AntiInflam Corticosteroid, Neoplasia Flashcards Preview

Disease & Defense - Unit 1 > AntiInflam Corticosteroid, Neoplasia > Flashcards

Flashcards in AntiInflam Corticosteroid, Neoplasia Deck (16)
Loading flashcards...
1

Describe the regulation of glucocorticoid secretion by the hypothalamic-pituitary-adrenal gland axis.

Diurnal rhythm of basal steroidogenesis, entrained by higher neuronal centers that release CRH in response to sleep-wake cycles. CRH stimulates ACTH release from pituitary which stimulates adrenal gland synthesis and release of cortisol.Negative feedback regulation by circulating corticosteroids (both endogenous hormones and exogenous agents used in therapy) at the hypothalamus and pituitary decreases ACTH release and steroidogenesis. NOTE: Chronic use of pharmacologic doses of glucocorticoids can suppress the HPA axis and result in adrenal atrophy and insufficient adrenal response to environmental stressors (known as an adrenal crisis). Marked increases in steroidogenesis in response to stress (injury, hemorrhage, severe infection, major surgery, hypoglycemia, cold, pain, and fear) can override negative feedback. Complex interactions between glucocorticoids and immune system may also have physiological role.

2

Describe the metabolic effects of glucocorticoids and explain how these effects can result in serious adverse conditions.

Adrenal crisis, hyperglycemia-diabetes like states, tissue breakdown and muscle wasting, atrophy of skin and connective tissue, centripetal obesity.Mineralocortocoid effects: increased absorption of Na, more secretion of H+ and K+, hypertension, edema, hypokalemia, metabolic acidosis

3

Explain the rationale for alternate day therapy and the necessity for slow withdrawal following chronic therapy with glucocorticoids.

Alternate day schedule can minimize adverse effects (lessens growth-suppressive effects because anti-inflammatory actions apparently outlast suppressive effect on HPA axis); make gradual transition to alternate day schedule after control of disease achieved.Terminate administration gradually if taken longer than 7-10 to 28 days, otherwise may cause severe rebound of disease or symptoms of adrenal insufficiency (adrenal crisis).

4

What are glucocorticoids used for in general?

Glucocorticoids are used in inflammatory-type disorders including: allergic reactions, collagen-vascular problems, eye diseases, GI diseases, hematologic disorders, neurologic disorders, pulmonary diseases, skin diseases, hypercalcemia, and mountain sickness

5

What is the mechanism of action for glucocorticoids?

Glucocorticoids act by suppressing T-cell activation, suppressing cytokine production, and preventing mast cells and eosinophils from releasing various chemical mediators of inflammation [histamine, prostaglandins, leukotrienes and other substances] that cause tissue damage, vasodilation and edema.

6

Hydrocortisone:Other nameUseMetabolic activation/inactivation, topical?Dosing considerations/formulationsAnti-inflammatory: Na+ retaining ratioRoutes of administration 

CortisolCommon in replacement therapy, emergenciesAlready active, yes can be used topically20mg1:1Oral, injectable, topical

7

What are some other dosage forms of glucocorticoids/

Other dosage forms include oral, topical, inhalants, opthalmic, intra-articular, enemas, and nasal sprays.

8

Review key concepts of normal cell growth and differentiation control

Active cell growth is a hallmark of normal development (morphogenesis), which starts with a single cell and ends with a complex multicellular organism, with highly specialized tissues functioning in an integrated manner. From the standpoint of individual cells, normal development is a highly dynamic process during which cells proliferate (increase in number), migrate, differentiate, change their relationship to neighboring cells, and undergo programmed cell death (apoptosis). All of these changes follow a precise program and are under tight regulatory control.

9

Define hypertrophy, hyperplasia, metaplasia, dysplasia, neoplasia, tumor.

Hypertrophy – increase in cell size, usually in response to some stimulus; can be physiologic (eg: pregnant uterus) or pathologic (eg: hypertensive cardiac hypertrophy)Hyperplasia – increase in cell number, often in response to some stimulus; can be physiologic (breast during puberty/pregnancy) or pathologic (endometrium); may predispose to neoplasiaMetaplasia -- change from one benign, differentiated cell type to another, usually in response to injury (eg: inflammation); may predispose to neoplasiaDysplasia - “Disordered growth”, In epithelia, hallmark of early premaligant neoplasia. Loss of cytologic uniformity, Loss of normal histologic maturation, Loss of architectural orientationNeoplasia – autonomous, progressive cell growth, involving clonal cell populationTumor – original meaning from Latin is “swelling”; however, in common usage, generally synonymous with neoplasm

10

Define and differentiate benign and malignant neoplasia.

Biologically benign (non-invasive, non-metastatic) neoplasms may remain such (benign), or may progress to malignant (invasive, metastatic) neoplasms. Malignant neoplasia is synonymous with “cancer”. A hallmark of malignant neoplasia is tumor “progression”, corresponding to the acquisition of additional genetic mutations and phenotypic traits, including the ability to invade surrounding tissue and vasculature, and “seed” distant organs (metastasis).

11

Discuss key general concepts related to malignant neoplasia (cancer)-Etiology-Epidemiology-Biology

Etiology: They include age (the longer you live, the greater the chance for a cancer-initiating event in one of your cells), lifestyle/ environmental exposures (eg: alcohol, tobacco), occupational hazards (eg: asbestos), radiation (eg: sunlight exposure), infectious agents (eg: Human Papilloma Virus), chonic inflammation (eg: inflammatory bowel disease) and genetics (inherited cancer predisposing mutations).Epidemiology: 1 in 5 Americans will die of cancerBiology: As discussed above in neoplasia, cancer cells activate growth-promoting oncogenes and inactivate growth-inhibitory tumor suppressor genes, often in combination. Mechanisms of such activation/inactivation include genetic mutation, gene copy amplification or deletion, promoter methylation (this silences gene expression) and chromosomal translocations that either result in inappropriate expression of normal genes or create “neogenes” with oncogenic activity. Additional important hallmarks of cancer include limitless replicative potential and angiogenesis.

12

Prednisone:UseMetabolic activation/inactivation, topical?Dosing considerations/formulationsAnti-inflammatory: Na+ retaining ratioRoutes of administration

Steroid burst therapyNot Activated. Activated hepatially, thus cannot use topically5 mg4 : 0.3Oral

13

Methylprednisolone:UseMetabolic activation/inactivation, topical?Dosing considerations/formulationsAnti-inflammatory: Na+ retaining ratioRoutes of administration

Steroid burstActive, can use topically4 mg5:0Oral, injectable, topical

14

Dexamethasone:UseMetabolic activation/inactivation, topical?Dosing considerations/formulationsAnti-inflammatory: Na+ retaining ratioRoutes of administration

Cerebral edema, chemotherapy induced vomitingActive, topical OK0.75 mg30:0Oral, injectable, topical 

15

TriamcinocloneUseMetabolic activation/inactivation, topical?Dosing considerations/formulationsAnti-inflammatory: Na+ retaining ratioRoutes of administration

Potent systemic agentVery potent topically4 mg5:0Oral, injectable, topical 

16

Discuss TNM classification, stage and relationship to clinical outcome.

TNM is used for staging"T= the size of the tumor and whether it has invaded nearby tissueN= describes any lymph nodes involvedM= describes distant matastasisMeasures of T N and M are looked at collectively to stage a cancer.  Different scales are used for different types of cancer. No TNM classification is done for brain tumors. "staging" is used to determine prognosis