Pharm Lecture 6 Red Stuff

Glucocorticoids: Physiologic Effects---Carbohydrate Metabolism

***Supplying the brain with glucose is essential for survival.*** •They promote glucose availability in four ways: (1) stimulation of gluconeogenesis, (2) reduction of peripheral glucose utilization, (3) inhibition of glucose uptake by muscle and adipose tissue, and (4) promotion of glucose storage (in the form of glycogen). •Increase glucose availability during fasting and thus help ensure that the brain will not be deprived of its primary source of energy. •Opposite to the effect of insulin. •When present chronically in high concentrations, glucocorticoids produce symptoms like diabetes.

Spironolactone: Potassium-Sparing Diuretics for Primary Hyperaldosteronism AE

***hyperkalemia others not red: endocrine effects: gynecomastia, menstrual irregularities, impotence, hirsutism, and deepening of the voice; benign adenomas of the thyroid and testes, malignant mammary tumors, and proliferative changes in the liver in higher dose

Mineralocorticoids: Aldosterone--Renal Actions

***•Acts on the collecting ducts of the nephron to promote sodium reabsorption in exchange for secretion of potassium and hydrogen. ***•As sodium is reabsorbed, water is reabsorbed along with it. •Aldosterone insufficiency causes hyponatremia, hyperkalemia, acidosis, cellular dehydration, and reduction of extracellular fluid volume. •Left uncorrected, the condition can lead to renal failure, circulatory collapse, and death.

Glucocorticoids: Physiologic Effects---Stress

***•In response to stress (e.g., anxiety, exercise, trauma, infection, surgery), the adrenal cortex secretes increased amounts of glucocorticoids, and the adrenal medulla secretes increased amounts of epinephrine. •Working together, glucocorticoids and epinephrine serve to maintain blood pressure and blood glucose content. •If the stress is extreme (e.g., trauma, surgery, severe infection), glucocorticoid deficiency can result in circulatory collapse and death.

Mineralocorticoids: Aldosterone---cardiovascular actions

***•When aldosterone levels are high, cardiovascular effects are harmful, increasing the risk of heart failure and hypertension. •Promotion of myocardial remodeling (which can impair pumping) •promotion of myocardial fibrosis (which increases the risk of dysrhythmias) •Activation of the sympathetic nervous system and suppression of norepinephrine uptake in the heart (both of which can promote dysrhythmias and ischemia) •promotion of vascular fibrosis (which decreases arterial compliance) •disruption of the baroreceptor reflex.

A patient with which condition would most likely be prescribed a glucocorticoid in low doses for replacement therapy? A.Addison's disease B.Rheumatoid arthritis C.Systemic lupus erythematosus D.Cushing's syndrome

A

The nurse teaches a patient with hypothalamic diabetes insipidus about desmopressin [DDAVP]. The nurse determines that the teaching was effective if the patient makes which statement? A."I should increase my fluid intake to prevent dehydration." B."The medication should be taken every day for 6 months." C."I can expect to urinate more often while taking this drug." D. "The medication can be taken by inhaling through my nose."

A

A patient takes levothyroxine [Synthroid] 0.75 mcg every day. It is most appropriate for the nurse to monitor which laboratory test to determine whether a dose adjustment is needed? A.Thyrotropin-releasing hormone (TRH) B.Thyroid-stimulating hormone (TSH) C.Serum free T4 test D.Serum iodine level

B

A patient with Cushing's syndrome is prescribed an antibiotic, ketoconazole [Nizoral] 600 mg/day, before an adrenalectomy. The patient asks the nurse why an antibiotic is needed. Which response by the nurse is best? A."The medication will prevent an abdominal infection after surgery." B."The medication will block the adrenal gland from producing steroids." C."You have a urinary tract infection that must be treated before surgery." D."It is essential to prevent skin infection in patients undergoing surgery."

B

A patient with a urinary creatinine clearance of 55 mL/min is prescribed desmopressin [DDAVP]. It is most important for the nurse to assess the patient for what? A.Irritability, muscle weakness, and back pain B.Drowsiness, listlessness, and headache C.Fever, tachycardia, and hypotension D.Decreased skin turgor, weight loss, and dry skin

B

The nurse cares for a patient with primary hypoaldosteronism who took excessive doses of fludrocortisone [Florinef]. It is most important for the nurse to assess the patient for what? • A.Increased urine output and bradycardia B.Muscle weakness and an irregular heartbeat C.Hypotension and poor skin turgor D.Weight loss and hyperactive reflexes

B

The nurse instructs a patient about taking levothyroxine [Synthroid]. Which statement by the patient indicates the teaching has been effective? A."To prevent an upset stomach, I will take the drug with food." B."If I have chest pain or insomnia, I should call my doctor." C."This medication can be taken with an antacid." D. "The drug should be taken before I go to bed at night."

B

A child with type 1 diabetes mellitus is diagnosed with growth hormone deficiency and is started on somatropin [Humatrope]. It is most appropriate for the nurse to monitor the child for which condition? A.Renal insufficiency B.Hypertension C.Hyperglycemia D.Hypothyroidism

C

Spironolactone: Potassium-Sparing Diuretics for Primary Hyperaldosteronism DD

Caution must be employed when combining with agents that raise potassium levels (i.e., potassium supplements, salt substitutes, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and direct renin inhibitors)

Dexamethasone AE

Central nervous system: Depression, emotional lability, euphoria, headache, increased intracranial pressure, insomnia, malaise, myasthenia, neuritis, neuropathy, paresthesia, personality changes, pseudotumor cerebri (usually following discontinuation), psychic disorder, seizure, vertigo Endocrine & metabolic: Adrenal suppression, carbohydrate intolerance, Cushing syndrome, decreased glucose tolerance, decreased serum potassium, diabetes mellitus, fluid retention, glycosuria, growth suppression (children), hirsutism, HPA-axis suppression, hyperglycemia, hypokalemic alkalosis, menstrual disease, moon face, negative nitrogen balance, protein catabolism, redistribution of body fat, sodium retention, weight gain peptic ulcer Infection myopathy osteoporosis Miscellaneous: Wound healing impairment

A patient with hyperthyroidism is taking propylthiouracil (PTU). It is most important for the nurse to assess the patient for which adverse effects? A.Gingival hyperplasia and dysphagia B.Dyspnea and a dry cough C.Blurred vision and nystagmus D. Fever and sore throat

D

The nurse teaches a patient with Addison's disease about hydrocortisone replacement therapy. Which statement, made by the patient, indicates that the teaching was effective? • A."I can expect my blood sugar levels to be high." B."If I become ill, the dose needs to be reduced." C."It's important to take the medication at bedtime." D."I should keep an emergency supply of this drug available at all times."

D

Glucocorticoids: Physiologic Effects

Occur at low levels of glucocorticoids

Propanolol in hyperthyroidism

In the absence of contraindications (e.g., asthma, heart failure), all patients should receive one immediately.

Hypothyroidism: Treatment

Replacement therapy: Levothyroxine (T4) & Liothyronine (T3): •levothyroxine (T4) alone or combined therapy with levothyroxine plus liothyronine (T3). •combined T3/T4 offers no advantage over T4 alone. Measurement of serum TSH is an important means of evaluation. •Successful replacement therapy causes elevated TSH levels to fall. However, TSH will not normalize quickly and often lags behind normalization of serum T3 and T4. Hence, evaluation should not be done until 6 to 8 weeks after starting treatment. Duration of Therapy: Lifelong therapy for most hypothyroid patients •Treatment provides symptomatic relief but does not produce cure.

Nonradioactive Iodine: Strong iodine solution (Lugol's solution) Therapeutic Use hyperthyroidism

as an adjunct therapy to suppress thyroid function in preparation for thyroidectomy and for treating thyrotoxic crisis .

Radioactive Iodine-131 (131I) hyperthyroidism tx

associated with a significant incidence of delayed hypothyroidism

Elevated TSH is an indicator of...

hypothyroidism the most sensitive method for diagnosing hypothyroidism because the anterior pituitary is exquisitely sensitive to changes in thyroid hormone levels. When replacement therapy is instituted, the TSH level should return to normal. Can distinguish primary hypothyroidism from secondary hypothyroidism. -In primary (thyroidal) hypothyroidism, TSH levels are high. However, in secondary hypothyroidism (hypothyroidism resulting from anterior pituitary dysfunction), TSH levels are low, normal, or even slightly elevated

Liothyronine (T3)

liothyronine may be used in situations that require speedy results, especially myxedema coma.

Pegvisomant Drug Interactions

opioid analgesics reduce the effect of pegvisomant

Prednisone AE

psychiatric disturbance (including euphoria, insomnia, mood swings, personality changes, severe depression) Endocrine & metabolic: Cushing's syndrome, decreased serum potassium, diabetes mellitus, fluid retention, growth suppression (children), hypokalemic alkalosis, hypothyroidism (enhanced), menstrual disease, negative nitrogen balance (due to protein catabolism), sodium retention peptic ulcer Infection Neuromuscular & skeletal: Amyotrophy, aseptic necrosis of bones (femoral and humeral heads), osteoporosis, pathological fracture (long bones), rupture of tendon (particularly Achilles tendon), steroid myopathy, vertebral compression fracture glaucoma Miscellaneous: Wound healing impairment

Glucocorticoids: Physiologic Effects---Central Nervous System

•Affect mood, central nervous system (CNS) excitability, and the electroencephalogram. ***•Glucocorticoid insufficiency is associated with depression, lethargy, and irritability. •When present in excess, glucocorticoids can produce generalized excitation and euphoria.

PTU Versus Methimazole: Current Role in Treating Hyperthyroidism.

•Because PTU is more toxic than methimazole and requires more daily doses, methimazole is preferred for most patients. However, there are three groups for whom PTU is preferred: •Pregnant women, but only during the first trimester. (Methimazole is preferred during the second and third trimesters.) •Patients experiencing thyroid storm. (Because PTU can block conversion of T4 to T3, it may be more effective than methimazole.) Patients who are intolerant of methimazole.

Hydrocortisone AE of chronically high-dose therapy

•Devoid of adverse effects in low dose •Adrenal suppression •Iatrogenic Cushing's Syndrome •Osteoporosis •Infection •Glucose Intolerance •Myopathy (muscle injury) •Fluid and electrolyte disturbance •Growth delay: suppress growth in children •Psychologic Disturbances •Mild reaction: insomnia, anxiety, agitation, or irritability. •Severe reaction (6%): delirium, hallucinations, depression, euphoria, or mania. Of these, up to one-third may become suicidal. •Cataracts and Glaucoma •Peptic Ulcer Disease by inhibiting prostaglandin synthesis

Dexamethasone indication

•Dexamethasone is used to diagnose adrenal dysfunction •Overnight dexamethasone test to diagnose Cushing's syndrome

Glucocorticoids: Physiologic Effects---Respiratory System in Neonates

•During labor and delivery, the adrenals of the full-term fetus release a burst of glucocorticoids. Within hours, these steroids act on the lungs to accelerate their maturation. •In the preterm infant, the adrenals produce only small amounts of glucocorticoids. As a result, preterm infants experience a high incidence of respiratory distress syndrome.

Growth Hormone preparation AE

•Hyperglycemia •GH is diabetogenic. When used in patients with pre-existing diabetes, significant hyperglycemia may result. •Glucose levels should be monitored, and insulin dosage should be adjusted •Neutralizing antibodies •Over the course of treatment, patients may develop neutralizing antibodies that bind with GH and thereby render the hormone inactive. If these antibodies develop, treatment with mecasermin may be effective. •Fatality in patients with Prader-Willi syndrome •Fatalities have occurred in PWS patients treated with GH. Major risk factors are severe obesity, upper airway obstruction, sleep apnea, and respiratory infection.

Growth Hormone preparation Drug Interactions

•Interaction with glucocorticoids •Glucocorticoids can oppose the growth-promoting effects of GH. •Glucocorticoid replacement doses must be carefully adjusted to avoid growth inhibition.

Hydrocortisone DD

•Interactions Related to Potassium Loss: digoxin and thiazide or loop diuretics •Nonsteroidal Anti-Inflammatory Drugs: same effects on the GI tract as do glucocorticoids •Insulin and oral hypoglycemics: patients with diabetes may require increased doses of insulin or another hypoglycemic agent. •Vaccines: glucocorticoids can decrease antibody responses to vaccines

Glucocorticoids: Physiologic Effects---Cardiovascular System

•Maintain the functional integrity of the vascular system. •When levels of glucocorticoids are depressed, capillary permeability is increased, the ability of vessels to constrict is reduced, and blood pressure falls. ****•Can increase RBC and Hb levels. Of the WBC, only counts of polymorphonuclear leukocytes increase. In contrast, counts of lymphocytes, eosinophils, basophils, and monocytes decrease.

Thyrotoxic Crisis (Thyroid Storm) Cause

•Patients with thyrotoxicosis who undergo significant stress (eg, surgery, illness) •Not triggered by a rise in thyroid hormones •Cannot be identified by laboratory testing

Somatropin [Humatrope, Nutropin, others] indications

•Pediatric growth hormone deficiency •Pediatric Non-Growth-Hormone-Deficient (NGHD) Short Stature. •Pediatric Short Stature Associated With Prader-Willi Syndrome. •Prader-Willi syndrome (PWS) is a complex genetic disorder characterized by short stature, mental impairment, incomplete sexual development, behavioral problems, low muscle tone, and the urge to eat constantly. •Growth Hormone Deficiency in Adults. •Other Uses. •pediatric growth failure associated with chronic renal insufficiency, cachexia or wasting in patients with AIDS, short-bowel syndrome, and short stature associated with Turner's syndrome or Noonan's syndrome

Glucocorticoids: Physiologic Effects---Fat Metabolism

•Promote lipolysis (fat breakdown). • When present at high levels for a long time, glucocorticoids cause fat redistribution, giving the patient a "potbelly," "moon face," and "buffalo hump" like Cushing's syndrome

Glucocorticoids: Physiologic Effects---Protein Metabolism

•Promote protein catabolism (breakdown) to provides amino acids for glucose synthesis. •If present at high levels for a prolonged time, glucocorticoids will cause muscle wasting, thinning of the skin, and negative nitrogen balance.

PTU Versus Methimazole: Contrasts With Methimazole.

•Propylthiouracil is much like methimazole, but with four significant differences: •First, and most important, PTU can cause severe liver injury, whereas methimazole does not. • Second, PTU has a shorter half-life than methimazole (90 minutes vs. 6 to 13 hours), and hence requires two or three daily doses rather than one. •Third, PTU crosses the placenta less readily than does methimazole and concentrations in breast milk are lower •Fourth, PTU blocks conversion of T4 to T3 in the periphery, whereas methimazole does not.

Propylthiouracil (PTU) AE

•Rash, nausea, arthralgia, headache, dizziness, and paresthesias. •Adverse effects Shared With Methimazole: agranulocytosis and hypothyroidism if the dosage is too high. •May harm the developing fetus and the breast-feeding infant. •Liver Injury.

Addison's disease (primary adrenocortical insufficiency) Treatment

•Replacement therapy with adrenocorticoids •Hydrocortisone is drug of choice •Both glucocorticoid and mineralocorticoid •If additional mineralocorticoid activity is needed, fludrocortisone can be added to the regimen.

Methimazole AE

•Should be avoided by women who are pregnant or breast-feeding. •neonatal hypothyroidism, goiter, and even congenital hypothyroidism. •The drug should be avoided during the first trimester. Use in the second and third trimesters is considered safe. •Methimazole therapy does not affect thyroid function or intellectual development in breast-fed infants with doses up to 20 mg daily •Agranulocytosis (reversable, most dangerous toxicity) •If agranulocytosis occurs, methimazole should be discontinued. Agranulocytosis will then reverse. •Treatment: granulocyte colony-stimulating factor (filgrastim [Neupogen])

Levothyroxine [Synthroid]

•Should be taken in the morning at least 30 to 60 minutes before breakfast since food reduces absorption.

Glucocorticoids: Physiologic Effects---Skeletal Muscle

•Support the function of striated muscle, primarily by maintaining circulatory competence. •Lack of sufficient levels of glucocorticoids can decrease muscle perfusion, causing work capacity to decrease as well.

Graves disease treatment

•Surgical removal of thyroid tissue •Destruction of thyroid tissue with radioactive iodine (preferred treatment for adults) •Suppression of thyroid hormone synthesis with an antithyroid drug (methimazole or propylthiouracil) (prefer treatment for younger patients) •Beta blockers (eg, propranolol) to suppress tachycardia •Nonradioactive iodine to inhibits synthesis and release of thyroid hormones.

Congenital adrenal hyperplasia

•The amounts of ACTH required for normalization are so large that synthesis of adrenal androgens becomes excessive.

In infants: Congenital hypothyroidism (infancy)

•Therapy strategy: Replacement therapy with thyroid hormones •Treatment should be initiated within a few days of birth to prevent abnormal physical and mental development.

Levothyroxine [Synthroid] Drug interactions

•To ensure adequate absorption of levothyroxine, patients should separate administration of levothyroxine and these drugs by 4 hours. •Warfarin: Levothyroxine accelerates the degradation of vitamin K-dependent clotting factors. So, effects of warfarin (an anticoagulant) are enhanced. •Catecholamines: Thyroid hormones increase cardiac responsiveness to catecholamines (epinephrine, dopamine, dobutamine), thereby increasing the risk of catecholamine-induced dysrhythmias. •Other: Levothyroxine can increase requirements for insulin and digoxin. When converting patients from a hypothyroid to a euthyroid state, dosages of insulin and digoxin may need to be increased.

Hypothyroidism during pregnancy

•To help ensure healthy fetal development, maternal hypothyroidism must be diagnosed and treated very early •Therapy strategy: If hypothyroidism is diagnosed, replacement therapy should begin immediately.

Thyrotoxic Crisis (Thyroid Storm) Treatment

•life threatening and requires immediate treatment •Treatments: •High doses of potassium iodide or strong iodine solution to suppress thyroid hormone release. •Methimazole to suppress thyroid hormone synthesis. •A beta blocker is given to reduce heart rate. •Additional measures: sedation, cooling, and use of glucocorticoids and IV fluids.

Adrenal Hormone Insufficiency---General therapeutic considerations:

•lifelong replacement therapy glucocorticoids (i.e., hydrocortisone, prednisone, and dexamethasone) in all patients •Some may require a mineralocorticoid (i.e., fludrocortisone) •Should mimic normal patterns of corticosteroid secretion •Since levels of glucocorticoids normally peak in the morning, the usual practice is to take the entire daily dose immediately after waking up. •An alternative is to divide the daily dose, give2/3 in the morning and 1/3 in the afternoon. •Mineralocorticoids can be administered once a day. •Doses of glucocorticoids and mineralocorticoids should approximate the amounts normally secreted by the adrenals. •When glucocorticoids are employed for replacement therapy, doses are much smaller than the doses employed for nonendocrine disorders. •Safety Alert: Dosage is increased in times of stress

Thyrotoxic Crisis (Thyroid Storm) S/S

•profound hyperthermia (105°F or even higher), severe tachycardia, restlessness, agitation, and tremor. Unconsciousness, coma, hypotension, and heart failure may ensue.

Methimazole (Therapeutic use: four applications in hyperthyroidism)

•used as the sole form of therapy for Graves' disease. •as an adjunct to radiation therapy until the effects of radiation become manifest. •suppress thyroid hormone synthesis in preparation for thyroid gland surgery (subtotal thyroidectomy). •patients experiencing thyrotoxic crisis