Pharmacology Chapter 15

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Cortisol

the main glucocorticoid secreted as part of the body's response to stress. ______________ is approximately 90% bound to plasma proteins, and this high degree of protein binding slows _____________ movement out of the plasma, so that it has a relatively long plasma half-life of 60 to 90 minutes. ________________ accounts for at least 95% of glucocorticoid activity; corticosterone and cortisone accounts for a small amount of activity.

Negative feedback mechanism

when the output of a system affects the stimulus for the system (e.g., hormone secretion produces an affect that shuts off the stimulus for further hormone secretion).

prednisone

- is now considered an intermediate acting corticosteroid, to be the prototype corticosteroid.

Inhibiting arachidonic acid metabolism

- normally when a body cell is injured or activated by various stimuli, the enzyme phospholipase A2 causes the phospholipids in cell membranes to release arachidonic acid. Free arachidonic acid is then metabolized to produce proinflammatory prostaglandins and leukotrienes. At sites of tissue or inflammation, corticosteroids induce the synthesis of proteins that suppress the activation of phospholipase A2. This action, in turn, decreases the release of arachidonic acid and the formation of prostaglandins and leukotrienes.

Impairing phagocytosis

-Corticosteroids inhibit the ability of phagocytic cells to leave the bloodstream and move into the injured or inflamed tissue.

Impairing lymphocytes

-Corticosteroids inhibit the ability of these immune cells to increase in number and perform their functions.

Inhibiting tissue repair

-Corticosteroids inhibit the growth of new capillaries, fibroblasts, and collagen needed for tissue repair.

Crohn's disease

Corticosteroids are given for GI disorders, such as ulcerative colitis and regional enteritis (________________________).

idiopathic thrombocytopenic purpura

Corticosteroids are given for hematologic disorders, such as _________________________________________________________________ and acquired hemolytic anemia.

cirrhosis

Corticosteroids are given for hepatic disorders characterized by edema, such as ________________ and ascites.

Hodgkin's disease

Corticosteroids are given for neoplastic disease, such as acute and chronic leukemias, ___________________________, other lymphomas, and multiple myeloma.

myasthenia gravis

Corticosteroids are given for neurologic conditions, such as cerebral edema, brain tumor, acute spinal cord injury, and _________________________________.

chorioretinitis

Corticosteroids are given for ophthalmic disorders, such as optic neuritis, sympathetic ophthalmia, and ______________________.

grafts

Corticosteroids are given for organ or tissue transplants and ______________ (e.g., kidney, heart, bone marrow). Corticosteroids suppress cellular and humoral immune responses and help prevent rejection of transplanted tissue. Drug therapy is usually continued as long as the transplanted tissue is in place.

nephrotic

Corticosteroids are given for renal disorders characterized by edema, such as the _______________ syndrome.

rhinitis

Corticosteroids are given for respiratory disorders, such as asthma, status asthmaticus, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of nasal mucosa (_______________).

ankylosing spondylitis

Corticosteroids are given for rheumatic disorders, such as _________________________________, acute and chronic bursitis, acute gouty arthritis, rheumatoid arthritis, and osteoarthritis.

Addisonian crisis

Corticosteroids are given for shock. Corticosteroids are clearly indicated only for shock resulting from ______________________________ (also known as adrenal or adrenocortical insufficiency), which may mimic hypovolemic or septic shock. The use of corticosteroids in septic shock has been highly controversial, and randomized studies and meta-analysis have indicated that corticosteroids PAGE 279.

dermatoses

Corticosteroids are used to treat allergic or hypersensitivity disorders, such as allergic reactions to drugs, serum and blood transfusions, and ________________ with an allergic component.

proteins

Corticosteroids can increase or decrease the transcription of many genes to alter the synthesis of ________________. These _____________ regulate many physiologic effects, such as the transportation of ________________. Metabolic effects do not occur for at least 45 to 60 minutes because of the time required for protein synthesis. Several hours or days may be needed for full production of proteins.

periarteritis nodosa

Corticosteroids treat collagen disorders, such as systemic lupus erythematosus, scleroderma, and ______________________________________. Collagen is the basic structural protein of connective tissue, tendons, cartilage, and bone, and it is therefore present in almost all body tissues and organ systems. The collagen disorders are characterized by inflammation of various body tissues. Signs and symptoms depend on which body tissue or organs are affected and the severity of the inflammatory process.

herpes zoster

Dermatologic disorders that may be treated with systemic corticosteroids include acute contact dermatitis, erythema multiforme, _________________________ (prophylaxis of postherpetic neuralgia), lichen planus, pemphigus, skin rashes caused by drugs, and toxic epidermal necrolysis.

adrenocortical insufficiency

Endocrine disorders, such as _____________________________________________________ and congenital adrenal hyperplasia. Corticosteroids are given to replace or substitute for the natural hormones (both glucocorticoids and mineralocorticoids) in cases of insufficiency and to suppress corticotropin when excess secretion causes adrenal hyperplasia. These conditions are rare and account for a small percentage of corticosteroid use.

immunosuppressant

Inhibiting the production of interleukin-1, tumor necrosis factor, and other cytokines. This action also contributes to the anti-inflammatory and _______________________________ effects of corticosteroids.

hydrocortisone

People once viewed ___________________________________,a short-acting corticosteroid and an exogenous equivalent of endogenous cortisol, as the prototype corticosteroid drug.

Addison's disease

Primary adrenocortical insufficiency with inadequate production of cortisol and aldosterone.

adrenal cortex

The _________________________ secretes male (androgens) and female (estrogens and progesterone) sex hormones. Compared with the effect of hormones produced by the testes and ovaries, the adrenal sex hormones have an insignificant effect on normal body function.

adrenal cortex

The _____________________________ produces approximately 30 steroid hormones, which are divided into glucocorticoids, mineralocorticoids, and adrenal sex hormones. Chemically, all corticosteroids are derived from cholesterol and have similar chemical structures. However, despite their similarities, slight differences cause them to have different functions.

HPA

The administration of exogenous corticosteroids suppresses the _________ axis. As a result, secretion of corticotropin decreases, causing atrophy of the adrenal cortex and decreased production of endogenous adrenal corticosteroids.

sympathetic nervous system

The stress response activates the ______________________________________ to produce more epinephrine and norepinephrine and the adrenal cortex to produce as much as 10 times the normal amount of cortisol. The synergistic interaction of these hormones increases the person's ability to respond to stress. However, the increased ________________________________________ activity continues to stimulate cortisol production (the main glucocorticoid secreted as part of the body's response to stress) and overrules the negative feedback mechanism. Excessive and prolonged corticosteroid secretion damages body tissues.

Strengthening or stabilizing biologic membranes

Two biologic membranes are especially important in inflammatory processes. Stabilization of cell membranes inhibits the release of arachidonic acid and production of prostaglandins and leukotrienes, as described above. Stabilization of lysosomal membranes inhibits release of bradykinin, histamine, enzymes, and perhaps other substances from lysosomes. (Lysosomes are intracellular structures that contain inflammatory chemical mediators and enzymes that destroy cellular debris and phagocytized pathogens.) This reduces capillary permeability and thus prevents leakage of fluid into the injured area and development of edema. It also reduces the chemicals that normally cause vasodilation and tissue irritation.

negative feedback mechanism

When plasma corticosteroid levels rise to an adequate level, secretion of corticosteroids slows or stops. The mechanism by which the hypothalamus and anterior pituitary "learn" that no more corticosteroids are needed is called a ______________________________________. This does not work during stress responses.

Congenital

__________________ adrenogenital syndromes and adrenal hyperplasia result from deficiencies in one or more enzymes required for cortisol production. Low plasma levels of cortisol lead to excessive corticotropin secretion, which then leads to excessive adrenal secretion of androgens and hyperplasia (abnormal increase in number of cells).

Exogenous

____________________ corticosteroids are used as drugs in a variety of disorders. Their use must be closely monitored, because they have profound therapeutic and adverse effects.

Plasma binding

_______________________ patients with serum albumin levels less than 3.5 g/dL are prone to increased effects of corticosteroids and symptoms of hypercorticism.

Corticosteroid

__________________________ secretion is controlled by the hypothalamus, the anterior pituitary, and the adrenal cortex (the hypothalamic-pituitary-adrenal, or HPA, axis). Various stimuli (e.g., low plasma levels of corticosteroids, pain, anxiety, trauma, illness, anesthesia) activate the system. These stimuli cause the hypothalamus of the brain to secrete corticotropin-releasing hormone or factor (known as CRH or CRF), which stimulates the anterior pituitary gland to secrete corticotropin, and corticotropin then stimulates the adrenal cortex to secrete corticosteroids.

Corticosteroids

___________________________ affect virtually every aspect of inflammatory and immune responses, they are used in the treatment of a broad spectrum of diseases with an inflammatory or immunologic component.

Protein binding

_______________________________ functions as a storage area from which the hormones are released and needed. This promotes more consistent blood levels and more uniform distribution to the tissues.

Hyperaldosteronism

______________________________________ is a rare disorder caused by adenoma ( a benign tissue from glandular tissue) or hyperplasia of the adrenal cortex cells that produce aldosterone. It is characterized by hypokalemia, hypernatremia, hypertension, thirst, and polyuria.

Secondary adrenocortical insufficiency

_______________________________________ produced by inadequate secretion of corticotropin, is most often caused by prolonged administration of corticosteroids. This condition is largely a glucocorticoid deficiency; mineralocorticoid secretion is not significantly impaired.

Adrenocortical hyperfunction

_______________________________________________ (Cushing's disease) may result from excessive corticotropin or a primary adrenal tumor. Adrenal tumors may be benign or malignant. Benign tumors often produce one corticosteroid normally secreted by the adrenal cortex, but malignant tumors often secrete several corticosteroids.

Androgen-producing tumors

_______________________________________________ of the adrenal cortex, which are usually benign, produce masculinizing effects.

Primary adrenocortical insufficiency

___________________________________________________ (Addison's disease) is associated with destruction of the adrenal cortex by disorders such as tuberculosis, cancer, or hemorrhage; with atrophy of the adrenal cortex caused by autoimmune disease or prolonged administration of exogenous corticosteroids; and with surgical excision of the adrenal glands. In primary adrenocortical insufficiency, there is inadequate production of both cortisol and aldosterone.

Glucocorticoid

adrenal cortical hormone that protects the body against stress and affects protein and carbohydrate metabolism. _______________________s include cortisol, corticosterone, and cortisone. _____________________________s are produced cyclically, with the largest amount being produced in the early morning hours and the smallest amount being produced in the evening hours (in people with normal day-night schedules). At the cellular level, ____________________________s account for most of the characteristics and physiologic effects of the corticosteroids.

Cushing's disease

adrenocortical hyperfunction; may result from excessive corticotropin or primary adrenal tumor.

Addisonian crisis

condition that mimics hypovolemic and septic shock; also known as adrenocortical insufficiency.

Steroid

lipid-soluble hormone produced by the gonadal organs or the adrenal cortex.

Aldosterone

mineralocorticoid hormone secreted by the adrenal cortex to increase sodium reabsorption by the kidneys and indirectly regulate blood levels of potassium, sodium, and bicarbonate; also regulates pH, blood volume, and blood pressure. __________________ is only 60% bound to plasma proteins and has a short half life of 20 minutes. ________________________ is responsible for approximately 90% of mineralocorticoid activity.

Mineralocorticoid

steroid hormone released by the adrenal cortex to promote sodium and water retention and potassium excretion.

Corticosteroid

steroid hormones produced by the adrenal cortex; examples include androgens, glucocorticoids, and mineralocorticoids. Disease results from inadequate or excessive secretion. _________________________ are secreted directly into the bloodstream.

Immunosuppression

suppression of the immune system.

androgens

Adrenal ____________________, secreted continuously in small quantities by both sexes, are responsible for most of the physiologic efforts exerted by the adrenal sex hormones. They increase protein synthesis (anabolism), which increases the mass and strength of muscle and bone tissue; they affect development of male secondary sex characteristics; and they increase hair growth and libido in women. Excessive secretion of adrenal __________________ in women causes masculinizing effects (e.g., hirsutism, acne, breast atrophy, deepening of the voice, amenorrhea). Female sex hormones are secreted in small amounts and normally exert few physiologic effects. Excessive secretion may produce feminizing effects in men (e.g., breast enlargement, decreased hair growth, voice changes).


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