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Pharmacology > Calcium Metabolism Drugs > Flashcards

Calcium Metabolism Drugs Flashcards

1
Q

What are the segments of the bone?

A

Spongy trabecular bone
Compact bone => bone mineralization process

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2
Q

What is the osteoblast differentiation factor?

A

RANK-L

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3
Q

What are the diff factors that affect bone turnover?

A

Humoral factors: PTH, VIt D, Calcitonin

Others: Glucocorticoids, TH, Gonadal steroids

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4
Q

What are the local factors that help fine tune bone remodeling?

A

IGF-1 = INC osteoblast proliferation
TGF-B & IL-6 = INC osteoClast activity
PGs = INC bone turnover
Bone morphogenetic proteins = bone formation

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5
Q

WHat are other factors affected by bone remodeling?

A

Local stresses: exercise
Electrical stimulation
Environmental: temp, O2 levels, ABB

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6
Q

What are the 3 hormones that regulat Ca?

A

PTH
Calcitonin
Vitamin D

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7
Q

What is the most important endocrine regulator of Ca homeostasis? What cell secretes it?

A

Parathyroid gland
Cell: Chief cells

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8
Q

How does plama Ca level stimulate PTH secretion?

A

Low plasma Ca levels => stimulates PTH secretion
High plama Ca levels => suppresses PTH secretion

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9
Q

What are the 3 organs acted on by PTH indirectly & directly?

A

Indirectly = GI tract
Directly = Kidneys & bone

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10
Q

From what cells is Calcitonin produced & released? IN response to what?

A

Parafollicular cells

In response to HYPERCALCEMIA —> inhibits resoprive activity of osteoclasts => DEC bone resorption & plasma Ca levels

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11
Q

In what organ is Vit D activated? What is Vit D’s purpose?

A

Kidneys

Regulator of PTH => Inhibits PTH synthesis & release => INC osteoClast activity

INC Ca uptake, binding protein (Calbindin), Ca to capillaries

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12
Q

What is the effect of Intermittend PTH signal?

A

INC bone formation & bone mass

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13
Q

What is the often cause of bone mineral disorders?

A

Disruption of bone turnover

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14
Q

WHat are the three factors that cannot be imbalanced for they can lead to poor mineralization of the bone?

A
  1. Abnormal levels of Vit D, PTH
  2. INC rate of bone remodeling
  3. Failure of organs that maintain mineral homeostasis
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15
Q

What are the 3 pharmacologic agents for Osteoporosis? WHat are its MOA?

A

Antiresorptive agents => inhibits bone resoprtion
Bone anabolic agents => stimulates bone formation
Supplements = given depending on stage of osteoporosis (oral Ca & Vit D)

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16
Q

What are the diff Bone anabolic agents?

A

Teriparataide, Abaloparatide, Stronitum ranelate, Fluoride

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17
Q

What is the effect of antiresopritve agents & what are the diff drugs under it?

A

INC osteoclast acitivity (rate of turnver)

Bisphosphonates
Calcitonin homrone replacement therapy
Selective estrogen receptor modulators
Denosumab

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18
Q

What pharmacological agents are given to px w/ CKD? What are its purpose?

A

Oral PO4 binders = DEC plasma PO4 levels
Vit D & Calcimimetic = DEC PTH synthesis & secretion

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19
Q

What drugs are given for px w/ Rickets, Osteomalacia, & HYPOthyroidism?

A

Oral Ca & Vit D = prevention & tx

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20
Q

WHat are the 3 drug clases for hormonal/mineral imbalance?

A

Vit D analogues
Vitamin D (Calcitriol)
Ca Analogues

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21
Q

What are the diff Vit D analgoues?

A

Calcitriol
Doxercalciferol
Paricalcitol
Doxercacliferol & Paricalcitol
CHolecalciferol, Ergocalciferol, Calcifediol
Calcipotriene

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22
Q

What Vit D analgue is given w/in 24-48 hrs for Vit D-dependent rickets?

A

Calcitriol

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23
Q

What vitamin D analogues are used for tx of Secondary hyperthyroidism of CKDs?

A

Doxercaliferol & Paricalcitol

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24
Q

What vit D analogues are used in tx of HYPOthyroidism, rickets, Osteomalacia, Osteoporosis, & CKD?

A

Cholecalciferol, Ergocalciferol, Calcifediol

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25
Q

What Vit D analogue is used as an adjuvant tx of psoriasis due to its immunomodulatory effects?

A

Calcipotriene

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26
Q

Of all the Vit D analogues, what are the only 2 drugs that are in activated form already?

A

Calcitriol & Paricalcitol

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27
Q

What is the stimulus & inhibition of Vit D/Calcitriol?

A

Stimulus: LOW Ca, LOW Phosphorus
Inhibition: HIGH Ca, HIGH P

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28
Q

WHat are the 3 actions of Vit D?

A

Activates Ca pump in the lumen
INC ATP w/ diverts Ca into the blood
INC Ca binding protein

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29
Q

Explain the photosynthesis & activation of Vit D/Calcitriol?

A

Endogenous vit D (synthesized on the skin)
=> 7-dehydrocholesterol —(sunlight) —> CHolecaliferol. (Vit D3)

Exogenous VIt D
CHolecalciferol (Vit D3) —> animal source OR
Ergocalciferol (Vit D2) —> plant source

Cholecaliferol —(25-hydroxylase: liver)—> 25 (OH) Cholecalciferol (calcifediol) —(1a-hyoxylase: kidneys)—> 1,25(OH)2 cholecalciferol (Calcitriol) —> active form

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30
Q

For what conditions are Ca analogues used?

A

Therapeutic & prophylactic use of:
- THerapy for HYPOcalcemia
- Prevention against Osteoporosis

31
Q

What Ca analogue is given for mild hypocalcemia?

A

Ca acetate => most accessible & readily absorbable
Ca citrate
Ca carbonate => most widely used due to low cost

32
Q

What Ca analogue is used for severe hypocalcemia?

A

Ca gluconate = less venous irritation
Ca Cl

33
Q

What are the different antiresorptive agents?

A

Seletive estrogen receptor modulators
Bisphosphonates (-dronates)
Monoclonal Ab
Mineral
Calcitonin analogs
Hormone replacement therapy

34
Q

What is the goal of Selective estrogen receptor modulators?

A

To retain the beneficial effects of estrogen in 1 or more tissues while eliminating theundesirable effects of estrogen in other tissues

35
Q

WHat is the only selective estrogen receptor modulator & its MOA?

A

Raloxifene

MOA: agonist in bone, Antagonist in Estrogen (endometrium & breast)

36
Q

What are the Indications, Effects, & AE of Raloxifene?

A

Indication:
- prevention & tx of Osteoporosis
- DEC risk for endometrial & breast cancer

SE:
- INC vertebral & non-vertebral bone mineral density
- DEC LDL-C levels

AEs: INC risk of venous thromboemboilsm, hot flashes, leg cramps

37
Q

What is the mOA of Bisphosphonates (SERMs)

A

MOA: inhibits bone resorption & osteoClast activity

DEC solubility of hydroxyapatite —> more resistant to osteoClastic bone resorption

38
Q

What are the 1st, 2nd & 3rd gen of Bisphosphonates?

A

1st gen = Etidronate
2nd gen = Alendronate, Ibandronate, Pamidronate
3rd gen = Risedronate, Zoledronate

39
Q

What are indications, AE, CI, & clinical trials of Bisphosphonates?

A

Indications:
- Postmenopausal, osteoporosis, Paget’s disease, & hypercalcemia of malignancy

AE:
- Esophageal erosion of ulcer
- Esophagitis, diarrhea
- Osteonecrosis of jaw

CI:
- tendencies to develop bone malignancies

CTs:
- INC spine & hip bone mass density
- DEC risk of vertebral & non vertebral fractures

40
Q

What is the only monoclonal Ab of Antiresoprtive agents? MOA? Indication?

A

MOA: binds to RANKL => prevent sstimulation of osteoClast differentiation & function —> prevents further bone loss

Indication: Postmenopausal osteoporosis

Breast & prostate CAs

41
Q

What is a mineral anti-resorptive agent? MOA, Indication, AE?

A

Strontium Ranelate

MOA: blocks differentiation & activation of osteoClasts while promoting their apoptosis, inhibits bone resorption

Indication: Osteoporosis

AEs: Skin rashes, venous thromboembolism

42
Q

What are the diff Calcitonin analogs & its MOA?

A

Fortical, Miacalcin, Calcimar, Salmonine

MOA: activates GPCR on osteoclats —> DEC resorptive acctivity of osteoclasts

43
Q

What are the indications, AEs, CI of Calcitonin analogs?

A

Indications: Paget’s disease, osteoporosis, Primary hyperparathyroidism, Hypercalcemic emergency, Vit D intoxication

AEs: Hypersensitivity rash, rhinitis, epistaxis, tachyphylaxis

CI: hypersensitivty

44
Q

What is an alternative to bisphosphonates in px who are unable or unwilling to take them?

A

Calcitonin analogs

45
Q

What hormone is used in hormone replacement therapy? Indication, MOA, AEs?

A

Estrogen

MOA: reduce bone resorption
Indication: Postmenopausal osteoporosis
AEs: vaginal bleeding, breast tenderness, venou thromboembolism, INC long term risk of breast cancer

Postmenopasual women => given w/ Progesterone to DEC risk of endometrial cancer

46
Q

What are the diff drugs that stimulate bone formation?

A

Recombinant human PTH analogs: Teriparatide, Abaloparatide, Natpara

Fluoride

47
Q

What are the MOA, Indications, AEs, C/I & Caution for Recombinant human PTH analogs?

A

MOA: INC osteoblast differentiation & activity
Indications: Postmenopausal osteoporosis & HYPOthyroidism

AEs: HYPERcalcemia, HYPERcalciuria, muscle weakness

Caution: Osteosarcoma development

C/I: bone malignancy, Piagets disease

48
Q

What is the diff betw recombinant human PTH analogs vs PTH?

A

PTH: continuous exposure => bone catabolism
PTH analog: bone anabolism

49
Q

What are the MOA, indications, & AE of Fluoride for bone formation?

A

MOA: stabilize hydroxyapatite crystal -> INC mineralization of trabecular bone (Hydroxyapatite-> Fluorapatite)

Indication: Tx of osteoporosis
AE: Osteomalacia

50
Q

What drug class is used for CKD?

A

Oral PO4 binders

51
Q

What is the MOA of Oral PO4 binders?

A

Lowers plasma PO4 levels by preventing dietary PO4 absorption

Produce non-absorbable form of PO4

52
Q

WHat are the diff oral PO4 binders?

A

Aluminum hydroxide
Ca Carbonate/ACetate
Sevelamer

53
Q

What are the MOA, indication, CI, AE & THerapeutic considerations of Aluminum hydroxide?

A

MOA: Al ppt with PO4 in GIT —> non-absorbable complexes

Indication: HYPERPO4emia

CI: HSN to aluminum hydroxide

AE: aluminum toxicity (anemia, osteomalacia, & neurotoxicity)!!!!!!!

54
Q

What are the MOA, Indication, CI, AE, & therapeutic considerations for Ca Carbonate/Acetate?

A

MOA: binds to dietary PO4 inhibitng its absorption

Indication: CKD, Osteoporosis, Hypocalcemia

CI: Hypercalcemia, Vit D toxicity

AE: Iatrogenic hypercalcemia, INC risk of vascular calcification, Milk-alkali syndrome, constipation

TCs: acidic environment for effective action, has antacid properties

55
Q

What are the MOA, indication, CI, AE, TC of Sevelamar?

A

MOA: Non-absorbable cationic ion-exchange resin that binds intestinal PO4 decreasing absorption of dietary PO4

Indication: CKD

CI: DEC plasma PO4, Bowel osbtruction

AE: binds bile acids interrupting enterophetatic circulation, DEC CHOLESTEORL ABSORPTION, thrombosis, HTN, constipation

TC: lowers serum cholesterol by binding bile acids

56
Q

What is the only Calcimimetic drug? Its MOA, Indi, CI, effect, & AE?

A

Clinacalcet

MOA: INC sensitivity of Ca-sensing receptors —> DEC PTH synthesis & secretion

Indication: 2ndary HYPERparathyroidism, HYPERcalcemia assoc w/ Parathyroid CA, CKD

AE: HYPOcalcemia, HTN, dizziness

57
Q

What are the most important modulators of bone remodeling and mineral homeostatsis?

A

PTH & VIt D

58
Q

What pharamcologic class is given if there is an INC in osteoClast activity?

A

Antiresorptive agents: SERMs, bisphosphonates, Denosumab, Strontium ranelate

59
Q

What pharmacologic agents are used in conditions where there is DEC in osteoBlast activity?

A

Bone anabolic agents: Teriparatide, Abaloparatide, Natpara

60
Q

What pharmacologic agents are given in CKD?

A

Vit D, PO4 binders, & Calcimimetics

61
Q

What drugs are given to INC bone anabolism?

A

Teriparatide, Abaloparatide

62
Q

What drugs are given to INC bone formation ?

A

HRT, SERM

63
Q

What drugs are given to DEC osteoclastic activity ?

A

Bisphosphonates, Calcitonin, HRT, SERM, Strontium ranelate

64
Q

What drugs are given to inhibit binding of RANKL to its receptor ?

A

Denosumab

65
Q

What causes primary hypoparathyroidism?

A

Post-thyroidectomy => DEC osteoclastic activity -> DEC Ca & PO4 resorption

66
Q

What are the effects & tx of primary hypoparathyroidism?

A

Effects:
Paresthesia, Neuromuscular excitability (CHOVESTEK’s sign), Hypocalcemia tetany

Tx: Ca & VIt D

67
Q

What are the causes of 2ndary hypoaprathyroidism? Effect, tx?

A

Causes: INC Vit D

Effect: Nephrocalcinosis!!!

Tx: Corticosteroids, Bisphosphonates

68
Q

What are the causes of primary HYPERparathyroidism? Effects, tx?

A

Tumor in PTG
INC osteoClastic activity

Effects:
Osteoporosis, Nephrolithiasis, Osteitis fibrosa cystica!!!

Tx: surgical removal of tumor, IV bisphosphonates

69
Q

What are the causes fo 2ndary HYPERparathyroidism? Effects, Tx?

A

DEC Vit D
Chronic renal failure

Effects: Osteomalacia, Osteitis fibrosa cystica!!

Tx: Cinacalcet, PO4 binders, Calcitriol, Paracalcitriol, Doxercalciferol

70
Q

What ar the effects of HYPERcalcemia? Tx used?

A

INC GI absorption, osteoClastic activity

DEC bone mineralization, urinary excretion

Tx:
- Thiaxide diuretics
- Oral PO4
- Bisphosphonate
- Calcitonin
- Prednisone
- Saline diuresis + loop diuretics

71
Q

What is plasma Ca level of mild & severe hYPERcalcemia?

A

Mild hypercalcemia = <12mg/dL
Severe hypercalcemia = >13-14mg/dL

72
Q

What are the effects of HYPOcalcemia? Tx?

A

DEC GI absorption
DEC bone resorption/INC mineralization
INC urinary excretion

Tx:
- loop diuretics
- Ca
- VIt D
- thiazide diuretics

73
Q

What is the normal plasma level of Ca?

A

8-10mg/dL

Pharmacology (19 decks)

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