Chapter 32 Antidiabetic Drugs Flashcards
The pancreas is both an?
- exocrine gland (secreting digestive enzymes through the pancreatic duct)
- endocrine gland (secreting hormones directly into the bloodstream and not through a duct)
Two main hormones that are produced by the pancreas are?
insulin and glucagon. Both hormones play an important role in the regulation of glucose homeostasis, specifically the use, mobilization, and storage of glucose by the body
Glucose is one of the primary sources of energy for the cells of the body. It is also the simplest form of carbohydrate (sugar) found in the body and is often referred to as?
dextrose
When the quantity of glucose in the blood is sufficient, the excess is stored as?
glycogen in the liver and, to a lesser extent, in skeletal muscle tissue, where it remains until needed. Glucose is also stored in adipose tissue as triglyceride body fat.
When more circulating glucose is needed, glycogen—primarily that stored in the liver—is converted back to glucose through a process called?
glycogenolysis. The hormone responsible for initiating this process is glucagon. Glucagon has only minimal effects on muscle glycogen and adipose tissue triglyceride stores.
Because of the critical role of the pancreas in producing and maintaining these two hormones, pancreatic or islet cell transplant are sometimes undertaken to treat?
type 1 diabetes that has not been successfully controlled by other means
Insulin normally facilitates removal of?
glucose from the blood and its storage as glycogen in the liver
-Insulin also has a direct effect on fat metabolism. It stimulates lipogenesis and inhibits lipolysis and the release of fatty acids from adipose cells.
Diabetes mellitus, more commonly referred to simply as diabetes, is primarily a disorder of?
carbohydrate metabolism that involves either a deficiency of insulin, a resistance of tissue (e.g., muscle, liver) to insulin, or both
Two major types of diabetes mellitus are type 1 and type 2. Type 1 diabetes was previously called insulin dependent diabetes mellitus or juvenile-onset diabetes.
Little or no endogenous insulin is produced by individuals with type 1 diabetes, which affects only about 10% of all diabetic patients. Patients with type 1 diabetes usually are not obese. Insulin therapy is required for type 1 diabetics; patients with the cognitive and financial ability are encouraged to consider insulin pumps with continuous glucose monitoring.
Type 2 diabetes was previously called?
non–insulindependent diabetes mellitus or adult-onset diabetes
The current key diagnostic criterion for diabetes mellitus is?
hyperglycemia with a fasting plasma glucose (FPG) level of higher than 126 mg/dL or a hemoglobin A1C (A1C) level
greater than or equal to 6.5%
The most common signs and symptoms of diabetes are?
elevated blood glucose level (fasting glucose level higher than 126 mg/dL) and polyuria, polydipsia, polyphagia, glucosuria, weight loss, blurred vision, and fatigue
A new term, estimated average glucose (eAG) is a mathematical conversion of the A1C into an average blood glucose level in the units of measure seen by patients on glucose meters for self-monitoring (mg/dL). Similar to A1C, eAG evaluates a patient’s overall?
success at controlling glucose levels and helps patients understand the monitoring of their long-term treatment
Type 1 diabetes mellitus is characterized by a lack of?
insulin production or by the production of defective insulin, which results in acute hyperglycemia. Affected patients require exogenous insulin to lower the blood glucose level and prevent diabetic complications
When blood glucose levels are high but no insulin is present to allow glucose to be used for energy production, the body may?
break down fatty acids for fuel, producing ketones as a
metabolic by-product and resulting in diabetic ketoacidosis (DKA). DKA is a complex multisystem complication of uncontrolled diabetes.
Another complication that is also triggered by extreme
hyperglycemia is?
hyperosmolar nonketotic syndrome (HNKS). The most common precipitator of DKA and HNKS is some type of physical or emotional stress. Both disorders can occur with diabetes of either type
Type 2 diabetes mellitus accounts for at least 90% of all cases of diabetes mellitus. Type 2 diabetes mellitus is caused by?
both insulin resistance and insulin deficiency, but there is no absolute lack of insulin as in type 1 diabetes
Type 2 diabetes is a multifaceted disorder. Although loss of blood glucose control is its primary hallmark, other conditions associated with it are?
obesity, coronary heart disease, dyslipidemia, hypertension, microalbuminuria, and an increased risk for thrombotic events
The goal for patients with diabetes is a blood pressure less than?
-and low-density lipid less than?
- blood pressure less than 130/80 mmHg
- low-density lipid less than 100 mg/dL
Gestational diabetes is a type of hyperglycemia that occurs in about 2% to 10% of pregnancies. Many patients are well controlled with diet, but the use of insulin may be necessary to decrease the risk of birth defects, hypoglycemia in the newborn, and high birth weight. As many as 30% of patients who experience gestational diabetes are estimated to develop?
type 2 diabetes within 10 to 15 years
Adults 45 years of age and older should be screened for elevated FPG levels every?
3 years
Patients diagnosed with type 1 diabetes always require insulin therapy. For patients with new-onset type 2 diabetes, lifestyle changes should be initiated as a first step in treatment.
Weight loss, improved dietary habits, smoking cessation, reduced alcohol consumption, and regular physical exercise are just a few examples of lifestyle changes
The glycemic goal recommended by the American Diabetes Association (ADA) for diabetic patients is an?
A1C level of less than 7%
The major classes of drugs used to treat diabetes mellitus are?
insulins and the oral antidiabetic drugs
Several new classes of injectable drugs with unique mechanisms of action have been developed that may be used in addition to insulins or oral antidiabetic drugs to treat resistant diabetes. All of these drugs are referred to as antidiabetic drugs and are aimed at producing a?
normoglycemic or euglycemic (normal blood glucose) state
Currently insulin is synthesized in laboratories using recombinant deoxyribonucleic acid technology and is referred to as human insulin. Insulin was originally isolated from cattle and pigs, but bovine and porcine insulins are associated with a higher incidence of allergic reactions and insulin resistance and are no longer available in the U.S. market. Exogenous insulin functions as a?
substitute for the endogenous hormone
The pharmacokinetic properties of insulin (onset of action, peak effect, and duration of action) can be altered by?
Making various minor modifications to either the insulin molecule itself or the drug formulation (final product)
- this practice has led to the development of many different insulin preparations, including several combination insulin products that contain more than one type of insulin in the same solution
- further modifications can be accomplished by mixing compatible insulin preparations in the syringe before administration
- thoroughly educate patients regarding how, when, and if they can (or cannot) mix different types of insuline
- some combinations are chemically incompatible and can result in alteration of glycemic effects
Exogenous insulin restores?
The patient’s ability to metabolize carbohydrates, fats, and proteins; to store glucose in the liver; and to convert glycogen to fat stores
-it does not reverse defects in insulin receptor sensitivity
When an insulin pump is used, insulin is administered
constantly over a?
24-hour period and the patient is then allowed to give bolus injections based on the amount of food ingested.
Insulin Indications: All insulin preparations can be used to treat?
both type 1 and type 2 diabetes, but each patient requires careful customization of the dosing regimen for optimal glycemic control.
• Additional therapeutic approaches such as lifestyle modifications (e.g., dietary and exercise habits) are also indicated and, for type 2 diabetes, oral drug therapy as well.
Insulin contraindications
- Known drug allergy
- NEVER administer to an already hypoglycemic patient
- blood glucose must ALWAYS be tested prior to administration
Insulin adverse effects
Hypoglycemia resulting from excessive insulin dosing can result in brain damage, shock, and possible death. This is the most immediate and serious adverse effect of insulin.
-other effects include: weight gain, lipodystrophy at site of repeated injections, and allergic reactions
Insulin interactions
Corticosteroids, estrogen, diuretics, thyroid drugs, nonselective beta blockers
Dosages for Insulin lispro (Humalog) (B)
- Rapid acting; human recombinant rapid-acting analgoue
- Usual dosage range: Subcut; 0.5-1 unit/kg/day; doses are individualized to desired glycemic control; rapid-acting insulins are best given at least 15 min before a meal
- may be given per sliding scale or as basal/bolus; may also be given via continuous subcut infusion pump
Dosages for insulin regular (Humulin R)
- Short acting, human recombinant short-acting insulin
- Subcut: same dosage as insulin lispro (0.5-1 u/kg/day); subcut doses of regular insulin are best given 30 min before a meal
- regular insulin may also be given per sliding scale or basal/bolus and is the insulin given IV as a continuous infusion
Dosages for insulin glargine (Lantus) (C)
- Long acting; human recombinant long-acting insulin analogue
- subcut ONLY: 0.2 units/kg/day given once or twice daily (basal dosing)
In emergency situations requiring prompt insulin action what can be given?
Regular insulin can be given IV
- insulin also is available as a U-500 (high alert medication)
- great care must be taken with its use to ensure that the correct dose is administered
- many hospitals do not allow U-500 insulin because of potential for errors
Two special patient populations for whom careful attention is required during insulin therapy are?
pediatric patients and pregnant women
- insulin dosages for both are calculated by weight
- usual dosage range: 0.5-1 units/kg/day as total daily dose
The rapid-acting insulin lispro is approved for use in?
Children older than 3, however, combination lispro product Humalog 75/25 is not currently approved for use in children younger than 18 years of age
Pregnant women require special care with regard to diabetes management. Although most of these mothers will?
Return to a normal glycemic state after pregnancy, they are at risk for developing diabetes again later in life.
All currently available oral and injectable antidiabetic drugs are classified as pregnancy category B or C drugs. Oral medications are generally not recommended for pregnant patients because of a?
lack of firm safety data. Insulin therapy is the only currently recommended drug therapy.
- insulin does not generally cross the placenta
- effective glycemic control during pregnancy is essential because infants born to women with gestational diabetes have a twofold to threefold greater risk for congenital anomalies
- incidence of stillbirth directly related to the degree of maternal hyperglycemia
- weight reduction not advised, it can jeopardize fetal nutritional status
- women w/gestational diabetes tend to have babies that weigh more, and these children may have low blood sugar in the postnatal period
- insulin excreted in human milk
There are currently four major classes of insulin, as determined by their pharmacokinetic properties:
(1) rapid-acting
(2) short-acting
(3) intermediate-acting
(4) long-acting
- The duration of action ranges from several hours to over 24 hours, depending on the insulin class
The insulin dosage regimen for all diabetic patients is highly individualized and may consist of?
One or more classes of insulin administered at either fixed dosages or variable dosages in response to self-measurements of blood glucose level or the number of grams of carbohydrate consumed
With the use of insulins what is important to understand for patient safety and for the prevention of adverse effects and complications?
Clarity, color, and appearance
- several insulins are clear, colorless solutions; these include regular insulin, insulin lispro (Humalog), and insulin glargine (Lantus)
- other insulins, such as NPH insulin (insulin isophane), are white opaque (cloudy) solutions
- all insulins are high alert medications
Rapid-Acting Insulin: Insulin lispro (Humalog)
- rapid onset of action (15 minutes) & shorter duration of action
- effect of insulin lispro most like that of endogenous insulin produced by pancreas in response to a meal
- after or during a meal, the glucose that is ingested stimulates the pancreas to secrete insulin. This facilitates the uptake of the excess glucose at hepatic insulin receptor sites for storage in the liver as glycogen
- in people w/diabetes, insulin response to meals is often imparied; therefore a rapid-acting insulin product is often used w/in 15 min of mealtime. This corresponds to the time required for the onset of action of these products
- essential for pt’s to eat a meal after injection, otherwise profound hypoglycemia results
Short-Acting Insulin: Regular Insulin (Humulin R)
- only short acting
- given IV bolus, IV infusion, IM, or subcutaneously
- those routes, especially IV infusion, often used in cases of DKA or coma associated with uncontrolled type 1 diabetes
- differences between these and rapid acting: rapid acting insulins are considered human insulin analogues meaning they are insulin molecules with synthetic alterations to their chemical structures that alter their onset or duration of action. They have a faster onset of action and a shorter time to peak level, but they also have a shorter duration of action than does regular insulin
- regular is made from human insulin sources using recombinant DNA technololgy
Intermediate-Acting Insulins: Insulin Isophane suspension (NPH)
- Only available intermediate-acting
- NPH acronym for neutral protamine Hagedorn insulin
- Sterile suspension of zinc insulin crystals and protamine sulfate in buffered water for injection
- suspension appears cloudy or opaque
- slower onset and longer duration of action than regular insulin
- often combined with regular insulin to reduce the number of insulin injections per day
Long-Acting insulins: Insulin glargine (Lantus) and insulin detemir (Levemir)
- Insulin detemir (Levemir) classified as intermediate or long acting since given twice daily. In clinical practice it’s long acting
- Insulin glargine: clear, colorless solution with a pH 4.0. Once injected into subcutcaneous tissue at physiologic pH, if forms microprecipitates that are slowly absorbed over 24 hrs. It is a DNA-produced insulin analogue and provides a constant level of insulin in the body. This enhances its safety because blood levels do not rise and fall as with other insulins
- Insulin glargin usually dosed once daily but may be dosed every 12 hours depending on the pt’s glycemic response
- because insulin glargine provides a more prolonged, consistent blood glucose level, it is sometimes referred to as a basal insulin
- insulin detemir has different MOA from glargine. The two different insulins are NOT considered interchangeable
- duration of action for detemir is dose dependent, so that lower doses require twice-daily dosing and higher doses may be given once daily
Fixed-combination insulins: Humulin 70/30, Humalog 50/50
- Each contain 2 different insulins: one intermediate acting type and either one rapid acting (Humalog) or one short acting (Humulin)
- numeric designations indicate percentages of each two components
- each adds up to 100%
- developed to closely simulate varying levels of endogenous insulin that occur normally in nondiabetic people
- developed to simplify dosing process
- allow for twice daily dosing but often result in glycemic control that is not as tight as daily dosing with meals
- pt’s who can’t afford frequent glucose monitoring or who refuse more than two injections per day may insist on using a combination insulin with twice daily dosing
Antidiabetic drugs: Review the appropriate laboratory test results (e.g., FPG level, A1C level) for any abnormalities compared with baseline levels. Assess the prescriber’s order for insulin, so that the correct drug, route, type of insulin (i.e., rapid-acting, short-acting, intermediate-acting, short- and intermediate-acting mixtures, and long-acting), and dosage are implemented correctly. Assess the specific insulin, paying additional attention to the?
specific pharmacokinetics such as onset of action, peak, and duration of action
- if more than one insulin type is prescribed, mixing of insulins may be ordered. Need to know the chemically compatible combinations to avoid glycemic effects
- always perform a second check of the prepared insulin dosage against the medication order with another RN
What do you assess PRIOR to administering insulin?
Blood glucose levels to avoid giving the drug to a patient who is already hypoglycemic
The 2015 ADA guidelines identify the current key diagnostic criterion for diabetes mellitus as?
Hyperglycemia with a fasting plasma glucose level of higher than 126 mg/dL or a hemoglobin A1C level greater than 6.5%
-Recommends: fasting blood glucose within the range of 70 to 130 mg/dL and/or a hemoglobin A1C less than 7%
Allergic reactions are less likely with which insulins?
Recombinant human insulins because their similarity with endogenous insulin; however, allergies may still occur
Drugs that work against the effect of insulin include?
Corticosteroids, thyroid drugs, diuretics
Drugs that increase the hypoglycemic effects of insulin include?
Alcohol, sulfa antibiotics, and salicylates
Assess medication order for all insulins, especially?
U-500 insulin
-must be administered with great caution
