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Key Points
- The first-line medication for type 2 DM is metformin.
- ADA and other professional guidelines inform prescribing decisions.
- Combination injectable therapy should be considered for immediate implementation in patients with an A1C of 10% or higher.
- TZDs, like Actos, can precipitate CHF and should be avoided in patients with heart failure.
- Older adults should be started on lower doses of levothyroxine.
- Radioactive iodine treatment results in lifelong hypothyroidism.
- When treating hypothyroidism, TSH levels should be monitored every 6-8 weeks until the patient achieves a euthyroid state. - Signs and symptoms of hypothyroidism and hyperthyroidism (pp. 418-419)
Hypothyroidism: The face is pale, puffy, & expressionless. The skin is cold & dry. The hair is brittle, & hair loss occurs. Heart rate & temperature are lowered. The patient may c/o lethargy, fatigue, & cold intolerance. Mentation may be impaired. Thyroid enlargement may occur if reduced levels of T 3 & T 4 promote excessive release of TSH.
Hyperthyroidism: Heartbeat is rapid & strong, & dysrhythmias & angina may develop. The CNS is stimulated, resulting in nervousness, insomnia, rapid thought flow, & rapid speech. Skeletal muscles may weaken & atrophy. Metabolic rate is raised, resulting in increased heat production, increased body temperature, intolerance to heat, & skin that is warm & moist. Increased appetite, but weight loss may occur if caloric intake fails to match the increase in metabolic rate. (Exophthalmos w/Graves’ disease).
- What adjunctive therapy is good to prescribe to control symptoms of
hyperthyroidism other than thyroid specific medications? Know drug classes and
examples of those drug classes. (pp. 419, 423)
Beta-blockers & nonradioactive iodine may be used as adjunctive therapy for hyperthyroidism.
Beta-blockers: Suppress tachycardia by blocking beta-receptors on the heart. (“-lol”)
Nonradioactive iodine: Inhibits synthesis & release of thyroid hormones. (Lugol Solution = mixture containing 5% elemental iodine & 10% potassium iodine).
- Monitoring needs and intervals for thyroid medications. (pp. 421, 423)
Hypothyroidism: Levothyroxine (T 4 ) (Brand-name: Levoxyl, Synthroid )
Therapeutic Goal: Resolution of signs & symptoms of hypothyroidism & restoration of normal lab values for serum TSH & free T 4.
Baseline Data: Obtain serum levels of TSH & free T 4.
Evaluating Therapeutic Effects: Monitor for weight gain, decreased heart rate, & other indications that levels of thyroid hormone have declined. Lab tests should indicate a decrease in serum free T 3 & free T 4.
Minimizing Adverse Effects:
Agranulocytosis: Inform patients about early signs of agranulocytosis, including fever or sore throat. If follow-up blood tests reveal leukopenia, methimazole should be stopped.
Hypothyroidism: Methimazole may cause excessive reductions in thyroid hormone synthesis. If signs of hypothyroidism develop or if plasma levels of T 3 & T 4 become subnormal, dosage should be reduced.
- Propylthiouracil (PTU) carries a risk for liver toxicity. Although rare, the FDA
recommends against using PTU as a first-line treatment due to potential for hepatic
toxicity. (p. 422)
Also a thionamide, PTU suppresses synthesis of thyroid hormones. Its therapeutic uses include pregnant women in the 1st^ trimester, thyroid storm, & patients w/intolerance to methimazole. It has caused rare cases of liver injury. Onset is sudden & progression is rapid.
- Effects of maternal hypothyroidism on offspring and appropriate patient teaching
related to need fortreatment. (p. 418)
Maternal hypothyroidism can result in permanent neuropsychological deficits in the child, including decreased IQ. The effect of maternal hypothyroidism is limited largely to the 1st^ trimester, a time during which the fetus is unable to produce thyroid hormones of its own. By the 2nd^ trimester, the fetal thyroid gland is fully functional, & hence the fetus can supply its own hormones from then on. To help ensure healthy fetal development, maternal hypothyroidism must be diagnosed & treated very early. Due to the unspecific symptoms or sometimes asymptomatic hypothyroidism, some experts recommend routine screening for hypothyroidism as soon as pregnancy is confirmed. If diagnosed, replacement therapy should begin immediately.
When women taking thyroid supplements become pregnant, dosage requirements usually increase—often by as much as 50%. The need for increased dosage begins between weeks 4 to 8 of gestation, levels off at approximately week 16, & then remains steady until giving birth. To ensure adequate hormone levels, some providers increase T 4 dosage by 30% as soon as pregnancy is confirmed. Further adjustments are based on serum TSH levels, which should be monitored closely.
- Patient teaching for thyroid medications. (pp. 420-423)
Levothyroxine: Take the drug exactly as prescribed. Take the dose at the same time each day, preferably in the morning at least 30-60 mins before breakfast, to maintain constant hormones levels. Taking the drug in the morning prevents insomnia. Report signs & symptoms of thyroid hormone overdose (chest pain, palpitations, sweating, nervousness) or aggravated cardiovascular disease (chest pain, dyspnea, tachycardia). Advise patients to check w/their prescriber before allowing a pharmacist to switch to a different levothyroxine product, as there are questions concerning the equivalence between them. Patients must be made fully aware that this medication provides symptomatic relief but does not cure hypothyroidism, therefore replacement therapy must usually continue for life.
Methimazole: Patients should be instructed to immediately report any fever, sore throat, or mouth sores (early signs of agranulocytosis) or skin eruptions (signs of hypersensitivity). Avoid being near people who are sick or have infections. If follow-up blood tests reveal leukopenia, this medication should be stopped. It may cause excessive reductions in thyroid hormone synthesis. If signs of hypothyroidism develop or if plasma levels of T 3 & T 4 become subnormal, dosage should be reduced.
groups within the ADA DM Guidelines linked in the Endocrine Case Studies and on your Student Lesson Plan.
The general goal is to keep the Hgb A1c less than 7%. A less stringent goal of less than 8% may be appropriate for some patients, such as those with a history of severe hypoglycemia, limited life expectancy, or advanced microvascular or macrovascular complications. Hgb A1c should be measured every 3 months until the value drops to 7% & at least every 6 months thereafter. (A value of 6.5% or greater is considered diagnostic of diabetes.)
Older Adults: Older adults who are otherwise healthy with few coexisting chronic illnesses & intact cognitive function & functional status should have lower glycemic goals (such as A1c <7.5%), while those with multiple coexisting chronic illnesses, cognitive impairment, or functional dependence should have less stringent glycemic goals (such as A1c <8.0-8.5%).
Children & Adolescents: A reasonable A1c target for most children & adolescents with type 2 diabetes treated with oral agents alone is <7%. More stringent A1c targets (such as <6.5%) may be appropriate for selected individual patients if they can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with short duration of diabetes & lesser degrees of beta-cell dysfunction & patients treated with lifestyle or metformin only who achieve significant weight improvement.
- Review diagnostic criteria and process for DM (p. 398)
Criteria for the Diagnosis of Diabetes Mellitus Fasting plasma glucose 126 mg/dL (no caloric intake for at least 8 hours) OR Random plasma glucose 200 mg/dL plus symptoms of diabetes (polyuria, polydipsia, & unexplained weight loss) OR Oral glucose tolerance test (OGTT): 2-hour plasma glucose 200 mg/dL (plasma glucose content is measured 2 hours after ingesting the equivalent of 75 grams of anhydrous glucose dissolved in water) OR
Hemoglobin A1C 6.5% or higher
- Know examples, mechanism of action, and contraindications for DM drug classes. (pp. 407-
Biguanides: Met formin ( Glucophage, Forta met , Glu met za, Rio met )
THE DRUG OF CHOICE FOR INITIAL THERAPY IN MOST PATIENTS W/TYPE 2 DM
MOA: Inhibits glucose production in the liver, slightly reduces glucose absorption in the gut, & sensitizes insulin receptors in target tissues (fat & skeletal muscle) & thereby increases glucose uptake in response to whatever insulin may be available.
Contraindications: GFR <30 (renal insufficiency), metabolic acidosis, diabetic ketoacidosis, lactic acidosis, hypoxemia, dehydration, sepsis, surgery, hepatic disease, alcoholics. BLACK BOX WARNING: Lactic Acidosis—Severe metabolic acidosis can occur with accumulation of metformin. Highest risk occurs in diabetic patients with significant renal impairment. (If a patient is
Contraindications: TZD should be avoided in patients with congestive heart failure (CHF) as it causes water retention &edema, which aggravates CHF. TZDs should also be avoided in patients with or a history of bladder cancer, active liver disease, type 1 DM, or pregnancy. TZDs may cause weight gain; therefore, monitoring weight and BMI is needed. Regular LFTs monitoring is also recommended due to the action of the drug in the liver.
BLACK BOX WARNING: Pioglitazone is associated with heart failure (HF) secondary to renal retention of fluid. If HF is diagnosed, pioglitazone should be discontinued or used in reduced dosage.
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: Alo gliptin ( Nesina ), Lina gliptin ( Tradjenta ), Saxa gliptin ( Onglyza ), Sita gliptin ( Januvia )
MOA: Enhances actions of incretin hormones to stimulate glucose dependent insulin & suppresses glucagon release.
Contraindications: No known clinically relevant drug interactions & no contraindications, including pregnancy. Use with caution in patient that have a history of pancreatitis. (May cause severe & disabling joint pain that can occur at any point during treatment, angioedema, & acute pancreatitis.)
Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors: Cana gliflozin ( Invokana ), Dapa gliflozin ( Farxiga ), Empa gliflozin ( Jardiance )
MOA: Reduces the reabsorption of glucose by the kidneys in the proximal nephron, increasing urinary excretion of glucose.
Contraindications: Use with caution in patients prone to vulvovaginal & urinary tract infections. (Due to SGLT2 actions on the kidneys, there is a risk for volume depletion and hypotension and can lead to diabetic ketoacidosis. SGLT2 drugs may cause weight loss as well. Creatinine should be monitored as well as urinalysis. With an increase of glucose in the urine, patients taking these medications are at higher risk for UTIs and pyelonephritis. There is also an increased risk for the need for leg and foot amputations in patients on SGLT2 drugs.)
Glucagon-like Peptide-1 (GLP-1) Receptor Agonists (AKA Incretin Mimetics): Exena tide ( Byetta ), Liraglu tide ( Victoza ), Dulaglu tide ( Trulicity ), Lixisena tide ( Adlyxin )
GIVEN BY SQ INJECTION
MOA: Lowers glucose by slowing gastric emptying, inhibits glucagon, suppresses appetite, & stimulates glucose-dependent release of insulin.
Contraindications: Contraindicated in patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2. Avoid use in patient with renal dysfunction or who have undergone renal transplant. Should be used with caution in pregnancy; benefits should clearly outweigh risks. May cause pancreatitis; therefore, monitoring of amylase and lipase is warranted, & use with caution in patients with a history of pancreatitis.
- Be able to calculate the total daily dose of insulin based on weight.
Calculate with the lowest possible dose unless otherwise specified. (p.
Initial dosages:
Type 1 DM: 0.5-0.6 units/kg/day
Increase insulin: High carb diet, infection, stress, obesity, adolescent growth spurt, & pregnancy after 1 st^ trimester.
Decrease insulin: Missed meal or low carb diet, exercise, & 1st^ trimester of pregnancy.
- Be familiar with frequency of Hgb A1C monitoring timeline. (p. 400)
*Hgb A1c provides an index of average glucose levels over the prior 2-3 months.
A1c should be measured every 3 months until the value drops to 7% & at least every 6 months thereafter.
- Know when to start insulin.
***** Start on all type 1 DM patients. *Drug of choice for gestational diabetes.
The ADA recommends initiation of basal insulin at 10 units/day or 0.1–0.2 units/kg/day, adjusted by 10– 15% or 2–4 units once or twice weekly to reach a target fasting plasma glucose (FPG) in patients whose A1c remains uncontrolled after >3 months of triple combination therapy ( Step 3 ) or patients with an A1c >10%.
With a fasting glucose level >300 or markedly symptomatic, start insulin therapy right away.
- Know how insulin is mixed (combination and amount) when Total
Daily Dose (TDD) iscalculated. (p. 404)
Mixing should be done only with insulins of proven compatibility. Of the 3 longer-acting insulins in current use, only NPH insulin is appropriate for mixing with short-acting insulins (regular, lispro, aspart, & glulisine insulins).
When a mixture is prepared, the short-acting insulin should be drawn into the syringe first to avoid contaminating the stock vial of the short acting insulin with NPH insulin.
- Know what type of insulin and how much is needed according to carbohydrate intake.
Total daily insulin dose (TDD) calculation includes basal insulin replacement & bolus insulin replacement. Basal insulin replacement encompasses approximately 50% of the total daily insulin dose which replaces insulin from fasting (overnight) & between meals. This dose is usually constant. Bolus insulin replacement encompasses approximately 50% of the total daily insulin dose & provides carbohydrate coverage & high blood sugar correction. The bolus dose for carbohydrate or food coverage is prescribed as an insulin to carbohydrate ratio, which represents how many grams of carbohydrate are covered or disposed of by 1 unit of insulin.
For example, the total daily dose (TDD) of insulin can be calculated by taking the total weight of the patient's weight in kilograms (kg) multiplied by 0.6 units. This means half of the TDD is the basal insulin dose of glargine (Lantus) (50%) & the other half is the rapid-acting bolus/mealtime insulin (50%). The mealtime carbohydrate-to-insulin dose is calculated using the 450-rule for regular insulin and the 500-rule for rapid-acting insulin; thus 500 is divided by the TDD insulin, then rounded to the nearest unit. The carbohydrate-to-insulin ratio is 1: “that number”. If the meal is x grams of carbohydrates, x is divided by “that number”, which equals the number of units of rapid-acting insulin for carbohydrate coverage.
- SABA therapy is evaluated through breath sounds assessment.
- Exercise-induced bronchospasm and the routine use of SABAs are markers of inadequate asthma control. - Be familiar with step therapy and asthma treatment so you know when which
medication would be appropriate for which type of asthma. (pp. 576-577)
-Know the description of each type or degree of asthma. (pp. 574-575)
Chronic Asthma has 4 Classes of Increasing Severity: ( based on Impairment & Risk )
Intermittent :
Symptoms= 2 days/week or less. Nighttime awakenings= none (2 times/month or less for 5 y.o. & up). SABA use= 2 days/week or less. Effect on activity= none.
Risk for exacerbations requiring systemic glucocorticoids= 0-1 time/year. ( STEP 1 )
( STEP 2 )
Moderate persistent: Symptoms= daily Nighttime awakenings= 3-4 times/month (more than once/week but less than nightly for 5 y.o. & up). SABA use= daily.
Effect on activity= some activity limitation. Risk for exacerbations requiring systemic glucocorticoids= increased frequency & intensity of exacerbations or wheezing. ( STEP 3 )
Severe persistent:
Symptoms= several times daily Nighttime awakenings= more than once/week (often nightly for 5 y.o. & up). SABA use= several times a day
Effect on activity= severe activity limitation.
Risk for exacerbations requiring systemic glucocorticoids= even greater increased frequency & intensity of exacerbations or wheezing.
0-4 y.o ( STEP 3 ), 5-11 y.o. ( STEP 3 OR 4 ), 12 y.o. & up ( STEP 4 OR 5 )
- Be familiar with examples of drug classes
(p. 560) Anti-inflammatory Drugs:
Glucocorticoids: USED TO CONTROL INFLAMMATION IN BOTH ASTHMA & COPD INHALED: Beclomethasone dipropionate ( QVAR ), Budesonide ( Pulmicort ), Fluticasone propionate ( Flovent HFA & Flovent Diskus )
ORAL: Methylprednisolone ( Medrol & Medrol Dose-Pak ), Prednisolone ( Orapred ), Prednisone ( Deltasone )
MOA: Decrease respiratory symptoms by suppressing inflammation, leading to reduced bronchial hyperreactivity & decreased airway mucus production.
Contraindications: Inhaled glucocorticoids are contraindicated for patients w/persistently positive sputum cultures for Candida albicans.
Leukotriene Receptor Antagonists: Montelukast ( Singulair ), Zafirlukast ( Accolate ), Zileuton ( Zyflo )
USED AS 2ND^ LINE THERAPY WHEN GLUCOCORTICOID CAN’T BE USED & AS ADD-ON THERAPY WHEN GLUCOCORTICOID ALONE IS INADEQUATE
MOA: Decrease bronchoconstriction & inflammatory responses such as edema & mucus secretion through suppressing the effects of leukotrienes (compounds that promote smooth muscle constriction, blood vessel permeability, & inflammatory responses through direct action as well as through recruitment of eosinophils & other inflammatory cells).
