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Endocrine - Matt > SM160 Calcium/PTH/Bone Pharm > Flashcards

SM160 Calcium/PTH/Bone Pharm Flashcards

1
Q

Normal serum calcium

A

8.5-10.5 mg/dL

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2
Q

Calcium forms in blood

A

50% ionized (active), 10% bound to anions, 40% protein bound

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3
Q

Active form of vit. D? Storage form?

A

Active: calcitriol - 1,25(OH)2D3
Storage: cholecalciferol/calcidiol - 25(OH)D3

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4
Q

Where is calcium absorption vit. D dependent?

A

Proximal duodenum

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5
Q

What type of diuretic gives you hypocalcemia and what type gives you hypercalcemia?

A

Loops cause hypocalcemia, thiazides cause hypercalcemia

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6
Q

PTH actions on kidney

A

Increased calcium absorption, potassium loss, stimulates 1alpha-hydroxylase

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7
Q

Calcium form in bone

A

Hydroxyapatite: Ca10[PO4]6[OH]2

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8
Q

Cell lineage of osteoclasts

A

Monocyte (related to macrophages)

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9
Q

Osteoclast differentiation

A

Osteoblasts express RANK-L, which stimulates osteoclasts and osteoclast precursors via the RANK receptor

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10
Q

Osteoprotegerin

A

RANK-L antagonist produced by osteoblasts, ratio of RANK-L to osteoprotegerin is important

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11
Q

Osteoclast action

A

Resorb collagenous bone matrix by secreting acid and proteases

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12
Q

Osteoblast action

A

Produces alkaline phosphatase (elevation indicates active osteoblasts), collagen (combines with hydroxyapatite to form bone), osteocalcin

Also promotes osteoclast differentiation, survival, and activity via RANK-L

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13
Q

Osteoblast stimulants

A

IGF-1, bone morphogenetic proteins, wnt signaling pathway

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14
Q

Osteocyte actions, effect on osteoblasts

A

Sense mechanical load

Produce sclerostin to inhibit wnt signaling and osteoblast differentiation (if you could block this you could stimulate bone formation)

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15
Q

Osteoporosis

A

Systemic condition in which osteoblastic activity can’t keep pace with osteoclastic activity

Results in loss of mineral and matrix, susceptibility to fracture

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16
Q

Paget’s disease of bone

A

Locally increased osteoclast activity is followed by increased osteoblast activity

Results in abnormal bone formations

17
Q

Vit. D synthesis

A

Starts with cholesterol, turned into Vit. D3 in skin (cholecalciferol - UVB light required), D3 is converted into 25(OH)D (calcidiol) in the liver and then into 1,25(OH)2D3 (calcitriol) in the kidney by 1a-hydroxylase

18
Q

Vit. D/calcitriol actions

A

Stimulates intestinal Ca++ and phosphate absorption in the proximal duodenum, blocks PTH

19
Q

Disease of deficient vit. D? Excess vit. D?

A

Deficiency: rickets and osteomalacia
Excess: hypercalcemia, osteoclastogenesis

20
Q

Indications for calcitriol and different forms available

A

Alphacalcidol: secondary hyperparathyroidism resulting from renal disease and impaired renal 1-hydroxylation (doesn’t require hydroxylation)

Calcipotriol (topical): proriasis

(Last 3 are in learning guide, not in slides)
Ergocalciferol: hypocalcemia, rickets, osteomalacia, hypoparathyroidism

Doxercalciferol: secondary hyperparathyroidism

Paracalcitol and 22-oxocalcitriol: suppress PTH with minimal effects on Ca and P, used for secondary hyperparathyroidism

21
Q

Vit. D/calcitriol pharmacokinetics

A

Oral, bound to alpha-globulin, inactivated by kidney, hepatic elimination

22
Q

Vit. D/calcitriol major side effect

A

Hypercalcemia

Treatment: stop drug, low calcium diet, glucocorticoids, fluids

23
Q

PTH generic drug name

A

Teriparatide

24
Q

What can suppress PTH?

A

Calcium (+ calcimimetics) via CaSR and vit. D (calcitriol)

25
Q

Cinacalcet: drug type, mechanism, indication, side effects

A

Calcimimetic
Activates CaSR to suppress PTH secretion
Hyperparathyroidism
Hypocalcemia, adynamic bone disease

26
Q

PTH actions on bone: continuous exposure vs. intermittent exposure

A

Continuous exposure: bone loss due to increased RANK-L expression

Intermittent exposure: bone formation from decreased osteoblast apoptosis, increased osteoblast differentiation, and sclerostin suppression

27
Q

Teriparatide: use, limitations

A

Osteoporosis

Hypercalcemia and osteosarcoma risk (though not yet seen in humans)

28
Q

PTHrP

A

Associated with hypercalcemia seen in malignancy

29
Q

Calcitonin: mechanism, use, limitations

A

Acts on mature osteoclasts via GPCR to inhibit bone resorption

Paget’s disease, hypercalcemia, and a minor role for osteoporosis

Low efficacy, can’t give orally, resistance develops

30
Q

Calcitonin-gene related peptide (CGRP): action, use

A

Potent vasodilator

Migraines

31
Q

Estrogen actions on bone

A

Inhibits bone resorption: less IL-6, more osteoprotegerin (RANK-L antagonist), more apoptosis of osteoclasts

32
Q

Glucocorticoids influence on calcium

A

Blocks absorption in the gut, block reabsorption in the kidney. Long-term can cause osteoporosis.

33
Q

FGF-23: what secretes it, action

A

Secreted by osteoblasts and osteoclasts in response to elevated calcitriol

Increases phosphate excretion in the kidney

34
Q

Estrogen use, role of progestin?

A

Prevention of postmenopausal bone loss

Progestin helps to prevent uterine hyperplasia and malignant changes

35
Q

Role of androgens in bone health

A

Androgens are aromatized to estrogen in bone, men with aromatase deficiency can get osteoporosis

36
Q

Raloxifene: drug type, mechanism, indications, side effects

A

SERM (selective estrogen response modulator)

Mechanism: estrogen agonist in bone, antagonist in breast

Uses: prevent postmenopausal osteoporosis and reduce the risk of bone metastasis from breast cancer

Side effects: thromboses and hot flashes

Contraindication: women that want to get pregnant

37
Q

Bisphosphonates: examples, mechanism, uses, side effects

A

Alenodrate (plus other -dronates), zoledronic acid

Pyrophosphate analogs, bind hydroxyapatite in bone, inhibit osteoclast activity

Paget’s, osteoporosis, hypercalcemia, bone metastases

GERD, esophageal irritation, osteonecrosis of the jaw

38
Q

Denosumab: mechanism, actions, use, side effects

A

Monoclonal Ab against RANK-L

Inhibits osteoclast differentation, function, and survival, increasing bone mineral density

Uses: osteoporosis, bone metastases

Side effects: hypocalcemia, rash, osteonecrosis of the jaw, immunosuppression

39
Q

What is the only currently used anabolic therapy for osteoporosis?

A

Teriparatide (PTH)

Endocrine - Matt (23 decks)

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