Endocrine Flashcards

1
Q

What are notable sites of extragonadal production of testosterone and other androgens?

A

Skin, adipose tissue, adrenals

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2
Q

What can testosterone be converted into?

A

Androstenedione (reverse rxn! This is a testosterone precursor), estradiol, and DHT

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3
Q

What enzyme converts testosterone to DHT?

A

5α-reductase

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4
Q

The hypothalamus secretes ______, which acts on gonadotrophs in the anterior pituitary

A

GnRH

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5
Q

GnRH stimulates the release of ________ from the gonadotrophs of the anterior pituitary

A

LH and FSH

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6
Q

GnRH secretion is _______

A

pulsatile

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7
Q

Continuous secretion of GnRH does what?

A

Suppresses the release of LH and FSH

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8
Q

LH acts on _______ cells

A

Leydig

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9
Q

What are Leydig cells? What do they do?

A

Interstitial cells in the testes

Produces testosterone

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10
Q

FSH acts on _______ cells

A

Sertoli

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11
Q

What are Sertoli cells? What do they do?

A

Cells in the testes in direct contact with the seminiferous tubules

Functions:

  • synthesis of P450 aromatase (converts testosterone to estradiol)
  • production of growth factors that support spermatogenesis
  • synthesis of inhibins
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12
Q

What does aromatase do?

A

Converts testosterone to estradiol

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13
Q

20,22-desmolase

A

Enzyme that converts cholesterol into pregnenolone

Rate limiting step

LH stimulates this rxn

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14
Q

What type of G protein receptor does GnRH bind to in the anterior pituitary?

A

Gq –> PLC –> IP3 + DAG

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15
Q

Theca cells have receptors for what hormone?

A

LH

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16
Q

Granulosa cells have receptors for what hormone?

A

LH and FSH

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17
Q

Which hormone decreases the release of GH?

A

Somatostatin

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18
Q

Mecasermin

A

Recombinant IGF (insulin-like growth factor)

Used to treat pts w/ growth hormone insensitivity

Ex: Laron dwarves

Concern for hypoglycemia, so ingest carbs prior to taking

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19
Q

Recombinant GH

A

Replacement tx in children w/ deficiency

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20
Q

Octreotide

A

Somatostatin analogue

Uses:
- excess GH 2/2 pituitary adenoma

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21
Q

Pegvisomant

A

GH receptor antagonist

1x daily dose, SQ

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22
Q

What molecule directly controls the release of prolactin?

A

Dopamine at D2 receptors in the hypothalamus

Dopamine INHIBITS prolactin release

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23
Q

Cabergoline

A

Dopamine agonist used to treat hyperprolactinemia (prolactinomas)

Preferred agent; more selective for D2 receptors and more effective

May cause hypotension, dizziness; valvular HD at higher doses

May inhibit GH secretion in some pts, but not as effective as SST analogues.

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24
Q

Bromocriptine

A

Dopamine agonist

Used to treat hyperprolactinemia

Also activates D1 receptors

Frequent side effects include N/V, headache, and postural hypotension; less frequently can see psychosis or insomnia

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25
Q

Vasopressin

A

= ADH

Tx parenteral admin, t1/2 = 20 min

Endogenous release occurs w/ rising blood osmolality –> retain water in body via adding water channels (aquaporins) in luminal membrane

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26
Q

Desmopressin (DDAVP)

A

ADH analogue that is more stable; t1/2 = 1.5-2.5 hours

No vasopressor effect

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27
Q

Central diabetes insipidus

A

Can result from head injury, pituitary tumors, cerebral aneurysm, or ischemia = inadequate secretion of ADH from posterior pituitary

Tx: desmopressin, chlorpropamide (1st gen sulfonylurea)

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28
Q

Nephrogenic diabetes insipidus

A

Congenital or drug-induced (lithium) = inadequate ADH action

Tx: fluids, low salt/protein diet, thiazide diuretics (paradoxical mechanism), NSAIDs like indomethicin (inhibit PGs, which lower ADH effects)

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29
Q

Syndrome of Inappropriate Secretion of ADH (SIADH)

A

Incomplete suppression of ADH secretion under hypoosmolar conditions. Thus, people retain water & urine is inappropriately concentrated.

Causes: malignancy, pulmonary diseases, trauma, infections

One of the most common causes of hyponatremia; occurs in 15-22% of hospitalized pts

Tx: restrict free water intake, V2 receptor antagonists, demeclocyline

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30
Q

What drugs induce SIADH?

A

SSRIs, haloperidol, TCADs

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31
Q

Demeclocyline

A

Inhibits ADH effect on distal tubule

Treats hyponatremia in SIADH

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32
Q

Tolvaptan or Conivaptan

A

V2 receptor antagonists

Tx for hyponatremia in SIADH

Warning against rapid correction of hyponatremia: cerebellar pontine myelinolysis!!!

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33
Q

What is an example of an adrenal glucocorticoid?

A

Cortisol

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34
Q

What is an example of an adrenal mineralocorticoid?

A

Aldosterone

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35
Q

What controls the release of ACTH? Where is it released from?

A

CRF (from hypothalamus) controls release of ACTH

ACTH is released from the anterior pituitary

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36
Q

If there’s an -OH group at 11 in corticosteroids, it’s _____.

A

active

Ex: cortisol, prednisolone

Liver does this

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37
Q

If there’s a ketone group at 11, it’s ______.

A

inactive

Ex: prednisone, cortisone

Kidney does this

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38
Q

When using corticosteroids to treat Addison’s Disease (physiologic use), what drug(s) should be used and why?

A

Cortisol (aka hydrocortisone)

It’s necessary to use an agent with both glucocorticoid and mineralocorticoid properties (cortisol is 1:1) to mimic the physiologic effects of the adrenals.

Unless the disease is mild, fludrocortisone (high mineralocorticoid activity) is usually required for sufficient salt-retaining effect.

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39
Q

When using corticosteroids to treat inflammation (pharmacologic use), what drug(s) should be used and why?

A

Prednisone, triamcinolone, dexamethasone

All have significantly higher glucocorticoid properties, which = anti-inflammatory properties

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40
Q

Which hormones are produced by the adrenal cortex?

A
  1. Cortisol
  2. Aldosterone
  3. Sex hormones (small amounts)
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41
Q

Which hormones are produced by the adrenal medulla?

A

Epinephrine and norepinephrine

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42
Q

Which one is active, prednisone or prednisolone?

A

Prednisolone is the active form

Prednisone gets converted by liver into active form

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43
Q

Ketoconazole

A

Inhibits downstream conversion of cholesterol into other hormones. Blocks 17α-hydroxylase and 17,20-lyase.

Used to treat Cushing’s Syndrome (hypercortisolism)

May inhibit androgen synthesis, leading to gynecomastia & impotence

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44
Q

Mifepristone

A

Glucocorticoid receptor antagonist

Used in Cushing’s Syndrome

Not a first-line drug - approved to control hyperglycemia secondary to hypercortisolism

Contraindicated for use during pregnancy - women of child-bearing age should use contraception

“My wife has pristine cushions”

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45
Q

Congenital adrenal hyperplasia

A

Due to congenital enzyme defects, the production of cortisol is severely diminished

Cortisol normally has negative feedback effect on ACTH levels; thus, here, ACTH levels are extremely high

Increased ACTH leads to overstimulation of adrenal gland and adrenal hyperplasia

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46
Q

How is congenital adrenal hyperplasia treated in children vs. adults?

A

Children - hydrocortisone
Adults - prednisone or dexamethasone

The goal of therapy is to replace deficient steroids while minimizing adrenal sex hormone (overproduction) and glucocorticoid excess (via overtreatment).

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47
Q

Pheochromocytoma

A

Excess epinephrine/norepinephrine production due to a tumor in the adrenal medulla

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48
Q

What does the pharmacological preparation for pheochromocytoma surgery consist of?

A

Prep w/ α-blockers for several days to control blood pressure

THEN, beta-blockade to control tachycardia and arrhythmias

Can supplement with CCBs (nefidipine) if blood pressure control is inadequate or side effects are not tolerated

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49
Q

Phenoxybenzamine

A

Irreversible α1-α2 receptor antagonist

Initial step of pheochromocytoma surgery prep

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50
Q

Metyrosine

A

Competitive inhibitor of catecholamine synthesis

Can be added to antihypertensive regimen to reduce catecholamine synthesis for inoperable or metastatic pheochromocytoma tumors

51
Q

Propylthiouracil (PTU)

A

Antithyroid agent - prevents the oxidation of iodide and thus blocks production of thyroid hormone

(Also inhibits the peripheral diodination of circulating T4 into T3, thus ameliorating sx of thyroid hormone excess)

52
Q

Pendred Syndrome

A

Characterized by hypothyroidism and sensorineural deafness

Mutation in the SLC26A4 gene, whose product, pendrin, is an anion transporter expressed on the apical surface of thyrocytes and in the inner ear

53
Q

What are some hormones that are tyrosine derivatives?

A

Epinephrine, norepinephrine, and dopamine

Also thyroid hormone (but it defies the rule of transporter, etc.)

54
Q

Prolactin acts via what pathway in the cell?

A

Cytokine receptors –> JAK/STAT pathway

55
Q

How is prolactin regulated?

A

Inhibitory control by dopamine (also called Prolactin Inhibitory Hormone, or PIH), released from the hypothalamus

56
Q

What type of meds will cause an increase in prolactin?

A

Dopamine D2 antagonists - commonly found in antipsychotic meds

57
Q

Growth hormone acts via what pathway in the cell?

A

Cytokine receptors –> JAK/STAT pathway

58
Q

What are the effects of GH?

A
  • increased lipolysis (via hormone-sensitive lipase) –> increased FFA
  • increased gluconeogenesis, glycogenolysis = antagonizes effects of insulin
  • increased uptake of aa into muscle tissue

Thus, diabetogenic

59
Q

What happens with an excess of prolactin?

A

Decrease in GnRH

= amenhorrhea, decreased sex drive

60
Q

What is the blood test to check GH levels?

A

IGF-1

61
Q

Galactorrhea

A

Excessive or inappropriate production of milk

62
Q

Cushing’s Syndrome - definition? Sx?

A

Excess cortisol - either meds or a tumor

Sx:

  • moon facies
  • central obesity
  • osteoporosis
  • HTN
  • peripheral wasting of fat/muscle
  • diabetes
  • hypertriglyceridemia
  • amenhorrhea/infertility
  • excess hair growth
  • impotence
  • edema
  • impaired immunity
  • neurocognitive changes/depression
  • acne
  • violaceous abdominal striae >1 cm
  • easy bruising, spontaneous ecchymoses
63
Q

Cushing’s Disease

A

Excess cortisol due to a pituitary adenoma

64
Q

What is the suppression test for Cushing’s Syndrome? Explain the 2 versions.

A

Low dose (1 mg) or high dose (8 mg) dexamethasone suppression test

If neither test suppresses high cortisol levels + low ACTH levels: hyper cortisol production is primary, from the adrenals

If cortisol is not suppressed by 1 mg test, but suppressed by 8 mg test (and high ACTH): Cushing’s Disease. Lots of ACTH being produced, but pituitary retains some feedback inhibition, and thus a high enough dose will downregulate ACTH (& cortisol) production

If cortisol is not suppressed by either test + ACTH is VERY high (hundreds): ectopic ACTH production from a tumor outside of pituitary

65
Q

What is the gold standard test for central adrenal insufficiency?

A

Insulin-induced hypoglycemia

Assesses entire HPA axis

66
Q

What is the cosyntropin test?

A

Test for central adrenal insufficiency

Give them cosyntropin, which is an ACTH analogue, at supraphysiologic dose; see if adrenals respond

67
Q

Apoplexy

A

Sudden infarct or hemorrhage of the pituitary gland

Causes headache, vision changes, ophthalmoplegia, and altered mental status

68
Q

Hyperpigmentation is a sign of?

A

ACTH excess and/or adrenal insufficiency

Reason: melanocyte-stimulating hormone (MSH) is a byproduct of the creation of ACTH from the larger molecule POMC

69
Q

What are the mechanistic actions of ADH?

A

V1 receptors –> vascular vasoconstriction, platelet aggregation

V2 receptors –> antidiuretic effects in the kidneys via moving aquaporins to the cell membrane = water reabsorption

70
Q

What is the type of pituitary tumor that frequently looks like other tumors and has a “sheet-like” appearance?

A

Gonadotroph adenoma

= most common type of clinically non-functional adenoma; most common type to come to surgery

71
Q

What is the one type of pituitary tumor that does not have surgery as a first-line treatment?

A

Prolactinomas

72
Q

SF-1 mutation

A

Gonadotrophs

FSH/LH-secreting pituitary adenoma

Also the mutation in most of the hormone negative adenomas

73
Q

TTF-1 mutation

A

Expressed in posterior gland and pituicytomas

74
Q

Pit-1 mutation

A

Somatotroph stem cell lineage

Can be:

  • GH secreting
  • prolactin secreting
  • mixed

Or acidophil stem cell adenoma

75
Q

T-pit mutation

A

Corticotrophs

ACTH-secreting pituitary adenoma

76
Q

Adamantinomatous craniopharyngioma

A

Mostly found in children

77
Q

Papillary craniopharyngioma

A

Mostly found in adults

78
Q

Tesamorelin

A

GHRH analog

Used in HIV patients with lipodystrophy 2/2 HAART

Reduces excess abdominal fat

79
Q

What is the order in which anterior pituitary hormones are lost (if there is dysfunction)?

A
  1. GH
  2. FSH, LH
  3. ACTH
  4. TSH
  5. PRL
80
Q

What two hormones are controlled by TRH from the hypothalamus?

A

TSH and prolactin

81
Q

What are some confirmation tests for hyperaldosteronism?

A

Oral salt test (high NaCl diet x3 days) or IV saline infusion (2 L NS x4 hours)

Normally, aldosterone levels should be undetectable (aldo retains Na+, so if you’re getting a huge Na+ dose, levels should plummet). If levels are still elevated after these tests = positive

82
Q

NP-59 adrenocortical scintigraphy

A

NP-59 is a cholesterol analog

Adrenals use it, just as they use cholesterol, as the base for the other hormones

Can be used to visualizes adrenal issues - bilaterally taken up = hyperplasia, unilaterally taken up = adenoma

83
Q

Pheochromocytoma triad (pt sx) + 1 sign?

A

Headaches, sweating, palpitations

Sign: hypertension

84
Q

What is the rule of 10’s for pheochromocytoma?

A

10% are malignant
10% are familial
10% are ectopic
10% are bilateral

85
Q

What are the tests for pheochromocytoma?

A
Urine metanephrines (=metabolites of catecholamines)
Positive = >1300 ug/24 hr

Urine catecholamines
Positive = >2 fold increase

^^More specificity

Plasma metanephrines
Positive = >0.5 nmol/L

^^More sensitivity

86
Q

What is the composition of the colloid in the thyroid gland?

A

Thyroglobulin (large concentrations thereof)

87
Q

How does estrogen raise the levels of total T4 and T3?

A

Estrogen causes the production of more TBG and albumin –> raises the total amount of serum binding proteins

Thus, levels of total T4 and T3 are raised, but not free

88
Q

Which of the thyroid hormone assays is not very reliable?

A

Free T3 is not reliable

If you need to know, order a total T3

89
Q

What is thyrotoxicosis vs. hyperthyroidism?

A

Thyrotoxicosis: elevated levels of circulating thyroid hormone

Hyperthyroidism: overproduction of circulating T3 and T4

90
Q

What is the name of the teratoma composed of ectopic thyroid tissue in the ovaries that produces TH?

A

Struma ovarii

91
Q

Methimazole

A

Antithyroid agent - prevents the production of thyroid hormone

92
Q

What is the clinical course of thyroiditis?

A

Initially (0-3 months): ↑ T4 (due to being released from dying cells), ↓ TSH (response)
= hyperthyroid picture

Later (3-6 months): ↓ T4 (stores depleted), ↑ TSH (pituitary kicks in, but thyroid is damaged and can’t respond)
= hypothyroid picture

20-25% remain hypothyroid

93
Q

Definition of subclinical hypothyroidism

A

↑ TSH

Normal free T4

94
Q

C cells

A

Parafollicular cells

Primary purpose is to secrete calcitonin

In the CT of the thyroid

95
Q

What is the most common type of thyroid cancer?

A

Papillary carcinoma

96
Q

What are the key diagnostic features of a papillary carcinoma?

A

Nuclei are empty w/ chromatin on the outside

Nuclei tend to be large w/ grooves in the nuclear envelope

Optically clear nuclei

Papillae with vascular core

On FNA, “coral” appearance

97
Q

Medullary carcinoma of the thyroid

A

Solid proliferation of cells with granular cytoplasm (C Cells)

Highly vascular stroma

Hyalinized collagen and/or amyloid

98
Q

What are some worrisome signs when you’re examining lumps?

A
Hard = more concerning
Fixation = usually means it's invading
99
Q

What is the approach to a patient with thyroid nodules?

A
  1. TSH level
  2. Diagnostic ultrasound
  3. (poss.) FNA
100
Q

What is the most common cellular pathway that is messed up in thyroid cancer?

A

MAP kinase

Ras –> BRAF –> MEK-ERK

101
Q

PAX8

A

Function: initiation of thyroid cell differentiation, maintenance of the differentiated state, and essential for thyroid cell proliferation

Mutations can lead to thyroid hypoplasia. AD inheritance

102
Q

TITF2

A

Migration of thyroid precursor cells and transcriptional control of the TG and TPO gene promoters in thyroid development

Homozygous mutations result in Bamforth-Lazarus syndrome: congenital hypoplasia, cleft palate, spiky hair, and variably bifid epiglottis and choanal atresia

103
Q

Interpret: if T3 uptake and T4 are going in the same direction (both low/both high)

A

Indicates thyroid disease

Low T3 uptake/low total T4 = hypothyroid

High T3 uptake/high total T4 = hyperthyroid

104
Q

Interpret: if T3 uptake and T4 are in different directions

A

TBG abnormality

High uptake and low total T4 = TBG deficiency

105
Q

Interpret: an adolescent girl has normal TSH but high total T4

A

Common, benign. Due to estrogen, likely OCPs

106
Q

Jod-Basedow phenomenon

A

Hyperthyroidism following administration of iodine, either as a dietary supplement or as contrast medium

107
Q

What does pain/tenderness with a goiter indicate?

A

Thyroiditis

108
Q

How does thyroid disease affect reproductive function in women?

A

High free T4 increases sex hormone binding globulin (SHBG) and this results in a lower free estradiol level that leads to lighter menstrual bleeding and amenorrhea

Low free T4 decreases SHBG, increases free estradiol and leads to hypermenorrhea

109
Q

MEN I

A

“The P’s:”

  • pituitary tumor
  • pancreatic islet tumors
  • parathyroid hyperplasia

Germline mutation, so pituitary & pancreatic tumors tend to be multiple.
You can test for menin gene mutations.

110
Q

MEN IIA

A
  • medullary thyroid carcinoma
  • pheochromocytoma
  • parathyroid hyperplasia

Germline mutation: Ret gene

111
Q

In a hospitalized patient, the most common cause of hypocalcemia is?

A

Low serum protein level

Thus, find the corrected serum calcium level

112
Q

Serum total calcium correction formula

A

Add 0.8 mg/dL to total calcium for every 1 g/L albumin is

113
Q

Pseudohypoparathyroidism - lab & clinical features

A

Labs:
↓ serum calcium
↑ serum phosphate
↑ serum PTH

Clinical:
Short 4th & 5th metacarpals

114
Q

Paracalcitol

A

Blocks PTH receptors at the parathryoid, but not elsewhere in the body

Treats secondary hyper-PTH via inhibiting release of PTH, but do not cause hypercalcemia

115
Q

Osteoprotegerin (OPG)

A

Decoy RANK-L receptor

Thus, binds RANK-L on osteoblasts and prevents osteoclasts (with their own RANK receptor) from being activated

116
Q

Effect of estrogen on bones

A

Major effect: ↓ osteoclast activity and #

Also ↑ osteoblast production of OPG

117
Q

Osteoporosis tx - anti-resorptive drugs

A
Bisphosphonates
Denosumab
Raloxifene
Calcitonin
Estrogen
118
Q

Osteopororsis tx - anabolic drugs

A

Teriparatide

Romosozumab

119
Q

Bisphosphonates - names? MOA?

A

Alendronate, risedronate, zoledronate, etc…

Have direct inhibitory effect on osteoclasts (induce apoptosis)

120
Q

Selective estrogen receptor modulator - name? MOA?

A

Raloxifene

Agonist on receptors in bone - reduces risk of osteoporotic fractures

Will cause hot flashes; increase clotting factor production in liver (due to liver receptors)

121
Q

Teriparatide

A

Synthetic PTH

Only agent for osteoporosis that stimulates bone formation

122
Q

Denosumab

A

Ab to RANK-L

Reduces osteoclast activity; improves bone mineral density

123
Q

What is the tx of choice for severe hypocalcemia?

A

Calcium gluconate

124
Q
Number of carbons in: 
cortisol
aldosterone
progestin
androgens
estrogen
A
cortisol - 21
aldosterone - 21
progestin - 21
androgens - 19
estrogen - 18