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Therapeutics 2 - Fall 2017 > Hockerman Ca2+ Homeostasis > Flashcards

Hockerman Ca2+ Homeostasis Flashcards

1
Q

what kind of cells PUT Ca2+ into bones?

A

osteoBLASTS (building bone)

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2
Q

what do osteocytes do?

A

are inside bone to control the osteoblasts and osteoclasts

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3
Q

what cells release PO4 and Ca2+ from bone?

A

osteoclasts

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4
Q

Bone is _____ sensitive: _______ force is detected by cell processes that extend into canaliculi which forms a network involving _______ and ______

A

load; mechanical; ACTIN; Connexin 43

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5
Q

Parathyroid Hormone:

  • is a ________ hormone secreted from parathyroid gland
  • it is ____ amino acids long; cleaved from a precursor that is _____ amino acids long;
  • what part of the hormone has full activity?
  • if ______ is deleted from the hormone - activity is lost
A

peptide; 84; 115; amino acids 1 - 34; amino acid 1 & 2

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6
Q

The parathyroid’s hormone is in charge of maintain what?

A

keeping a constant Ca2+ concentration in extracellular serum

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7
Q

what actions does PTH do?

  • increase Ca2+ reabsorption from ______
  • increase Ca2+ resorption from ______
  • increased _____ lost in urine
  • increased ______ produced by kidney
A

collecting tubules; bone; PO4-; Vit. D

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8
Q

what is the first step of Vitamin D Synthesis

A

7 dehydrocholesterol –> Vitamin D3 (Cholecalciferol) via UV light

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9
Q

Liver’s Role in Vitamin D synthesis - ?

A

Vitamin D3 –> 25 hydroxyvitamin D3 via Vit D 25- hydroxylase

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10
Q

Kidney’s Role in Vitamin D Synthesis - ?

A

hydroxylase enzyme (1a or 24) to make 1,25 Vit. D3 or 24,25 Vit. D3

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11
Q

What are the actions of Vit. D

  • increased _________ absorption from small intestine
  • increases reabsorption of _______
  • feedback inhibition of ______
  • will have indirect (slow or fast) effects on cells
A

ca2+/PO4; Ca2+/PO4; PTH; slow

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12
Q

How does Vit. D help with absorption of Ca2+ from intestines

A

it up regulates TrpV6, Calbindin-D9k; Ca2+ATPase - all of those help Ca2+ go from lumen to the blood

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13
Q

Role of TrpV6 in absorbing Ca2+ from the intestine

A

Ca2+ channel

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14
Q

Role of Calbindin-D9k in absorbing Ca2+ from the intestine

A

it is the calcium “chaperone” guides Calcium across the cell

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15
Q

Role of Ca2+ATPase in absorbing Ca2+ from the intestine

A

pushes Ca2+ out into the plasma from the cell

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16
Q

_______ is released from the thyroid gland and is a negative regulator of serum Ca2+

A

Calcitonin

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17
Q

How does calcitonin act as a negative regulator of serum Ca2+

A
  • inhibits osteoclastic bone resorption

- increases Ca2+ and PO4 loss in urine (aka less is absorbed)

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18
Q

Calcitonin is triggered to be release by what?

A

high levels of Ca2+

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19
Q

Explain Paget’s Disease

A
  • UNCONTROLLED OSTEOCLASTIC BONE RESOPRTION AND SECONDARY BONE FORMATION (bone pain/deformities, loss of hearing and hypercalcemia)
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20
Q

Paget’s Disease patients are at risk of having (hypo or hyper) calcemia

A

Hyper - because hella osteoclastic bone resorption is occurring

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21
Q

Risk Factors for Osteoporosis

A

Physical inactivity (try weight lifting); age; low Ca2+ intake in early years; long term glucocorticoid

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22
Q

Possible causes for Hypercalcemia

A
  • hyperparathyroidism

- malignant tumors

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23
Q

Hypercalcemia can cause what ?

A

CNS symptoms (depression, coma)

24
Q

Hypocalcemia can be caused by what?

A
  • Hypoparathyroidism

- vit. D deficiencies

25
Hypocalcemia can cause what?
- neuromuscular distrubances - paresthesias, tetany, muscle cramps
26
Different Preparations of Vit. D that are available
- Vit D.3 ( OTC - doesn't have that 1 or 25 OH) - therefore needs kidney AND liver function - 25OH Vit. D3 - NEEDS KIDNEY FUNCTION - 1,25 OH Vit. D3 - does not need function of kidney or liver
27
Clinical uses for Vit. D
- hypocalemia - hypoparathyroidism (used as supplement bc usually PTH stimulates Vit. D to be made) - hyperparathyroidism (secondary to CKD - used as feedback inhibition to have PTH chill)
28
Bisphosphonates: inhibit bone ______
resorption
29
Bisphosphonates: MOA - 2 ideas/options - reduce ________ and ________ of hydroxyapatitie crystals OR - disrupt _______, induce _______ and inhibit FPP synthesis in _________
formation; dissolution; cytoskeleton; apoptosis; osteoclasts
30
Bisphosphonates: Counseling tips
- taken w/ H20 - take 30 min before breakfast (because drug interactions..?) - gastric irritation (therefore sit up after taking it) - may cause Hypocalcemia
31
List all the bisphosphonates
- alendronate - risendronate - ibandronate - zoledronate - eitdronate - tiludronate - pamidronate
32
What bisphosphonates are approved for Paget's and cancer (NOT osteoporosis)
- pamidronate - tiludronate - etidronate
33
what bisphosphonates ARE approved osteoporosis
- alendronate - risedronate - ibandronate - zoledronate
34
MOA of Bisphosphonates: - ________ of farnesyl pyrophosphate synthase - disrupts prenylation of proteins in _________ - affects isoprenoid activity and ______ can induced
inhibition; osteoclasts; apoptosis
35
Second line treatment for Osteoporosis
Estrogens and SERMs
36
Calcitonin will _______ osteoclast activity and thats why it can be used for ________
osteoporosis (only as alternative for ERT)
37
side effects of Calcitonin (given as Calcimar or Miacalcin)
urticaria; hand swelling, nausea
38
Clinical Uses of Calcitonin (given as Calcimar or Miacalcin)
- pagets disease - hypercalcemia (secondary to malignancy) - Alt. therapy for osteoporosis (alt. to ERT)
39
what kind of drug is Forteo?
its the first 34 amino acids of PTH
40
forteo = ? (generic)
Teriparatide
41
usually don't want parathyroid because stimulates resorption of bones BUT forteo can be used to help with osteoporosis - HOW?
- given periodically - and Ca2+ and Vit. D are supplemented | - this will preferentially stimulate osteoblasts NOT osteoclasts
42
List the components for differentiating osteoclasts
- RANKL - RANK - OPG (osteoprotegerin)
43
Describe how osteoclasts are differentiated
- RANKL (a ligand on an osteoblast) will bind to RANK (a receptor on an osteoclast precursor) - will create an osteoclast - RANKL can bind to OPG which prevents osteoclast differntiation
44
Continuous PTH - will lead to.... | _____ RANKL and _____ OPG
MORE RANKL and LESS OPG (that means more osteoclast differentiating!
45
Risk of _______ with Tymlos (abaloparatide) - a PTH related peptide
osteocarcinoma
46
________ drug is a humanized monoclonal Ab against RANKL - aka will prevent osteoclast precursos from differentiating into osteoclasts
Prolia (Denosumab)
47
New strategy for Osteoporosis: - drug involving serotonin....
serotonin INHIBITS osteoblast proliferation TPH1 helps serotonin in the gut be made - therefore inhibit TPH1 to decrease serotonin and therefore serotonin too
48
New strategy for Osteoporosis: - drug involving cathepsin K
cathespin K - is released by osteoclasts and will degrade type 1 collagen in bone = therefore use a cathepsin K inhibitor
49
Normal Ca2+ plasma level (only Free Ca2+)
1.1 - 1.3 mM
50
Drug classes listed that affect Ca2+ levels
- loop diuretics (increased Ca2+ excretion) - Thiazides (decreased excretion) - PPIs/H2 antagonists (decreased absorption) - Carbemazepine, isoniazid, theophylline, rifampin (induction of vit. D catabolites
51
how do loop diuretics affect Ca2+
increase Ca2+ excretion
52
how do thiazides affect Ca2+
decrease Ca2+ excretion
53
how do PPIs and H2 antagonists affect Ca2+
decrease absorption
54
Cinacalcet (Sensipar) is used to treat what?
Hyperparathyroidism
55
Cinacalcet (Sensipar) binds to _______ on the ______ to inhibit the release of ______
CaR (calcium sensing receptor); PTH gland; inhibit PTH
56
Cinacalcet (Sensipar) will decrease both ______ and _____ levels
Ca2+ and PTH

Therapeutics 2 - Fall 2017 (22 decks)

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