is immediate. IV regular insulin should be prepared in a non-PVC container. Often given with NPH twice daily, 30 min before breakfast and dinner. Lunch is covered by the NPH, and possibly some residual regular insulin. This regimen requires just 2 injections per day (since the insulins can be mixed). Five times as concentrated as regular insulin; many safety risks. Recommended only when patients require > 200 units of insulin per day. The prescribed dose of Humulin R U-500 should always be expressed in units of insulin. • All patients using the U-500 insulin vial must be prescribed U-500 insulin syringes to avoid dosing errors; see the Syringes and Needles section for details. • Do not mix with any other insulin; only administer as SC injection (not IV, IM or in an insulin pump), 623 44 I DIABETES Intermediate-Acting (Basal) Insulin NPH (Humulln N, Novolin N) Cloudy Rx and OTC • Given as a basal insulin, typically dosed twice daily as an add-on to oral drugs. Can be a less expensive alternative, but has more hypoglycemia. • If nocturnal hypoglycemia occurs with NPH dosed once daily QHS, the dose can be split (e.g., 2/3 QAM, 1/3 QHS). • Usually injected once daily; detemir may need to be given twice daily. Insulin glarglne (Lantus, Toujeo, Basaglar, Semglee) • Caution required: Lantus is 100 units/ml and Toujeo is a concentrated insulin glargine with 300 units/ml (an option when > 20 units/day of insulin glargine is needed). • Toujeo has max effect by the 5th day; the coverage may not be adequate initially. Clear and colorless • Lantus and Toujeo [and the rapid-acting insulins Admelog (lispro) and Apidra (glulisine)] are made by the same manufacturer and all of them use the same SoloStar pen. • Do not mix with any other insulins. Ultra-Long-Acting (Basal) Insulin Insulin degludec (Tresiba) • Insulin degludec comes in a vial and the Tresiba FlexTouch pen. The vial has 100 units/ml. Tresiba FlexTouch pens come in 100 units/ml and 200 units/ml. Tresiba can be useful when insulin detemir or glargine causes nocturnal hypoglycemia. Premixed Insulin 70/30MIXES 70% NPH/30% regular (Humulln 70/30, Novolln 70/30) 70% aspart protamine/30% aspart (Novolog Mix 70/30) Rx and OTC 75/25MIX Given BID (before breakfast and dinner), or sometimes TIO (with rapid-acting insulin). O If the mixture contains rapid-acting insulin: inject 15 minutes before a meal. O If the mixture contains regular insulin: inject 30 minutes before a meal. In premixed insulins, the percentage of NPH or protamine insulin is listed first and the percentage of short-acting or rapid-acting insulin is listed secorid (e.g., Humulin 70/30 contains 70% NPH and 30% regular). NPH or protamine (which are both cloudy) make the mixes cloudy. 75% lispro protamine/25% lispro (Humalog Mix 75/25) 50/S0MIX 50% lispro protamine/50% lispro (Humalog Mix 50/50) CASE SCENARIO A 35-year-old female injects Humulin 70/30 60 units before breakfast and 20 units before dinner. What Is her TDD of regular Insulin? Humulln 70/30 is 70% NPH and 30% regular. The regular dose in the morning is 60 units x 0.3 = 18 units. The regular dose in the evening ls 20 units x 0.3 = 6 units. The TDD of regular insulin is 24 units. DRUG INTERACTIONS • Rosiglitazone: 1' 1iisk of heart failure when taken with insulin; do not use together. • Pramlintide: must reduce mealtime insulin by 50% when starting pramlintide to avoid severe hypoglycemia. • Avoid the combination of insulin with sulfonylureas 01• meglitinides (monitor closely if used together). May need to _[, insulin dose when used with drugs that can cause hypoglycemia, including SGLT2 inhibitors, GLP-1 agonists, TZDs and DPP-4 inhibitors. May need to -l- insulin dose when used with direct acting antivirals (DAAs) for hepatitis C treatment due to risk of hypoglycemia. INSULIN AVAILABLE OTC Regular, NPH and premixed 70% NPH/30% Regular insulins can be sold OTC or can be dispensed with a prescription for insurance coverage. All basal and rapid-acting insulins are available by prescription only. 624 Rx PREP 2 022 COU RSE BOO K I Rx PREP ©2021, © 2 0 2 2 INSULIN DOSING AND CALCULATIONS STARTING INSULIN IN TYPE 2 DIABETES If an injectable medication is needed to reduce the AlC in T2D, a GLP-1 receptor agonist is preferred and should be considered first. If the patient is already on a GLP-1 agonist (or a GLP-1 agonist is not appropriate), insulin should be started. An exception is when using insulin initially to treat very high BG at diagnosis (AlC > 10% or BG > 300 mg/dL) or if symptoms of catabolism are present (e.g., DKA) . Starting insulin in T2D should follow a step-wise approach (see image below). Starting Insulin in Type 2 Diabetes STARTING A BASAL-BOLUS INSULIN REGIMEN IN TYPE 1 DIABETES , 1 ; - The typical starting dose for TlD is 0.5 units/kg/day. Insulin is dosed using total body weight(~) . Commonly, 50% of the total daily dose (TDD) is administered as basal insulin and 50% as prandial (bolus) insulin. Steps: _,,_,, 1. Calculate TDD (0.5 units/ kg/ day, using TBW) 2. Divide the TDD into 50% basal insulin and 50% bolus (rapid-acting) insulin 3. Divide the bolus insulin evenly among 3 meals (or allocate more insulin for larger meals and less for smaller meals). ---- Add basal insulln -- _j 10 units SC daily or 0.1·0.2 units SC/ kg/day Titrate based on fasting plasma glucose (FPG) CASE SCENARIO Start a basal-bolus regimen with Lantus and Humalag in a patient with type 1 diabetes that weighs 84 kg. 1. Calculate the TDD: If FPG not at goal or signs that prandial insulin is needed (e.g., FPG at goal or below goal, but AlC above goal) 0.5 units/kg/day x 84 kg = 42 units 2. Split the dose in half for basal and rapid-acting insulin: 21 units Lantus and 21 units Humalag 3. Split rapid-acting insulin into 3 even doses: 7 units Humalag TIO AC Add prandfal lnsulln 4 units or 10% of basal dose SC once daily prior to largest meal Titrate based on prandial blood glucose; add on doses prior to other meals if needed l Not at AlC goal ! 71 Mixed Insulin rlllfmen FuU basal/bolus realmen Basal insuRn dally + prandial Insulin befcre-NCh meal J Twice dally NPH -+ short/rapid seir•mlxed or pmnbced Answer: 21 units lantus daily and 7 units Humalog TID AC Starting a Regimen with NPH and Regular Insulin NPH and regular insulin regimens are not preferred; neither insulin has a profile that can mimic the natural insulin release from the pancreas as well as basal and rapid-acting insulin combinations. However, the lower cost and ability to use less injections (since these insulins can be mixed) make this type of regimen more feasible for some. The starting TDD of insulin is the same as with basal-bolus regimens, but % of the TDD is given as NPH and % is given as reguladnsulin. STARTING INSULIN IN TYPE 1 DIABETES TREATMENT WITH AN INSULIN PUMP All people with TlD require insulin. Most are treated with an insulin pump or muJ tiple daily injections of insulin designed to mimic the normal pattern of insulin secretion. Rapidacting injectable insulins and long-acting basal insulins are preferred (over short- and intermediate-acting insulins), because they have less hypoglycemia risk and better mimic the physiologic pattern of insulin made by the body. Pumps can provide excellent BG control and require less daily insulin injections. Users must be motivated, willing to test their BG frequently and be able to understand the pump's operation. Prio1 ex perience with multiple daily injections is a requirement for switching to a pump. Pumps hold insulin in a reservoir (see image on the next page) . The insulin runs out of the pump through tubing to a small infusion set placed on the skin, usually on the abdomen, through a small cannula (needle) that inserts under the skin. The cannula tip rests in subcutaneous fatty tissue, where the insulin is released. The insulin reservoir, t ubing and infusion set need to be replaced regularly. 62 5 44 I DIABETES Insulin pumps deliver rapid-acting insulin (preferred) by two complementary methods, continuous and bolus dosing. Continuous doses: small amounts of insulin are released every few minutes to provide a basal insulin level. 1. 2. Bolus doses: pumps can be programmed to release a number of insulin units to match the carbohydrates in a meal. The bolus dose is calculated by the patient's insulin to carbohydrate ratio (ICR), see Mealtime Insulin Dosing Options section. The bolus dose is adjusted based on the current BG level (e.g., if low, use less insulin). I l - The insulin is held in a reservoir that is inserted into the pump. The tubing connects the pump to the infusion set, which has a cannula that inserts under the skin. ADJUSTING INSULIN BASED ON BLOOD GLUCOSE TRENDS BG readings from a meter can be written on a paper log or downloaded from a meter's memory (see later section on Self-Monitoring Blood Glucose). Changes to an insulin dose are not based on single measurements; there needs to be a trend showing that the BG runs too high or too low. BG is ideally checked before breakfast (FPG), lunch and dinner and at bedtime. l'·. high or low BG reading is reflective of the insulin dose prior to that reading; look backwards to see which insulin/s are active and could be contributing to the trend. Adjusting Basal Insulin Fasting BG highs or lows, and/or similar trends that last most of the day (except with BG spikes after eating), typically indicate that the basal insulin dose needs to be changed. Low BG trend: J, the basal or NPH insulin dose. - -- -- High BG trend: 1_ the basal or NPH insulin dose. Adjusting Mealtime Insulin If the postprandial BG is high or low following the same meal on most days, the regular or rapid-acting insulin dose taken prior to that meal should be increased for high BG, or decreased for low BG. If the preprandial BG is high or low before the same meal (e.g., lunch) on most days, the regular or rapid-acting insulin dose taken before the previous meal (e.g., breakfast) should be increased for high BG, or decreased for low BG. 626 CASE SCENARIO RC. a 47-year-old male with type 2 diabetes, takes Toujeo 18 units SC QHS and Novo/og 5 units SC TID AC. He presents with two days of BG readings. taken before meals and at bedtime. BREAKFAST LUNCH Day 1 (mg/dl) 105 118 Day 2 (mg/dL) 97 115 DINNER BED 126 197 122 What adjustment should be made to RC's insulin regimen? The Novolog dose taken prior to lunch should be increased. Explanation: the goal range for preprandial blood glucose is 80130 mg/dl. The readings are all within the normal range except for the readings before dinner. The high readings before dinner indicate that RC is not taking enough insulin before lunch. The lunchtime dose should be increased. Fasting BG is most affected by the basal insulin. If the prebreakfast readings were high, the Toujeo dose should be increased. If the readings at dinner were taken postprandially (instead of preprandially). the Novo/og dose before dinner should be increased . MEALTIME INSULIN DOSING OPTIONS Option 1: Use the Same Insulin Dose Every Time The mealtime (rapid-acting or regular) insulin can be set at the same dose everyday for a meal (e.g., 20 units of insulin lispro before dinner). This assumes that about the same grams of carbohydrates are eaten at dinner every day. "' This method results in high or low BG when the carbohydrate intake is higher or lower, respectively. Option 2: Calculate an Insulin Dose at Each Meal When different amounts of carbohydrates are eaten at each meal (which is common), a simple calculation can provide the right amount of rapid-acting or regular insulin needed. The bolus dose is calculated with the insulin-tocat•bohydrate ratio (lCR). The ICR indicates the grams of carbohydrates covered by 1 unit of insulin. There are two variations of the ICR formula, depending on the type of insulin being used. Regular insulin uses the Rule of 450, and rapid-acting insulin uses the Rule of 500. The TDD of insulin used in the formula should account for both long-acting and short- or rapid-acting insulins included in the regimen. RxPREP 2022 COURSE BOOK I RxPREP ©2021, ©2022 ICR: Rule of 450 for lffGULAH L , grams of carbohydrates covered by 1 unit of regular insulin 450 total daily dose of insulin (TDD) Calculate the Correction Factor Correction Factor - 1,500 Rule for r- - 1,500 correction factor for 1 unit of regular insulin total daily dose of insulin (TDD) ICR: Rule of 500 '- REGULAR for RAPID-ACTING 500 L total dally dose of insl1lin {TDD) = grams of carbohydrate - ] covered by 1 unit of rapid acting insulin CASE SCENARIO ST is a 70 kg female with T1D who uses an insulin lispro pump. The continuous (basal) dose delivered by the pump in a 24 hour period is 26 units insulin lispro. The average daily amount of insulin lispro administered as bolus doses with meals is 24 units. Correction Factor - 1,800 Rule for RAPID-ACTING I I total daily dose of insulin (TDD) correction factor for 1 uni: l of rapid-acting insulin _ ] 2. Next, calculate the correction dose, which is the total units of insulin needed to return the BG to the target range. The formula for the correction dose is the same for both regular and rapid-acting insulin. Calculate the Correction Dose eorHrYP£s I Calculate the ICR. = 1,800 (B~onr::t~~:::::rBG) _ _ _ _ correction dose ] ST uses rapid-acting insulin. Use the Rule of 500. L 500 total dally dose of insulin (TDD) 500 grams of carbohydrate covered by 1 unit of ra pid-acting insulin 10 SO units CASE SCENARIO JJ is a 35-year-old male with T2D, currently treated with Lantus 50 units SC QHS and Novolog 15 units SC TIO AC 1. What is JJ's correction factor? Since Novolog is a rapid-acting insulin, use the Rule of 1,800 to calculate JJ's correction factor. She has an ICR of 1:10, which means 1 unit of rapid-acting insulin covers 10 grams of carbohydrates. ST will eat a hamburger (24 g carbohydrate) and fries (28 g carbohydrate) for lunch. She adds up the total carbohydrates and divides by 10 to calculate the bolus dose: 24 g (bun) + 28 g (fries) 10 (her ICR) = 1 unit of rapid-acting total daily dose of insulin (TDD) 50 units Lantus 1,800 5,2 units ST enters 5.2 units on the pump. If she was using a syringe or pen to inject, she would round to the nearest whole number. CORRECTION DOSES FOR ELEVATED BLOOD GLUCOSE BG that is higher than the targeted range can be corrected with a bolus called a correction dose. o To calculate the correction factor, use the 1,500 Rule for regular insulin and the 1,800 Rule for rapid-acting insulin. The TDD of insulin used in the formula should account for both long-acting and short- or rapidacting insulins included in the regimen. + insulin 45 units Novolog 18 _947 = 19 95 units = 95 units TDD Round to the nearest whole # He has a correction factor of 19, which means 1 unit of rapidacting insulin will lower the BG by 19 mg/dl. 2. JJ has a target premeal BG of 140 mg/dL. He checks his BG before dinner and it is 200 mg/dL. What dose of Novolog should JJ administer before dinner? Determine the correction dose using the formula ~ blood glucose now) - (target blood glucose) "' correction factor 1. The first step is to calculate the correction factor, which indicates how much the BG will be lowered (in mg/dL) by 1 unit of insulin. correction factor for 1,800 correction dose 200 mg/dL - 140 mg/dl 19 = 3 units Add the correction dose to the number of units he usually administers before meals to get the dose he needs before dinner: 3 units + 15 units = 18 units Novolog INSULIN CONVERSIONS Most insulin conversions are 1:1 (the same dose is used), but the regimen might need to be split up differently. The exceptions involve converting twice daily NPH and different forms of glargine; see the Study Tip Gal on the next page. 627 44 I DIABETES be fa tal when used incorrectly. Fortunately, most concentrated insulin comes in pens, which are simply dialed to the correct dose. The concentrated insulin that comes in both a pen and a vial is regular insulin U-500, which has higher risk. Most Insulin conversions are 1:1 The dose of the new insulin is usually the same as the old insulin* Exception #1 NPH dosed insulin glargine (Lantus, Toujeo, Basaglar or Semglee) dosed daily Use 80% of the NPH dose Example: NPH 30 units AC breakfast and 20 units AC dinner= 50 units NPH daily 50 x 0.8 = 40 units insulin glargine once daily Exception #2 Toujeo insulin glargine (Lantus, Basaglar, Semglee) or insulin detemir (Levemir) Use 80% of the Toujeo dose 'The dose of the new insulin might need to be adjusted when the BG is not controlled (e.g., using a higher dose for hyperglycemia). INSULIN ADMINISTRATION INSULIN STRENGTHS AND CONTAINERS Most insulin products contain 100 units/mL of insulin. Some insulins have> 100 units/mL; these are concentrated insulins (see below). Insulin is available in: • Vials (usually 10 mL), ready to be drawn up with an insulin syringe. Humulin R U-500 comes in a 20 mL vial. • Pens, ready to inject once a needle is attached. Pens are dialed to the number of units needed. All pens contain mL of insulin, except Toujeo comes as two sizes: 1.5 mL and 3mL. All insulin pens are multi-dose; needles must be dispensed with all insulin pens. Some pens are disposable, and others have replaceable cartridges. Insulin pens are easy to use; simply dial the units to inject. Example of providing a 20-unit dose of Lantus 100 units/mL with a pen or with a vial and syringe: • The Lantus Solostar pen would be dialed to 20 units, which would provide 0.2 mL. JII . l Regular Insulin Humu/in R U-500 KwikPen and vial: 500 units/ml Long-Acting Insulins Tresiba F/exTouch pen (degludec): 200 units/ml Toujeo SoloStar, Toujeo Max SoloStar pens (glargine): 300 units/ml Example of providing an 80-unit dose with Tresiba FlexTouch U-100 and U-200: Pens of either strength would be dialed to 80 units. The difference is the volume of the injection. • An 80-unit dose with U-100 is 0.8 mL. • An 80-unit dose with U-200 is 0.4 mL (half the volume). Very Concentrated Regular U-500 Humulin R U-500 is five times as concentrated as U-100 insulin. It is useful for patients taking > 200 units/day, but has a high risk for dosing errors. Methods to avoid dosing errors with U-500 insulin: • The prescribed dose of Humulin R U-500 should always be expressed in units of insulin. Only dispense with U-500 sycinges (see Selecting an Insulin Syringe section). • Humulin R U-500 KwikPen provides up to 300 units with one injection and has a lower risk of dosing errors. Dispensing insulin in an outpatient pharmacy requires a calculation of the days' supply and rounding up to the nearest vial/pen size. For example, if a patient is taking 35 units of Lantus daily, _._. how many Lantus SoloStar pens would be dispensed to provide a 30-day supply? Step 1: calculate the total number of units needed. 35 units/day x 30 days = 1,050 units of insulin needed Step 2: calculate the number of units per insulin pen, based on the concentration of insulin. Lantus 100 units/ml x 3 mL per pen = 300 units per pen • The Lantus 10 mL vial provides the same dose by drawing up 0.2 mL with a U-100 syringe. Step 3: calculate the number of pens to be dispensed. Remember, Concentrated Insulin pens cannot be broken, so round up. 1,050 units needed x (1 pen I 300 units) = 3.5 pens Injecting high doses of U-100 insulin requires a volume that can feel uncomfortable and, with very high doses (> 100 units), can require more than one syringe. Concentrated insulin is useful to reduce the volume of the injection, but can 628 ,. Rapid-Acting Insulin Humalog KwikPen, Lyumjev KwikPen (lispro): 200 units/ml - Answer: 4 pens must be dispensed to provide enough Insulin Remember, insulin pens require priming with 2 units prior to each dose. Some pharmacists account for this in their calculation of days' supply, but it is not a standard practice to do so. RxPREP 2022 COURSE BOOK INSULIN STABILITY I RxPREP ©2021, ©2022 SYRINGES AND NEEDLES Unused insulin vials, pens and cartridges are stored in the refrigerator. The expiration date of refrigerated insulin is the manufacturer's expiration date on the label. Once the insulin is in use it can be kept at room temperature, but the expiration date no longer applies. The insulin must be used within a specific number of days based on the type of insulin (see table below). This is an important counseling point for patients. Selecting an Insulin Syringe Use the smallest syringe that will hold the units of insulin. It is easier to read the unit markings on smaller syringes, which makes them more accurate. 0.3 mL syringe for up to 30 units 0.5 mL syringe for 30 - 50 units 1 mL syringe for 51-100 units Notice in the table that most insulin is stable at room temperature for 28 days including all rapid-acting insulin. The insulins with shorter stability are typically pens. A 1 mL U-100 insulin syringe holds up to 100 units. Use smaller syringes to inject up to 5 0 units. ROOM TEMPERATURE STABILITY OF INSULIN 1-2 Weeks Humalog Mix 50/50 and 75/25 pens 10 days Humulin 70/30 pen 2 Weeks Humulin N pen Humu!in R U-500 insulin v:ials can only be dispensed with U-500 syringes. The U-500 vials have a dark green cap and the U-500 syringes (Rx only) have dark green needle covers. In contrast, U-100 syringes have orange caps. A U-500 syringe holds up to 250 units; a U-100 1 mL syringe holds up to 100 units. 14 days Novolog Mix 70/30 pen Selecting an Insulin Pen Needle -4 Weeks Needles are chosen by the length and the gauge (thickness). The higher the gauge, the thinner the needle [e.g., 28G (thickest) - 32G (thinnest)]. The 32G cannula is thinnest and has a width of -2 human hairs. Shorter needles and highergauge needles cause less pain. Apidra, Humalog, Novolog, Admelog, Lyumjev, Fiasp vials and pens Humalog Mix 50/50 and 75/25 vials Novo/og Mix 70/30 vial 28 days The shortest needles are 4 mm and 5 mm in length and are preferred for most pens. They do not require the skin to be pinched during administration and are good for thinner patients and children. Novo/in R U-100, N and 70/30 pens Humulin R U-500 pen Lantus, Basaglar, Semglee vials and pens Humulin R U-100, N and 70/30 vials 8 mm needles are long enough for most patients; pinch up the skin before injecting. 31 days -6Weeks Humu/in R U-500 vial Novo/in R U-100, N and 70/30 vials 42 days Levemirvial and pen 12.7 mm (1/2 inch) needles may be needed for obese patients; pinch up the skin before injecting. 40days Common brands for needles and syringes include BD, Comfort EZ and Easy Touch. Needles require a prescription in some states. INSULIN INJECTION COUNSELING Toujeo pen 1. Get supplies. Wash hands. 2. Check insulin for discoloration and particles. Discard if present. 3. If insulin contains NPH or protamine, it is a suspension and needs to be resuspended (do not shake): o Vials: roll the bottle gently between the hands. o Pens: invert (turn up/down) 4 - 5 times. 629 44 I DIABETES 4. Clean injection site (area of the skin). If using a vial, wipe the top (after removing the plastic cover) with an alcohol swab. 5. Pens: o Use a new needle for each injection. Prior to each injection, prime the needle by turning the knob to units (can vary based on the insulin), face the needle away from you and press the injection button. o Turn the dosing knob to the correct number of units, then inject (see number 7, below). 6. Vials: o Useanewsyringeforeachinjection; syringes come with a needle already attached. Inject an equal volume of air into the vial before withdrawing the insulin. Limit bubbles in the syringe. o Ifmix.ingNPHand~·egularorrapid-actinginsulininthe same syringe, the clear insulin (regular or rapidacting) should be drawn into the syringe before the cloudy (NPH) insulin. Tip: inject air into the cloudy insulin first, then inject air into the clear insulin before withdrawing it out. 7. Insulin is best absorbed in the abdomen (p1-efened). Alternative sites for injection: posterior upper arm, superior buttocks and lateral thigh area (shaded areas of image). ..__ _, SELF-MONITORING BLOOD GLUCOSE Self-monitoring blood glucose (SMBG) refers to patients tracking their BG using a glucose meter or a continuous glucose monitor (CGM). CGMs are taped to the skin and have a probe that passes through the skin and into the fatty tissue. The probe provides measurements of the glucose level in the interstitial fluid between the cells. PREPARING TO USE A GLUCOSE METER If the meter requires calibration, recalibrate each time a new canister of test strips is opened, if the meter was left in extreme cold or heat, if it was dropped or if the BG value does not match what the patient is feeling. Keep the test strips in the original container, with the cap closed. Light and air damage test strips. Check the expiration date; expired test strips can give false results. Wash hands vigorously, using warm water. Dry hands thoroughly; water can dilute the blood sample and give a false result. Allow arm to hang down for 30 seconds so blood can pool into the fingertips. Do not squeeze the finger. TESTING WITH A GLUCOSE METER Insert test strip into meter. y Front J Back 8. With needles> 5 mm, gently pinch a 2 inch portion of skin between your thumb and first finger first (typically not required with shorter needles). 9. Insert the needle all the way in. Pens are injected straight down (at a 90 degree angle). Syringes are injected at 90 degrees fo:r most or 45 degrees if the patient is thin. 10. Press the injection button (pen) or plunger (syringe) all the way down to inject the insulin. Count 5 - 10 seconds before removing the needle. 11. Rotate injection sites around the abdomen regularly to prevent skin damage. 12. Properly dispose of needles or entire syringes (see below). Prick side of fingertip (side is less painful) with a lancet. Apply a drop of blood to the test strip. Record the result in a logbook, or the meter might store the results. Dispose the used lancet in a sharps container. Alternative Site Testing Some meters are approved to test blood from both the fingertip and alternative sites (forearm, palm or thigh), which can hurt less than the side of a fingertip. Alternative testing sites are useful only when the BG is steady. The BG level can be -20 minutes old. Do not use when the BG is changing quickly (e.g., after eating, after exercise and when hypoglycemia is suspected). • The lancing device might need to have a special cap screwed onto the tip to use on an alternative site. Do not store pens with needle attached. HYPOGLYCEMIA DEVICE DISPOSAL 630 Used needles, syringes, single-dose pens (with needles attached) and lancets should be placed in a sharps disposal container and taken to a disposal site. Locations are provided by the local public health agency. Alternatively, a heavy plastic milk bottle (not glass) or metal coffee can works well. Hypoglycemia is defined as a BG < 70 mg/dL. Low BG can have severe consequences, including falls, motor vehicle accidents and death. Each episode contributes to irreversible cognitive itnpail•meut. More stringent AlC goals can be overly aggressive in som_e cases and cause hypoglycemia (e.g., RxPREP 2022 COURSE BOOK an AlC goal of < 6.5% for an elderly female with recurrent hypoglycemia would be too aggressive). I RxPREP ©2021, ©2022 Raise Blood Sugar with 15 Grams of Simple Carbs HYPOGLYCEMIA SYMPTOMS Symptoms include dizziness, anxiety/irritability, shakiness, headache, diaphoresis (sweating}, hw1ger, con.fusion, nausea, ataxia, tremors, palpitations/tachycardia and blurred vision. Severe hypoglycemia can cause seizures, coma and death. All episodes of hypoglycemia are dangerous and should be reported to the prescriber. Monitoring with a CGM can help by displaying the BG every few minutes and sounding an alert when the BG level falls too low. .___. 4 ounces (1/2 cup) of Juice 1 Tablespoon Sugar, Honey or Corn Syrup 8oz. (1 cup) Milk 4 oz. Regular Soda (not diet) 3-4 Glucose Tablets or 1 Serving Glucose Gel (follow package instructions) fGl ©RxPrer HYPOGLYCEMIA TREATMENT iStock.com/Taisiia /aremchuk, pioner2_001, AnnaSqBerg, Vasilyevalara, blueringmedia Treatment if Conscious and Able to Swallow Alcohol, especially if taken on an empty stomach, can cause hypoglycemia when used with insulin or sulfonylureas. Pure glucose, in tablets or gel, is preferred, but any form of carbohydrate that contains glucose will work (see image). Added fat (e.g., a chocolate candy bar) is not recommended; it slows absorption and prolongs the hypoglycemia. To treat, follow the "rule of 15": 1. Take 15 - 20 ro;ams of glucose or simple carbohydrates. Caution: beta-blockers, especially if non-selective, can cause hypoglycemia and mask ackenergic symptoms of hypoglycemia (e.g., shakiness, palpitations, anxiety). Sweating and hunger are not masked. Counsel to recognize symptoms and test BG if unsure. 2. Recheck BG after 15 minutes. 3. If hypoglycemia continues, repeat steps 1 & 2. DRUGS THAT CAUSE HYPERGLYCEMIA 4. Once BG is normal, eat a small meal or snack. It is preferable, but not always possible, to avoid drugs that increase BG (see Key Drugs Guy). If not avoidable (e.g., using tacrolimus post-transplant), the increase in BG will need to be managed. Treatment if Unconscious When oral treatment is not possible, treat with dextrose (if there is IV access) or with glucagon. Caregivers of someone at high-risk for hypoglycemia should know how to use a glucagon 1 mg SC injection (GlucaGen, Gvoke), dasiglucagon injection (Zegalogue) or glucagon nasal spray (Baqsimi). If using glucagon, place the patient in a lateral recumbent position (on side) to protect the airway and prevent choking when consciousness returns. DRUG-INDUCED HIGH OR LOW BLOOD GLUCOSE DRUGS THAT CAUSE HYPOGLYCEMIA Insulin is the primary cause of drug-induced hypoglycemia. Sulfonylureas and meglitinides {"insulin secretagogues"), and pramlintide are high-risk. GlybtU·ide, glimepiride and first-generation sulfonylureas (e.g., chlorpropamide) are not recommended in the elderly due to this risk. GLP-1 agonists, DPP-4 inhibitors, TZDs andSGLT2 inhibitors have a low risk for hypoglycemia when used alone. When used in combination with insulin or a sulfonylurea, the risk is higher, and the insulin or sulfonylurea dose may need to be lowered. DRUGS THAT AFFECT BLOOD GLUCOSE Beta-Blockers• Thlazlde & Loop Diuretics Tacrolimus, Cyclosporine Protease Inhibitors Qulnolones* Antlpsychotlcs (e.g., olanzapine, quetiapine) Statins Steroids (systemic) Cough Syrups Niacin Beta-Blockers• Qulnolones• Tramadol Others: Linezolid Octreotide• Pentamidine Others: Azole Antifungals (systemic) Beta-Agonists Octreotide* 'Can cause hypo or hyperglycemia 631 44 I DIABETES INPATIENT GLUCOSE CONTROL HYPERGLYCEMIC CRISES The target BG range for most non-critical and critical care patients in the hospital is between 140 - 180 mg/dL. More stringent goals might be appropriate for select patients. Treatment should be proactive and attempt to maintain BG in this range, rather than treating BG when it is high. DIABETIC KETOACIDOSIS The use of sliding scale insulin (SSI) alone to control BG in the hospital setting is strongly discouraged. This method of administering insulin in response to elevated BG levels is reactionary (treats BG after it becomes elevated, rather than preventing elevated BG) and leads to poor outcomes. In addition, most sliding scales used are not patient-specific. See the Sliding Scale Example below. • Insulin is used for most hospitalized patients; the regimen depends primarily on oral intake. • If oral intake is adequate, a regimen with basal, bolus (prandial) and correction doses (usually added to the mealtime bolus dose) is preferred. • A basal and correction dose strategy is recommended if the patient is not eating well (poor intake). • Correct;ion dose insulin is given when BG is already high. Like sliding scale insulin, the insulin dose given will correlate with the BG, on a scale. The difference is that the correction dose scale is designed for a specific patient. It is based on the patient's insulin sensitivity factor (same as the col'rection factor), which indicates how much the.BG will drop with each unit of insulin. Sliding scales, like the one below, and correction dose insulin use rapid-acting or regular insulin. Rapid-acting insulin will lower the BG quicker, and is preferable. Diabetic ketoacidosis (DKA) is a life-threatening crisis with high BG, ketoacidosis and ketonuria (i.e., ketones in the urine). DKA is most common in TlD, but can occur in T2D. DKA is commonly the initial presentation in TlD, or caused by insulin non-adherence (e.g., a mechanical pump failure) or subtberapeutic insulin dosing (e.g., increased insulin requirements due to a stressor, like an infection). In DKA, ketones are present because triglycerides and amino acids are used for energy, which produces free fatty acids (FFAs) and glucagon converts the FFAs into ketones. Insulin normally prevents this conversion, but in DKA, insulin is absent or severely lacking. Recognizing DKA: • BG> 250 mg/dL Ketones (urine and serum, can be recognized as "fruity" breath), nausea and vomiting Anion gap acidosis (arterial pH< 7.35, anion gap> 12) HYPEROSMOLAR HYPERGLYCEMIC STATE Hyperosmolar hyperglycemic state (HHS) has a higher mortality rate than DKA, but is less common. HHS is most common in T2D. The primary cause is illness (e.g., infection, stroke) that leads to less fluid intake. This, along with fluid shifts and osmotic diuresis, leads to severe dehydration with altered consciousness. Ketones are not present because in T2D the patient still makes insulin. Recognizing HHS: a Confusion, delirium • BG> 600 mg/dL, with high serum osmolality > 320 mOsm/L • Extreme dehydration SLIDING SCALE EXAMPLE I BLOOD GLUCOSE READING (MG/DL) -- <60 pH> 7.3, bicarbonate> 15 mEq/L I INSTRUCTION I Hold insulin; contact MD 150-200 Give 2 units of insulin 201-250 Give 4 units of insulin - 251-300 - 301-350 351-400 1401-450 The primary treatment is aggressive fluids (first) and insulin to treat the hyperglycemia I Give 8 units of insulin Give 6 units of insulin Give 10 units of insulin CallMD - FLUIDS first for all patients Start with NS When blood glucose reaches 200 mg/dl, change to D5W½NS REGULAR insulin infusion (regular is preferable In IV solutions) 1) 0.1 unit/kg bolus, then 0.1 units/kg/hr continuous infusion OR 2) 0.14 units/kg/hr continuous infusion PREVENT hypokalemia Insulin shifts K+ into the cells; the K+ will fall Monitor K+ and keep serum level between 4-5 mEq/L TREAT acidosis If pH < 6.9; acidosis may be corrected by fluids Give sodium bicarbonate if needed 632