Insulin is used to treat diabetes by regulating blood sugar levels. There are various types of insulin differentiated by their onset, peak time and duration of effect. Rapid-acting insulins work within 15 minutes, short-acting within 30 minutes to 1 hour, intermediate within 2-4 hours and long-acting up to 24 hours. Proper administration and storage of insulin is required to ensure safety and efficacy.

1. INSULINS Rabia Tahir, Pharm.D. New York Harbor Healthcare System

2. HISTORY of INSULIN Diabetes -> 3500 years. “ Control” only by diet in past. Insulin discovered in 1921. Insulin used in 1 st diabetic patient in 1922. 1 st protein -> chemically synthesized in 1963.

3. INSULIN INDICATIONS Type I Diabetes Absolute deficiency of insulin Type II Diabetes Insulin resistance Relative insulin deficiency

4. INSULIN INDICATIONS Insulin may be provided in two ways Basal supplement with an intermediate to long-acting preparation to suppress hepatic glucose production and maintain near normoglycemia in the fasting state. Premeal bolus dose of rapid-acting or short-acting insulin to cover the extra requirements after food is absorbed.

5. TYPES of INSULIN 20 types available Which one should be used? Individuals lifestyle Physicians preference Patients blood sugar level

6. TYPES of INSULIN Which one should be used? Source of insulin Obtained from pork pancreas or is made chemically identical to human insulin by recombinant DNA technology. Beginning in January 2006, pork insulin for human use will no longer be manufactured or marketed in the U.S.. How soon it starts working -> onset. When it starts working the hardest -> peak. How long it lasts in body -> duration.

7. TYPES of INSULIN Insulin onset, peak, and duration of effect must match meal patterns and exercise schedules -> achieve near normal blood glucose values throughout the day. Four basic forms Rapid-acting insulins Short-acting insulins Intermediate-acting insulins Long-acting insulins

8. RAPID-ACTING INSULINS Type Onset (h) Peak (h) Duration (h) Appearance insulin lispro 15-30 min 1-2 3-4 Clear HUMALOG insulin aspart 15-30 min 1-2 3-5 Clear NOVOLOG insulin glulisine 15-30 min 1-2 3-4 Clear APIDRA NOVOLOG (insulin aspart) -> formulary

9. RAPID-ACTING INSULINS Administrative Options HUMALOG (insulin lispro) Pen, U-100 vial, or 1.5 ml or 3 ml pen cartridge NOVOLOG (insulin apart) Pen, U-100 vial, 3 ml pen cartridge APIDRA (insulin glulisine) U-100 Vial

10. RAPID-ACTING INSULINS Within 10 minutes of meal. Better efficacy in post prandial blood glucose. Minimizes delayed postmeal hypoglycemia. Normally used in regimens with intermediate or long-acting insulin. Rapid-acting insulin can be mixed with NPH and lente -> the mixture should be injected within 15 minutes prior to a meal.

11. SHORT-ACTING INSULINS Type Onset (h) Peak (h) Duration (h) Appearance Regular 0.5-1.0 2-3 3-6 Clear HUMULIN R NOVOLIN R NOVOLIN R -> formulary

12. SHORT-ACTING INSULINS Administrative Options HUMULIN R U-100 vial, 10 ml vial or U-500, 20 ml vial NOVOLIN R Insulin pen, U-100 vial, or 3 ml pen cartridge, and Innolet

13. SHORT-ACTING INSULINS Relatively slow onset of action when given SQ. Requires injection 30 minutes prior to meal to achieve optimal post prandial glucose control and to prevent delayed postmeal hypoglycemia. Eating within a few minutes after or before injecting is discouraged because it substantially reduces the ability of that insulin to prevent a rapid rise in blood glucose and may increase the risk of delayed hypoglycemia.

14. INTERMEDIATE-ACTING INSULIN Type Onset (h) Peak (h) Duration (h) Appearance NPH 2-4 4-6 8-12 Cloudy HUMULIN N NOVOLIN N Lente 3-4 6-12 12-18 Cloudy HUMULIN L

15. INTERMEDIATE-ACTING INSULIN Administrative Options HUMULIN N U-100 vial, prefilled pen NOVOLIN N U-100 vial, prefilled pen, and Innolet HUMULIN L U-100 vial

16. LONG-ACTING INSULIN Type Onset (h) Peak (h) Duration (h) Appearance Glargine 4-5 − 22-24 Clear LANTUS

17. LONG-ACTING INSULIN Administrative Options LANTUS U-100 vial

18. LONG-ACTING INSULIN LANTUS ‘ peakless’’ analog -> less nocturnal hypoglycemia than NPH when given at bedtime Usually given once a day only

19. PREMIXED INSULIN Fixed ratio insulins are dosed according to patient needs 15 minutes before meals Premixed insulin analogs HUMALOG Mix 75/25 (75% neutral protamine lispro, 25% lispro) U-100 vial, prefilled pen NOVOLOG Mix 70/30 (70% aspart protamine suspension, 30% aspart) U-100 vial, prefilled pen, 3 ml pen cartridge

20. PREMIXED INSULIN NPH-regular combinations HUMULIN 70/30 Vial, prefilled pen NOVOLIN 70/30 Vial, pen cartridge, Innolet HUMULIN 50/50 Vial

23. ADVERSE EFFECTS of INSULIN Hypoglycemia causes Missing or delaying meals. Taking to much insulin. Exercising or working more than normal. An infection or illness (diarrhea and vomiting). Interactions with other drugs that lower blood glucose -> oral antidiabetic agents, salicylates, sulfa ab’s, certain antidepressants . Consumption of alcoholic beverages.

24. ADVERSE EFFECTS of INSULIN Hypoglycemia S&S Mild to moderate Sweating - Drowsiness Dizziness - Sleep disturbances Palpitation - Anxiety Tremor - Blurred vision Hunger - Slurred speech Restlessness - Depressed mood Tingling in hands, feet, lips, or tongue - Irritabilty Lightheadedness - Abnormal behavior Inability to concentrate - Unsteady movement Headache - Personality changes

25. ADVERSE EFFECTS of INSULIN Hypoglycemia S&S Severe Disorientation Unconsciousness Seizures Death

26. ADVERSE EFFECTS of INSULIN Hypoglycemia Treatment (< 50mg/dl). Mild to moderate Rule of 15 -> 15g carbohydrate every 15 min until BG is greater than 70mg/dl, then follow simple meal. Severe or continuing Unable to take sugar by mouth or are unconscious may need Dextrose 50% 50 ml infusion or Glucagon 1mg IM, SQ, or IV.

27. ADVERSE EFFECTS of INSULIN Allergic reaction Generalized reaction Uncommon but life threatening -> itchy rash over entire body, SOB, wheezing, confusion, low BP, tachycardia, sweating. Local reaction At injection site and is common -> itching, redness, hardness, or swelling.

28. ADVERSE EFFECTS of INSULIN Lipodystrophy Change in fat below injection site Lipoatrophy Lipohypertrophy Avoid injections in areas of skin that have theses reactions.

29. MIXING INSULINS Formulations and particle size distribution vary with insulin products. Mixing -> physiochemical changes can occur either immediately or over time. Serum insulin concentrations tend to reach a single peak.

30. MIXING INSULINS GUIDELINES Pt’s well controlled on mixed insulin regimen -> maintain their standard procedure. No other medication or diluents should be mixed with insulin. Glargine (LANTUS) should not be mixed with any insulin. Use of commercially available premixed insulins may be used if insulin ratio is appropriate to Pt insulin requirement. NPH and short-acting insulin when mixed can be used immediately or stored for future use.

31. MIXING INSULINS GUIDELINES Rapid-acting insulin can be mixed with NPH, lente, and ultralente. When rapid acting insulin is mixed with either an intermediate or long-acting insulin -> mixture should be injected within 15 min before meal. Mixing of short-acting and lente insulins is not recommended except for Pt already adequately controlled on such mixture. Phosphate-buffered insulins (NPH) should not be mixed lente insulins.

32. INSULIN STORAGE Unopened vials, cartridges and pens. If refrigerated use until expiration date (standard) If room temperature (below 30 º C) use within 28 days Opened Vials within 28 days at room temperature or refrigerated Pen and pen cartridges within 28 days at room temperature ( do not refrigerate) Do not use if insulin has been frozen or exposed to high temperatures (<2 º C or > 30 º C). Excess agitation should be avoided.

33. INSULIN ADMINISTRATION Check vial before use to inspect for changes -> loss of potency. Vial and pens should be rolled in palms of hands before drawing with needle -> except with rapid and short acting insulin. If mixing insulins -> clear insulin should be drawn into syringe first.

34. INSULIN DELIVERY DEVICES Insulin pens Pens with cartridges -> users turn a dial to select the desired dose of insulin -> press a plunger on the end to deliver insulin. Needle should be embedded within skin for 5 seconds after complete depression of plunger. Air bubbles in pen reduces rate of insulin flow. Avoid leaving needle on pen between injections and prime needle with 2 units of insulin.

35. INSULIN DELIVERY DEVICES Jet injectors Option for people who do not want to use needles. Use high pressure air to send a fine spray of insulin through the skin as a fine stream. Have no needles -> advantage in patients unable to use syringes or with needle phobias. More rapid absorption of short-acting insulins Costly and may traumatize skin.

36. INJECTION SITE Subcutaneous tissue of upper arm. Anterior and lateral aspects of the thigh, buttocks, and abdomen. IM not recommended. Rotation of injection site recommended. Prevent lipohypertrophy and lipoatrophy. Rotating within one area is recommended.

37. INJECTION SITE Variable absorption between sites. Abdomen > arms >thighs > buttocks Exercise increases rate of absorption. Areas of lipohypertrophy have slower absorption. IM > SC absorption.

38. PREVENTING PAINFUL INJECTIONS Inject insulin at room temp. Make sure no air bubbles remain in syringe before injection. Wait for topical alcohol to evaporate before injection. Relax muscle at injection site at time of injection Penetrating skin quickly. Not changing direction of needle during insertion or withdrawal.

39. CONCLUSION Insulin type and species Injection technique Site of injection Individual Pt response differences Onset Peak Duration