Class: Insulins
ATC Class: A10AB01
VA Class: HS501
Molecular Formula: C257H383N65O77S 6
CAS Number: 11061-68-0
Brands: Humulin, Humulin 70/30, Humulin 70/30 Pen, Humulin 50/50, Humulin L, Humulin N, Humulin R, Humulin U Ultralente, Novolin, Novolin 70/30, Novolin 70/30 Innolet, Novolin 70/30 PenFill, Novolin N, Novolin R
Introduction
Antidiabetic agent; a biosynthetic protein that is structurally identical to endogenous insulin secreted by the beta cells of the human pancreas.1 2 3 5 6 38 53 65 71 75 76 Available as short-acting, rapid-acting, intermediate-acting, or long-acting insulins.1 2 3 5 6 38 53 65 71 75 76
Uses for Insulin Human
Diabetes Mellitus
Replacement therapy for the management of diabetes mellitus.5 6 7 8 12 113 Human insulin manufactured using recombinant DNA technology is replacing pork insulin; future availability of animal insulins is uncertain.103
Insulin is required in all patients with type 1 diabetes mellitus, and mandatory in the treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic states.
Also used in patients with type 2 diabetes mellitus when weight reduction, proper dietary regulation, and/or oral antidiabetic agents have failed to maintain satisfactory glycemic control in both the fasting and postprandial state.
Diet should be emphasized as the primary form of treatment when initiating therapy for patients with type 2 diabetes mellitus who do not have severe symptoms; caloric restriction and weight reduction are essential in obese patients.
The American Diabetes Association (ADA) and many clinicians recommend the use of physiologically based, intensive insulin regimens (i.e., 3 or more insulin injections daily with dosage adjusted according to the results of multiple daily blood glucose determinations [e.g., at least 4 times daily], dietary intake, and anticipated exercise) in most type 1 and type 2 diabetic patients who are able to understand and carry out the treatment regimen, are not at increased risk for hypoglycemic episodes, and do not have other characteristics that increase risk or decrease benefit (e.g., advanced age, end-stage renal failure, advanced cardiovascular or cerebrovascular disease, other coexisting diseases that shorten life expectancy).
Goals of insulin therapy in all patients generally should include maintenance of blood glucose as close as possible to euglycemia without undue risk of hypoglycemia; avoidance of symptoms attributable to hyperglycemia, glycosuria, or ketonuria; and maintenance of ideal body weight and of normal growth and development in children.
The ADA states that human insulin is preferred for intermittent use and those initiating insulin therapy.103
Diabetic Ketoacidosis or Hyperosmolar Hyperglycemic States
Used in the emergency treatment of diabetic ketoacidosis or hyperosmolar hyperglycemic states when rapid control of hyperglycemia is required.5 6 7 8 12 113 Regular insulin (e.g., insulin human [regular], insulin [regular]) is the insulin of choice in the treatment of such emergency conditions because of its rapid onset of action and because it can be administered IV.113
AMI
Has been used IV early in suspected AMI† in combination with IV potassium chloride and dextrose (d-glucose) (referred to as glucose-insulin-potassium or GIK therapy).95 96 97 98 99
Acute Stroke
Insulin injection (e.g., insulin human) also has been used IV in combination with IV potassium chloride and dextrose (i.e., GIK therapy) in a limited number of patients with acute stroke† and mild to moderate hyperglycemia.
Critical Illness
Has been used to reduce morbidity and mortality in patients with critical illness† requiring intensive care.
Gestational Diabetes Mellitus
The ADA states that human insulin is preferred for use in pregnant women or women considering pregnancy.103 The ADA recommends that insulin therapy (using insulin human) be considered in patients with gestational diabetes who, despite dietary management, have fasting plasma glucose concentrations exceeding 105 mg/dL or 2-hour postprandial plasma glucose concentrations exceeding 130 mg/dL.
Insulin Human Dosage and Administration
General
Adjust dosage of insulin based on blood and urine glucose determinations and carefully individualize to attain optimum therapeutic effect.e
Because urine glucose concentrations correlate poorly with blood glucose values, urine glucose concentrations should be used only in patients who cannot (e.g., patients with severe neuropathies, severe vision impairment, Raynaud’s syndrome, paralysis, or those receiving anticoagulants) or will not test blood glucose concentrations.
Some clinicians state that in some geriatric patients in whom control of hyperglycemic symptoms is the treatment goal, monitoring of urine glucose concentrations may be adequate.
Patients receiving conventional insulin regimens should self-monitor blood glucose concentrations with a frequency ranging from once or twice daily to several times weekly.
In patients receiving intensive insulin regimens, the decision to supplement or decrease the previous preprandial dose of short- or rapid-acting insulin is made on the basis of blood glucose determinations obtained before each preprandial insulin injection.
Transferring from Therapy with Other Insulins
Make any change in insulin preparation or dosage regimen with caution and only under medical supervision.5 6 7 8 80 88 93 94 103 Changes in purity, strength, brand, type, and/or species source or method of manufacture may necessitate a change in dosage.5 6 7 8 77 78 79 80 88 93 94
Not possible to clearly identify which patients will require a change in dosage when therapy with a different preparation is initiated.5 6 7 8 May need adjustments with the first dose or may occur over a period of several weeks.5 6 7 8
In patients who are currently controlled on purified pork insulins, no change in dosage is usually required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12 However, hypoglycemic reactions reported in patients who were transferred from pork insulin to insulin human (regular).
Administration
Insulin human (regular), isophane insulin human suspension, and insulin human zinc suspension usually are administered sub-Q.12 54 55 71 75 82 84 88
May administer insulin human (regular) IM or IV for the treatment of diabetic ketoacidosis or hyperosmolar hyperglycemia.12 113 Insulin human (regular) is the only form of insulin human that may be administered IV.54 55
Insulin human (regular) in a dry-powder formulation has been used via oral inhalation† with some success in a limited number of patients to avoid the pain and inconvenience of multiple daily injections.104 105 106 107 108 109 110
Do not administer isophane insulin human suspension and insulin human zinc suspension IV.54 55
Sub-Q Administration
Administer insulin human (regular) injection, isophane insulin human suspension, and insulin human zinc suspension usually by sub-Q injection.12 55 71 75 82 84 88
Avoid excessive agitation of the vial prior to withdrawing the insulin human regular dose since loss of potency, clumping, frosting, or precipitation may occur.67 101
Since suspensions contain insulin in the precipitate, gently agitate the vial to assure a homogeneous mixture for accurate measurement of each dose.6 8 75 84 92 93 Slowly rotate and invert or carefully shake the vial several times before withdrawal of each dose.6 8 75 84 Avoid vigorous shaking since frothing may interfere with correct measurement of a dose.6 8
Administer into the thighs, upper arms, buttocks, or abdomen using a 25- to 28-gauge needle, one-half to five-eighths inch in length.e g h j
Most individuals should grasp a fold of skin lightly with the fingers at least 3 inches apart and insert the needle at a 90° angle; thin individuals or children may need to pinch the skin and inject at a 45° angle to avoid IM injection, especially in the thigh area.
Routine aspiration to check for inadvertent intravascular injection generally is not necessary.
Inject over a period of 2–4 seconds.g h j Slow sub-Q injection of insulin suspensions may result in clogging of the tip of the needle.6 8
Press injection site lightly for a few seconds after the needle is withdrawn; do not rub.e g h j
Rotate sites so that any one site is not injected more than once every 1–2 weeks.
IV Administration
In general, reserve IV route for use in patients with circulatory collapse, diabetic ketoacidosis, hyperosmolar hyperglycemia, or hyperkalemia.54 55 113 Has also been administered by IV infusion for metabolic modulation in AMI or hyperglycemia associated with critical illness.12 112
Dilution
For IV infusion, usually dilute insulin human (regular) injection in 0.9% sodium chloride injection.54 55 However, has been diluted in 10 or 25% dextrose injection for IV infusion as GIK therapy in AMI†.95 96
Dosage
Patients receiving insulin should be monitored with regular laboratory evaluations, including blood glucose determinations and glycosylated hemoglobin (hemoglobin A1c [HbA1c]) concentrations, to determine the minimum effective dosage of insulin when used alone, with other insulins, or in combination with an oral antidiabetic agent.
Pediatric Patients
Diabetes Mellitus
Sub-Q
Dosage must be individualized.o
In newly diagnosed children with severe diabetes mellitus, unstable diabetes mellitus, or diabetes mellitus with complications, insulin (regular) (i.e., purified pork insulin) generally is given sub-Q in a dosage of 2–4 units, 15–30 minutes before meals and at bedtime.e
In patients who are currently controlled on purified pork insulins, no change in dosage usually is required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12
Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
IV
In children and adolescents <20 years of age, the ADA recommends initially an IV infusion of regular insulin at a rate of 0.1 units/kg per hour.113 An initial direct IV injection of regular insulin is not recommended in such patients.113
IM, then Sub-Q
If IV access is unavailable, regular insulin may be given IM in an initial dose of 0.1 units/kg, followed by 0.1 units/kg per hour sub-Q or IM until acidosis is resolved (i.e., venous pH >7.3, serum bicarbonate concentration >15 mEq/L).113
Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q
Upon resolution of ketoacidosis or the hyperosmolar state, the regular insulin IV infusion rate should be decreased to 0.05 units/kg per hour until sub-Q replacement insulin therapy is initiated.113
Initiate replacement therapy at an insulin dosage of 0.5–1 units/kg daily given sub-Q in divided doses ((2/3) of the daily dosage in the morning [(1/3) as short-acting insulin, (2/3) as intermediate-acting insulin] and (1/3) in the evening [½ as short-acting insulin, ½ as intermediate-acting insulin]).113 In pediatric patients with newly diagnosed diabetes mellitus, may administer 0.1–0.25 units/kg of regular insulin every 6–8 hours during the first 24 hours to determine insulin requirements.113
Adults
Diabetes Mellitus
Sub-Q
Dosage must be individualized.
In newly diagnosed patients with severe diabetes mellitus, unstable diabetes mellitus, or diabetes mellitus with complications, insulin (regular) (i.e., purified pork insulin) generally is given sub-Q in a dosage of 5–10 units, 15–30 minutes before meals and at bedtime.e
In patients who are currently controlled on purified pork insulins, no change in dosage usually is required when transferring to insulin human, except routine dosage adjustments that are necessary to maintain stable glycemic control.12
Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic States
Mild Diabetic Ketoacidosis
IV, then Sub-Q or IM
For the treatment of mild diabetic ketoacidosis (plasma glucose >250 mg/dL with an arterial pH of 7.25–7.3 and serum bicarbonate of 15–18 mEq/L), the ADA recommends a loading dose of 0.4–0.6 units/kg of regular insulin administered in 2 doses, with 50% given by direct IV injection and 50% by sub-Q or IM injection.113 After the loading dose, administer 0.1 units/kg per hour of regular insulin sub-Q or IM.113
Moderate to Severe Diabetic Ketoacidosis
IV
For the treatment of moderate to severe diabetic ketoacidosis (plasma glucose >250 mg/dL with arterial pH ≤7–7.24 and serum bicarbonate ≤10–15 mEq/L) or hyperosmolar hyperglycemia in adults, the ADA recommends a loading dose of 0.15 units/kg of regular insulin by direct IV injection, followed by continuous IV infusion of 0.1 units/kg per hour.113
If plasma glucose concentrations do not fall by 50 mg/dL within the first hour of insulin therapy, insulin infusion rate may be doubled every hour, provided the patient is adequately hydrated, until plasma glucose decreases steadily by 50–75 mg/dL per hour.113
When a plasma glucose concentration of 250 or 300 mg/dL is achieved in patients with diabetic ketoacidosis or hyperosmolar hyperglycemia, respectively, may decrease the insulin infusion rate to 0.05–0.1 units/kg per hour.113 May need to adjust the rate of insulin administration or the concentration of dextrose to maintain glucose concentration until resolution of diabetic ketoacidosis (i.e., serum glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia (i.e., patient mentally alert, serum osmolality of ≤315 mOsm/kg).b
Dosage Following Resolution of Diabetic Ketoacidosis
IV, then Sub-Q
Upon resolution of diabetic ketoacidosis (i.e., plasma glucose <200 mg/dL, venous pH >7.3, serum bicarbonate ≥18 mEq/L) or hyperosmolar hyperglycemia in patients who are unable to eat, continue IV insulin and fluid replacement; may give sub-Q regular insulin as needed every 4 hours.113 May give regular insulin sub-Q in 5-unit increments for every 50-mg/dL increase in blood glucose concentrations above 150 mg/dL, to a dose of up to 20 units of regular insulin for a blood glucose of ≥300 mg/dL.113
When the patient is able to eat, initiate a multiple-dose, sub-Q insulin regimen consisting of a short- or rapid-acting insulin and an intermediate- or long-acting insulin.113 Continue regular insulin IV for 1–2 hours after initiation of the sub-Q insulin regimen to ensure adequate plasma insulin concentrations during the transition.113 Abrupt discontinuance of IV insulin with the institution of delayed-onset sub-Q insulin may lead to worsened glycemic control.113 Patients with known diabetes mellitus may reinstitute the insulin regimen they were receiving before the onset of hyperglycemic crises, and the regimen may be adjusted further as needed for adequate glycemic control.113
Patients with newly diagnosed diabetes mellitus should receive a total daily insulin dosage of 0.5–1 units/kg as part of a multiple-dose regimen of short- and long-acting insulin, until an optimal dosage is established.113 May manage some patients with newly diagnosed type 2 diabetes mellitus with diet therapy and oral antidiabetic agents following resolution of hyperglycemic crises.113
AMI†
IV
For metabolic modulation in patients with AMI†, a low-dose GIK solution (containing regular insulin 20 units/L and potassium chloride 40 mEq/L in 10% dextrose injection) has been infused at a rate of 1 mL/kg per hour for 24 hours, and a high-dose solution (containing regular insulin 50 units/L and potassium chloride 80 mEq/L in 25% dextrose injection) has been infused at a rate of 1.5 mL/kg per hour for 24 hours.95 96 High-dose regimen may be more effective and is therefore preferred.95 96
Cautions for Insulin Human
Warnings/Precautions
Warnings
Hypoglycemia
Care should be taken in patients who are most at risk for the development of these effects, including patients who are fasting or those with defective counterregulatory responses (e.g., patients with autonomic neuropathy, adrenal or pituitary insufficiency, those receiving β-adrenergic blocking agents).
Reduce the potential for late postprandial hypoglycemia by altering the timing, frequency, and content of meals; altering exercise patterns; frequently monitoring blood glucose concentrations; adjusting insulin dosage; and/or switching to a more rapid-acting insulin (i.e., insulin lispro).
Use intensive insulin therapy with caution in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes. Higher target blood glucose concentrations (e.g., fasting blood glucose concentrations of 140 mg/dL and 2-hour postprandial concentrations of 200–250 mg/dL) are advisable in these patients.
Exercise extreme caution when concentrated (U-500) insulin human (regular) injection is used in patients with marked insulin resistance (i.e., daily insulin requirements >200 units).o Inadvertent overdosage may result in irreversible insulin shock.o Serious consequences may result if this concentrated injection is used without constant medical supervision.o
Sensitivity Reactions
Local reactions (e.g., pain at injection site, erythema, pruritus, swelling) reported.c Warming refrigerated insulin to room temperature prior to use will limit local irritation at the injection site.67 101
Generalized hypersensitivity reactions (e.g., rash, shortness of breath, wheezing, hypotension, tachycardia, diaphoresis) reported less frequently, but may be life-threatening.c
Insulin human is less immunogenic than purified pork insulin.34 35 45 46 59 The incidence of allergic reactions may have decreased with the availability of more purified insulin (e.g., insulin human, insulin lispro). In patients who may have selective allergic reactions to pork insulin or proteins, prevent further allergic reactions by substitution of an insulin that contains less protein (i.e., purified insulins, including insulin human). The ADA states that human insulin is preferred for use in individuals with allergies to animal-derived insulins.103
Insulin Resistance
Chronic insulin resistance resulting from immunity has been decreased by changing to a purified insulin preparation (e.g., insulin human). The ADA states that human insulin is preferred for use in individuals with immune resistance to animal-derived insulins.103
General Precautions
Lipodystrophy
Atrophy or hypertrophy of subcutaneous fat tissue may occur at sites of frequent insulin injections.c Rotate injection site to reduce or prevent these effects.d
Hypokalemia
Care should be taken in patients who are most at risk for the development of hypokalemia, such as those who are receiving potassium-lowering drugs.
Since diabetic ketoacidosis often is associated with hypokalemia, the possibility of potassium imbalance should be evaluated and, if present, corrected before administration of insulin as long as adequate renal function is assured.
Concurrent Illness
Illness, particularly nausea and vomiting, and changes in eating patterns may alter insulin requirements.c
Use of Fixed Combination
When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.
Specific Populations
Pregnancy
Category B.
Most clinicians recommend initiation of intensive insulin therapy (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) prior to conception in diabetic patients who are well controlled on oral hypoglycemic agents and who are considering pregnancy.
Geriatric Use
The safety of an intensive insulin regimen (3 or more insulin injections daily with dosage adjusted according to results of at least 4 daily blood glucose determinations, dietary intake, and anticipated exercise) in geriatric patients has been questioned. Increased incidence of hypoglycemia associated with intensive insulin therapy may increase the probability of strokes and heart attacks in such patients.
Hypoglycemic reactions in geriatric diabetic patients may mimic a cerebrovascular accident.d An increased incidence of macrovascular disease in geriatric patients with type 2 diabetes mellitus may make such patients more vulnerable to serious consequences of hypoglycemia (e.g., fainting, seizures, falls, stroke, silent ischemia, MI, sudden death).
Common Adverse Effects
Hypoglycemia.
Interactions for Insulin Human
Specific Drugs
- Drugs That May Potentiate Hypoglycemic Effects
Alcohol
ACE inhibitors
Disopyramide
Fibrate derivatives
Fluoxetine
Guanethidine
MAO inhibitors
Oral antidiabetic agents
Propoxyphene
Salicylates
Somatostatin derivatives (e.g., octreotide)
Sulfa anti-infectives
- Drugs That May Antagonize Hypoglycemic Effects
Calcium-channel blocker
Corticosteroids
Danazol
Diuretics
Estrogens and progestins (e.g., oral contraceptives)
Isoniazid
Niacin
Phenothiazines
Somatropin
Sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline)
Thyroid hormones
- Drugs That May Have a Variable Effect on Glycemic Control
Alcohol
β-Adrenergic blocking agents
Clonidine
Lithium salts
Pentamidine
- Drugs That May Reduce or Eliminate Signs of Hypoglycemia (Sympatholytic Agents)
β-Adrenergic blocking agents
Clonidine
Guanethidine
Reserpine
Insulin Human Pharmacokinetics
Absorption
Bioavailability
Because of its protein nature, insulin is destroyed in the GI tract and usually is administered parenterally.e
Following sub-Q injection, insulin human (regular) appears to be absorbed more rapidly than purified pork insulin (regular).17 24 28 29 30 42
Following IM or IV administration, serum insulin concentrations are similar for insulin human (regular) and purified pork insulin (regular).17 18 19 31 32 43
Onset and Duration of Action of Human Insulins
Formulation | Onset (hours) | Peak (hours) | Duration (hours) |
|---|---|---|---|
Short-Acting | |||
Insulin (regular) 71 | 0.5 | 2.5–5 | 8 |
Intermediate-Acting | |||
Insulin Zinc (Lente) | 1–3 | 6–14 | 16–24+ |
Isophane Insulin (NPH) humanf g | 1.5 | 4–12 | 24 |
Long-Acting | |||
Insulin zinc, extended (Ultralente) | 4–6 | 8–20 | 24–28 |
Insulin Mixtures | |||
Insulin Human and Insulin Isophane (Humulin 50/50) | 0.5–1 | 1.5–4.5 | 7.5–24 |
Insulin Human and Insulin Isophane (Novolin 70/30, Humulin 70/30)h q | 0.5 | 2–12 | 24 |
In patients with diabetes mellitus, insulin human appears to have a slightly faster onset and shorter duration of action than purified pork insulin.58
Distribution
Extent
Rapidly distributed throughout extracellular fluids.e
Elimination
Metabolism
Rapidly metabolized mainly in the liver and to a lesser extent in the kidneys and muscle tissue.e
Elimination Route
Excreted in the urine principally as metabolites.e
Half-life
Insulin has a plasma half-life of a few minutes in healthy individuals.e The biologic half-life may be prolonged in diabetic patients, probably as a result of binding of the hormone to antibodies.
Special Populations
In patients with renal impairment, the biologic half-life may be prolonged as a result of altered degradation/decreased clearance.
Stability
Storage
Parenteral
Solution for Injection
With unopened vials or cartridges of insulin human injections than have not been placed in a delivery device, 2–8°C; do not freeze.5 7 53 64 67 71 82 89 93 100 101 c j Vials in use, below 30°C; protect from excessive heat or cold and light.67 c
Novolin PenFill 3-mL cartridges of insulin human (regular) injection assembled in a delivery device are stable for 28 days at room temperature.71 Discard unrefrigerated Novolin Penfill cartridges not used within this time period.67 Protect from excessive heat or cold and light.71
Discard insulin human (regular) injection exhibiting discoloration, turbidity, or unusual viscosity,5 7 71 82 88 89 since these changes indicate deterioration or contamination.5 7 101
Suspension for Injection
With unopened vials, pens, prefilled syringes, or cartridges containing insulin human zinc or isophane insulin human suspensions, 2–8°C in the original container; do not freeze.6 8 53 64 65 80 84 92 93 100 101 f g h i k l m p q With vials in use, below 30°C; protect from heat and light.80 g h i k l m r Freezing will cause isophane insulin human and insulin human zinc to resuspend improperly, preventing accurate measurement of a dose.54 55 In addition, agglomeration of particles may occur, altering absorption from the injection site.54 55
Preparations of insulin isophane suspension available with a delivery device (Novolin N PenFill cartridges, Humulin N pen) are stable below 30°C for 14 days.67 f m Protect from excessive heatf m or coldf and light.f m
Preparations of insulin human and isophane insulin human suspensions available with a delivery device (Novolin 70/30 PenFill 3-mL cartridges assembled in a delivery device, Novolin 70/30 Innoletprefilled syringes, Humulin 70/30 pen) are stable below 30°C for 10 days.67 f p q Should discard unrefrigerated insulin after 10 days.p Protect from excessive heat and light.p
Should discard isophane insulin human and insulin human zinc if the suspensions are clear, if they remain clear after the vial is rotated, if the precipitate has become clumped or granular in appearance, or if solid particles have adhered to the wall of the vial.6 8 64 65 75 76 80 83 84 90 92 93 101
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution CompatibilityHID (Human Insulin Regular)
10% insulin loss
Incompatible |
|---|
Sodium chloride 0.9% |
Drug Compatibility (Human Insulin Regular)
Incompatible |
|---|
Ranitidine HCl |
Compatible |
|---|
Clarithromycin |
Dobutamine HCl |
Doxapram HCl |
Indomethacin sodium trihydrate |
Milrinone lactate |
Pentobarbital sodium |
Propofol |
Sodium bicarbonate |
Incompatible |
Ranitidine HCl |
Variable |
Digoxin |
Diltiazem HCl |
Levofloxacin |
ActionsActions
Supplements deficient levels of endogenous insulin and temporarily restores the ability of the body to properly utilize carbohydrates, fats, and proteins.e Facilitates cellular uptake of glucose in muscle and fat cells.d e
Inhibits output of glucose from the liver.d e In the liver, insulin facilitates phosphorylation of glucose to glucose-6-phosphate which is converted to glycogen or further metabolized.e
Stimulates lipogenesis and inhibits lipolysis and release of free fatty acids from adipose cells.e Insulin also stimulates protein synthesis.e
Promotes an intracellular shift of potassium and magnesium and thereby appears to temporarily decrease elevated blood concentrations of these ions.e
When used in patients following an AMI, insulin in combination with dextrose (d-glucose) and potassium (referred to as glucose-insulin-potassium [GIK] therapy) decreases both circulating concentrations of free fatty acids (FFAs) and myocardial uptake of FFAs. Rationale for G1K therapy: Stimulation of myocardial potassium uptake by insulin via Na+-K+-ATPase and provision of glucose (substrate) for glycolic ATP production. Aids in critical membrane functions such as calcium and sodium homeostasis.
Insulin human has essentially identical pharmacologic effects compared with purified pork insulin.12 13 17 18 19 20 21 22 23 38 39 40
Advice to Patients
Importance of strict adherence to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens or pumps.n
Provide instructions regarding insulin storage and injection technique.d n
Provide instructions regarding the use of intensive insulin therapy with multiple injections.d Advise patients of the risks of such therapy (e.g., hypoglycemia).
Provide instructions regarding self-monitoring of blood glucose concentrations.c n Particular importance of frequent self-monitoring of blood glucose concentrations in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.
Provide instructions regarding adherence to meal planning, regular physical exercise, periodic hemoglobin A1c (HbA1c) monitoring, and management of hypoglycemia or hyperglycemia.d n
Importance of changing insulin dosage with caution and only under medical supervision.d Discuss potential for alterations in insulin requirements in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances or other stresses).c d Discuss potential for alterations in insulin requirements as a result of changes in physical activity, missed doses, or inadvertent administration of incorrect doses.c d
Importance of not changing the order of mixing insulins or the model or brand of syringe or needle without medical supervision.c e When mixing with other insulin preparations, importance of drawing regular insulin into the syringe first.e n
Importance of informing clinicians of the development of skin reactions (erythema, pruritus, edema, lipodystrophy) at injection site.c
Importance of informing clinicians of the development of generalized hypersensitivity reactions (shortness of breath, hypotension, wheezing, whole body rash, tachycardia, diaphoresis).c
Importance of patient wearing a medical identification bracelet or pendant, carrying ample insulin supply and syringes on trips, having carbohydrates (sugar or candy) on hand for emergencies, and of noting time-zone changes for dose schedule when traveling.c n
Inform patient that use of marijuana may increase insulin requirements.n
Importance of patient not smoking within 30 minutes after insulin injection due to potential for decreased absorption of insulin.n
Instruct patient on the appropriate measures for safe disposal of needles.n
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.c
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.c
Importance of informing patients of other important precautionary information.c (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injectable suspension | 100 units/mL | Humulin U Ultralente | Lilly |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 100 units/mL | Humulin R | Lilly |
Novolin R (with cresol) | Novo Nordisk | |||
500 units/mL | Humulin R (concentrated U-500) | Lilly | ||
Injection, for use with NovoPen or other compatible device (e.g., NovolinPen) only | 100 units/mL (150 units) | Novolin R PenFill (with cresol) | Novo Nordisk |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Suspension, sterile | 100 units/mL | Humulin L | Lilly |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Suspension, sterile | 100 units/mL | Humulin N (with phenol) | Lilly |
Humulin N Pen (available as prefilled cartridge preassembled into pen) | Lilly | |||
Novolin N (with cresol and phenol) | Novo Nordisk | |||
Suspension, sterile, for use with NovoPen or other compatible device (e.g., NovolinPen) only | 100 units/mL (150 units) | Novolin N PenFill (with cresol and phenol) | Novo Nordisk |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|
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