Term
What are the hormones of the Anterior Pituitary? |
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Definition
1. Growth Hormone (GH) 2. Prolactin 3. Lutenizing Hormone (LH) 4. Follicle-Stimulating Hormone (FSH) 5. Thyroid-Stimulating Hormone (TSH) 6. Adrenocorticotropin (ACTH) |
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Term
What are the types of Feedback Loops? |
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Definition
-Long, short, ultrashort -Primary: target organ pathology (problem with Thyroid gland) -Secondary: pituitary Dz (unable to secrete TSH) -Tertiary: Hypothalmus problem |
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Term
What are the 5 types of Endocrine Axis? |
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Definition
1. Hypothalamic-Pituitary-GH Axis 2. Hypothalamic-Pituitary-Prolactin Axis 3. Hypothalamic-Pituitary-Thyroid Axis 4. Hypothalamic-Pituitary-Adrenal Axis 5. Hypothalamic-Pituitary-Reproductive Axis |
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Term
Discuss the Hypothalamic-Pituitary-GH Axis |
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Definition
-Regulates processes promoting growth -Regulators of GH secretion -GHRH enhances secretion -Somatostatin inhibits secretion -Ghrelin and GHRH act synergistically on GH release -GH stimulates IGF-1 secretion, which promotes bone growht -Ultimate target acts on liver at IGF-1 |
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Term
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Definition
-Growth Hormone Deficiency Tx MECH Stimulates release of IGF-1 from the liver DOSE: Usually dosing SC/IM 3X/WK. Depot injxn available monthly CLIN: Tx of GH deficiency in children (regardless of 1*, 2* or 3*) SE: Bone pain and edema |
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Term
What is Growth Hormone Excess? |
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Definition
-Results from somatotroph adenoma (pituitary tumor) -Gigantism: pediatric onset -Acromegaly: adult onset -Standard Tx involves surgical removal of tumor -Meds available |
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Term
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Definition
-GH Excess Tx: Somatostatin Analogues -MECH: Inhibits systemic release of insulin, glucagon, and gastrin. Constricts blood vessels. Reduces portal BP in bleeding varices PHARM-K: Half-Life longer than natural compound DOSE: SQ/IM 3X/Day. Depot injxn available monthly. Pt on drip fro emergency Tx of esophageal varices CLIN: Esophageal varices (most common), acromegaly, secretory diarrheas, vasoactive intestinal peptide SE: Nausea and decrease GI motility |
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Term
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Definition
-GH Excess Tx: GH Receptor Antagonists -MECH: Decreases IGF-1 levels -PHARM-K: Long Half-Life (6 days), Once daily SQ; routine monitoring of LFTs CLIN: Acromegaly (2nd-line therapy) SE: Nausea and diarrhea |
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Term
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Definition
-GH Excess Tx: Dopamine Agonists MECH: Acromegaly Pts have a paradoxical decrease in GH secretion CLIN: Adjunct Tx of acromegaly |
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Term
Discuss the Hypothalamic-Pituitary-Prolactin Axis |
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Definition
-Anterior pituitary gland produces and secretes prolactin -TRH enhances prolactin release -Hypothalamic release of dopamin inhibits lactotrophs - chronically suppressing prolactins -NOT regulated by negative feedback -Anything that causes a block of Dopamine release can cause a rise in prolactin levels |
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Term
Bromocriptine Pergolide Cabergoline |
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Definition
-Prolactin Excess Tx: Dopamine Receptor Agonists -MECH: Inhibits lactotroph cell growth -DOSE: PO -CLIN: Excess Prolactin -SE: N/V |
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Term
Discuss the Hypothalamic-Pituitary-Thyroid Axis |
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Definition
-Hypothalmus secretes TRH secretion/secretion of TSH/secretion of thyroid hormone from the thyroid gland -Thyroid Hormone negatively controls release of TRH and TSH |
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Term
Discuss the Hypothalamic-Pituitary-Adrenal Axis |
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Definition
-Hypothalamus secretes CRH - binds to corticotrophs of the anterior pituitary - release of ACTH - binds to ACTH receptors on the adrenal cortex - stimulates secretion of steroid hormones |
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Term
Discuss the Hypothalamic-Pituitary-Reproductive Axis |
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Definition
-Gonadotropin-releasing Hormone (GnRH) stimulates gonadotrophs to secrete two hormones: -Lutenizing Hormone (LH) -Follicle-stimulating hormone (FSH) -Gonadotrophins promote synthesis androgens and estrogens -Gonadotrophs are feedback-inhibited by testosterone and estrogen -Giving continuous GnRH will cause decreased production of sex hormones |
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Term
Leuprolide Goserelin Nafarelin Histrelin |
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Definition
-Excess Sex Hormone Tx: GnRH Receptor Agonists -MECH: Synthetic analogues which act as agonists at GnRH receptors. Continuous administration suppresses production of sex hormones PHARM-K: Gonadotroph suppression is transient DOSE: Most come as Depot injxn monthly or every 3 months CLIN: Prostate cancer, endometriosis, precocious puberty -Leuprolide/Goserelin: prostate cancer -Nafarelin: nasal spray used for endometriosis -Histrelin: SQ implant release over 1 year for advanced prostate cancer SE: hot flashes, bone pain, edema, and diminished libido |
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Term
What does the posterior pituitary gland secrete? |
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Definition
1. ADH - Plasma volume and osmolarity 2. Oxytocin - uterine contraction and lactation |
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Term
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Definition
-Antidiuretic hormone (produced in hypothalmus) -Increased osmolarity stimulates ADH secretion -Two types of receptors: 1. V1 receptors - cause vasoconstriciton 2. V2 receptors - cause increased H2O reabsorption in the collecting duct |
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Term
What occurs with an Excess secretion of ADH? |
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Definition
-Syndrome of inappropriate ADH (SIADH) -Stimulation of V1/V2 receptors leads to HTN and fluid retention; Edema and hyponatremia also occurs -Pt comes in and they are hyponatremic: SIADH, SSRI cna cause SIADH like syndrome; small cell lung cancer can also cause reduced Na -Tx: Fluid restriction is the main Tx modality; can also use salt tablets; can also use a Demeclocylcine to induce nephrogenic DI |
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Term
What occurs with a Decreased Respons to ADH? |
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Definition
-Diabetes Insipidus (DI): Two Types: 1. Neurogenic DI: inability of hypothalamus to synthesize or secrete ADH 2. Nephrogenic DI: inability of renal collecting duct cells to respond to ADH |
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Term
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Definition
-ADH Agonist -MECH: ADH analogue; Selectively stimulates V2 receptors -DOSE: oral, IV, SC, nasal spray -CLIN: neurogenic DI, Nocturnal enuresis -SE: hyponatremia |
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Term
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Definition
-ADH Antagonist -MECH: Conivaptan selective antagonist of vasopressin V1/V2 receptors; Tolvaptan selective for only V2 -CLIN: euvolemic or hypervolemic hyponatremia |
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Term
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Definition
-Oxytocin Agonist -MECH: Physiologic roles involve muscular contractions: Lactation, uterine contraction CLIN: used for labor induction and lactation |
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Term
What are the types of Thyroid cells? |
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Definition
1. Follicular: thyroxine (T4) converted to T3; T3 active form; reverse (rT3) inactive form 2. Parafollicular C Cells: calcitonin |
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Term
What are the types of Thyroid Dz? |
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Definition
-Disturbance of the hypothalamic-pituitary-thyroid axis -Increased or decreased thyroid hormone secretion -Grave's Dz vs Hashimoto's Thyroiditis |
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Term
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Definition
PATHOLOGY: Thyroid-stimulating immunoglobulin acts on TSH receptor. Stimulates release of thyroid hormone. Thyroid-stimulating immunoglobulin continues to stimulate thyroid fxn. -Hyperthyroidism occurs |
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Term
What is Hashimoto's Thyroiditis? |
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Definition
-PATHOLOGY: antibodies selectively destroy the thyroid gland. Gradual inflammatory destruction. Transient elevation (initial elevation) in thyroid hormone occurs early in the Dz then is followed by low thyroid hormone -Hyperthyroidism occurs |
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Term
Perchlorate Thiocynate Pertechnetate |
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Definition
-Hyperthyroidism Tx: Inhibitors of Iodide Uptake -MECH: Compete with iodide for reuptake (via Na+/I- symporter) into the thyroid follicular cell. Reduce the intrathyroidal supply of iodide available for synthesis of more thyroid hormone CLIN: Hyperthyroidism Tx SE: Aplastic anemia |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release -MECH: 131I is a radioactive iodide isotope. Concentrated radioactive iodide destroys the thyroid gland -CLIN: Alternative to Sx for hyperthyroidism SE: Tx commonly results in hypothyroidism |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release -MECH: Inhibits thyroid hormone synthesis and release -PHARM-K: negative feedback effect is reversible and transient meaning it is not useful for long term use -CLIN: Good for pre-op control of hyperthyroidism in thyroid gland Sx |
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Term
THIOAMINES: Propylthiouracil Methimazole |
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Definition
-Hyperthyroidism Tx: Inhibitors fo Organification and hormone release -MECH: Competes for oxidized iodide; selective decrease in thyroid hormone production. -Propythiouracil: inhibits thyroid peroxidase AND peripheral T4 to T3 conversion -Methimazole: Inhibits thyroid peroxidase -PHARM-K: Effects are not seen for several wks -CLIN: Propythiouracial: Hyperthyroidism in pregnancy (3X/day); Methimazole: Hyperthyroidism agent preferred overall (2X/Day) SE: Goiter formation, pruritic rash, arthralgias, agranulocytosis, hepatotoxicity, vasculitis |
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Term
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Definition
-Hyperthyroidism Tx: Inhibitors of Peripheral thyroid hormone metabolism -MECH: High thyroid hormone levels resemble B-adrenergic stimulation -CLIN: Provides symptomatic Tx of hyperthyroidism |
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Term
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Definition
-Hypothyroidism Tx -MECH: Replace missing endogenous thyroid hormone with exogenous thyroid hormone -DOSE: Large dosing range (25mcg-300mcg); Monitor TSH at 4-6 wks after initiation of dosage change -CLIN: Hypothyroidism -SE: Hyperthyroidism |
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Term
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Definition
-Hypothyroidism Tx -MECH: Replace missing endogenous thyroid hormone with exogenous thyroid hormone. Synthetic T3 -PHARM-K: Short half-life -CLIN: useful in myxedema coma (rare, life-threatening hypothyroidism) -SE: Hyperthyroid symptoms |
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Term
What is the role of the Adrenal Gland (Cortex)? |
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Definition
-Synthesizes and secretes steroid hormones -Salt balance -Intermediary metabolism -Androgenic actions (females) -3 classes of hormones: 1. Mineralocorticoids 2. Glucocorticoids 3. Androgens |
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Term
Discuss the Zona Glomerulosa |
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Definition
-HORMONE: Mineralocorticoids (aldosterone) -REGULATORY SYSTEM: Angiotensin II and plasma K+ -RECEPTORS: receptors confined to excretory organs (kidney, colon, salivary and sweat glands) |
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Term
Discuss the Zona fasiculata |
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Definition
-HORMONE: Glucocorticoids (cortisol) -ACTION: involved in normal metabolism and resistance to stress -REGULATORY SYSTEM: regulated by adrenocorticotropic hormone (ACTH) -RECEPTORS: receptors widely distributed throughout the body |
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Term
Discuss the Zona Reicularis |
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Definition
-HORMONE: Androgens (dihydroepiandesrosterone -DHA) -ACTION: Sex hormones -REGULATORY SYSTEM: Regulated by adrenocorticotropic hormone (ACTH) |
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Term
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Definition
-Glococorticoid -SYNTHESIS: From cholesterol -METABOLISM: Highly protein bound to CBG and albumin; Type I: found in liver, converts inactive cortisone back to cortisol; Type II: found in kidney; converts cortisol to inactive cortisone -RECEPTORS: Type I: (mineralocorticoid) expressed in organs of excretion; Type II: androgen (glucocorticoid) widely distributed -->Results in Metabolic and Anti-Inflammatory effects -REGULATION: Hypothalamic-Pituitary unit coordinates production. Hypothalamus produces and releases CRH and ACTH -NEGATIVE FEEDBACK REGULATION: High cortisol levels decrease synthesis and release of CRH and ACTH |
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Term
What occurs with Adrenal insufficiency? |
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Definition
-Addison's Dz (primary): Adrenal cortex destroyed via T cell-mediated AI rxn -Secondary Adrenal insufficiency: Hypothalamic or pituitary disorders. Hypothalamic-pituitary-adrenal (HPA) axis suppression -Can be life-threatening |
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Term
What occurs with Adrenal Excess? |
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Definition
-Cushing's Syndrome -Symptoms reflect amplification of the normal physiologic actions of glucocorticoids SE: HTN, fungal infxns, diabetes |
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Term
What are the effects of Glucocorticoids? |
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Definition
-Promote normal intermediary metabolism -Increase resistance to stress -Alters plasma blood cell composition -Anti-inflammatory action -Other endocrine effects -Other system effects |
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Term
What are the routes of administration for Glucocorticoids? |
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Definition
-Oral -IM -IV -Inhalation -Topical -Depot injxn |
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Term
What are the SE from Glucocorticoids? |
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Definition
-HTN, edema, osteoporosis, increased risk of infxn, peptic ulcers, glaucoma, increased appetite, emotional disturbances, hypokalemia, hirsutism |
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Term
What are the clinical uses of Glucocorticoids? |
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Definition
-Inflammation: COPD/asthma, acute gout, RA -Immunosuppression: Transplantation, AI disorders, Cushing's -Congenital Adrenal hyperplasia -Allergies -Lung maturation |
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Term
What is Glucocorticoid withdrawal? |
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Definition
-Abrupt removal of glucocorticoids causes an acute adrenal insufficiency syndrome. -Chronic glucocorticoid Tx must be tapered down. |
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Term
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Definition
-Mineralocorticoid -SYNTHESIS: from cholesterol; enzymes expressed only in the zona glomerulosa -METABOLISM: Low binding affinity, short elimination half-life, extensive metabolism through the liver -REGULATION: -RAAS: stimulates aldosterone synthesis; Plasma K+ levels: increase aldosterone synthesis; ACTH |
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Term
What are the effects of Aldosterone Hypofxn? |
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Definition
-Decreased aldosterone synthesis -Addison's Dz (zona glomerulosa destruction) -Decreased renin production |
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Term
What are the effects of Aldosterone Hyperfxn? |
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Definition
-Bilateral zona glomerulosa adrenal hyperplasia -Aldosterone-producing adenoma |
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Term
What are the effects of Mineralocorticoids? |
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Definition
-Help control the body's water volume -Help control electrolytes -Increase reabsorption of Na+, HCO3-, H2O -Decrease reabsorption of K+ and H+ ion |
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Term
What are the clinical uses of Mineralocorticoids? |
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Definition
-Adrenal insufficiency: cortisol stem test shows a pt in the trauma unit has adrenal insufficiency - typically treated by hydrocortisone -Orthostatic hypotension |
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Term
Dehydroepiandrosterone (seriously?) |
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Definition
-Androgen -MECH: Prohormone that is converted to more potent androgens (testosterone) -CLIN: Source of testosterone for females, useful in hypoaldosteronism, chronic fatigue syndrome |
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Term
Aminoglutethimide Ketoconazole Metyrapone Trilostane |
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Definition
-Inhibitors of Hormone Synthesis -Aminogluthimide: inhibits side-chain cleavage enzyme and aromatase -Ketoconazole: Antifungal which inhibits fungal P450 enzymes. Enzymes that mediate adrenal and gonadal synthesis. Inhibits side-chain cleavage enzyme. Broadly inhibits adrenocortical hormone synthesis -Metyrapone: Inhibits 11B-hydroxylation --> Impaired cortisol synthesis. Useful to test for ACTH reserve -Trilostane: Inhibits 3B-hydroxysteriod dehydrogenase. Reduced aldosterone and cortisol production |
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Term
What are the Tx goals of Type I DM? |
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Definition
-Must rely on exogneous insulin -Maintain glucose level as close to normal as possible -Use long acting insulin throughout the day then use short term for meal time -Avoid diabetic ketoacidosis (DKA) |
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Term
What are the Tx goals of Type II DM? |
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Definition
-Maintain blood glucose concentrations within normal limits -Prevent development of long-term complications -Wt loss, exercise, and dietary changes decrease insulin resistance |
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Term
What is the progression of Type II DM? |
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Definition
-3 labs: 1. Fasting (12 hrs): >126 is diagnostic 2. Random (pt comes in off street): >200 is diagnostic 3. A1C: >7 is diagnostic |
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Term
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Definition
-Measures the glycosylation of RBCs (which occurs at a rate proportional to blood glucose levels) -Estimates average blood glucose over 3-4 mths. -RBC life span is 120 days |
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Term
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Definition
-DOSE: Pt dependent; avoid insulin stacking by Lispro -PHARM-K: inactivated by insulin protease - kidney injury can cause hypoglycemia from O/D insulin -CLIN: only Tx for Type I DM or approved for gestational diabetes -SE: Site rxns, hypoglycemia, insulin stacking |
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Term
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Definition
-Alpha-glucosidase Inhibitors -MECH: bind to glucosidase enzymes - which are responsible for cleaving complex carbohydrates to make glucose. Increases the time required for the body to absorb carbohydrates. Only effective with meals. -PHARM-K: Acarbose is poorly absorbed; miglitol well absorbed (no systemic effects); no risk of hypoglycemia -CLIN: reduced postprandial blood glucose levels -SE: Abdominal pain, bloating, diarrhea -CONTRA: DKA, cirrhosis, IBD, bowel obstruction -OVERALL: Lowers A1c ~0.7-1.0% |
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Term
Glimepride Glipizide Glyburide |
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Definition
-Insulin Secretagogues: Sulfonylureas -MECH: Increases circulating levels of insulin. No B-cell fxn, won't work -PHARM-K: longer half-lives; active metabolits (except glipizide) -CLIN: First line therapy for newly Dx DM II -SE: Hypoglycemia, dizziness, nausea and diarrhea -CONTRA: DKA, avoid in renally impaired pts OVERALL: Lowers A1c ~1.0-2.0% |
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Term
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Definition
-Insulin Secretagogues: Meglitinides -MECH: If you have no B-cell fxn, won't work -PHARM-K: very short half-life; metabolized to inactive products -CLIN: N/A -SE: Hypoglycemia, dizziness, nausea and diarrhea -CONTRA: DKA, avoid in renally impaired pts -OVERALL: Lowers A1c ~1.0-2.0% |
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Term
Pioglitazone Rosiglitazone |
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Definition
-Insuline Sensitizers: Thiazolidinediones -MECH: Decreases levels of circulating insulin. You need to have insulin to make this work -PHARM-K: Metabolized via CYP450 enzymes. Increased LDL (rosi); increased HDL (both) -CLIN: N/A -SE: hepatotoxicity (monitor LFTs twice/year), edema, worsening HF -CONTRA: NYHA class III/I, or any symptomatic HF; Rosi has risk of MI -OVERALL: Lowers A1c~ 1.0-1.25% |
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Term
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Definition
-Insuline Sensitizers: Bignuanides -MECH: Inhibits hepatic gluconeogenesis and glycogenolysis; Doesn't promote insulin secretion - it is an insulin synthesizer. Because is doesn't cause insulin release, it doesn't matter if you're eating or not -PHARM-K: Well absorbed; not metabolized; excreted in urine; associated with wt loss -CLIN: Commonly used as 1st-line or as part of an escalating therapy -SE: diarrhea, N/V, lactic acidosis -CONTRA: HF, EtOH abuse, renal Dz/impairment -OVERALL: Lowers A1c ~1.5% |
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Term
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Definition
-Dipeptidyl Peptidase: IV inhibitors -MECH: Increased insuline release in response to meals and reduces inappropriate glucagon secretion -PHARM-K: excreted in the urine -CLIN: N/A -SE: Hypoglycemia, HA, Nausea, diarrhea, pancreatitis; does not alter wt -CONTRA: Type I DM, DKA -OVERALL: Lowers A1c ~0.5-0.8% |
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Term
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Definition
-Amylin Analog -MECH: Delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety -ADMIN: SubQ injxn (immediately prior to meals) -CLIN: Adjunct to mealtime insulin in Type I and II DM -SE: Hypoglycemia, N/V -CONTRA: gastroperesis, avoid in pts who cannot recognize and manage hypoglycemia -OVERALL: Lowers Ac1 ~0.5% |
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Term
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Definition
-GLP-1 Agonist -MECH: Slows gastric emptying, decreases postprandial glucagon secretion, promotes B-cell proliferation, decreases appetite -CLIN: N/A -ADMIN: SubQ injxn only, short duration -SE: wt loss, hypoglycemia, N/V/diarrhea, HA -CONTRA: Type I DM, DKA -OVERALL: Lowers Ac1 ~0.5-1.0% |
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Term
What are Dr. Carr's Tx recommendations? |
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Definition
-Try to max out the meds that the pts are on first -Type II DM: 1. Start with one of the Sulfonylureas or metformin 2. Pioglitazone next 3. Sitagliptin next 4. Pramlintide or Exenatide next 5. If it is a post-prandial problem, add Acarbose -If you have a pt with A1c of 10, start with the drug that effects the A1c the most |
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