Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
218 Cards in this Set
- Front
- Back
|
What are the sources of bone mineral (calcium + phosphate) (3)
|
1) Gut - intake
2) Kidney - excretion/recovery 3) Bone - storage/release |
|
|
Describe what Parathyroid hormone does to Ca2+ and PO43- levels.
|
PTH stimulates free calcium in blood and inhibits phosphates. The increase in calcium feedback negatively to PTH
|
|
|
what receptors reduces the output of PTH?
|
Calcium sensing - G-protein coupled receptors
|
|
|
What does PTH do the calcium and phosphate in the gut, kidney, and bones?
|
gut - increases calcium and phosphate intake
kidney - decreases calcium/increases phosphate excretion bones - increases calcium and phosphate release |
|
|
Where is vitamin D activated?
|
kidney
|
|
|
What is the function of activated vitamin D?
|
Increases calcium transport in the gut
|
|
|
Explain the vitamin D loop. What is essential for its operation?
|
-Activated vitamin D inhibits PTH secretion
-Activated vitamin D inhibits the activation of vitamin D Kidney is essential for operation of vitamin D loop |
|
|
What is the effect of estrogen on bones?
|
It decreases mineral release from bones; it promotes osteoblast - osteoblasts bluids bone
|
|
|
WHow does Calcitonin and Glucocorticoids affect bone regulation?
|
Calcitonin - antagonizes PTH
Glucocorticoids - antagonizes vitamin D |
|
|
What are the causes of Hyperparathyroidism?
|
1) parathyroid gland dysfunction - over production
2) Kidney disease - loss of feedback inhibition with activated vitamin D |
|
|
What is the difference between osteomalacian and osteoporosis?
|
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 |
|
|
What is Paget's disease?
|
A chronic disorder resulting in enlarged and deformed bones and bone pain. Caused by excessive and disorganized bone remodeling
|
|
|
What is Teriparatide? MOA? Clinical indication?
|
A recombinant PTH
Moa: acts on the PTH receptor Indication: osteoporosis - low dose to be beneficial, high dose causes bone loss |
|
|
What vitamin D is produced in animals? Plants?
|
Animal - D3 - Cholecalciferol
Plants - D2 - ergocalciferol |
|
|
Describe the activate of Vitamin D?
|
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
|
|
|
Why is D3 in milk and not activated Vit. D?
|
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
|
|
|
What are the effects of activated vitamin D in gut, kidney, and bones?
|
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 |
|
|
What is calcitriol? Clincal indication? Toxcitiy? Contraindication?
|
Activated Vitamin D3
Indication: hypocalcemia due to renal deficiency; secondary hyperparathyroidism Toxicity: hypercalcemia, hyperphosphatemia, hypercalciuria CI: hypercalcemia, vitamin D toxicity |
|
|
What is Doxercalciferol? Clinical Indication? Toxicity? Contraindication?
|
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 |
|
|
What is paricalcitol? Clinical Indication? Toxicity?
|
Analog of calcitriol, the activated D3
MOA: more selective on hyperparathyroidism Indication: secondary hyperparathyroidism Toxicity: less vitamin D toxicity |
|
|
What is the function of calcimimetics?
|
It mimics calcium so you don't have to deal with Vitamin D drugs and the risk for vitamin D toxicity
|
|
|
What is Cinacalcet? Indication? Toxicity?
|
It is a calcimimetic
MOA: increasing the sensitivity of calcium-sensing receptor to free calcium -> lower PTH output Indication: secondary hyperparathyroidism Toxicity: seizure, hypocalcemia |
|
|
What are the functions of calcitonin on gut, bones, kidney?
|
gut - inhibit calcium intake
bone- inhibit calcium release Kidney - inhibit calcium and phosphate resorption by kidney |
|
|
How is calcitonin administered?
|
IV and NASAL SPRAY
|
|
|
what are the clinical indications for calcitonin? What is the contraindications?
|
Indication: Paget's disease; hypercalcemia; osteoporosis
Contraindication: allergy to salmon |
|
|
What is the function of prednisone on calcium in bone, gut, and kidney? What is its indications? Side effects?
|
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 |
|
|
List 3 bisphosphonates
|
Pamidronate
alendronate risedronate |
|
|
What is the MOA of bisphosphonates?
|
High affinity for the site of bone resorption; blocks turnover of hydroxyapatie in bones; the nitrogen containing bisphosphonates preferentially inhibits osteoclasts
|
|
|
What are bisphosphonates clinically indicated for?
|
Osteoporosis
Paget's Disease Bone metastasis Bone metastasis-related hypercalcemia |
|
|
What are the toxicities a/w bisphosphonates? Contraindications?
|
Toxicities - erosive esophagitis, osteonecrosis of the jaw
Contraindication - abnormalities of the esophagus which delay esophageal emptying; hypocalcemia |
|
|
What is Raloxifene? Toxicities? Indications?
|
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 |
|
|
What is Gallium Nitrate used for in relation to calcium?
|
indicated for cancer-related hypercalcemia. Also known to inhibit osteoclast-mediated bone resorption.
|
|
|
What is plicamycin
|
Indicated for patients with malignant tumors of the testis. Also known to inhibit RNA synthesis of osteoclasts
|
|
|
What is the effect of furosemide on calcium and sodium?
|
Increases renal excretion of NA and Ca
|
|
|
What is effect of thiazide diuretics on sodium and calcium?
|
Lose Na
Gain Ca |
|
|
What is sevelamer?
|
A phosphate binding gel that is indicated for patients on dialysis. It sequesters dietary phosphate in food.
|
|
|
What is the most common contraceptive method?
|
Oral Contraceptive
|
|
|
What is the most effective contraceptive method?
|
Implanon with typical failure rate of .05%
|
|
|
What is the function of estrogens in contraception?
|
-Inhibits ovulation by decreasing FSH and LH production
-Inhibits ovum implantation and breaks down the corpus luteum |
|
|
What is the function of progestins in contraception?
|
-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 |
|
|
Why do progestins have androgenic activity?
|
Progestins have structural similarity to testosterone. It can affect free testosteron levels through effects on sex hormone binding globulin
|
|
|
Describe the metabolism of estrogen
|
Estrogen undergoes Hepatic/first pass metabolism - the conjugates of EE are broken down by colonic bacteria - active metabolites are resorbed
|
|
|
What is Drospirenone? What was it promoted for?
|
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 |
|
|
What does monophasic formulation mean?
|
Fixed ratio of estrogen and progestin for 21 days
|
|
|
What is biphasic formulation mean?
|
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) |
|
|
What does triphasic formulation mean?
|
Fixed estrogen dose with variable progestin concentration
|
|
|
What is the benefit of triphasic formulation
|
-mimics normal cycle
-decrease total progestin intake -decrease midcycle BTB |
|
|
What kind of formulation is estradiol valerate and dienogest?
|
Four-phasic
|
|
|
What are some side effects with progestin only products?
|
Menstrual irregularity, weight gain, delayed return to fertility, decreased bone mineral density
|
|
|
How does implanon work? What are its adverse reactions?
|
-Subdermal Progestin implants - rod inserted in upper arm
-Long-term contraception - 3 years Adverse reactions: irregular bleeding, amenorrhea, weight gain, acne |
|
|
What agents are preferred for nursing mothers? Why? When should you be cautious?
|
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 |
|
|
What is seasonale?
|
-Extended/Continuous Formulation
-Active pills for 3 months - 84 active pills, 7 placebo/low dose estrogen |
|
|
What is Lybrel?
|
Active pill taken every day
No pill-free interval |
|
|
Who are the patient candidate for extended and continuous formulation contraceptions?
|
Patients with endometriosis, anemia, dysmenorrhea, menstrual headache
|
|
|
When do you start combined oral contraceptive?
|
-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 |
|
|
What happens if you miss 1 or more pills during week 1?
|
Take the missed pill ASAP
Then take the next pill at the regular time -Use back up for 7 days |
|
|
What happens if you miss 1 or more pills during weeks 2 or 3?
|
-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 |
|
|
What are adverse reactions related to estrogen?
|
Nausea, breast neoplasia, cyclic weight gain from fluid retention, breast tenderness, increased in bile cholesterol, thromboembolic complications, cerebrovascular accidents, hypertension
|
|
|
What are adverse reactions related to progestins?
|
Increased appetite & weight gain, depression, fatigue, decreased libido, acne, oily skin, diabetogenic effect, hirsutism, increased LDL and decreased HDL cholesterol, headache
|
|
|
What is the most common complaint with contraception? How would you adjust the contraception?
|
Breakthrough bleeding and spotting
-Early in cycle, increase EE -Late in cycle, increase progestin -Switch from biphasic to triphasic |
|
|
Why could there be an absence of withdrawal bleeding?
|
-more common with EE <50mcg and low potency progestin products
-Check compliance -R/o pregnancy -Increase EE or switch to triphasic agents |
|
|
Why do people gain weight with contraception?
|
increase appetite - due to progestin excess
-retaining fluid - EE excess |
|
|
True or False. Cardiovascular complications increase for smokers on OCP.
|
True!!
OCP is contraindicated for smokers >35 y/o |
|
|
Why does estrogen increase risk for thromboembolic disease?
|
EE Increase concentration of clotting factors and platelet adhesiveness; it decreases fibrinolytic activity
If patient is at risk, use progestin only product |
|
|
Which antibiotics decrease the efficacy of antibiotics? (5)
|
Ampicillin
Metronidazole quinolone tetracycline doxycyline |
|
|
What is Ortho Evra?
|
A transdermal formulation
3 weeks of active patch 1 week patch free for females less than 90 KG |
|
|
What is the MOA for Mirena/IUD?
|
-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 |
|
|
What are the adverse reactions for IUD?
|
-Risk for PID
-Irregular menstruation/spotting w/in 3 months -amenorrhea -systemic absorption of hormones - headache, acne, breast tenderness, or depression |
|
|
What kind of contraception would you give to obese women?
|
since there is decreased efficacy, you would use longer-acting progestin or nonhormonal method
|
|
|
What kind of contraception product would you use on smoking populations?
|
Low dose EE products or progestin only products
|
|
|
What contraceptive method would you give to people on anticonvulsants?
|
Higher dose formulations or deo-medroxyprogesterone, IUD
|
|
|
What kind of contraceptive product would you give to a person with diabetes?
|
Progestin only esp for patients with complications such as nephropathy, HTN, retinopathy
|
|
|
What is the MOA of Levonorgestrel?
|
Plan B delays/inhibits ovulation
.75mg bid or 1.5 mg once OTC for ages >17 Use w/in 72 hrs of even |
|
|
What is the definition of menopause?
|
Permanent cessation of menses following loss of ovarian follicular activity
12 consecutive months of amenorrhea |
|
|
What are menopausal symptoms
|
Hot Flush
Vaginal symptoms - dryness, discomfort, itching, dyspareunia |
|
|
What are the proposed benefits of HRT? (5)
|
-Symptomatic management
-Prevention and treatment of bone loss -Protection against urogenital atrophy -Preservation of cognitive function -Possibly prevention of CVD and dementia? |
|
|
What HRT regimen would you give someone with an intact uterus? hysterectomy?
|
-Intact: estrogen + progestin
-Hysterectomy - estrogen only |
|
|
How long should a woman be on HRT?
|
As long as symptom control is necessary. Approx. 2 -3 years
|
|
|
What is Premarin?
|
Urine of pregnant mare
Conjugated equine estrogens |
|
|
What are 2 oral formulations of estrogens for HRT?
|
-Conjugated equine estrogens - CEE
-Micronized estradiol -Ethinyl estradiol (EE) |
|
|
Whats the benefit of using a transdermal estrogen?
|
Bypasses first pass liver metabolism and bypasses GI tract
Good for women with elevated triglyceride concentrations or significant abnormal liver function |
|
|
What do vaginal creams/tablets/rings treat?
|
Urogenital atrophy
|
|
|
Why is it necessary for progestin therapy for females with intact uterus?(3)
|
-Limits endometrial proliferation
-Decrease risk of endometrial hyperplasia and cancer -Decrease estradiol receptor concentrations |
|
|
What is the MOA for progestins in HRT?
|
-decrease nuclear estradiol receptor concentrations
-Suppress DNA synthesis -increase the enzyme activity converting estradiol to estrone |
|
|
What is the progestin regiment like in HRT?
|
Minimum of 12-14 days for each month
Cyclic/daily throughout the month |
|
|
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 |
|
|
What are the long term benefits of HRT?
|
Decrease spinal and hip fractures
Relief of menopausal symptoms |
|
|
What does the HERS trial say about HRT?
|
No significant difference between tx and placebo groups but increased thromboembolic events and gallbladder disease
|
|
|
What does the WHI say about HRT?
|
There's a slight increase in breast cancer, CAD, stroke and PE
Decrease risk in colorectal cancer and hip fracture |
|
|
Explain phytoestrogens? Where are they found?
|
Estrogen like activity
Weak estrogen receptor binding capacity Found in soy beans, flaxseeds, alfalfa sprouts |
|
|
What are the effectiveness of phytoestrogens?
|
Inconsistent data
Decrease LDL and triglyceride |
|
|
What is the action of thyroid hormone?
|
Influences the growth and maturation of tissue, total energy expenditure and turnover of essentially all substrates, vitamins and hormones
|
|
|
What is the 3 general mechanisms by which hyperthyroidism can occur? (according to clinical patho)
|
-thyroid over secretes thyroid hormone - primary hyperthyroidism
-pituitary over stimulates the thyroid to secrete thyroid hormone - secondary hyperthyroidsm -exogenous source of thyroid hormone exists |
|
|
Describe the regulation of thyroid function.
|
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
|
|
|
Where is Thyroxine formed>
|
100% formed in thyroid gland
35-40% converted peripherally to T2 Half-life: 7 days |
|
|
Where is T3/Triidothyronine formed?
|
20% in thyroid gland. 80% formed from peripheral conversion of T4 to T3
4x more active that T4 Shorter half life - 1.5 days |
|
|
Give example of states a/w decreased peripheral conversion of T4 to T3
|
Fasting, malnutrition, systemic illness, physical trauma, postoperative state D
Drugs - propylthiouracil, propranolol, amiodarone |
|
|
Which thyroid hormone can diffuse into cells?
|
Free unbound thyroxine
|
|
|
What states cause you to have increased thyronine/thyroxine binding globulin levels?
|
Pregnancy
Newborn Oral contraceptive tamoxifen ingection/chronic active hepatitis Perphenazine |
|
|
What states cause you to have decreased thyronine/thyroxine binding globulin levels?
|
Androgenic steroids
Glucocorticoids Salicylates Chronic liver disease severe systemic illness nephrosis |
|
|
How is T4 and T3 metabolized?
|
In the liver via conjugation with glucuronic and sulfuric acids
-Exceted through bile and kidney |
|
|
What is the gold standard in primary thyroid function test? What is the normal value?
|
Free T4 - FT4
Used to dx hypo/hyperthyroidism and monitor hyperthyroidism tx Normal - .8 - 1.5 ng/dl |
|
|
What is the most sensitive test to evaluate thyroid function? What is the normal range?
|
TSH - detects pituitary TSH level
Normal: .5-4.7mU/L |
|
|
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 |
|
|
What is the most common cause of hyperthyroidism? What demographics?
|
Most common cause = Grave's disease
Incidence: Women/men = 8/1 peak incidence - 30-40 y/o |
|
|
In Primary hyperthyroidism, TSH will be high or low?
|
Low because they thyroid itself secretes lots of hormone and increase the negative feedback on pituitary
|
|
|
In secondary hyperthyroidism, the TSH will be high or low?
|
High because the over secretion of TSH by pituitary causes the thyroid to produce more hormornes
|
|
|
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
|
|
|
What are signs and symptoms of hyperthyroidism?
|
Thyroid hormone stimulates:
-high metabolism tachycardia duspnea heat intolerance hot skin increased appetite tremor nervousness |
|
|
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 |
|
|
What are the target goals of treatment of hyperthyroidism?
|
eliminate excess thyroid hormone
reduce/control symptoms prevent long-term consequence prevent re-occurence |
|
|
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* |
|
|
What is the MOA of thiomides? Give 2 thiomides
|
Propylthiouracil, methimazole
blocks synthesis of thyroid hormones by inhibiting organification and coupling reactions |
|
|
What is the MOA of Propylthiouracil? PTU?
|
inhibits peripheral conversion of T4 to T3
|
|
|
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 |
|
|
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?
|
A disease characterized by adrenal gland hypersecretion of hormone (cortisol)
|
|
|
What is Addison's syndrome?
|
A disease characterized by adrenal cortical insufficiency
|
|
|
What are the hormones secreted by the zona glomerulosa, fasciculata, and reticularis
|
Glomerulosa - aldosteron
fasciculata cortisol reticularis - androgens |
|
|
What hormones are involved in the hypothalamic-pituitary-adrenal axis?
|
Corticotropin releasing hormone is released by the hypothalamus and stimulates the anterior pituitary to release adrenocorticotropin to stimulate the adrenal cortex
|
|
|
Describe the normal cycle of Cortisol. When are the peaks?
|
- 1st peak at 6 -8 am
- 2nd peak at 4 -5 pm - Nadir at midnight - Peak at 2 - 6am |
|
|
Give 4 reasons why the circadian rhythm regulation of cortisol may be lost.
|
-Hypercortisolism
-Impaired consciousness -Anorexia nervosa -Infants less than 1 year old |
|
|
When is there increased Cortiosteroid binding globulin?
|
estrogen therapy, pregnancy, hyperthyroidism, diabetes mellitus, hematologic disorders, congenital
|
|
|
When is there increased secretion of cortisol?
|
Exercise, physical stress, anxiety/depression, anorexia nervosa, alcoholism, chronic renal failure
|
|
|
What are the mineralocorticoids? What are their effects
|
Aldosterone - salt, water and other mineral metabolism
|
|
|
What are the glucocorticoid effects on carbohydrate metabolism?
|
-increased gluconeogenesis
-increased glycogen synthesis and storage in liver -diminished glucose utilization |
|
|
What is the glucocorticoid effect on lipid metabolism?
|
Redistribution of body fat - buffalo hump, moon facies
Enhanced lipolysis in adipose tissue leads to increased in free fatty acids |
|
|
What are the glucocorticoid effects on inflammation?
|
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* |
|
|
What is the cardiovascular effect of adrenal hormone?
|
increased risk for HTN, atherosclerosis, stroke and hypertensive cardiomyopathy
|
|
|
What are the bone effects of adrenal hormones?
|
increased bone catabolism and reduced bone formation - antagonized effect of vit D on calcium absorption
|
|
|
What happens to skeletal growth in pediatric of those with adrenal hormone use?
|
Decrease linear bone growth and premature epiphyseal closure, impairment of growth hormone release
|
|
|
What are the etiologies of Cushing's syndrome?
|
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 |
|
|
What are the symptoms of general Cushing Syndromes?
|
moon facies/buffalo hump
central obesity weakness/fatigue purplish abdominal striae, bruising, osteopenia, depression, hypertension, glucose intolerance |
|
|
What is the symptom of excess ACTH?
|
skin hyperpigmentation
|
|
|
What are the SSx of excess androgen secretion?
|
Acne, hirsutism, thinning of the scalp hair, amenorrhea
|
|
|
What are non-pharmacological tx of Cushing's syndrome?
|
-Surgery
-Radiation -Bilateral adrenalectomy - requires glucocorticoid/mineralocorticoid replacement for life |
|
|
How do you monitor pharmacological therapy for cushing's disease?
|
AM plasma cortisol
24 hour urinary cortisol |
|
|
What is Mitotate MOA?
|
-inhibition of steroid synthesis
-alteration of peripheral steroid metabolism -inhibition of adrenal cortisol release |
|
|
What are the adverse effects of Mitotate?
|
-GI: nausea/anorexia/diarrhea
-Neuromuscular: Fatigue/muscle weakness, CNS depression |
|
|
What is the MOA for Aminoglutethimide?
|
-Inhibition of cholesterol desmolase (cholesterol side chain cleaving enzyme)
-Overall, reduced the synthesis of adrenal glucocorticoid, mineralcorticoid, estrogen, aldosterone and androgens |
|
|
What are the adverse effects of aminoglutethimide?
|
drowsiness, bone marrow suppression, drug-induced lupus!
|
|
|
What is the MOA of Metyrapone?!
|
-inhibited steroid 11 Beta-hydroxylase (final step in cortisol biosynthesis, and inhibits ACH secretion at high doses)
|
|
|
What are the adverse effects of metyrapone?
|
hypokalemia, edema, lightheadedness, rash, hirsutism
|
|
|
What is the MOA of Ketoconazole? How do you monitor therapy?
|
-inhibit steroid 17 alphahydroxylase, 11 Betahydrozylase, and cholesterol desmolase at high doses, potent inhibitor of testosterone
-Urinary free cortisol levels to monitor therapy |
|
|
What are the adverse side effects of Ketoconazole?
|
Increased LFTs, gynecomastia, decreased libido, impotence and GI symptoms
|
|
|
What is Mifepristone?
|
Glucocorticoid and progesterone antagonist; difficult to monitol
|
|
|
What should you tell a patient on mifepristone therapy?
|
Signs of adrenal insufficiency - fatigue, weakness, flu-like symptoms
|
|
|
What are the causes of Addison's disease?
|
*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 |
|
|
How much tissue function is lost before ssx of addison's appear?
|
90%
|
|
|
What are the Clinical SSx of Addison's disease?
|
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 |
|
|
What are the 3 options for hydrocortisone replacement?
|
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 |
|
|
How do you monitor cortisol therapy?
|
Urinary cortisol level
|
|
|
What is fludrocortisone acetate?
|
A potent synthetic mineralocorticoid
Adjust dose bases on potassium level and BP |
|
|
Describe the symptoms of acute adrenal insufficiency
|
Endocrine emergency
Flu-like symptoms initially, then progress to fever, hypotension and shock Electrolyte abnormalities |
|
|
What is the therapy for acute adrenal insufficiency
|
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 |
|
|
Differentiate between Glucocorticoids and Anabolic steroids
|
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 |
|
|
What are the indications for corticosteroid use?
|
-replacement therapy
-anti-inflammatory activity -immunosuppressive effects |
|
|
What is the most potent glucocorticoid?
|
Betamethasone
|
|
|
What is the least potent glucocorticoid
|
Cortisone
|
|
|
Do you want the mineralocorticoid potency to be high or low for glucocorticoids?
|
Low because you don't want to have water retention
|
|
|
Which has more adverse effects? IV? IM? Oral? or Inhaled formulations?
|
IV/IM > Oral>> Inhaled
|
|
|
What are the hematological adverse effects of glucocorticoid use?
|
-Lymphocytopenia - decreases circulating count by redistributing to other body compartments
-Neutrophilia - stimulate bone marrow release Eosinopenia, monocytopenia |
|
|
What is the preventative therapy for osteoporosis with use of glucocorticoids?
|
Calcium supplement
Vitamin D Weight-Bearing Exercise Bisphosphonates: alendronate, risedronate |
|
|
Why does glucocorticoid use cause hyperglycemia?
|
Stimulates gluconeogenesis and inhibits peripheral utilization of glucose; Promotes glycogenolysis by stimulating glucagon release
|
|
|
What are the advantages of alternative day therapy for glucocorticoid use?
|
Decreased HPA suppression
Decreased Cushingoid side effects Recommended for prolonged therapy |
|
|
What are interventions to minimize adverse effects for glucocorticoids
|
singel daily use
not long-acting agents lowest effect dose don't stop chronic therapy abruptly |
|
|
What do you want to be careful off when you withdraw glucocorticoid therapy?
|
-Disease flare-up
-Acute adrenal insufficiency |
|
|
Why does acute adrenal insufficiency occur?
|
HPA suppression - adrenocotical atrophy and unresponsiveness due to lack of ACTH secretion from the pituitary for long period of time
|
|
|
What are symptoms of acute adrenal insufficiency?
|
nausea, fatigue, anorexia, dyspnea, hypotension, hypoglycemia, myalgia, fever, malaise, arthralgia, dizziness
|
|
|
What are factors that affect HPA Axis suppression?
|
Dose
Duration of therapy Type of corticosteroid administered |
|
|
How do you discontinue the use of corticosteroids?
|
Tapering schedule:
-Taper daily dose to physiologic dose -Switch to short-acting agent when near physiologic dose like hydrocortisone or prednisone -administer cosyntropin test |
