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218 Cards in this Set
- Front
- Back
What are the sources of bone mineral (calcium + phosphate) (3)
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1) Gut - intake
2) Kidney - excretion/recovery 3) Bone - storage/release |
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Describe what Parathyroid hormone does to Ca2+ and PO43- levels.
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PTH stimulates free calcium in blood and inhibits phosphates. The increase in calcium feedback negatively to PTH
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what receptors reduces the output of PTH?
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Calcium sensing - G-protein coupled receptors
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What does PTH do the calcium and phosphate in the gut, kidney, and bones?
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gut - increases calcium and phosphate intake
kidney - decreases calcium/increases phosphate excretion bones - increases calcium and phosphate release |
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Where is vitamin D activated?
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kidney
|
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What is the function of activated vitamin D?
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Increases calcium transport in the gut
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Explain the vitamin D loop. What is essential for its operation?
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-Activated vitamin D inhibits PTH secretion
-Activated vitamin D inhibits the activation of vitamin D Kidney is essential for operation of vitamin D loop |
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What is the effect of estrogen on bones?
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It decreases mineral release from bones; it promotes osteoblast - osteoblasts bluids bone
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WHow does Calcitonin and Glucocorticoids affect bone regulation?
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Calcitonin - antagonizes PTH
Glucocorticoids - antagonizes vitamin D |
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What are the causes of Hyperparathyroidism?
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1) parathyroid gland dysfunction - over production
2) Kidney disease - loss of feedback inhibition with activated vitamin D |
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What is the difference between osteomalacian and osteoporosis?
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Osteomalacia - decreased bone mineralization in adults due to deficiency in vitamin D activation
Osteoporosis - loss of bone mass due to imbalance of osteoclast vs. osteoblast activities |
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What is Paget's disease?
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A chronic disorder resulting in enlarged and deformed bones and bone pain. Caused by excessive and disorganized bone remodeling
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What is Teriparatide? MOA? Clinical indication?
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A recombinant PTH
Moa: acts on the PTH receptor Indication: osteoporosis - low dose to be beneficial, high dose causes bone loss |
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What vitamin D is produced in animals? Plants?
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Animal - D3 - Cholecalciferol
Plants - D2 - ergocalciferol |
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Describe the activate of Vitamin D?
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D3 and D2 are converted into 25-hydroxyvitamin D in the liver; the kidney converts them into 1,25 hydroxyvitamin D or 1,25(OH)2D (activated vitamin D) which is regulated by PTH
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Why is D3 in milk and not activated Vit. D?
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You can overdose on D3 without much toxicity. Too much activated vitamin D active form can lead too hypercalcemia because it bypasses the regulatory mechanism
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What are the effects of activated vitamin D in gut, kidney, and bones?
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Gut - increases calcium and phosphate intake
kidney - increases calcium and phosphate resorption bones - increases calcium and phosphate release from bones Net = increase calcium and phosphate levels in blood |
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What is calcitriol? Clincal indication? Toxcitiy? Contraindication?
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Activated Vitamin D3
Indication: hypocalcemia due to renal deficiency; secondary hyperparathyroidism Toxicity: hypercalcemia, hyperphosphatemia, hypercalciuria CI: hypercalcemia, vitamin D toxicity |
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What is Doxercalciferol? Clinical Indication? Toxicity? Contraindication?
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An analog of vitamin D2 and prodrug for activated vitamin D
MOA: Liver-dependent, kidney-independent activation Indication: Secondary hyperparathyroidism Toxicity: hypercalcemia, hyperphosphatemia, hypercalciuria CI: hypercalcemia, vitamin D toxicity |
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What is paricalcitol? Clinical Indication? Toxicity?
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Analog of calcitriol, the activated D3
MOA: more selective on hyperparathyroidism Indication: secondary hyperparathyroidism Toxicity: less vitamin D toxicity |
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What is the function of calcimimetics?
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It mimics calcium so you don't have to deal with Vitamin D drugs and the risk for vitamin D toxicity
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What is Cinacalcet? Indication? Toxicity?
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It is a calcimimetic
MOA: increasing the sensitivity of calcium-sensing receptor to free calcium -> lower PTH output Indication: secondary hyperparathyroidism Toxicity: seizure, hypocalcemia |
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What are the functions of calcitonin on gut, bones, kidney?
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gut - inhibit calcium intake
bone- inhibit calcium release Kidney - inhibit calcium and phosphate resorption by kidney |
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How is calcitonin administered?
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IV and NASAL SPRAY
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what are the clinical indications for calcitonin? What is the contraindications?
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Indication: Paget's disease; hypercalcemia; osteoporosis
Contraindication: allergy to salmon |
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What is the function of prednisone on calcium in bone, gut, and kidney? What is its indications? Side effects?
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Bone - suppreses bone forming cells
Gut- decrease calcium transport Kidney - increase calcium secretion Indication - cancer associated hypercalcemia SE: retards bone growth in children; induces osteoporosis in adults |
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List 3 bisphosphonates
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Pamidronate
alendronate risedronate |
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What is the MOA of bisphosphonates?
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High affinity for the site of bone resorption; blocks turnover of hydroxyapatie in bones; the nitrogen containing bisphosphonates preferentially inhibits osteoclasts
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What are bisphosphonates clinically indicated for?
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Osteoporosis
Paget's Disease Bone metastasis Bone metastasis-related hypercalcemia |
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What are the toxicities a/w bisphosphonates? Contraindications?
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Toxicities - erosive esophagitis, osteonecrosis of the jaw
Contraindication - abnormalities of the esophagus which delay esophageal emptying; hypocalcemia |
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What is Raloxifene? Toxicities? Indications?
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Selective estrogen receptor modulator - agonist on bone and antagonist on uterus and breast
Toxicities: hot flashes and leg cramps Indications: osteoporosis in POSTMENOPAUSAL women; breast cancer CI: lactating/pregnant women; women with hx of thromboembolism |
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What is Gallium Nitrate used for in relation to calcium?
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indicated for cancer-related hypercalcemia. Also known to inhibit osteoclast-mediated bone resorption.
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What is plicamycin
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Indicated for patients with malignant tumors of the testis. Also known to inhibit RNA synthesis of osteoclasts
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What is the effect of furosemide on calcium and sodium?
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Increases renal excretion of NA and Ca
|
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What is effect of thiazide diuretics on sodium and calcium?
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Lose Na
Gain Ca |
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What is sevelamer?
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A phosphate binding gel that is indicated for patients on dialysis. It sequesters dietary phosphate in food.
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What is the most common contraceptive method?
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Oral Contraceptive
|
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What is the most effective contraceptive method?
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Implanon with typical failure rate of .05%
|
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What is the function of estrogens in contraception?
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-Inhibits ovulation by decreasing FSH and LH production
-Inhibits ovum implantation and breaks down the corpus luteum |
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What is the function of progestins in contraception?
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-Promotes thick cervical mucus to decrease sperm transport and sperm penetration
-Inhibits ovulation by decreasing the midcycle surge of FSH and LH -Produces endometrial changes unfavorable for ovum implantation |
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Why do progestins have androgenic activity?
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Progestins have structural similarity to testosterone. It can affect free testosteron levels through effects on sex hormone binding globulin
|
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Describe the metabolism of estrogen
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Estrogen undergoes Hepatic/first pass metabolism - the conjugates of EE are broken down by colonic bacteria - active metabolites are resorbed
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What is Drospirenone? What was it promoted for?
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It is an analogue of spironolactone, has potent progestogenic activity
-anti-androgenic/anti-mineralocoticoid activity: increase in sodium and water excetion Was promoted for weight loss - less bloating a/w menstrual activity |
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What does monophasic formulation mean?
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Fixed ratio of estrogen and progestin for 21 days
|
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What is biphasic formulation mean?
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increased ratio of progestin in the second half of the cycle but overall decreased total progestin dose than monophasic
(may increase midcycle spotting and late cycle BTB) |
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What does triphasic formulation mean?
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Fixed estrogen dose with variable progestin concentration
|
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What is the benefit of triphasic formulation
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-mimics normal cycle
-decrease total progestin intake -decrease midcycle BTB |
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What kind of formulation is estradiol valerate and dienogest?
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Four-phasic
|
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What are some side effects with progestin only products?
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Menstrual irregularity, weight gain, delayed return to fertility, decreased bone mineral density
|
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How does implanon work? What are its adverse reactions?
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-Subdermal Progestin implants - rod inserted in upper arm
-Long-term contraception - 3 years Adverse reactions: irregular bleeding, amenorrhea, weight gain, acne |
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What agents are preferred for nursing mothers? Why? When should you be cautious?
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Progestin only products
-Less impact on milk production, estrogen could cause estrogenic effects in breast-fed infants - Use w/ caution - Hx of lactation failure, low milk supply, hx of breast surgery, multiple births, preterm births |
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What is seasonale?
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-Extended/Continuous Formulation
-Active pills for 3 months - 84 active pills, 7 placebo/low dose estrogen |
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What is Lybrel?
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Active pill taken every day
No pill-free interval |
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Who are the patient candidate for extended and continuous formulation contraceptions?
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Patients with endometriosis, anemia, dysmenorrhea, menstrual headache
|
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When do you start combined oral contraceptive?
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-Immediately - need a non-hormonal back up for at least 7 days
-First day of menses or -First sunday after next menses begins - need backup for 7 days |
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What happens if you miss 1 or more pills during week 1?
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Take the missed pill ASAP
Then take the next pill at the regular time -Use back up for 7 days |
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What happens if you miss 1 or more pills during weeks 2 or 3?
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-Take a pill ASAP and continue with current pack
-Skip placebo pills and go straight to a new pack -Use nonhormonal back up for 7 days -Consider emergency contraception |
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What are adverse reactions related to estrogen?
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Nausea, breast neoplasia, cyclic weight gain from fluid retention, breast tenderness, increased in bile cholesterol, thromboembolic complications, cerebrovascular accidents, hypertension
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What are adverse reactions related to progestins?
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Increased appetite & weight gain, depression, fatigue, decreased libido, acne, oily skin, diabetogenic effect, hirsutism, increased LDL and decreased HDL cholesterol, headache
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What is the most common complaint with contraception? How would you adjust the contraception?
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Breakthrough bleeding and spotting
-Early in cycle, increase EE -Late in cycle, increase progestin -Switch from biphasic to triphasic |
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Why could there be an absence of withdrawal bleeding?
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-more common with EE <50mcg and low potency progestin products
-Check compliance -R/o pregnancy -Increase EE or switch to triphasic agents |
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Why do people gain weight with contraception?
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increase appetite - due to progestin excess
-retaining fluid - EE excess |
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True or False. Cardiovascular complications increase for smokers on OCP.
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True!!
OCP is contraindicated for smokers >35 y/o |
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Why does estrogen increase risk for thromboembolic disease?
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EE Increase concentration of clotting factors and platelet adhesiveness; it decreases fibrinolytic activity
If patient is at risk, use progestin only product |
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Which antibiotics decrease the efficacy of antibiotics? (5)
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Ampicillin
Metronidazole quinolone tetracycline doxycyline |
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What is Ortho Evra?
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A transdermal formulation
3 weeks of active patch 1 week patch free for females less than 90 KG |
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What is the MOA for Mirena/IUD?
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-thickens cervical mucus
-reduces sperm motility and penetration -decreases proliferation of the endometrium IUD doesn't cause weight gain/acne problems -Very little system absorption |
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What are the adverse reactions for IUD?
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-Risk for PID
-Irregular menstruation/spotting w/in 3 months -amenorrhea -systemic absorption of hormones - headache, acne, breast tenderness, or depression |
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What kind of contraception would you give to obese women?
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since there is decreased efficacy, you would use longer-acting progestin or nonhormonal method
|
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What kind of contraception product would you use on smoking populations?
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Low dose EE products or progestin only products
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What contraceptive method would you give to people on anticonvulsants?
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Higher dose formulations or deo-medroxyprogesterone, IUD
|
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What kind of contraceptive product would you give to a person with diabetes?
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Progestin only esp for patients with complications such as nephropathy, HTN, retinopathy
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What is the MOA of Levonorgestrel?
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Plan B delays/inhibits ovulation
.75mg bid or 1.5 mg once OTC for ages >17 Use w/in 72 hrs of even |
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What is the definition of menopause?
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Permanent cessation of menses following loss of ovarian follicular activity
12 consecutive months of amenorrhea |
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What are menopausal symptoms
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Hot Flush
Vaginal symptoms - dryness, discomfort, itching, dyspareunia |
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What are the proposed benefits of HRT? (5)
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-Symptomatic management
-Prevention and treatment of bone loss -Protection against urogenital atrophy -Preservation of cognitive function -Possibly prevention of CVD and dementia? |
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What HRT regimen would you give someone with an intact uterus? hysterectomy?
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-Intact: estrogen + progestin
-Hysterectomy - estrogen only |
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How long should a woman be on HRT?
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As long as symptom control is necessary. Approx. 2 -3 years
|
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What is Premarin?
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Urine of pregnant mare
Conjugated equine estrogens |
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What are 2 oral formulations of estrogens for HRT?
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-Conjugated equine estrogens - CEE
-Micronized estradiol -Ethinyl estradiol (EE) |
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Whats the benefit of using a transdermal estrogen?
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Bypasses first pass liver metabolism and bypasses GI tract
Good for women with elevated triglyceride concentrations or significant abnormal liver function |
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What do vaginal creams/tablets/rings treat?
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Urogenital atrophy
|
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Why is it necessary for progestin therapy for females with intact uterus?(3)
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-Limits endometrial proliferation
-Decrease risk of endometrial hyperplasia and cancer -Decrease estradiol receptor concentrations |
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What is the MOA for progestins in HRT?
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-decrease nuclear estradiol receptor concentrations
-Suppress DNA synthesis -increase the enzyme activity converting estradiol to estrone |
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What is the progestin regiment like in HRT?
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Minimum of 12-14 days for each month
Cyclic/daily throughout the month |
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Say is these products are Progestogen or Combinations?
Povera Activalla Climara Pro Proterium Premphase Prempro |
Provera - Prgestoge
Prometrium - progestogen Premphase - combo oral prempro - combo oral activalla, climara pro - transdermal combo |
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What are the long term benefits of HRT?
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Decrease spinal and hip fractures
Relief of menopausal symptoms |
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What does the HERS trial say about HRT?
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No significant difference between tx and placebo groups but increased thromboembolic events and gallbladder disease
|
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What does the WHI say about HRT?
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There's a slight increase in breast cancer, CAD, stroke and PE
Decrease risk in colorectal cancer and hip fracture |
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Explain phytoestrogens? Where are they found?
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Estrogen like activity
Weak estrogen receptor binding capacity Found in soy beans, flaxseeds, alfalfa sprouts |
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What are the effectiveness of phytoestrogens?
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Inconsistent data
Decrease LDL and triglyceride |
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What is the action of thyroid hormone?
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Influences the growth and maturation of tissue, total energy expenditure and turnover of essentially all substrates, vitamins and hormones
|
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What is the 3 general mechanisms by which hyperthyroidism can occur? (according to clinical patho)
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-thyroid over secretes thyroid hormone - primary hyperthyroidism
-pituitary over stimulates the thyroid to secrete thyroid hormone - secondary hyperthyroidsm -exogenous source of thyroid hormone exists |
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Describe the regulation of thyroid function.
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Hypothalamus secretes thyrotropin releasing hormone (TRH) which stimulates the anterior pituitary to secrete TSH which stimulates the thyroid to release T4 and T3. T4/T3 negatively feedback on the anterior pituitary and hypothalamus
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Where is Thyroxine formed>
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100% formed in thyroid gland
35-40% converted peripherally to T2 Half-life: 7 days |
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Where is T3/Triidothyronine formed?
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20% in thyroid gland. 80% formed from peripheral conversion of T4 to T3
4x more active that T4 Shorter half life - 1.5 days |
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Give example of states a/w decreased peripheral conversion of T4 to T3
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Fasting, malnutrition, systemic illness, physical trauma, postoperative state D
Drugs - propylthiouracil, propranolol, amiodarone |
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Which thyroid hormone can diffuse into cells?
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Free unbound thyroxine
|
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What states cause you to have increased thyronine/thyroxine binding globulin levels?
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Pregnancy
Newborn Oral contraceptive tamoxifen ingection/chronic active hepatitis Perphenazine |
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What states cause you to have decreased thyronine/thyroxine binding globulin levels?
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Androgenic steroids
Glucocorticoids Salicylates Chronic liver disease severe systemic illness nephrosis |
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How is T4 and T3 metabolized?
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In the liver via conjugation with glucuronic and sulfuric acids
-Exceted through bile and kidney |
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What is the gold standard in primary thyroid function test? What is the normal value?
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Free T4 - FT4
Used to dx hypo/hyperthyroidism and monitor hyperthyroidism tx Normal - .8 - 1.5 ng/dl |
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What is the most sensitive test to evaluate thyroid function? What is the normal range?
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TSH - detects pituitary TSH level
Normal: .5-4.7mU/L |
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What are the clinical uses of thyroid-stimulating hormone?
|
Screening for thyroid disorder
Dx for: primary hypothyroidism (elevated TSH), hyperthyroidism (low/undetectable TSH), monitor thyroid replacement therapy, asses suppressive therapy for thyroid cancer and goiter |
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What is the most common cause of hyperthyroidism? What demographics?
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Most common cause = Grave's disease
Incidence: Women/men = 8/1 peak incidence - 30-40 y/o |
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In Primary hyperthyroidism, TSH will be high or low?
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Low because they thyroid itself secretes lots of hormone and increase the negative feedback on pituitary
|
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In secondary hyperthyroidism, the TSH will be high or low?
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High because the over secretion of TSH by pituitary causes the thyroid to produce more hormornes
|
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What is Graves disease?
|
An autoimmune disorder where autoantibodies bind to the TSH receptros in the thyroid and act like TSH to stimulate the thyroid to release thyroid hormone
|
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What are signs and symptoms of hyperthyroidism?
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Thyroid hormone stimulates:
-high metabolism tachycardia duspnea heat intolerance hot skin increased appetite tremor nervousness |
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What are laboratory changes in hyperthyroidism?
|
increase in FT4, TT3
supressed TSH Increase in alk phosphate, calcium, ast +TSab - Graves disease +antithyroglobulin antibody +antimicrosomal antibodies |
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What are the target goals of treatment of hyperthyroidism?
|
eliminate excess thyroid hormone
reduce/control symptoms prevent long-term consequence prevent re-occurence |
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What can you use to decrease palpitations, anxiety, tremor, heat intolerance in people with hyperthyroidism?
|
Beta - blockers like propranolol
Diltiazem - if beta blockers are contraindicated *Keep on tx for only as long as sx lasts* |
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What is the MOA of thiomides? Give 2 thiomides
|
Propylthiouracil, methimazole
blocks synthesis of thyroid hormones by inhibiting organification and coupling reactions |
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What is the MOA of Propylthiouracil? PTU?
|
inhibits peripheral conversion of T4 to T3
|
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which is the preferred agent? Methimazole or propylthiouracil? Why?
|
Methimazole
10x more potent that PTU compliance, better tast, cost crosses placenta and appears in breast milk |
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What are adverse reactions of thiomides?
|
Rash
Arthralgias Leukopenia Agranulocytosis Hepatotoxicity - need to routinely test LFT |
|
What tests do you need to monitor for thioamide therapy?
|
FT4 and TSH monthly initially then every 2-3 months
CBC if sx of agranulocytosis LFTs if hx of liver disease and EtOh user |
|
What is the MOA of Radioactive I131? (RAI)
|
Disrupts hormone synthesis initially and leads to destruction of the follicles and surrounding area
|
|
What is are adverse effects a/w RAI?
|
mild thyroidal pain/tenderness, dysphagia, transient thinning of hair, hypothyroidism
|
|
What are advantages and disadvantages of RAI?
|
Advantage - inexpensive, easy to administer, few side effects, preferred in elderly and in patients who failed drug therapy
Disadvantage - delayed onset of action (6-8 weeks for improvement), contraindicated in pregnancy |
|
When is surgery the treatment option for people with hyperthyroidism?
|
When they have carcinoma, compressive goiters, or contraindicated to thiomides or RAI
|
|
What is the MOA of Iodine? When is it used?
|
-inhibits hormone release and production
-short acting - break through effects after 2 -3 weeks -short term uses: symptomatic improvement, to prepare patient for surgery, thyroid storm |
|
What are adverse reactions to iodine?
|
rash, drug fever, rhinitis, iodism (metallic taste, burning mouth and throat, head cold)
|
|
What is the MOA of lithium in hyperthyroidism?
|
inhibits release of formed hormones but last resort due to narrow therapeutic window
|
|
Why would corticosteriods be used in hyperthyroidism?
|
blunt and delay rise in antibodies to TSH receptor - tx Graves opthalmopathy and thyroid storm
|
|
What is the effect of hyperthyroidism in pregnancy?
|
Greater risk of preterm delivery, severe preeclampsia and heart failure
|
|
What is used to treat hyperthyroidism in pregnancy?
|
either PTU or methimazole - PTU has less impact on breast milk than methimazole
|
|
What is thyroid storm?
|
A medical emergency. high fever, tachycardia, tachypnea, delirium, psychosis, weight loss, shock, coma, dehydration, jaundic and cardia decompensation
|
|
How do you treat thyroid storm?
|
supportive care, inhibition of hormal synthesis, blockade of hormone release, antagonism of thyroid hormones, steroids, elimination of precipitating factors
|
|
In primary hypothyroidism, the TSH level will be high or low?
|
High because there's no hormone to produce feedback on pituitary
|
|
In secondary hypothyroidism, the TSH level is high or low?
|
Low because the pituitary is not producing TSH
|
|
What are the causes of primary hypothyroidism? (2)
|
Hoshimotos
Iatrogenic |
|
What are causes of secondary hypothyroidism?
|
Pituitary failure
Hypothalamic failure infection, inflammation, infiltration, hemorrhage or tumor |
|
What is hashimoto'sthyroiditis?
|
An autoimmune disease. Antibodies are directed against thyroid peroxidase and thyroglobuline resulting in lymphocyte infiltration of throid gland which causes it to cease function partially or entirely
|
|
Why can iodine deficiency cause hypothyroidism?
|
Iodine is necessary for thyroid hormone synthesis.
|
|
What is tertiary hypothyroidism caused by?
|
hypothalamic under activity or tumor
|
|
What are the SSx of hypothyroidism?
|
weigh gain, cold intolerance, fatigue, weakness, bradycardia, hypoventilation, constipation, myalgias, arthralgias, and/or anemia
|
|
What do lab test show of hypothyroidism?
|
decreased TT4, FT4
increased TSH + antibodies for hoshimoto's increased cholesterol |
|
How do you treat hypothyroidism?
|
Levothyroxine sodium (T4) synthetic thyroid hormone
or Liothyronine sodium (T3) = not as useful as levothyroxine, erratic blood levels through out day, difficult to monitor or Liotrix - thyrolar: fixed 4:1 ratio of T4:T3 |
|
When is Thyrolar used in therapy?
|
Hypothyroidism
Useful in tx of myxedema coma, where peripheral conversion of T4 to T3 is reduced *should NOT be used in most patients* |
|
What do studies say about T4:T3 vs T4 monotherapy?
|
No significant difference except T4:T3 is more expensive
|
|
What is armour thyroid?
|
A dessicated thyroid.
Potential allergies - animal source: hog, beef or sheep Should not be used for most patients, only those who have been maintain on it |
|
What are 3 recommendations regarding therapy of hypothyroidism?
|
-Start low and go slow!!! you don't want to cause hyperthyroidism
-Response evident w/in 2 week -W/ aging, you may need to reduce dose bc of age-associated decrease in T4 clearance |
|
What is the average replacement dose for young adults with hypothyroidism?
|
130mcg/day
|
|
What is the average replacement dose for elderly with hypothyroidism?
|
110 mcg/day but at with 25mcg daily and titrate carefully
monitor for ssx of angina |
|
Does pregnancy increase or decrease maternal thyroid hormone requirement?
|
It increases the maternal thyroid hormone requirement in women with hypothroidism required before pregnancy
pregnancy doubles TBG due to increase in estradiol concentration |
|
WWhat can increase TBG binding capacity? (2)
|
Estrogen
Oral Contraceptive |
|
What can decrease TBG binding capacity? (3)
|
Androgens
Salicylate Glucocorticoids |
|
What can induce enzymes?
|
Phenytoin
Phenobarbital Carbamazepine Rifampin |
|
What can decrease bioavailability of levothyroxine?
|
Cholestyramine
Colstipol Aluminum hydroxide Sucralfate Iron sulfate Calcium |
|
What is myxedema coma?
|
Life threatning coma resulting from long-standing, uncorrected hypothyroidism
Precipitating factors - stress, infection, MI, trauma, surgery, cold exposure Presentation - hypothermia, hyponatremia, hypoglycema, hypoventilation, delayed DTRs, altered sensorium, paranoid psychosis, shock, coma death |
|
What is the treatment for myxedema coma?
|
Supportive
Eliminate precipitating factor Thyroid replacement ASAP through IV |
|
Ehat is subclinical thyroid disease?
|
Abnormal biochemical measurement of thyroid hormones without and SSX of thyroid disease or hx of thyroid dysfuction/therapy
|
|
What is subclinical hyperthyroidism a/w? (3)
|
atrial fibrillation, dementia, osteoporosis
|
|
What are risk factors for subclinical hypothyroidism?
|
women
advanced age greater dietary iodine intake |
|
When should you treat subclinical hypothyroidism?
|
When TSH levels >10microIU/ml
|
|
List 3 anterior pituitary drugs
|
-corticotropin
-somatotropin -octreotide |
|
List 2 posterior pituitary drugs
|
-vasopressin
-desmopressin |
|
What is the function of vasopressin/desmopressin as an antidiuretic?
|
Balances the body's regulation of water and uring
-primary use is to decrease urine output in pts with polyuria due to diabetes insipidus or head trauma |
|
What is the function of desmopressin/vasopressin as a vasoconstrictor
|
Used to control bleeding with GI variceals - decreases portal pressure and variceal pressure
|
|
What are the two most important things to remember about 5th self-incrim priv?
|
[1] Only testimonial E is protected. Thus, a Δ has no self-incrim basis to object to a lineup or other ID procedure – even if he is asked to say certain words (e.g., “your money or your life”). This procedure does not involve testimonial E; the words are used for ID purposes and not as testimony.
[2] Likewise, only compelled testimonial E is privileged. Thus, if Δ produced a writing of his own free will (e.g., took incriminating notes in a meeting), the police may seize this writing or the Δ may be compelled to produce it by subpoena, b/c he was not compelled to make the statement originally. |
|
What are the routes of administration for desmopressin and vasopressin?
|
Desmopressin - PO, IV, Nasal
Vasopressin - IM, SQ, cotton pledgets |
|
What is the function of cortisol?
|
Responsible for the regulation of fat, carbohydrate and protein metabolism
|
|
Why is cushing's syndrome?
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A disease characterized by adrenal gland hypersecretion of hormone (cortisol)
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What is Addison's syndrome?
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A disease characterized by adrenal cortical insufficiency
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What are the hormones secreted by the zona glomerulosa, fasciculata, and reticularis
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Glomerulosa - aldosteron
fasciculata cortisol reticularis - androgens |
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What hormones are involved in the hypothalamic-pituitary-adrenal axis?
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Corticotropin releasing hormone is released by the hypothalamus and stimulates the anterior pituitary to release adrenocorticotropin to stimulate the adrenal cortex
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Describe the normal cycle of Cortisol. When are the peaks?
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- 1st peak at 6 -8 am
- 2nd peak at 4 -5 pm - Nadir at midnight - Peak at 2 - 6am |
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Give 4 reasons why the circadian rhythm regulation of cortisol may be lost.
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-Hypercortisolism
-Impaired consciousness -Anorexia nervosa -Infants less than 1 year old |
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When is there increased Cortiosteroid binding globulin?
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estrogen therapy, pregnancy, hyperthyroidism, diabetes mellitus, hematologic disorders, congenital
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When is there increased secretion of cortisol?
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Exercise, physical stress, anxiety/depression, anorexia nervosa, alcoholism, chronic renal failure
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What are the mineralocorticoids? What are their effects
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Aldosterone - salt, water and other mineral metabolism
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What are the glucocorticoid effects on carbohydrate metabolism?
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-increased gluconeogenesis
-increased glycogen synthesis and storage in liver -diminished glucose utilization |
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What is the glucocorticoid effect on lipid metabolism?
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Redistribution of body fat - buffalo hump, moon facies
Enhanced lipolysis in adipose tissue leads to increased in free fatty acids |
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What are the glucocorticoid effects on inflammation?
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Suppress the activation of T lymphocytes, suprress the production of cytokines, prevent release of chemical mediators, stabilize lysosomal membranes, vasoconstriction/decrease in capillary permeability
*Anti inflammatory effect* |
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What is the cardiovascular effect of adrenal hormone?
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increased risk for HTN, atherosclerosis, stroke and hypertensive cardiomyopathy
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What are the bone effects of adrenal hormones?
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increased bone catabolism and reduced bone formation - antagonized effect of vit D on calcium absorption
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What happens to skeletal growth in pediatric of those with adrenal hormone use?
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Decrease linear bone growth and premature epiphyseal closure, impairment of growth hormone release
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What are the etiologies of Cushing's syndrome?
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Hypercortisolism
-Pituitary disorder - excessive pituitary ACTh production, ACTH dependent -Adrenal disorders - autonomous secretion of cortisol by adrenal glands due to adenoma; ACTH independent -Ectopic Cushing's - Tumors outside HPA axis producing ACTH like substance -Iatrogenic |
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What are the symptoms of general Cushing Syndromes?
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moon facies/buffalo hump
central obesity weakness/fatigue purplish abdominal striae, bruising, osteopenia, depression, hypertension, glucose intolerance |
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What is the symptom of excess ACTH?
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skin hyperpigmentation
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What are the SSx of excess androgen secretion?
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Acne, hirsutism, thinning of the scalp hair, amenorrhea
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What are non-pharmacological tx of Cushing's syndrome?
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-Surgery
-Radiation -Bilateral adrenalectomy - requires glucocorticoid/mineralocorticoid replacement for life |
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How do you monitor pharmacological therapy for cushing's disease?
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AM plasma cortisol
24 hour urinary cortisol |
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What is Mitotate MOA?
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-inhibition of steroid synthesis
-alteration of peripheral steroid metabolism -inhibition of adrenal cortisol release |
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What are the adverse effects of Mitotate?
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-GI: nausea/anorexia/diarrhea
-Neuromuscular: Fatigue/muscle weakness, CNS depression |
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What is the MOA for Aminoglutethimide?
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-Inhibition of cholesterol desmolase (cholesterol side chain cleaving enzyme)
-Overall, reduced the synthesis of adrenal glucocorticoid, mineralcorticoid, estrogen, aldosterone and androgens |
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What are the adverse effects of aminoglutethimide?
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drowsiness, bone marrow suppression, drug-induced lupus!
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What is the MOA of Metyrapone?!
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-inhibited steroid 11 Beta-hydroxylase (final step in cortisol biosynthesis, and inhibits ACH secretion at high doses)
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What are the adverse effects of metyrapone?
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hypokalemia, edema, lightheadedness, rash, hirsutism
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What is the MOA of Ketoconazole? How do you monitor therapy?
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-inhibit steroid 17 alphahydroxylase, 11 Betahydrozylase, and cholesterol desmolase at high doses, potent inhibitor of testosterone
-Urinary free cortisol levels to monitor therapy |
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What are the adverse side effects of Ketoconazole?
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Increased LFTs, gynecomastia, decreased libido, impotence and GI symptoms
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What is Mifepristone?
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Glucocorticoid and progesterone antagonist; difficult to monitol
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What should you tell a patient on mifepristone therapy?
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Signs of adrenal insufficiency - fatigue, weakness, flu-like symptoms
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What are the causes of Addison's disease?
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*Adrenal Insuffiency*
-adrenal level abnormality, autoimmune disease, infection such as TB, metastatic cancer -MCC - due to long term use of glucocorticoid therapy -Secondary causes - Glucocorticoid therapy, lack of adrenal stimulators (ACTH, MSH) and tumors |
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How much tissue function is lost before ssx of addison's appear?
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90%
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What are the Clinical SSx of Addison's disease?
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Weakness, weight loss, anorexia, n/v/d, abdominal pain, constipation
-Hyperkalemia, HYPOnatremia, HYPOglycemia, HYPERcalcemia, HYPO thyroidism -salt craving, orthostatic hypotension, syncope, hypovolemia, hypersensitivity to tast, smell, hearing -mental slowing, depression, hyperpigmentation |
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What are the 3 options for hydrocortisone replacement?
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1 - 15mg in the morning and 10mg in the afternoon
2 - TID dosing - awakening, breakfast, evening meal; this mimicks more of a physiological dose 3 - prednisone or dexamethasone, one/day; least inconvenient but patient needs to take it for life |
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How do you monitor cortisol therapy?
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Urinary cortisol level
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What is fludrocortisone acetate?
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A potent synthetic mineralocorticoid
Adjust dose bases on potassium level and BP |
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Describe the symptoms of acute adrenal insufficiency
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Endocrine emergency
Flu-like symptoms initially, then progress to fever, hypotension and shock Electrolyte abnormalities |
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What is the therapy for acute adrenal insufficiency
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Hydrocortisone 100 mg stat, then q6-8hrs and then taper 20-30% until maintenance dose
-Correct volume depletion, dehydration, hypotension and hypoglycemia with fluids -remove/tx the precipitating factor |
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Differentiate between Glucocorticoids and Anabolic steroids
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Corticosteroids - produced by the adrenal gland; cortisol is an endogenous hormone that regulates the metabolism and the mineral/fluid balance
-Anabolic - produced by the testes, chemically similar to male sex hormone testosterone to increase strength and muscle mass |
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What are the indications for corticosteroid use?
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-replacement therapy
-anti-inflammatory activity -immunosuppressive effects |
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What is the most potent glucocorticoid?
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Betamethasone
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What is the least potent glucocorticoid
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Cortisone
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Do you want the mineralocorticoid potency to be high or low for glucocorticoids?
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Low because you don't want to have water retention
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Which has more adverse effects? IV? IM? Oral? or Inhaled formulations?
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IV/IM > Oral>> Inhaled
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What are the hematological adverse effects of glucocorticoid use?
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-Lymphocytopenia - decreases circulating count by redistributing to other body compartments
-Neutrophilia - stimulate bone marrow release Eosinopenia, monocytopenia |
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What is the preventative therapy for osteoporosis with use of glucocorticoids?
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Calcium supplement
Vitamin D Weight-Bearing Exercise Bisphosphonates: alendronate, risedronate |
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Why does glucocorticoid use cause hyperglycemia?
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Stimulates gluconeogenesis and inhibits peripheral utilization of glucose; Promotes glycogenolysis by stimulating glucagon release
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What are the advantages of alternative day therapy for glucocorticoid use?
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Decreased HPA suppression
Decreased Cushingoid side effects Recommended for prolonged therapy |
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What are interventions to minimize adverse effects for glucocorticoids
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singel daily use
not long-acting agents lowest effect dose don't stop chronic therapy abruptly |
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What do you want to be careful off when you withdraw glucocorticoid therapy?
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-Disease flare-up
-Acute adrenal insufficiency |
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Why does acute adrenal insufficiency occur?
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HPA suppression - adrenocotical atrophy and unresponsiveness due to lack of ACTH secretion from the pituitary for long period of time
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What are symptoms of acute adrenal insufficiency?
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nausea, fatigue, anorexia, dyspnea, hypotension, hypoglycemia, myalgia, fever, malaise, arthralgia, dizziness
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What are factors that affect HPA Axis suppression?
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Dose
Duration of therapy Type of corticosteroid administered |
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How do you discontinue the use of corticosteroids?
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Tapering schedule:
-Taper daily dose to physiologic dose -Switch to short-acting agent when near physiologic dose like hydrocortisone or prednisone -administer cosyntropin test |