Glucocorticoids Flashcards
(26 cards)
Glucocorticoids
- steroid hormones produced in the adrenal cortex
- influence carbohydrate metabolism and other processes
Glucocorticoids: Pharmacologic Effects
- occur at high levels of glucocorticoids
- achieved when administered in large doses required to treat disorders unrelated to adrenocortical function (allergic reactions, asthma, inflammation, cancer)
- can also be reached when production of endogenous glucocorticoids is excessive, as occurs in Cushing’s disease
Glucocorticoids: Physiologic Effects
- carbohydrate metabolism
- protein metabolism
- fat metabolism
- cardiovascular system
- skeletal muscle
- CNS
- Stress
- Respiratory distress in neonates
- renal processing of sodium, potassium, and hydrogen
Glucocorticoids: Carb metabolism
promotes glucose availability in 4 ways:
1. stimulation of gluconeogenesis
2. reduction of peripheral glucose utilization
3. inhibition of glucose uptake by muscle and adipose tissue
4. promotion of glucose storage in the form of hydrogen
Glucocorticoids: Protein metabolism
- opposite action to insulin
- provide amino acids for glucose synthesis
- if present at high levels for a prolonged time, glucocorticoids will cause muscle wasting, thinning of skin, and negative nitrogen balance
Glucocorticoids: Fat metabolism
- promote lypolysis
- when present at high levels for extended periods (Cushing’s syndrome), glucocorticoids cause fat redistribution, giving patient a potbelly, moon face, and buffalo hump
Glucocorticoids: Cardiovascular system
- Required to maintain functional integrity of vascular system
- When levels are depressed, capillary permeability is increased, the ability of vessels to constrict is reduced, and BP falls
- Multiple effects on blood cells - increase RBC and hemoglobin, polymorphonuclear leukocytes increase; counts of lymphocytes, eosinophils, basophils, and monocytes decrease
Glucocorticoids: Skeletal muscle
- support function of striated muscle, primarily by maintaining circulatory competence.
- in the absence of sufficient levels of glucocorticoids, muscle perfusion decreases, causing capacity to decrease as well
Glucocorticoids: CNS
- Affect mood, CNS excitability and the electroencephalogram
- Insufficiency associated with depression, lethargy, and irritability; rarely, psychosis occurs
- When present in excess, can produce generalized excitation and euphoria
Glucocorticoids: Stress
- Working together, glucocorticoids and epinephrine serve to maintain blood pressure and blood glucose content.
- If glucocorticoid levels are inadequate, hypotension and hypoglycemia can occur.
- If the stress is extreme (e.g., trauma, surgery, severe infection), glucocorticoid deficiency can result in circulatory collapse and death.
Glucocorticoids: Respiratory Depression 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
- Betamethasone or dexamethasone commonly used - injected 24h before baby’s birth
mineralocorticoids - aldosterone - physiologic effects
- promotes sodium and potassium hemostasis and helps maintain intravascular volume
- harmful CV effects at high levels
Aldosterone: adverse CV effects
- promotion of myocardial remodelling - impair pumping
- promotion of myocardial fibrosis - risk for dysrhythmia
- activation of SNS and suppression of NE - risk for dysrhythmia and ischemia
- promotion of vascular fibrosis - decrease atrial compliance
Adrenal hormone excess causes ____ syndrome
Cushing’s
Cushing’s Syndrome: Causes
- hyper-secretion of ACTH by pituitary due to adenoma
- hyper-secretion of glucocorticoids by adrenal adenomas and carcinomas
- administration of glucocorticoids in large doses used to treat arthritis and other non-endocrine disorders
Cushing’s Syndrome: Treatment
- for adrenal adenoma and carcinoma: surgical removal of adrenal gland; replacement with gluco- and mineralicorticoids needed
- inoperable carcinoma: anticancer drug that produces selective destruction of adrenocortical cells (mitotane)
- pituitary adenoma: partial removal of pituitary gland lowers ACTH to safe levels; alternative is pituitary radiation
- drug therapy: limited. only employed as adjunct to radiation and surgery; most effective drug = ketoconazole - antifungal drug that blocks glucocorticoid synthesis; can cause significant liver dysfunction
Adrenal hormone insufficiency causes ____ disease
Addisons
Addison’s Disease: Causes
- most caused by autoimmune destruction of adrenal tissue
- tuberculosis and other infections
- adrenal hemorrhage
- cancers
- certain drugs (ketoconazole, rifampin)
Addison’s Disease: Treatment
- replacement therapy with adrenocorticoids required
- hydrocortisone drug of choice
- if additional mineralicorticoid activity needed, fludrocortisone is the only mineralicorticoid available which can be added to the regimen
Hydrocortisone: Therapeutic Use
Endocrine Applications
- Replacement therapy for adrenocortical insufficiency; has mineralocorticoid actions and may suffice as sole therapy for adrenal insufficiency, even when salt loss is a sx
Nonendocrine Applications
- broad spectrum: allergic reactions to inflammation to cancer
- doses required significantly higher
Hydrocortisone: Adverse Effects
When given in low doses for replacement therapy:
- devoid of adverse effects
Large doses for nonendocrine disorders
- highly toxic
- adrenal suppression
- promotion of Cushing’s syndrome
Hydrocortisone: Care planning
- take whole dose PO in morning, immediately after waking
- if fatigued in afternoon, split dose - take 2/3 in morning, and 1/3 around 4:00PM
Fludrocortisone: Overview & Therapeutic Use
- Potent mineralocorticoid that also possesses significant glucocorticoid activity
- Preferred drug for treating adrenal insufficiency, primary hypoaldosteronism, and CAH even when salt wasting occurs
- Must be used in combination with glucocorticoid in most cases
Fludrocortisone: Adverse Effects
high doses: salt and water retained in excess, while amounts of potassium are lost; results in:
- expansion of blood volume
- hypertension
- edema
- cardiac enlargement
- hypokalemia