Pharmacology - Endocrine Drugs

Thyroid Drugs

Synthroid (levothyroxine, T4) and Liothyronine (Cytomel)

• It may take several weeks to see improvement.
• Overcorrection is to be avoided to prevent decreased heart rate and angina.
• Adverse effects of antithyroid drugs: tachycardia, palpitations, angina, hypertension, insomnia, tremors, headaches, anxiety, nausea, diarrhea, menstrual irregularities, weight loss, sweating, heat intolerance, fever.
• Interventions:
  • Monitor $T4$ and $TSH$ levels.
  • Take on an empty stomach with a full glass of water before breakfast.
  • Requires lifelong treatment.
• Indications for Levothyroxine: Hypothyroidism
• Mode of Action: Acts as a synthetic form of thyroid hormones
• Avoid foods with iodine.

Propylthiouracil (PTU)

• Anti-thyroid drug. First trimester is the drug of choice during pregnancy, because during the other trimesters are rare case of liver damage in people taking PTU.
• Methimazole is a better choice than PTU for nursing women to avoid liver side effects.

Methimazole

• Used for the treatment of hyperthyroidism and Grave’s disease.
• Class: Antithyroid agents
• Contraindications: Hypersensitivity
• Adverse Effects: Hepatotoxicity, Stevens-Johnson Syndrome, Toxic epidermal necrolysis, agranulocytosis, aplastic anemia, and bleeding.
• Nursing Considerations:
  • Monitor for agranulocytosis, instruct to report to doctors immediately.
  • Filgrastim can be used to treat agranulocytosis.
  • Monitor for signs and symptoms of hypothyroidism (drowsiness, depression, weight gain, edema, bradycardia, anorexia, cold intolerance, and dry skin).
  • Monitor CBC for leukopenia or thrombocytopenia.

Adrenal Drugs

Glucocorticoids: Prednisone, Solu-medrol

• Indications: Wide variety of illnesses: asthma, autoimmune disorders, inflammatory disorders
• Mode of Action: Decreases inflammation and suppresses the immune response
• Side Effects: Bone loss, weight gain/fluid retention, hyperglycemia, hypokalemia, infection, peptic ulcer disease, adrenal gland suppression, skin fragility, GI upset
• Monitor for signs of infection and peptic ulcer diseases (coffee ground emesis, tarry stools). Periods of stress may require additional doses. Do not stop suddenly (must taper off slowly). Take Vitamin D and Calcium supplements. Avoid NSAIDs

Glucocorticoid: Beclomethasone (Beclovent)

• Indications: Used for chronic asthma and helps produce Surfactant
• Mode of Action: Decreases inflammation and suppresses the immune response
• Side Effects: Bone loss, weight gain/fluid retention, hyperglycemia, hypokalemia, infection, peptic ulcer disease, adrenal gland suppression, skin fragility, GI upset
• Does not relax smooth muscles in the lungs; it is a steroid, so use a metered-dosed inhaler.

Survanta Lung Surfactant

• Used for respiratory distress in neonates, given through ET tube.

Endocrine Drugs

Pancreas

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

Insulin

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

Diabetes Mellitus (DM)

• Not a single disease but a group of progressive diseases; often regarded as a syndrome rather than a disease.
• Two Types
  • Type 1
  • Type 2
• Signs and symptoms:
  • Polyuria
  • Polydipsia
  • Polyphagia
  • Glycosuria
  • Unexplained weight loss
  • Fatigue
  • Blurred vision

Confirming the diagnosis of type 2 diabetes:

• Fasting plasma glucose: 126 mg/dL or higher on 2 separate occasions
• HbA1c: 6.5% or higher on 2 separate occasions
• Oral glucose tolerance test (OGTT): 2-hour post OGTT blood glucose 200 mg/dL or higher
• FBG, HbA1c, or OGTT high on 2 occasions indicate diabetes.

Type 1 vs Type 2 Diabetes

Type 1 Diabetes Mellitus

• Lack of insulin production or production of defective insulin
• Affected patients need exogenous insulin.
• Fewer than 10% of all DM cases are type 1.
• Complications:
  • Diabetic ketoacidosis (DKA)
  • Hyperosmolar hyperglycemic syndrome (HHS)

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
  • Microalbuminemia (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.

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.

HHS

DIABETIC KETOACIDOSIS

• Metabolic acidosis is seen
• Fruity breath
• Frequent urination, loss of ketones, dehydration
• Treatment: ICU, insulin drip, IV fluids, monitor ABGs, monitor BMP, neuro, CV, hemodynamics, respiratory

HYPEROSMOLAR HYPERGLYCEMIC SYNDROME (HHS)

• Symptoms similar like in DKA
• Hyperglycemia, dehydration, & serum osmolality more severe
• Vascular thrombosis
• Treatment: Same treatment like for DKA

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 to 15 years.

Screening for Diabetes

Prediabetes

• Categories of increased risk for DM
• HbA1C of 5.7% to 6.4%
• Fasting plasma glucose levels higher than or equal to 100 mg/dL but less than 126 mg/dL
• Impaired glucose tolerance test (oral glucose challenge)
• Screening recommended every 3 years for all patients 45 years and older

Blood Test Levels for Diagnosis of Diabetes and Prediabetes

Nonpharmacologic Treatment Interventions

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

Glycemic Goal of Treatment

• HbA1C of less than 6.5%
• Fasting blood glucose goal for diabetic patients of 70 to 130 mg/dL

Types of Antidiabetic Drugs

• Insulins
• Oral hypoglycemic drugs
• Both aim to produce normal blood glucose states
• Some new injectable hypoglycemic drugs may be used in addition to insulin or antidiabetic drugs.

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

Types of Insulin

Rapid-Acting

• Most rapid onset of action (5 to 15 minutes)
• Peak: 1 to 2 hours
• Duration: 3 to 5 hours
• Patient must eat a meal after injection.
• Insulin lispro (Humalog)
• Similar action to endogenous insulin
• Insulin aspart (NovoLog)
• Insulin glulisine (Apidra)
• May be given subcutaneously (SQ) or via continuous SQ infusion pump (but not intravenously [IV])

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

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)

Intermediate-Acting Insulins

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

Long-Acting Insulins

• 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 to 2 hours
• Peak: none
• Duration: 24 hours
• Toujeo: more concentrated U-300
• Insulin detemir (Levemir)
• Duration of action is dose dependent.
• Lower doses require twice-daily dosing.
• Higher doses may be given once daily.
• Insulin glargine (Basaglar)
• Biosimilar insulin, U100
• Insulin degludec (Tresiba)
• Ultra long acting
• Once daily, U100 or U200

Oral Antidiabetic Drugs

Biguanide

• 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
• Adverse Effects: 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; does not cause hypoglycemia

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, hematologic effects, nausea, epigastric fullness, heartburn

Glinides

• Repaglinide (Prandin), nateglinide (Starlix)
• Indication: type 2 DM
• Action similar to sulfonylureas: increase insulin secretion from the pancreas
• Adverse effects: headache, hypoglycemic effects, dizziness, weight gain, joint pain, upper respiratory infection, or flulike symptoms

Thiazolidinediones (Glitazones)

• Pioglitazone (Actos), rosiglitazone (Avandia)
• Only available through specialized manufacturer programs
• Insulin-sensitizing drugs, indication: type 2 DM, MOA: decrease insulin resistance; increase glucose uptake and use in skeletal muscle; inhibit glucose and triglyceride production in the liver
• Adverse Effect: Heart Failure

Alpha-Glucosidase Inhibitors

• Acarbose (Precose), miglitol (Glyset), indication: type 2 DM
• Reversibly inhibit the enzyme alpha-glucosidase in the small intestine, result in delayed absorption of glucose; must be taken with meals to prevent excessive postprandial blood glucose elevations (with the “first bite” of a meal)
• Adverse effects: flatulence, diarrhea, abdominal pain; do not cause hypoglycemia, hyperinsulinemia, or weight gain

Dipeptidyl Peptidase-IV (DPP-IV) Inhibitors

• Sitagliptin (Januvia):
• Delay breakdown of incretin hormones by inhibiting the enzyme DPP-IV, incretin hormones increase insulin synthesis and lower glucagon secretion, reduce fasting and postprandial glucose concentrations
• Adverse effects: upper respiratory tract infection, headache, and diarrhea; hypoglycemia can occur and is more common if used in conjunction with a sulfonylurea
• Indications: 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 DM

Serum Glucose Cotransporter (SGLT2) Inhibitor Drugs

• Canagliflozin, Dapagliflozin (Farxiga), and Empagliflozin (Jardiance)
• Uses: DM II and gets rid of the amount of sugar when you urinate.
• Adverse Effects: Genital yeast infections
• Black Box Warning: Increase risk of leg and foot amputations
• Nursing Implications:
  • Take by mouth once daily in the morning.
  • May cause hypovolemia and hypotension
  • Not safe for use in pregnancy.

Injectable Antidiabetic Drugs

Amylin agonist

• Pramlintide (Symlin)

Incretin mimetics

• Exenatide (Byetta)
• Dulaglutide (Trulicity)
• Liraglutide (Victoza)
• Albiglutide (Tanzeum)
• Lixisenatide (Adlyxin)

Combo agent

• Soliqua (insulin glargine and lixisenatide)
• Xultophy (insulin degludec and liraglutide)
• Mechanism of Action: Mimics the incretin hormones, enhances glucose-driven insulin secretion from beta cells of the pancreas, only used for type 2 DM, Exenatide: injection pen device
• Adverse Effects:
  • Amylin agonist: nausea, vomiting, anorexia, headache
  • Incretin mimetics: nausea, vomiting, and diarrhea, rare cases of hemorrhagic or necrotizing pancreatitis, weight loss

Hypoglycemia

• Abnormally low blood glucose level (below 50 mg/dL)
• Mild cases can be treated with diet—higher intake of protein and lower intake of carbohydrates—to prevent rebound postprandial hypoglycemia.
• Symptoms:
  • Early: Confusion, irritability, tremor, sweating
  • Late: Hypothermia, seizures, coma and death will occur if not treated.

Glucose-Elevating Drugs

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

Nursing Implications

• Before giving drugs that alter glucose levels, obtain and document:
  • A thorough history
  • Vital signs
  • Blood glucose level, HbA1C level
  • Potential complications and drug interactions
• 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 the primary care provider to clarify orders for antidiabetic drug therapy
• Keep in mind that overall concerns for any patient with DM increase when the patient:
  • Is under stress
  • Has an infection
  • Has an illness or trauma
  • Is pregnant or lactating
• Insulin order and prepared dosages are second checked with another nurse.
• When insulin is ordered, ensure: Correct route, Correct type of insulin, Timing of the dose, Correct dosage
• 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.
• 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.
• Assess for signs of hypoglycemia. If hypoglycemia occurs: Administer oral form of glucose if the patient is conscious; give the patient glucose tablets or gel, corn syrup, honey, fruit juice, or nondiet soft drink or have the patient eat a small snack, such as crackers or a half sandwich; deliver D50W or glucagon IV if the patient is unconscious; monitor blood glucose levels.
• Monitor for therapeutic response: Decrease in blood glucose levels to the level prescribed by physician; measure HbA1C to monitor long-term compliance with diet and drug therapy; monitor for hypoglycemia and hyperglycemia.

Endocrine Drugs Chart

Other Key Notes

• When on steroids, monitor blood sugar.
• Oral Antidiabetics: Sulfonylureas (Glipizide, Glimepiride): Take when blood sugar is elevated, induced by meals; PO: Onset—1 hr; Peak 1-3 hrs; Half-life: 2-5 hr; Duration of Action: 6-8 hrs. Should not be given to Type 1 pts; Take 30 minutes before meal; Do not use alcohol; Wear sunscreen. Side effects: Hypoglycemia: Tachycardia, diaphoresis, shakiness, headache, weakness; Photosensitivity, GI upsets
• Other Popular Diabetic Meds: Oral Antidiabetics: Biguanides - Metformin (Glucophage): Indications: Type 2 diabetes; used to control blood sugar levels; Mode of Action: Decreases glucose production in liver and increases glucose uptake; Side Effects: GI Upsets , metallic taste, lactic acidosis, and B12 deficiency.
• MUST TAKE WITH MEALS. Do not use alcohol, take B12 supplement if indicated. Discontinue metformin for procedures requiring NPO or contrast dye. Monitor for signs of lactic acidosis (diarrhea, dizziness, hypotension, bradycardia, weakness)
• How do Steroids affect blood sugar? → Steroids can cause insulin resistance

Mixing Insulin

1. Wash hands.
2. Gently rotate NPH insulin bottle.
3. Wipe off tops of insulin vials with alcohol swab.
4. Draw back amount of air into the syringe that equals total dose.
5. Inject air equal to NPH dose into NPH vial. Remove the syringe from the vial, taking care not to touch the needle tip to fluid.
6. Inject air equal to the regular dose into the regular vial.
7. Invert the regular insulin bottle and withdraw the regular insulin dose.
8. Without adding more air to the NPH vial, carefully withdraw the NPH dose, taking care not to push fluid back into the container, as this will contaminate the NPH insulin with regular insulin.