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Calcium Metabolism Drugs Flashcards

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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
What Vit D analogue is used as an adjuvant tx of psoriasis due to its immunomodulatory effects?
Calcipotriene
26
Of all the Vit D analogues, what are the only 2 drugs that are in activated form already?
Calcitriol & Paricalcitol
27
What is the stimulus & inhibition of Vit D/Calcitriol?
Stimulus: LOW Ca, LOW Phosphorus Inhibition: HIGH Ca, HIGH P
28
WHat are the 3 actions of Vit D?
Activates Ca pump in the lumen INC ATP w/ diverts Ca into the blood INC Ca binding protein
29
Explain the photosynthesis & activation of Vit D/Calcitriol?
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
30
For what conditions are Ca analogues used?
Therapeutic & prophylactic use of: - THerapy for HYPOcalcemia - Prevention against Osteoporosis
31
What Ca analogue is given for mild hypocalcemia?
Ca acetate => most accessible & readily absorbable Ca citrate Ca carbonate => most widely used due to low cost
32
What Ca analogue is used for severe hypocalcemia?
Ca gluconate = less venous irritation Ca Cl
33
What are the different antiresorptive agents?
Seletive estrogen receptor modulators Bisphosphonates (-dronates) Monoclonal Ab Mineral Calcitonin analogs Hormone replacement therapy
34
What is the goal of Selective estrogen receptor modulators?
To retain the beneficial effects of estrogen in 1 or more tissues while eliminating theundesirable effects of estrogen in other tissues
35
WHat is the only selective estrogen receptor modulator & its MOA?
Raloxifene MOA: agonist in bone, Antagonist in Estrogen (endometrium & breast)
36
What are the Indications, Effects, & AE of Raloxifene?
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
What is the mOA of Bisphosphonates (SERMs)
MOA: inhibits bone resorption & osteoClast activity DEC solubility of hydroxyapatite —> more resistant to osteoClastic bone resorption
38
What are the 1st, 2nd & 3rd gen of Bisphosphonates?
1st gen = Etidronate 2nd gen = Alendronate, Ibandronate, Pamidronate 3rd gen = Risedronate, Zoledronate
39
What are indications, AE, CI, & clinical trials of Bisphosphonates?
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
What is the only monoclonal Ab of Antiresoprtive agents? MOA? Indication?
MOA: binds to RANKL => prevent sstimulation of osteoClast differentiation & function —> prevents further bone loss Indication: Postmenopausal osteoporosis Breast & prostate CAs
41
What is a mineral anti-resorptive agent? MOA, Indication, AE?
Strontium Ranelate MOA: blocks differentiation & activation of osteoClasts while promoting their apoptosis, inhibits bone resorption Indication: Osteoporosis AEs: Skin rashes, venous thromboembolism
42
What are the diff Calcitonin analogs & its MOA?
Fortical, Miacalcin, Calcimar, Salmonine MOA: activates GPCR on osteoclats —> DEC resorptive acctivity of osteoclasts
43
What are the indications, AEs, CI of Calcitonin analogs?
Indications: Paget’s disease, osteoporosis, Primary hyperparathyroidism, Hypercalcemic emergency, Vit D intoxication AEs: Hypersensitivity rash, rhinitis, epistaxis, tachyphylaxis CI: hypersensitivty
44
What is an alternative to bisphosphonates in px who are unable or unwilling to take them?
Calcitonin analogs
45
What hormone is used in hormone replacement therapy? Indication, MOA, AEs?
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
What are the diff drugs that stimulate bone formation?
Recombinant human PTH analogs: Teriparatide, Abaloparatide, Natpara Fluoride
47
What are the MOA, Indications, AEs, C/I & Caution for Recombinant human PTH analogs?
MOA: INC osteoblast differentiation & activity Indications: Postmenopausal osteoporosis & HYPOthyroidism AEs: HYPERcalcemia, HYPERcalciuria, muscle weakness Caution: Osteosarcoma development C/I: bone malignancy, Piagets disease
48
What is the diff betw recombinant human PTH analogs vs PTH?
PTH: continuous exposure => bone catabolism PTH analog: bone anabolism
49
What are the MOA, indications, & AE of Fluoride for bone formation?
MOA: stabilize hydroxyapatite crystal -> INC mineralization of trabecular bone (Hydroxyapatite-> Fluorapatite) Indication: Tx of osteoporosis AE: Osteomalacia
50
What drug class is used for CKD?
Oral PO4 binders
51
What is the MOA of Oral PO4 binders?
Lowers plasma PO4 levels by preventing dietary PO4 absorption Produce non-absorbable form of PO4
52
WHat are the diff oral PO4 binders?
Aluminum hydroxide Ca Carbonate/ACetate Sevelamer
53
What are the MOA, indication, CI, AE & THerapeutic considerations of Aluminum hydroxide?
MOA: Al ppt with PO4 in GIT —> non-absorbable complexes Indication: HYPERPO4emia CI: HSN to aluminum hydroxide AE: aluminum toxicity (anemia, osteomalacia, & neurotoxicity)!!!!!!!
54
What are the MOA, Indication, CI, AE, & therapeutic considerations for Ca Carbonate/Acetate?
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
What are the MOA, indication, CI, AE, TC of Sevelamar?
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
What is the only Calcimimetic drug? Its MOA, Indi, CI, effect, & AE?
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
What are the most important modulators of bone remodeling and mineral homeostatsis?
PTH & VIt D
58
What pharamcologic class is given if there is an INC in osteoClast activity?
Antiresorptive agents: SERMs, bisphosphonates, Denosumab, Strontium ranelate
59
What pharmacologic agents are used in conditions where there is DEC in osteoBlast activity?
Bone anabolic agents: Teriparatide, Abaloparatide, Natpara
60
What pharmacologic agents are given in CKD?
Vit D, PO4 binders, & Calcimimetics
61
What drugs are given to INC bone anabolism?
Teriparatide, Abaloparatide
62
What drugs are given to INC bone formation ?
HRT, SERM
63
What drugs are given to DEC osteoclastic activity ?
Bisphosphonates, Calcitonin, HRT, SERM, Strontium ranelate
64
What drugs are given to inhibit binding of RANKL to its receptor ?
Denosumab
65
What causes primary hypoparathyroidism?
Post-thyroidectomy => DEC osteoclastic activity -> DEC Ca & PO4 resorption
66
What are the effects & tx of primary hypoparathyroidism?
Effects: Paresthesia, Neuromuscular excitability (CHOVESTEK’s sign), Hypocalcemia tetany Tx: Ca & VIt D
67
What are the causes of 2ndary hypoaprathyroidism? Effect, tx?
Causes: INC Vit D Effect: Nephrocalcinosis!!! Tx: Corticosteroids, Bisphosphonates
68
What are the causes of primary HYPERparathyroidism? Effects, tx?
Tumor in PTG INC osteoClastic activity Effects: Osteoporosis, Nephrolithiasis, Osteitis fibrosa cystica!!! Tx: surgical removal of tumor, IV bisphosphonates
69
What are the causes fo 2ndary HYPERparathyroidism? Effects, Tx?
DEC Vit D Chronic renal failure Effects: Osteomalacia, Osteitis fibrosa cystica!! Tx: Cinacalcet, PO4 binders, Calcitriol, Paracalcitriol, Doxercalciferol
70
What ar the effects of HYPERcalcemia? Tx used?
INC GI absorption, osteoClastic activity DEC bone mineralization, urinary excretion Tx: - Thiaxide diuretics - Oral PO4 - Bisphosphonate - Calcitonin - Prednisone - Saline diuresis + loop diuretics
71
What is plasma Ca level of mild & severe hYPERcalcemia?
Mild hypercalcemia = <12mg/dL Severe hypercalcemia = >13-14mg/dL
72
What are the effects of HYPOcalcemia? Tx?
DEC GI absorption DEC bone resorption/INC mineralization INC urinary excretion Tx: - loop diuretics - Ca - VIt D - thiazide diuretics
73
What is the normal plasma level of Ca?
8-10mg/dL

Pharmacology (19 decks)

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