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ANTIDIABETIC AGENTS INSULIN O R A L H Y P O G LYC E M I C S Fall 2013 INSULIN Insulin is a hormone produced in the beta cells of the pancreas, secreted at a rate of 0.5 to 1 unit per hour. Average insulin secretion in adult is 30-50 Units per day. Insulin is required for entry of glucose into skeletal and heart muscle and fat. Insulin is important in protein and lipid metabolism. Decrease in insulin = decrease in glucose into cell = hyperglycemia Beef and pork discontinued in US in 2005 Biosynthetic insulins are now available for most patients INSULIN CONCENTRATION 100 Units per mL Regular insulin may come 100 Units / mL or 500 Units / mL for IV use ONLY USE INSULIN SYRINGE Mechanism of Action Exogenous insulin works the same as endogenous insulin Transports glucose FROM the blood to the INSIDE of cells and Takes excess glucose to the liver for storage This results in LOWERING of the blood glucose level THERAPEUTIC USES Insulin is the drug of choice for type 1 and type 2 uncontrolled by diet, exercise or oral hypoglycemic agents Hormonal replacement - remember insulin is a hormone Goal - maintain stable blood glucose levels ADMINISTRATION Subcutaneous injection Syringe and needle Pen injectors Jet injectors Inhalation Exubera Subcutaneous infusion Portable insulin pumps Implantable insulin pumps Intravenous infusion ADVERSE EFFECTS The most significant adverse effect is HYPOGLYCEMIA The signs & symptoms are the same for any hypoglycemic reaction / state BLOOD GLUCOSE MUST BE MONITORED DOSAGE INDIVIDUALIZED Insulin dosage is “tailored” to each patient specifics metabolic needs to achieve stable blood glucose levels INSULIN PEAK / ONSET / DURATION It is important to know the insulin’s onset, peak and duration Onset- time required for the med to have an initial effect Peak – when agent will have the maximum effect Duration – length of time the agent remains active in the body RAPID ACTING Humalog (lispro) or (Novolog) aspart Synthetic form Clear solution Can be given separately or mixed with intermediate or long acting insulins More rapid and shorter acting than human regular Insulin Onset / Peak / Duration = 10 min / 1 -3 hr / 3-6 hrs Administer within 10 – 15 minutes of a meal Apidra (insulin glulisine) Onset / Peak / Duration = 10-15 min / 1-1.5 hr / 3-5 hrs Give within 15 min before meal Can be used in insulin pump Can be mixed with NPH for subcutaneous injection SHORT DURATION Regular Insulin Humulin R, Novolin R Onset / Peak / Duration = 30 to 60 min / 1-5 / 6-10 hrs Can be given Sub Q and IV Routes: IV, sub Q, IM, inhalation Administer no sooner than 30 minutes before meal Exubera – inhaled insulin Onset / Peak / Duration = 15 to 30 min / 0.5-1.5 hrs / 6.5 hrs Fine powder of regular insulin Intermediate Acting Insulins NPH (Neutral protamine Hagedorn) Onset / Peak / Duration 2-4 / 4-12 / 16-20 hrs Contains specific amounts of regular insulin and protamine Onset is delayed and action is extended. Cloudy solution, must be gently agitated before drawing up. Usually administered twice daily PREMIXED INSULIN COMBINATIONS Humalog Mix 75 – 25 (75% Lispro protamine solution with 25 % Lispro solution) Rapid onset with intermediate duration Onset / Peak / Duration 15-30 min / 1-6.5 /12-24 hrs Humulin 50/50 (R=50, N=50) Humulin 70/30, Novolin 70/30, (N=70, R=30) 30 min / 2-12 hr / 24 hr LONG ACTING INSULINS Insulin detemir (Levemir) Onset / Peak / Duration / 6-8 / 12-24 Slow onset and dose dependent duration Provides basal glycemic control As compared with NPH, has slower onset and longer duration Clear solution Administered once or twice daily Long Acting Humulin U (Ultralente) Onset / Peak / Duration 6-8 / 12-16 / 20-30 VERY LONG ACTING INSULIN Very Long Acting Insulin glargine (Lantus) Onset 1 hour no pronounced peak Duration 24 hours LANTUS NOT to be confused with LENTE Long lasting basal insulin Slow steady release of insulin needed to control blood glucose & keep cells supplied with energy when no food is being digested ONCE-A-DAY - AT BEDTIME usually Steady absorption - NO PRONOUNCED PEAK Works twice as long as NPH (Lantus 24 hrs, NPH 14.5 hrs) Used for adults with Type 2 or children and adults with Type 1 LANTUS Does NOT replace short-acting insulins Can be used with oral anti-diabetic medications MUST NOT be diluted or mixed with any other insulin or solution MUST use U-100 syringe NOT intended for IV use Patients experience same side effects (hypoglycemia & injection-site reactions) STOP AND THINK if you administer 10 units of regular insulin at 7:00 am when should you observe for hypoglycemia? if you administer 5 units of Humulin R insulin and 22 units of Humulin N at 7:30 am when will you observe for hypoglycemia? if you administer 7 units of Humulin R at 11:30 am when will you observe for hypoglycemia? if your patient is NPO for breakfast and is due insulin at 7:30 am what should you do? INSULIN STORAGE Insulin should not be allowed to freeze, nor be heated above room temperature. Insulin should be stored in the refrigerator until opened, then may be stored at room temperature until gone. At sustained temperatures above room temperature, insulins lose potency rapidly. Excess agitation should be avoided to prevent loss of potency, clumping or precipitation. All insulins except Regular, Lispro and Aspart should be gently rolled in the palms to resuspend solution. (Do not shake) NURSING IMPLICATIONS when mixing insulins - CLEAR TO CLOUDY do not “shake” insulin vial to resuspend cloudy mixtures - gently rotate / roll vial in palm of hand or swirl, avoids bubbles insulin must be stored in a stable temperature, refrigeration prolongs shelf life, in clinical settings opened vial MUST be dated & initialed schedule snacks to coincide with insulin PEAK’s SAFE PRACTICE FOR INSULIN ADMINISTRATION BEFORE ADMINISTERING: Check the original doctor’s order KNOW your patient’s blood sugar and “trends or patterns” Check the last time your patient ate (what & how much) Check other drugs patient is taking and question yourself about interactions REVIEW ADMINISTRATION ADMINISTERED SUBQ (unless emergency and then ONLY Short ACTING insulin can be given IV) 45 or 90 degree angle 27 - 25 G needle (microfine) (Only administer in an insulin syringe) 5/8 inch do not have to aspirate NURSING IMPLICATIONS ALL insulin dosages MUST be DOUBLE CHECKED by a second LISCENED person administer insulin only with an insulin syringe calibrated for that concentration of insulin BEFORE ADMINISTERING: check the original doctor’s order KNOW your patient’s blood sugar and “trends or patterns” Check the last time your patient ate Check other drugs patient is taking and question yourself about interactions SITE ROTATION Diabetics should be taught to ROTATE their injection sites This is done to prevent “lipoatrophy” / scarring at the injection site - which results in variable insulin absorption SUBCUTANEOUS INSULIN ADMINISTRATION: METHODS OF DELIVERY: INSULIN PENS INSULINS THAT CAN BE USED IN PUMPS: REGULAR, LISPRO, ASPART, GLULISINE INSULIN ADMINISTRATION: METHODS OF DELIVERY: INSULIN INJECTORS COMPLICATIONS OF INSULIN THERAPY Local Reactions Redness, tenderness, swelling, induration 1-2 hours after insulin administration May occur at beginning of therapy and resolve COMPLICATIONS OF INSULIN THERAPY: INSULIN LIPODYSTROPHY Localized reaction Lipoatrophy loss of subcutaneous fat, appears as dimpling or pitting in of subcutaneous fat Lipohypertrophy the development of fibrofatty masses at the injections site. Caused by repeated use of same injections site. Insulin injected into scarred areas, absorption is delayed DIABETICS IN THE HOSPITAL SETTING Hospitalization may drastically affect insulin requirements because of stress (infections, surgery, acute illness, inactivity, variable food intake) It is often used to monitor patients on hyperalimentation Blood glucose checks are ordered at specific intervals - most often ac & at bedtime The insulin dose is then adjusted to a predetermined “scale” ordered by the physician The ONLY type of insulin used in sliding scale is Short Acting (Regular Insulin) SLIDING SCALE Method of insulin “dosing” Dose is adjusted according to blood glucose results This method of dosing is most often used for hospitalized diabetics Sliding Scale Order Blood glucose < 200 - give 0 units Regular Insulin Blood glucose 201 - 249 give 4 units Regular Insulin Blood glucose 250 - 299 give 6 units Regular Insulin Blood glucose > 300 call Dr. At 0730 your patient is scheduled to receive 20 units of Humulin N and 5 units of Humulin R, their blood sugar level is 247, what will you give? SLIDING SCALE ORDER EXAMPLE: Blood glucose < 200 - give 0 units Regular Insulin Blood glucose 201 - 249 give 4 units Regular Insulin Blood glucose 250 - 299 give 6 units Regular Insulin Blood glucose > 300 call Dr. At 1130 your patient’s blood sugar is 284, how much insulin will you give? Sliding Scale Order Blood glucose < 200 - give 0 u Blood glucose 201 - 249 give 4 u Blood glucose 250 - 299 give 6 u Blood glucose > 300 call Dr. Order: Regular Insulin per sliding scale AC & HS Order: Lantus 10 Units sub Q at bedtime. Your patient’s blood glucose at 2100 is 278, how much insulin will you give? How would you administer it? ORAL HYPOGLYCEMICS Oral hypoglycemic agents work in one of three ways: STIMULATE the pancreas to produce more insulin DECREASE glucose production INCREASE glucose uptake by the cell by enhancing the effectiveness of insulin Oral hypoglycemics are usually only given to Type II diabetics SULFONYLUREA ORAL HYPOGLYCEMICS: SECOND GENERATION EXAMPLES Diabeta, Micronase (glyburide); Glucotrol (glipizide), Amaryl (glimepiride) Action: Lowers blood sugar by stimulating the release of insulin from beta cells of the pancreas Adverse reactions: hypoglycemia, nausea, heartburn, bloating, flatulence, anorexia, skin reactions, photosensitivity, allergic reaction, CNS - paresthesia, tinnitus, dizziness, wt gain, edema Contraindicated with Sulfonamide allergy Monitor for hepatotoxicity, blood dyscrasias, dermatologic reactions Drug interactions: Beta Blockers may mask hypoglycemic reactions, alcohol may result in Anabuse like reaction BIGUANIDE ORAL HYPOGLYCEMIC AGENTS metformin (GLUCOPHAGE) Action: Decreases glucose released from liver Decreases intestinal absorption of glucose, metformin Improves insulin sensitivity Resulting in improved blood glucose control USES: Type II diabetes May be combined with other antidiabetic agents SIDE / ADVERSE EFFECTS: Primarily GI effects - bloating, nausea, cramping, diarrhea Advantage: Does not cause hypoglycemia, does not cause wt gain, favorable effect on triglycerides Increased risk for lactic acidosis and renal failure, Stop Metformin 48 h prior to and 48 h after diagnostic procedures using a contrast agent. ALPHA-GLUCOSIDASE INHIBITORS accarbose (Precose), miglitol (Glyset) Action: Delay absorption of complex carbohydrates in intestine, slow entry of glucose into systemic circulation, does not increase insulin secretion. SE: hypoglycemia, GI affects Administration: taken with first bite of food Monitor: LFT Not systemically absorbed NON-SULFONYREA INSULIN SECRETAGOGUES Examples ◦Repaglinide (Prandin) (SE – hypoglycemia) ◦Nateglinide (Starlix) Action: Stimulate release of insulin from beta cells in the pancreas Rapid action and short half life Taken before each meal THIAZOLIDINEDIONE ORAL HYPOGLYCEMICS (TZD) (THIGH-A-ZOE-LID-EEN-DIE-OWN) Rosiglitazone (row-sih-GLIT-uh-zone) Avandia Pioglitazone (pie-oh-GLIT-uh-zone) Actos Action: Increases sensitivity of muscle and fat tissue to insulin, allowing more glucose to enter the cells May inhibit hepatic glycogenesis and decrease hepatic glucose output SE Expected: N/V, anorexia, Abd cramps SE unexpected: hypoglycemia, hepatotoxicity, wt. gain Drug Interactions: Beta Blockers ay ask signs of hypoglycemia, may cause BC pills to be ineffective DRUG INTERACTIONS There are SIGNIFICANT potential drug interactions between oral hypoglycemics and multiple classifications Sulfonylureas: alcohol, oral anticoagulants, antibiotics (sulfa), corticosteroids, thiazides, furosemide, thyroid drugs Biguanides: furosemide, digoxin, nifedipine, cimetidine Thiazolidinediones: reduces effectiveness of BC TEACHING PLAN medication regime signs / symptoms (hypo & hyper glycemia) blood glucose monitoring avoidance of alcohol medic alert identification measures to deal with sun exposure (sulfonylureas) • follow up care • • • • • • Monitor lab test to determine BS control An accurate long term index of the patient’s average blood glucose level Reflects the average blood glucose level over the past 100-120 days Good control = 2.5 – 5.9 % Fair Control = 6-8% Poor control = > 8% HBA1C: GLYCOSYLATED HEMOGLOBIN A1C Using the Glucometer – (Measures capillary blood glucose) • Wash hands •Sterile 2x2, alcohol swab, towel, Glucometer, non-sterile gloves •Open sterile packages, place in reach, Don gloves •Select finger – lateral aspect of fingertips •Apply warm compress if cold fingers •Place towel under hand •Cleanse and allow to air dry •Puncture finger and squeeze •Wipe off 1st drop with 2x2 •Collect blood on strip – cover entire area. 2x2 to site GLUCOSE TESTING TEST YOUR KNOWLEDGE A patient in the ICU requires intravenous insulin. The nurse is aware that: A. insulin aspart or glargine can be administered IV. B. any form of insulin can be used IV at the same dose ordered for subcutaneous administration. C. insulin should never be given IV, and this order should be questioned. D. only regular insulin can be administered IV. TEST YOUR KNOWLEDGE A type 1 diabetic patient on insulin reports taking propranolol for hypertension. This provokes the concern that: A. the beta blocker can produce insulin resistance. B. the two agents used together will increase the risk of ketoacidosis. C. propranolol will increase insulin requirements because of receptor blocking. D. the beta blocker can mask the symptoms of hypoglycemia. TEST YOUR KNOWLEDGE A nurse counsels a diabetic patient starting therapy with an alpha-glucosidase inhibitor. The patient should be educated about the potential for which adverse reaction(s)? You may select more than one answer. A. Hypoglycemia B. Flatulence C. Elevated iron levels in the blood D. Fluid retention E. Diarrhea TEST YOUR KNOWLEDGE A diabetic client taking daily NPH insulin has been started on therapy with dexamethasone (Decadron). The nurse anticipates that which of the following adjustments in medication dosage will be made? 1. Decreased NPH insulin 2. Increased NPH insulin 3. Lower dose of dexamethasone (Decadron) than usual 4. Higher dose of dexamethasone (Decadron) than usual TEST YOUR KNOWLEDGE The nurse monitors the blood glucose level of the client who received NPH insulin at 7 AM knowing that the client may experience a hypoglycemic reaction between: A. 9 to 11 AM B. 1 to 7 PM C. 7 to 11 PM D. Midnight to 6 AM