Pharmacology Chapter 32

Non-Insulin Antidiabetic drugs: Adverse effects (Thiazolidinediones: Glitazones)

- Can cause or exacerbate heart failure - contraindicated if heart failure is present - Peripheral edema - Weight gain (fluid retention and increased adipose tissue) - Decreased bone marrow density with increased risk for fractures

Sliding scale insulin dosing

- SQ rapid-acting (lispro or aspart) or short-acting (regular) insulins are adjusted according to blood glucose test results. - Typically used in hospitalized diabetic patients or those on total parenteral nutrition or enteral tube feedings - SQ insulin is ordered in an amount that increases as the blood glucose increases - Disadvantage: delays insulin administration until hyperglycemia occurs; results in large swings in glucose control

Incretin Mimetics Dipeptidyl Peptidase-IV (DPP-IV) inhibitors ("gliptins")

- Sitagliptin (Januvia) - Saxagliptin (Onglyza) - Linagliptin (Tradjenta) - Alogliptin (Nesina)

Nursing Implications (Cont.)

--Before giving drugs that alter glucose levels: -Assess the patient's ability to consume food -Assess for nausea or vomiting -Hypoglycemia may be a problem if antidiabetic drugs are given and the patient does not eat -If a patient is NPO for a test or procedure, consult primary care provider to clarify orders for antidiabetic drug therapy

Nursing Implications (Cont.)

--When insulin is ordered, ensure: -Correct route -Correct type of insulin -Timing of the dose -Correct dosage --Insulin order and prepared dosages are second-checked with another nurse**

Long-acting insulins

-Long acting Insulin glargine (Lantus) - clear, colorless solution - constant level of insulin in the body - Usually dosed once daily - can be dosed every 12 hours -referred to as basal insulin - Onset: 1-2 hours - Peak: None - Duration: 24 hours - Toujeo: more concentrated U-300 form Insulin detemir (Levemir) - Duration of action is dose dependent - Lower doses require twice-daily dosing - Higher doses may be given once daily Insulin glargine (Lantus or Basaglar) - biosimilar insulin -U100 Insulin degludec (Tresiba) -ultra long acting -once daily U100 or U200

amylin agonist

-pramlintide (Simylin) Mimics the natural hormone Amylin Slows gastric emptying Suppresses glucagon secretion, reducing hepatic glucose output Centrally modulates appetite and satiety Used when other drugs have not achieved adequate glucose control SUBQ injection

Case Study

A male patient who has a history of type 2 diabetes mellitus is admitted to the medical unit with a diagnosis of pneumonia. The patient has many questions regarding his care and asks the nurse why everyone keeps telling him about HbA1C. What can the nurse inform the patient about the use of HbA1C in diabetes mellitus? C. Will aid in monitoring patient adherence to treatment regimen for several months previously. Rationale: HbA1C is a good indicator of the patients compliance with the drug regimen for several months previously.

Hypoglycemia

Abnormally low blood glucose level (below 70 mg/dL) Mild cases can be treated with diet- higher intake of protein and lower intake of carbohydrates-to prevent rebound postprandial hypoglycemia.

Which percentage value of A1C indicates type 2 diabetes?

Above 6.5

Non-insulin Antidiabetic drugs: Alpha- glucosidase inhibitors

Acarbose (Precose), miglitol (glyset) Indication: type 2 diabetes mellitus Contraindications: certain bowel disorders

Rapid acting insulins

Afrezza - Rapid-acting insulin that is inhaled - Peak of 12 to 15 minutes - Short duration of action of 2 to 3 hours - Administered within 20 minutes before each meal - Must be given in conjunction with long-acting insulins or oral diabetic agents (for type 2 DM) - Side effects: hypoglycemia, cough, and throat pain - Contraindicated: smokers and those with chronic lung diseases - Black box warning regarding the risk of acute bronchospasms

Nursing implications

Before giving drugs that alter glucose levels, obtain and document: A thorough history Vital signs Blood glucose level, A1C level Potential complications and drug interactions

Which category of antidiabetics does metformin belong to?

Biguanides

GLP-1 agonists adverse effects

Black box warning: risk of developing thyroid C- cell tumors Nausea, vomiting, and diarrhea Rare cases of hemorrhagic or necrotizing pancreatitis Patients may; experience weight loss of 5-10 pounds

After the 0700 report, the day shift nurse notices that a patient has a 0730 dose of insulin due and goes to the automated dispensing machine to retrieve the insulin. The nurse sees that the night shift nurse had removed the 0730 dose of insulin, but the medication administration record has not been signed by the nurse. The patient is confused and says she "thinks" the night nurse gave her the insulin. The patient's blood glucose level is 142 mg/dL. What will the day shift nurse do? A.Give the insulin because it was not signed off. B.Hold the insulin because the patient thinks she received it, and it is recorded in the machine. C.Ask the charge nurse to call the night nurse at home to clarify whether the insulin was given. D.Report this to the nursing supervisor.

C. Ask the charge nurse to call the night nurse at home to clarify whether the insulin was given. Rationale: Never guess whether a drug was given. Taking the drug out of the machine does not mean it was given. The nurse should ask the night nurse what was done.

Case Study: The patient was taking metformin before this hospitalization. To facilitate better glucose control, the patient has been switched to insulin therapy while hospitalized. The patient asks the nurse why it is so important to time meals with the insulin injection and to give him an example of a long acting insulin. Which drug will the nurse tell the patient is a long acting insulin?

C. Insulin Detemir Rationale: The nurse should inform the patient that timing of meals with insulin and oral antidiabetic therapy is important to prevent hypoglycemia and to obtain the most optimal results from the antidiabetic therapy. Whereas insulin detemir (Levemir) is a long acting insulin, insulin glulisine (Apidra) is a rapid acting insulin. Insulin isoprene suspension (NPH) is an intermediate acting insulin, and regular insulin (Humulin R) is a short acting insulin.

A woman who has type 2 DM is now pregnant. She wants to know whether to take her oral antidiabetic medication. What instructions will she receive? A. She should continue the antidiabetic medication at the same dosage. B. The antidiabetic medication dosage will be increased gradually throughout her pregnancy. C. She will be switched to insulin therapy while she is pregnant. D. She will not receive any antidiabetic medication while pregnant and will need to monitor her dietary intake closely.

C. She will be switched to insulin therapy while she is pregnant. Rationale: Oral antidiabetic medications are generally not recommended for pregnant patients because of a lack of firm safety data. Insulin therapy is the currently recommended drug therapy for pregnant women.

Which drug inhibits the metabolism of metformin?

Cimetidine

SGLT2 inhibitors

Contraindications: DKA, moderate to severe kidney impairment Adverse effects: Genital yeast infections Urinary tract infections Increased urination Hypotension Hypovolemia Hyperkalemia Possible ketoacidosis, acute kidney injury 2018 FDA warning: necrotizing fasciitis of the perineum (Fournier gangrene)

Case study: The patient is being discharged home with insulin lispro and insulin isophane suspension (NPH). Which information does the nurse include when providing discharge teaching to the patient?

D. Draw up the insulin lispro first and then draw up the NPH into the same syringe. Rationale: The rapid acting and then the intermediate acting insulins should be mixed in the syringe after the appropriate amount of air has been injected. Insulin is stored at room temperature when it will be used within the month. The injection should be administered at a 90 degree angle for patients who have adequate body fat and at a 45 degree angle for patients who are very thin. Insulins should be rolled before administration and not shaken.

The nurse has just administered the morning dose of a patients lispro (Humalog) insulin. Just after the injection, the dietary department calls to inform the patient care unit that breakfast trays will be 45 minutes late. What will the nurse do next?

D. Give the patient food, such as cereal and skim milk, and juice. Rationale: Lispro insulin's onset of action is 15 minutes. It is essential that a patient with diabetes mellitus eat a meal after injection. Otherwise profound hypoglycemia may result.

Acute diabetic complications

DKA Hyperglycemia Ketones in the serum Acidosis Dehydration Electrolyte imbalances Approximately 25% to 30% of patients with newly diagnosed type 1 DM present with DKA

DPP-IV inhibitors mechanism of action

DPP-IV inhibitors - Delay breakdown of incretin hormones by inhibiting the enzyme DPP-IV Reduce fasting and postprandial glucose concentrations

DPP-IV inhibitors Indication

DPP-IV inhibitors - Improve glycemic control in patients with Type 2 diabetes. - Used as an adjunct to diet and exercise

Biguanides: Mechanism of action

Decrease production of glucose by the liver Decrease intestinal absorption of glucose Increase uptake of glucose by tissues Do not increase insulin secretion from the pancreas (does not cause hypoglycemia)

Diabetes mellitus

Diabetes mellitus (DM) actually is not a single disease but a group of progressive diseases. It is often regarded as a syndrome rather than a disease. TWO TYPES: Type 1 Type 2

Incretin Mimetics

Dipeptidyl Peptidase IV inhibitors (DPP-IV) & Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists Mimic naturally secreted Incretin hormones Incretin hormones increase insulin synthesis and lower glucagon secretion Oral and injectable forms

Insulin

Direct effect on fat metabolism Stimulates lipogenesis and inhibits lipolysis Stimulates protein synthesis Promotes intracellular shift of potassium and magnesium into cells. Cortisol, epinephrine, and growth hormone work synergistically with glucagon to counter the effects of insulin.

Hypoglycemia symptoms

Early: - confusion, irritability, tremor, sweating Late: - hypothermia,seizures - Coma and death will occur if not treated

Signs and symptoms of diabetes mellitus

Elevated fasting blood glucose (higher than 126 mg/dL) or a hemoglobin A1C (HbA1C) level greater than or equal to 6.5% Polyuria Polydipsia Polyphagia Glycosuria Unexplained weight loss Fatigue Blurred vision

Incretin mimetics for Glucagon-Like peptide-1 Agonists

Enhance glucose dependent insulin secretion, and suppresses elevated glucagon secretion. Slows gastric emptying -Increases first and second phase insulin secretion

Which condition is seen in a patient with hyperosmolar hyperglycemic syndrome (HHS)?

Extreme hyperglycemia

Non-Insulin Antidiabetic Drugs: Adverse Effects (Alpha glucosidase inhibitors)

Flatulence Diarrhea Abdominal pain Do not cause hypoglycemia, hyperinsulinemia, or weight gain

Insulins

Function as a substitute for the endogenous hormone. Effects are the same as normal endogenous insulin Restores the diabetic patient's ability to: - Metabolize carbohydrates, fats, and proteins - Store glucose in the liver - Convert glycogen to fat stores Human insulin - Derived using recombinant DNA technologies - Recombinant insulin produced by bacteria and yeast. Goal: tight glucose control - To reduce the incidence of long-term complications

Which laboratory test provides evidence of adequate glucose management and adherence to a diabetes treatment regimen over the past few months?

Glycosylated hemoglobin (HbA1c)

Glycemic goal of treatment

HbA1C of less than 7% - A1C goals are higher in. Those with multiple comorbidities or living in an institution, such as a nursing home. -HbA1C diagnostic criteria; <5.7=normal 5.7-6.4=prediabetes >6.5= type 2 diabetes Fasting blood glucose goal for diabetic patients of 80 to 130 mg/dL Estimated average glucose

Fixed-Combination Insulins

Humulin 70/30 Humulin 50/50 Novolin 70/30 Humalog Mix 75/25 Humalog 50/50 NovoLog 70/30 Each contains two different insulins , fixed combinations -one intermediate-acting type -Either one rapid-acting type or one short acting type

Which insulin is administered intravenously?

Humulin R

Gestational diabetes

Hyperglycemia that develops during pregnancy Insulin must be given to prevent birth defects Usually subsides after delivery 30% of patients may develop type 2 DM within 10-15 years.

Non- Insulin antidiabetic drugs: Adverse effects (Glinides)

Hypoglycemia and weight gain

Non-Insulin Antidiabetic Drugs: Incretin mimetic and Amylin agonists

Incretin mimetics - Dipeptidyl Peptidase IV inhibitors (DPP-IV) -Glucagon-like peptide-1 receptor agonists (GLP-1) Amylin Agonists

GLP-1 Agonists Indications

Indicated for patients with type 2 diabetes who have not been able to achieve blood glucose control with metformin, a sulfonylurea and/or a glitazone

Non-Insulin Antidiabetic drugs: Sodium Glucose cotransporter inhibitors (SGLT2 inhibitors)

Inhibition of SGLT2 leads to a decrease in blood glucose caused by an increase in renal glucose excretion. SGLT2 inhibitors: new class of oral drugs for the treatment of type 2 diabetes mellitus Canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Steglatro) and others in development. Action: Work independently of insulin to prevent glucose reabsorption from the glomerular filtrate, resulting in a reduced renal threshold for glucose and glycosuria. Other effects: May increase insulin sensitivity and glucose uptake in the muscle cells and decrease gluconeogenesis Results: improved glycemic control, weight loss, and a low risk of hypoglycemia

Which characteristic is related to glucagon hormone?

Initiates the glycogenolysis process

Glucagon-Like Peptide-1 (GLP-1) Agonists

Injectable GLP-1 - Exanatide -Dulaglutide - Liraglutide - Albiglutide - Lixisenatide - Semaglutide (Ozempic) Oral Form - Ryblesus- oral form of semaglutide Combination products - Soliqua (insulin glargine and lizisenatide) -Xultophy (insulin degludac and liraglutide)

Nursing Implications (Cont.)

Insulin -check blood glucose level before giving insulin -roll vials between hands instead of shaking them to mix suspensions - ensure correct storage of insulin vials - Only use insulin syringes, calibrated in units, to measure and give insulin - Ensure correct timing of insulin dose with meals - When drawing up two types of insulin in one syringe, always withdraw the regular or rapid acting insulin first. - Provide thorough patient education regarding self administration of insulin injections, including timing of doses, monitoring blood glucose levels, and injection site rotations.

Which long-acting insulin mimics natural basal insulin with its duration of 24 hours?

Insulin glargine (Lantus)

Types of antidiabetic drugs

Insulins Oral hypoglycemic drugs- both aim to produce normal blood glucose states Some news injectable hypoglycemic drugs may be used in addition to insulin or antidiabetic drugs.

Intermediate-acting insulins

Intermediate acting Insulin isophane suspension (also called NPH) Cloudy appearance Often combined with regular insulin Onset-1-2 hours Peak- 4-8 hours Duration- 10-18 hours

Nursing Implications (Cont.) 2

Keep in mind that overall concerns for any patient with diabetes mellitus increase when the patient: - is under stress - has an infection - has an illness or trauma - is pregnant or lactating

Type 1 diabetes mellitus

Lack of insulin production of defective insulin Affected patients need exogenous insulin. Fewer than 10% of all DM cases are type 1. Complications: Diabetic ketoacidosis and hyperosmolar hyperglycemia syndrome

Pancreas

Located behind stomach Both exocrine and endocrine gland Produce two hormones that play an important role in regulation of glucose homeostasis: Insulin Glucagon Glycogen: Excess glucose stored in liver and skeletal muscle tissue. Glycogenolysis-the conversion of glycogen into glucose when needed

Major Long-Term Complications of Both Types of Diabetes

Macrovascular (atherosclerotic plaque) Coronary arteries Cerebral arteries Peripheral vessels Microvascular (capillary damage) Retinopathy Neuropathy Nephropathy

Non-insulin antidiabetic drugs: Biguanides

Metformin (Glucophage) First-line drug and is the most commonly used oral drug for the treatment of type 2 DM Not used for type 1 DM

Nursing Implications (Cont.)

Monitor for therapeutic response: - decrease in blood glucose levels to the level prescribed by the physician. - Measure HbA1C to monitor long-term compliance with diet and drug therapy. - Monitor for hypoglycemia and hyperglycemia.

Type 2 diabetes mellitus

Most common type: 90% of all cases Caused by insulin deficiency and insulin resistance Many tissues are resistant to insulin: Reduced number of insulin receptors Insulin receptors less responsive Several comorbid conditions: Obesity Coronary heart disease Dyslipidemia Hypertension Microalbuinemia (protein in the urine) Increased risk for thrombotic (blood clotting) events These comorbidities are collectively referred to as metabolic syndrome, also known as insulin resistance syndrome, or syndrome X.

Which long-term consequence is associated with macrovascular complication?

Myocardial infarction

Which precaution would the nurse advise about insulin U-500 to a patient with type 2 diabetes?

Need to take three times before mealtime

Which insulin is an example of intermediate-acting insulin?

Neutral protamin Hagedorn

Which characteristic is associated with type 1 diabetes?

Occurs due to autoimmune destruction of beta-cell

Nursing implications

Oral antidiabetic drugs - Always check blood glucose levels before giving - Usually given 30 minutes before meals - Alpha glucosidase inhibitors are given with the first bite of each main meal. - Metformin is taken with meals to reduce GI effects. - Metformin will need to be discontinued if the patient is to undergo studies with contrast dye because of possible renal effects; check with the prescriber.

Glucose elevating drugs

Oral forms of concentrated glucose Buccal tablets, semisolid gel 50% dextrose in water (D50W) Glucagon

Amylin Agonist Indications

Patients with Type 1 and Type 2 diabetes who receive mealtime insulin and who have failed to achieve optimal glycemic control with insulin. Contraindications: Gastroparesis The patients usual insulin dose usually needs to be reduced by 50% Give 1 hour before other oral medications as it can delay oral absorption of other drugs

Which statement made by the patient about type 1 diabetes mellitus indicates effective learning?

Patients with type 1 diabetes mellitus require exogenous insulin

Non-Insulin Antidiabetic Drugs: Thiazolidinediones (Glitazones)

Pioglitazone (Actos) Rosiglitizone (Avandia) -Only available through specialized manufacturer programs Insulin sensitizing drugs Indication: Type 2 diabetes Mechanism of Action: - decreases insulin resistance - "Insulin sensitizing drugs" - Increase glucose uptake and use in skeletal muscle - inhibit glucose and triglyceride production in the liver

Basal-bonus insulin dosing

Preferred method of treatment for hospitalized patients with diabetes mellitus Mimics a healthy pancreas by delivering basal insulin constantly as a basal and then as needed as a bolus. Basal insulin is a long-acting insulin (insulins glargine) Bolus insulin (insulin lispro or insulin aspart)

Biguanides: Adverse effects (metformin)

Primarily affects gastrointestinal (GI) tract: abdominal bloating, nausea, cramping, diarrhea, feeling of fullness. May also cause metallic taste , reduced vitamin B12 levels Lactic acidosis is rare but lethal if it occurs. Contraindicated in renal or hepatic disease. Does not cause hypoglycemia

Insulins continued

Rapid-acting treatment for types 1 and 2 DM -most rapid onset of action (5-15 minutes) -peak 1-2 hours -Duration 3-5 hours - Patient must eat a meal after injection - insulin lispro (Humalog) Similar action to endogenous insulin - insulin as part (Novolog) - insulin glulisine (Apidra) -May be given subcutaneously (SUBQ) or via continuous SUBQ infusion pump (but not intravenously [IV])

Non-insulin antidiabetic drugs: Glinides

Repaglinide (Prandin), nateglinide (Starlix) Indication: Type 2 diabetes mellitus Action: Similar to sulfonylureas. Increase insulin secretion from the pancreas

Non-insulin antidiabetic drugs: mechanism of action (Alpha-glucosidase inhibitors)

Reversible inhibit the enzyme alpha glucosidase in the small intestine Results in delayed absorption of glucose Must be taken with meals to prevent excessive postprandial blood glucose elevations (with the first bite of a meal)

Non-insulin antidiabetic drugs: Sulfonylureas

Second generation: glimepiride (Amaryl), glipizide (Glucotrol), glyburide (DiaBeta) - Stimulate insulin secretion from the beta cells of the pancreas, thus increasing insulin levels. - Beta cell function must be present - Improve sensitivity to insulin in tissues - Result in lower blood glucose level - Adverse effects: hypoglycemia, hematologist effects, nausea, epigastric fullness, heartburn, and many others.

Short-acting insulins

Short acting - Regular insulin (Humulin R) - Routes of administration: IV bolus, IV infusion, intramuscular (IM), SQ - Onset (SQ route): 30 to 60 minutes - Peak (SQ route): 2.5 hours - Duration (SQ route): 6 to 10 hours IV route - immediate onset - duration 2-6 hours

Which clinical indicator of hypoglycemia will the nurse identify for the patient and family?

Sweating Headache Tachycardia

Which category of the oral antidiabetic drug can regulate genes involved in glucose metabolism?

Thiasolidinediones

Nursing implications

Thorough patient education is essential regarding: - Disease process - Diet and exercise recommendations -Self administration of insulin or oral drugs - potential complications

Treatment for diabetes

Type 1- insulin therapy Type 2- Lifestyle changes Oral drug therapy Insulin when the above no longer provide glycemic control

Nonpharmacologic treatment interventions

Type 1: always requires insulin therapy Type 2: Weight loss Improved dietary habits Smoking cessation Reduced alcohol consumption Regular physical exercise

Insulin dosing and syringes

U100: Standard for most (100 units/mL) U200: Insulin pen U300: Insulin pen U500: Newer concentration for those patients needing very high doses of insulin (500 units/mL)

DPP-IV inhibitors adverse effects

Upper respiratory tract infection, headache, and diarrhea Hypoglycemia can occur and is more common if used in conjunction with a sulfonylurea Possible pancreatitis

Non-Insulin Antidiabetic Drugs: Indications (Alpha glucosidase inhibitors)

Used alone or in combination with other drugs and/or diet and lifestyle changes to lower the blood glucose levels in patients with type 2 diabetes mellitus

Non-insulin antidiabetic drugs

Used for type 2 DM Effective treatment involves several elements Careful monitoring of blood glucose levels Therapy with one or more drugs Treatment of associated comorbid conditions such as high cholesterol and high blood pressure 2018 American Diabetes Association guidelines: New onset type 2 diabetes mellitus treatment - Lifestyle interventions - Oral biguanide drug met for in - If lifestyle modifications and the maximum tolerated metformin dose do not achieve the recommended HbA1C goals after 3-6 months, other antidiabetic agents will be ordered in addition to the metformin.

A patient with type 1 DM is admitted to the medical unit with an acute exacerbation of chronic obstructive pulmonary disease. He is placed on IV piggyback antibiotics, nebulizer treatments with albuterol, and an IV corticosteroid, and he is also taking a proton pump inhibitor for gastroesophageal reflux disease. He is taking a dose of glargine insulin every evening. This evening the nurse notes that his blood glucose level is 170 mg/dL. The next morning, his fasting glucose level is 202 mg/dL.

What is the most likely cause of his elevated glucose levels? A. Albuterol B. The antibiotics C. The proton pump inhibitor D. The corticosteroid Answer: D. The corticosteroid Rationale: Corticosteroids antagonize the hypoglycemic effects of insulin, resulting in elevated blood glucose

Which site should be used for injecting insulin?

abdomen

Nursing Implications

assess for signs of hypoglycemia. If hypoglycemia occurs: - administer oral form of glucose is the patient is conscious. - Give the patient glucose tablets or gel, corn syrup, honey, fruit juice, or non diet soft drink or have the patient eat a small snack, such as crackers or half a sandwich - Deliver IV dextrose or SUBQ glucagon if the patient I unconscious. - Monitor blood glucose levels

Which class of medication increases blood glucose levels when administered with insulin?

diuretics

Amylin Agonist Adverse effects

nausea, vomiting, anorexia, headache

Which type of insulin can be given IV?

regular insulin