160b Ca/PO4/Bone pharm

Question 1

what form of serum calcium is active?

Answer 1

ionized only

50% of serum calcium (rest is bound to proteins)

Question 2

What percentage of Ca from the diet is absorbed in the intestine?

Answer 2

10-20% absorbed

Question 3

How is calcium absorbed in the intestine?

Answer 3

1) passive diffusion throughout

2) Vit-D controlled in proximal duodenum (+ PO4)

Question 4

What effect do glucocorticoids have on Ca absorption in the intestine?

Answer 4

Reduce

Question 5

diuertics: thiazide vs furosemide and Ca

Answer 5

loops (furosemide) lose Ca to urine

thiazides save Ca from urine

Question 6

what increases PO4 excretion in the kidney?

Answer 6

FGF-23 and PTH

Question 7

axial bone vs appendicular

Answer 7

axial - highly trabecular with more marrow and fat

affected with Ca diseases

Question 8

osteoclast - from what cell type?

Answer 8

from precursor monocyte (also gives rise to macrophages)

Question 9

what ligand controls osteoclast differentiation?

Answer 9

osteoblasts –> RANKL cytokine –> increases fusion, activity, survival via RANK on osteoclast

Question 10

osteoprotegerin - function?

Answer 10

Blocks RANKL activity thus decreasing OC activity

Question 11

osteoblast - markers for activity?

Answer 11

osteocalcin

alkaline phosphatase

Question 12

OB - from what cell type?

Answer 12

pluripotent precursor which also makes adipocytes

Question 13

what signals activate OB?

Answer 13

IGF-1

wnt pathway

Question 14

sclerostin - what makes it and fxn?

Answer 14

Osteocytes

–I wnt signals and OB differentiation –> blocks bone formation

Question 15

osteoporosis - basic disease process?

Answer 15

OB can’t keep up with increases OC activity

Question 16

pagets disease of bone - basic disease process?

Answer 16

local increased OC activity followed by disordered OB activity –> abnormal bone

Question 17

vitamin D - active form

Answer 17

1,25 (OH)2 D3 aka calcitriol

Question 18

what is the storage form of Vit D

Answer 18

25 (OH) vit D –> measure this when testing for Vit D deficiency, not 1,25 form

Question 19

1a-hydroxylation - where does it occur? what is made?

Answer 19

kidney

makes calcitriol (1,25 (OH)2 Vit D)

Question 20

calcitriol receptors type? fxn?

Answer 20

steroid –> nuclear receptors

increases transcription

Question 21

calcitriol effect on PTH?

Answer 21

decreases PTH secretion

Question 22

alphacalcidol -Rx? form?

Answer 22

Rx - 2ndary hyper PTH from renal disease

1-OH vit D – converted via liver to active form

Question 23

calcipotriol - topical

Answer 23

psoriases treatment to increase cell differentiation

Question 24

teriparatide - what is it? Rx? dosing? SE?

Answer 24

PTH analog with full activity (1st 34 aa of PTH_

Rx for osteoporosis –> anabolic

once a day = intermittent affect (anabolic)

osteosarcoma?

Question 25

PTH secretion pattern normally?

Answer 25

pulsatile manner –> anabolic effect

Question 26

what decreases PTH secretion?

Answer 26

calcimimetics
Ca
Vit-D

Question 27

cinacalcet - what is it? what does it treat?

Answer 27

calcimimetic –> allosteric activator of CaSR (increases sensitivity to Ca)

suppresses excess PTH secretion

Question 28

PTH - continuous exposure vs intermittent?

Answer 28

continuous - bone resorption from increased RANKL expression on OB

intermittent - bone formation via decreased OB apoptosis, suppresses sclerostin

Question 29

PTHrP - what is? what can it cause?

Answer 29

8 of first 13 aa like PTH

can cause hypercalcemia in cancers

Question 30

calcitonin - from what? what causes releases? what does it do? Rx for what?

Answer 30

c-cells of thyroid gland

increased secretion by high Ca

inhibits bone resorption on OC

Rx - Paget’s disease

Question 31

CGRP

Answer 31

calcitonin gene related peptide

potent vasodilator in migraines

Question 32

estrogen effect on bone?

Answer 32

–I RANKL and IL-6 –> blocks resorption

osteoclast apoptosis

Question 33

androgen effect on bone?

Answer 33

aromatased to estrogen

Question 34

raloxifene

Answer 34

selective estrogen response modulators (SERMS)

acts as estrogen on bone but anti-estorgen effect elsewhere (mammary gland)

Question 35

bisphosphonates

Answer 35

alendronate
_dronate

analogs of pyrophosphate –> interfere with OC action

Rx- osteoporosis, paget’s, hypercalcemia, metastases

Question 36

denosumab

Answer 36

human monoclonal AB –I RANKL

inhibits osteoclast

Rx- osteoporosis and bone metastases

Question 37

what is the only anabolic bone Rx?

Answer 37

teriparatide