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123 Cards in this Set
- Front
- Back
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Zona gomerulosa
secretes: regulated by: receptors: |
secretes mineralocorticoids
regulated by angiotensin II and plasma potassium receptors confined to excretory organs (kidney, colon, salivary glands) |
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Zona fasiculata
secretes: involved in: regulated by: receptors: |
secretes glucocorticoids
involved in normal metabolism and resistance to stress regulated by ACTH receptors widely distributed throughout body |
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Zona reticularis
secretes: regulated by: |
secretes androgens (DHEA)
sex hormones regulated by ACTH |
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Cortisol
synthesized from: RLS: metabolism: |
endogenous glucocorticoid
synthesized from cholesterol cholesterol --> pregnenolone RLS -can generate mineralocorticoids, glucocorticoids, or androgens Metabolism: highly protein bound; liver and kidneys are primary sites of metabolism |
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Glucocorticoids
Type I Type II |
Type I: in the liver- converts cortisone back to cortisol
Type II: in the kidney converting cortisol into ainactive cortisone |
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Glucocorticoids have 2 types of receptors
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Type I (mineralocorticoid): expressed inorgans of excretion
Type II: widely distributed |
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Glucocorticoids
Dimerized hormone-receptor complex binds to GRES--> |
metabolic effects
anti-inflammatory effects |
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Glucocorticoids regulation:
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hypothalamic pituitary unit
corticotropin releasing hormone (CRH) Adrenocorticotropic hormone (ACTH --negative feedback- high cortisol levels decrease synthesis and release of CRH and ACTH |
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Glucocorticoid effects
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promote normal intermediary metabolism
increase resistance to stress alters plasma blood composition antiinflammatory other endocrine effects= inhibits ACTH release, inhibits glucocorticoid/TSH synthesis, activates GH synthesis Facilitates normal GF; high doses stimulate gastric acid; may influence mental status; chronic therapy can cause severe bone loss |
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Glucocorticoids potency
--minimal salt retaining effect; major antiinflammatory effect |
Betamethasone>Dexamethasone>Paramethasone>Triamcinolone/Methylprednisolone/Prednisolone>Hydrocortisone>Coritsone
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Glucocorticoids S/E
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osteoporosis; impaired wound healing; increased appetite; euphoria/depression; HTN; edema; peptic ulcers; glaucoma; hypokalemia; hirsutism
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Therapeutic uses for glucocorticoids
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inflammation (COPD/asthma; acute gout; RA)
immunosuppresion (transplantation/autoimmune disorders) cushing's syndrome congenital adrenal hyperplasia (deficiency in cortisol production) allergies lung maturation |
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Aldosterone
synthesized: regulation: |
Mineralocorticoids
synthesized from cholesterol- enzymes expressed inthe zona glomerulosa Regulation: RAAS; plasma K+ levels (increased K+ increases aldosterone synthesis); ACTH |
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Mineralcocorticoids effects
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help control body's water volume
help control electrolytes -increase reabsorption of Na+, bicarb, water -decrease reabsorption of K+ and H ion |
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Mineralocorticoids (2)
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Fludrocortisone
Deoxycorticosterone |
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Mineralocorticoids therapeutic uses
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adrenal insufficiency
orthostatic hypotension |
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Adrenal Androgens
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Dehydroepiandrosterone (DHEA)
prohormone that is converted to more potent androgens (testosterone) |
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DHEA uses
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Adrenal Androgen
-source of testosterone for females -hypoaldosteronism -chronic fatigue syndrome |
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Inhibitors of cortisol synthesis
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Aminoglutehimide
Ketoconazole Metyrapone Trilostane |
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Aminoglutethimide
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inhibitors of synthesis
-inhibits side chaine cleavage enzyme and aromatase |
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Ketoconazole
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inhibitors of synthesis
-antifungal which inhibits fungal P450 enzymes- enzymes that mediate adrenal and gonadal hormone synthesis -inhibits side chain cleavage enzyme -broadly inhibits adrenocortical hormone synthesis |
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Metyrapone
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inhibitors of synthesis
-inhibits 11B hydroxylation--> impaired cortisol syntehsis -useful test for ACTH reserve |
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Trilostane
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inhibitors of cortisol synthesis
-inhibits 3B hydroxysteroid dehydroggenase -reduced aldosterone and cortisol production |
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thyroid hormones regulate
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growth, metabolism, and energy expenditure
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Thyroid follicular cells concentrate iodide intracellular via
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Na+-iodide symport
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Iodide is oxidized by
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thyroid peroxidase--> couples on thyrogloulin
organification--> monoiodotyrosine and diodotyrosine MIT+DIT= 3 DIT+DIT= 3 |
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Thyroid gland stores large quantities of thyroid prohormone in the form of
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thyroglobulin
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Grave's Disease
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thyroid stimulating immunoglobulin acts on TSH receptor- stimulates release of thyroid hormone
thyroid stimulating immunoglobulin continues to stimulate thyroid function--> hyperthyroidism |
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Hashimoto's Thyroiditis
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antibodies selectively destroy the thyroid gland
gradual inflammatory destruction- transient elevation in thyroid hormone occurs early in the disease--> results in hypothyroidism |
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Hyperthyroidism Tx
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inhibitors of iodide uptake
inhibitors of organificatino and hormones release inhibitors of peripheral thyroid hormone metabolism (symptomatic tx) |
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Inhibitors of iodide uptake (3)
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Perchlorate
Thiocynate Pertechnetate |
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Perchlorate
Thiocynate Pertechnetate |
inhibitors of iodide uptake
-compete with iodide for reuptake via Na+/I- symporter into the thyroid follicular cell -reduce the intrathyroidal supply of iodide available for synthesis s/e APLASTIC ANEMIA |
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Inhibitors of organification and hormone release
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Iodides
Inorganic iodide Thioamines (Propylthiouracil, Methimazole) |
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Iodides
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inhibitors of organification and hormone release
131I- is a radioactive iodide isotope Follicular cell membranes cannot distinguish from normal iodide concentrated radioactive iodide destroys the thyroid gland -alternative to surgery/tx commonly results in hypothyroidism |
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Inorganic iodide
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inhibitors of organification and hormone release
inhibits thyroid hormone synthesis and release negative feedback effect is reversible and transient -not useful therapy long term -helpful prior to thyroid gland surgery |
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Thioamines
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Propylthiouracil
Methimazole inhibitors of organification and hormone release -competes for oxidized iodide--> selective decrease in thyroid hormone production -iodinated thioamines may also bind to thyroglobulin -effects are not seen for several weeks -tx often results in goiter -generally effective at controlling hyperthyroidism |
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Thioamines (2)
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Propylthiouracil
Methimazole |
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Propylthiouracil
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Thioamine
-inhibits thyroid peroxidase and peripheral T4 to T3 conversion -dosed 3x daily -preferred in pregnancy |
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Methimazole
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Thioamine
-inhibits thyroid peroxidase -dosed 2x daily -PREFERRED overall agent |
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S/E of thioamines (Propylthiouracil/Methimazole)
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pruiritic rash
arthralgias agranulocytosis hepatoxicity vasculitis |
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B blockers
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used in hyperthyroidism tx- inhibitors of peripheral thyroid hormone metabolism
high thyroid levels resemble B-adrenergic stimulation provides symptomatic tx |
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Levothyroxine (Synthroid)
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exogenous thryoid hormone
L isomer of T4 large dosing range monitor TSH at 4-6 wks after initiation or dosage change (q 6 months if stable) ADMINISTER ON AN EMPTY STOMACH |
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Liothyronine (Cytomel)
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Synthetic T3
short half life useful in myxedema coma |
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Somatroph
-stimulatory hypothalamic factors -inhibitory hypothalamic factors -pituitary hormones released -major target organ -target gland hormones |
-stimulatory hypothalamic factors: GHRH Ghrelin
-inhibitory hypothalamic factors: somatostatin -pituitary hormones released: GH -major target organ: liver -target gland hormones: insulin-like growth factor |
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Lactotroph
-stimulatory hypothalamic factors -inhibitory hypothalamic factors -pituitary hormones released -major target organ -target gland hormones |
-stimulatory hypothalamic factors: TRH
-inhibitory hypothalamic factors: dopamine, somatostatin -pituitary hormones released: Prolactin -major target organ: mammary glands -target gland hormones: None |
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Gonadotroph
-stimulatory hypothalamic factors -inhibitory hypothalamic factors -pituitary hormones released -major target organ -target gland hormones |
-stimulatory hypothalamic factors: GnRH
-inhibitory hypothalamic factors: none known -pituitary hormones released: LH and FSH -major target organ: Gonads -target gland hormones: estrogen, progesterone and testosterone |
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Thyrotroph
-stimulatory hypothalamic factors -inhibitory hypothalamic factors -pituitary hormones released -major target organ -target gland hormones |
-stimulatory hypothalamic factors: TRH
-inhibitory hypothalamic factors: somatostatin -pituitary hormones released: TSH -major target organ: Thyroid gland -target gland hormones: Tyroxine and triidothyronine |
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Corticotroph
-stimulatory hypothalamic factors -inhibitory hypothalamic factors -pituitary hormones released -major target organ -target gland hormones |
-stimulatory hypothalamic factors: CRH
-inhibitory hypothalamic factors: None known -pituitary hormones released: ACTH -major target organ: adrenal cortex -target gland hormones: cortisol, adrenal androgens |
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Somatropin
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Growth hormone deficiency treatment
-recombinant human growth hormone -stimulates release of IGF-1 from the liver- responsible for growth hormone like actions -usually dosing is SC/IM 3x weekly -S/E: edema; bone pain -uses: tx of GH deficiency in children |
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Somatostatin Analogs
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Sandostatin (Octreotide)
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Sandostatin (Octreotide)
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somatostatin analogue
-bind to SSTR2 and SSTR5--> suppresses GH, IGF-1, and TSH release -inhibits release of insulin, glucagon, and gastrin -vasoconstricts blood vessels, and reduces portal vessel pressure in bleeding varices -1/2 life long than natural compound -dosed SQ/IM 3x daily -SE: nausea and decreased GI motility -Uses: acromegaly, esophageal varices, secretory diarrheas, vasoactive intestinal peptide tumors, carcinoid tumor |
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GH receptor antagonist
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Pegvisomant (Somavert)
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Pegvisomant (Somavert)
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GH receptor antagonist
-recombinant GH receptor antagonist--> binds to GH receptors--> decreases IGF-1 levels -long half life 6 days -routine monitoring of LFTs -S/E: nausea and diarrhea -Uses: acromegaly (2nd line therapy) |
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Dopamine agonist
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Bromocriptine
Cabergolide Pergolide |
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Bromocriptine
Cabergolide Pergolide |
Dopamine agonist
-paradoxical decrease in GH secretion -used adjunctively for the tx of acromegaly ALSO tx excess prolactin -inhibits lactotroph cell growth -orally bioavailable -systemic actions result in side effects (nausea and vomiting) |
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Cortisol stimulation test use
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Cosyntropin
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GnRH receptor agonist
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excess sex hormone treatment
leuprolide (Eligard) Goserelin (Zoladex) Nafarelin (Synarel) Histrelin (Vantas or Supprelin LA) |
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Leuprolide (Eligard)
Goserelin (Zoladex) Nafarelin (Synarel) Histrelin (Vantas) GnRH receptor agonist |
synthetic analogues which act as agonist at GnRH receptors
continuous administration suppresses production of sex hormones -gonadotroph suppression is transient -depot injection--> once every 3 months -SE include hot flashes, bone pain, edema, diminished libido -Uses: prostate cancer, endometriosis, precocious puberty |
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2 types of ADH receptors
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V1 systemic arterioles--> vasoconstriction
V2 nephrone--> increase water reabsorption in the collecting duct |
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Desmopressin (DDAVP)
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-ADH analogue
-selectively stimulates V2 receptors (no HTN) -oral, IV, SC, nasal spray -S/E: hyponatremia -Uses: DI; nocturnal enuresis |
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Conivaptan (Vaprisol)
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Vasopressin antagonist
selective vasopressin V1 and V2 receptor antagonist Uses: euvolemic or hypervolemic hyponatremia |
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Pancreas
alpha- beta- gamma- |
alpha- glucagon
beta- insulin, amylin gamma- somatostatin |
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insulin is inactivated by
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insulin protease (found mainly in the liver and kidney)
--if admitted to hospital w/ kidney injury- take not- decreased clearance--> hypoglycemia |
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Ultrarapid-Acting Insulin
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Lispro
onset: 0.2-0.5 hours peak: 0.5-2 duration: 3-4 use for meals or acute hyperglycemia |
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Short-Acting Insulin Regular
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Regular
onset: 0.5-1 peak: 2-3 Duration: 6-8 |
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Short Acting Insulin
Semilente |
onset: 1-2
peak: 2-5 durationL 8-12 |
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NPH
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Intermediate acting insuline
onset: 1.3 peak: 4-10 duration: 16-24 provides basal and overnight coverage |
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Lente
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Intermediate acting insulin
onset: 1.5-3 peak: 7-15 duration: 16-24 |
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Ultralente
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long acting insulin
onset: 4-6 peak: 8-30 duration: 24-36 |
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Glargine
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long acting insulin
onset: 4-6 peak: none duration: 18-24 |
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Insulin secretagogues
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sulfonylureas
meglitinides |
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insulin sensitizers
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thiazolidinediones
biguanides |
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a-glucosidase inhibitors
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bind to glucosidase enzymes- which are responsible for cleaving complex carbs to make glucose- increase the time required for the body to abosrb carbohydrates
-ONLY effective w/ meals -reduce postprandial blood glucose levels -S/E: abdominal pain, bloating, diarrhea -contraindications: DKA, cirrhosis, IBD, bowel obstruction Overall effect lovers A1c 0.7-1% Acarbose (Precose) Miglitol (Glyset) |
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Acarbose (Precose)
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a-glucosidase inhibitor
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Miglitol (Glyset)
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a-glucosidase inhibitor
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Sulfonylureas (3)
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Glimerpride (Amaryl)
Glipizide (Glucotrol) Glyburide (Glynase) |
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Sulfonylureas
Glimerpride (Amaryl) Glipizide (Glucotrol) Glyburide (Glynase) |
stimulate the release of insulin from pancreatic B cells--> increase circulating levels of insulin- action dependent on function of pancreatic B cells
-S/E: hypoglycemia, dizziness, N&D -Contraindications: DKA; pts w/ renal impairment of those who cannot recognize hypoglycemia overall effect: lowers A1c 1-2% can use glipizide in kidney injury |
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Meglitinides (2)
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Nateglinide (Starlix)
Repaglinide (Prandin) |
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Meglitinides
Nateglinide (Starlix) Repaglinide (Prandin) |
bind to a distinct site on the sulfonylurea receptor of ATP-senstive potassium channels--> release of insulin
-action dependent on function pancreatic B cells -very short half life, rapid onset- take w/ meals -metabolized to inactive products CYP450 -S/E: hypoglycemia, dizziness, N&D -Contraindication: DKA; renal impairment Lowers A1c 1-2% |
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Thiazolidinediones (2)
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Pioglitazone (Actos)
Rosiglitazone (Avandia) |
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Thiazolidinediones
Pioglitazone (Actos) Rosiglitazone (Avandia) |
Target the peroxisome proliferator activated receptor gamma--> regulat adipocyte production and secretion of fatty acids, and glucose metabolism--> increased insulin sensitivity in adipose tissue, live, and skeletal muscle
-decreases levels of circulating insulin -CYP450, increases LDL, HDL; once daily dosing; no risk of hypoglycemia S/E: hepatotoxicity, edema, worsening of HF- contraindicated in class 3 or 4, or any symptomatic HF Lowers A1c 1-1.25 |
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Bignuanides
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increases glucose uptake and utilization--> decreased insulin resistance (increases insulin sensitivity)
-inhibits hepatic gluconeogensis and glycogenolysis -does not promote insulin secretion Metformin (Glucophage) |
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Bignuanides
Metformin SE: Contraindications: Overall effect: |
well absorbed; not metabolized; excreted in urine; associated w/ weight loss; no risk of hypoglycemia
SE: diarrhea, N&V, lactic acidosis Contraindications: HF; ETOH abuse; renal disease (SCr >1.5 males; >1/4 females) Overall effect lowers A1c 1.5% |
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Dipeptidyl Peptidase IV inhibitors
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inhibits the enzyme DPP-IV--> prolongs the activity of incretin hormones--> increased insulin release in response to meals and reduces inappropriate glucagon secretion
Sitagliptin (Januvia) Saxgliptin (Onglyza) |
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Sitagliptin (Januvia)
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dipeptidyl peptidase IV inhibitors
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Sitagliptin (Januvia)
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dipeptidyl peptidase IV inhibitors
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Sitagliptin (Januvia)
Saxgliptin (Onglyza) SE: contraindications: |
dipeptidyl peptidase inhibitors
-excreted in urine; does not alter weight -S/E: hypoglycemia; HA; N&D; pancreatitis Contraindications: type I DM; DKA overall effect lowers A1c 0.5-0.8% |
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amylin analog
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synthetic amylin analog (amylinomimetic)--> delays gastric emptying, decreases postprandial glucagon secretion, and improves satiety
adjunct to mealtime insulin in type I and II DM |
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Amylin Analog (1)
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Pramlintide (Symlin)
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Pramlintide (Symlin)
SE Contraindications overall effects |
amylin analog
SQ injection; decrease meal time insulin 50% when initiating pramlinitide; cannot mix w/ insulin SE: hypoglycemia; N&V CON: gastropresis; pt who cannot recognize hypoglycemia Overall effects lowers A1c 0.5% |
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GLP-1 Agonist (1)
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Exenatide (Byetta)
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GLP-1 Agonist
Exenatide (Byetta) |
incretin mimetic: improves glucose dependent insulin secretion; slows gastric emptying time; decreases postprandial glucagon secretion; promotes B cell proliferation; decreases appetite
-SQ only; short duration of action; causes weight loss SE: hypoglycemia; NVD; HA CON: type I DM; DKA lowers A1c 0.5-1% |
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Calcium absorption is increased in the presence of
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calcitriol
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Primary regulators of bone mineral homeostasis
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parathyroid hormone
vitamin D |
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secondary regulators of bone mineral homeostasis
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calcitonin
glucocorticoids estrogens |
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2 major elements of bone
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calcium and phosphorus
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most important regulator of calcium homeostasis
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parathyroid hormone
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parathyroid hormone acts on three organ systems
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kidney
bone GI tract |
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vitamin D relates to 2 compounds
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cholecalciferol (vitamin D3)
ergocalciferol (vitamin D2) |
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calcitriol effect
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increased absorption of calcium in the small intestine
inhibits PTH synthesis increase osteoclast activity--> increased bone resorption increased reabsorption of calcium and phosphate |
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calcitonin produced and released by
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thyroid gland
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calcitonin binds to
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receptors on osteoclasts--> inhibits resorption activity--> decreases bone resorption and calcium levels
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bone mineral metabolism
glucocorticoids |
-decrease intestinal absorption of Ca and renal tubular reabsorption
-inhibit osteoblast maturation and activity -promote osteoclast apoptosis |
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bone mineral metabolism
thyroid hormone |
stimulate bone resorption--> osteopenia
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bone mineral metabolism
estrogens |
-inhibit osteoclastic activity
-pro-apoptotic effect on osteoclasts -anti-apoptotic effect on osteoblasts and osteocytes |
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estrogen therapy
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-reduces bone resorption
-promotes apoptosis of osteoclasts -inhibits apoptosis of osteoblasts and osteocytes -maintains bone mass and slows bone loss SE: vaginal bleeding, breast tenderness, venous thromboembolism, breast cancer |
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selective estrogen receptor modulators
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ralxifene (Evista)
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Ralxifene (Evista)
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selective estrogen receptor modulators (SERMS)
bind to estrogen receptors and have tissue-selective effects -agonist effects in bone -antagonist effects in uterine and breast tissue -reduces resorption of bone -decreases overall bone turnover BENEFITS: reduction in vertebral fractures; lowers total cholesterol and LDL; reduces risk of breast cancer SE: hot flashes; leg cramps; venous thromboembolism |
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bisphosphonates
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Alendronate (Fosamax)
Rissedronate (Actonel) Pamidronate (Aredia) Ibandronate (Boniva) Zoledronic acid (Zometa or Reclast) |
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Alendronate (Fosamax)
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bisphophonate
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Rissedronate (Actonel)
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bisphosphonate
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Pamidronate (Aredia)
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bisphosphonate
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Ibandronate (Boniva)
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bisphosphonate
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Zoledronic acid (Zometa or Reclast)
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bisphophonate
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Alendronate (Fosamax)
Rissedronate (Actonel) Pamidronate (Aredia) Ibandronate (Boniva) Zoledronic acid (Zometa or Reclast) benefits, s/e, indications |
Benefits: increase BMD of hip and spine; decrease risk of vertebral and nonvertebral fractures
SE: GI disturbances; hypocalcemia; caution in decreased renal function Indications: osteoporosis (male or female); hypercalcemia of malignancy; Paget's disease |
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Calcitonin-salmon (Miacalcin)
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Calcitonin
Binds to and activates osteoclasts -inhibits bone resorption; derived from salmon -benefits: reduces incidence of new vertebral fxs -adverse effects: rhinitis, irritation, epistaxis -indications: osteoporosis; paget's disease |
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Phosphate binders (containing calcium) 2
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Calcium acetate (Phoslo)
calcium carbonate |
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Phosphate binders (non-calcium containing) 2
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Sevelamer HCL (Renagel)
Sevelamer carbonate (Renvela) |
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phosphate binders calcium containing
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taken w/ meals to bind dietary phosphorus;
can limit further problems associated w/ chronic kidney disease BENEFITS: can tx hypocalcemia; inexpensive S/E: hypercalcemia |
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phosphate binders non calcium containing
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use when calcium phophorus factor >55 mg/dl
decreases LDL and increases HDL SE: hypocalcemia ; GI disturbances |
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Vitamin D analogues
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calcitriol (Calcijex)
Paricalcitol (Zemplar) Doxercalciferol (Hectoral) |
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calcitriol (Calcijex)
Paricalcitol (Zemplar) Doxercalciferol (Hectoral) |
Vitamin D Analogues
-suppress PTH synthesis--> reducing PTH concentrations -bypass the need for hydroxylation in the kidney -increase calcium absorption--> reduces PTH secretion Indications: secondary hyperparathyroidism (all); hypocalcemia (calcitrol) SE: hypercalcemia; edema; NVD |
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Cinacalcet (Sensipar)
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Calcimimetics
-binds to calcium receptor on parathyroid gland- negative feedback suppression of PTH secretion BENEFITS: can be used w/ or w/o phosphate binders and or vitamin D analogues SE: hypocalcemia- do no use if ca <8.4; ND; caution on seizure disorders INDICATIONS: secondary hyperparathyroidism; hypercalcemia associated w/ parathyroid carcinoma |
