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Pharmacology II > Agents that affect Calcium/Bone Homeostasis > Flashcards

Agents that affect Calcium/Bone Homeostasis Flashcards

(51 cards)

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1
Q

what are the conditions that can lead ot hypercalcmemia?

A
  • hyperparathyroidism
    • parathyroid adenoma / carcinoma / hyperplasia
  • Cancers +/- bone metastasis
  • Hypervitaminosis (Vit D)?
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2
Q

what are the conditions that can lead to hypocalcemia?

A
  • Hypoparathyroidism (autoimmune, psuedohypothyroidism)
  • insufficient gut Ca++ absorption:
    • Vitamin D deficiency (rickets, osteomalacia)
      • CKD? but its secondary hyperthyroidism?
    • other reason for alabsorption - Ca++ not absorbed in gut
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3
Q

what is osteoporosis?

how does it present?

A

a generalized loss of bone mass and strength from excessive bone resorbption

increased risk of fractures

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4
Q

what is pagets disease of the bone?

how does it present?

A

localized increases in bone turnover due to excessive bone resorption, followed by replacement with structurally abnormal bone

presentation: skeletal deformities (misshapen bones) + fractures

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5
Q

what is the role of

  • estrogen
  • calicitonin
  • PTH

in bone metabolism?

A
  • inhibits osteoclast activity, PREVENTING bone resorption:
    • estrogen:
      • (this is why estrogen loss in women during age weakens bones)
    • calticonin
  • promotes osteoclast activity, INDUCING bone resorption
    • PTH
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6
Q

what two major classes of drugs are used to treat osteoporosis?

A
  1. anti-resorptive agents
  2. anabolic agents
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7
Q

what are the anti-resorbtive agents used to treat osteoporosis?

in what situations are they used?

what do they all have in common?

A
  • bisphophonates - 1st line
  • denosumab - 1st line
  • raloxifene - 1st in in post-menopausal
  • calcitonin - in post-menopausal (not first line)

all suppress osteoclast activity

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8
Q

what are the anabolic hormones used to treat osteoporosis?

A
  • teriparatide (PTH analog)
  • sclerostin inhibitor
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9
Q

bisphosphonates

incudes what drugs?

A

“dronate and dronic”

  • - dronate: alendronate, risedronate, ibandronate, pamidronate
  • zoledronic acid
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10
Q

bisophosphonate MOA

A

anti-resorptive agent

  • inhibit bone resorbtion by suppressing osteoclasts
    1. permanently incorporate into bone* - have effects post discontuation
    2. induce osteocast apoptosis
    3. disrupt osteoclast activity
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11
Q

bisphosphonates - clinical uses

A
  • osteoporosis - 1st line tx
  • Paget’s disease
  • bone metastasis / hypercalcemia of malignancy
  • reduction of bone fracture risk
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12
Q

bisphosphonates AEs / CIs

A
  • AEs
    • esophageal & gastric irratitation / ulcers
    • hypocalcemia & related consequences:
      • jaw osteonecrosis (ONJ)
      • atypical femur fracturefs (AFF)
  • C/I:
    • esophgeal disorders / peptic ulcers
    • severe hypocalcemia (renal disease)
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13
Q

bisphosphonates - pharmokinetics

A

poor oral absorption that is inhibited by food.

pt must take in FASTED STATE (water only)

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14
Q

alendronate

what kind of drug?

available in what forms?

A

bisphosphonate

  • oral: daily, weekly
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15
Q

risendonrate

what kind of drugs?

available in what forms?

A

bisphosphonate

  • oral: daily, weekly
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16
Q

ibandrate

what kind of drug?

available in what forms?

A

bisphosphonate

  • oral: daily, monthly
  • IV: quarterly
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17
Q

pamidronate

what kind of drug?

available in what forms?

A

bisphosphonate

  • IV only: monthly injection
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18
Q

zoldronic acid

what kind of drug?

available in what forms?

A

bisphosphonate

  • IV only: given yearly or (for osteoporosis prevention) once every 2 years
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19
Q

how should a patient be instructed to take an oral bisphosphonate?

A
  • dronates
  • take it fasting (water only) - bisphosphonates have poor oral bioavability
  • sit upright for 30 min after taking - prevents formation of gastric & esophageal ulcers
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20
Q

denosumab

what kind of drug?

MOA?

A
  • an anti-resorptive drug (thus, suppresses osteoclasts)
    • MOA: is an RANKL-antibody that binds RANK-L, inhibiting its binding with RANK receptors on osteoclasts. this inhibits osteoclast activation
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21
Q

denosumab - clinical uses

Study These Flashcards
A

= RANK-L inhibitor

  • osteoporosis - 1st choice - used as an alternative to bisphosphonates
  • hypercalcemic malignancy

(similar to bisphosphonates)

22
Q

denosumab

is available in what form?

Study These Flashcards
A
  • injections (subcutucaneous) - given every 6 mos
23
Q

denosumab- AEs / CIs?

Study These Flashcards
A
  • AE
    • hypocalcemia & related effects
      • jaw osteonecrosis (ONJ)
      • atypical femur fractures (AFF)
  • CI
    • hypocalcemia

(similar to bisphosphonates)

24
Q

which osteoporosis drug can cause an increase in bone mass density (BMD) that persists beyond discontinuation of therapy?

why?

Study These Flashcards
A

bisphosphonates (dronates & zoldedronic acid)

this is because they permanently incorporate themselves into bone

25
raloxifene * what kind of drug? * MOA?
* is an antiresorptive drug * MOA: specifically a **SERP**: **selective estrogen receptor modulator** * **​**raloxifene is an _agonist_ in some tissue but an _antagonist_ in others * _agonism_ in certain tissues (bone) serves to stimulate estrogen, thus **inhibiting osteoclasts activity** * _antagonism_ in certain tissues (breast, endometrium) serves to inhibit estrogen, preventing cancer development
26
raloxifene -clinical uses?
= SERM (selective estrogen receptor modulator) * to prevent/treat **osteoporosis in postmenopausal females**
27
raloxefine - AEs / CIs?
= SERM (selective estrogen receptor modifiers) * AEs: * **leg -** _arthralgia /cramps / muscle spasms_ * **increases risk of thromboembolism** * hot flashes * CI: * in pts with hx/current venous thromboembolitic disorders\*
28
_compare_ and _contrast_ bisphosphonates to RANK-L inhibitors | (what are the drug names in each of these classes?)
bisphosphonates: - **dromate (**oral/IV**),** zoledronic acid (IV only) RANK-L inhibitor: **denosumab** (injection) * **both:** * are anti-resorptive drugs * treat 1. osteoporosis (1st line) 2. bone metastasis / hypercalcemia malignancy * AEs * hypocalcemia (+ ONJ, AFF) * C/I in: severe hypocalcemia * **only bisphosphonates**: * increase BMD after drug discontinuation * can treat: _Paget's disease_ * can cause: _esophageal / gastric ulcers_ irritation * C/I in: hx of esophgeal / gastric disorders * must taken while fasting & while pt is upright for 30 min\*
29
estrogens * MOA * have what clinical uses? * AEs /CIs?
* MOA: antiresorptive via osteoclast supression * uses: * to treat **osteoporosis** **in postmenopausal women** - _NOT_ first choice * to relief other postmenopausal symptoms * AEs: * **endometrial / breast carcinoma** * **venous thrombombolism**
30
calcitonin * what kind of "drug"? * MOA? * clinical uses? * available in what forms? * AEs / CI?
* grouped with resorptive drugs * MOA: * secreted by thyroid in response to hypercalcemia * **lowers both Ca and PO4** * clinical uses: * _postmenopausal osteoporosis_ - not first line * _paget's disease_ - not 1st line * hypercalcemia * formulations: * human calcitonin * "salmon" calcitonin = intranasal / sc / im; *longer half life* * AEs: * hypersensitivity / flushing * nausea / GI cramps
31
what are the AEs of calcitonin?
* hypersensitivity / flushing * nausea / GI cramps
32
what drugs are _specifically indicated_ for postemenopausal osteoporosis? how are they different?
* estrogen & raloxafine (SERM) - * _both:_ are risk factors for a **venous thromboembolism (stroke)** * **raloxifene** - _1st choice_ * **estrogen** - _NOT first choice_ * is also a factor for breast/emdometrial cancer calcitonin also used for postemenopausal osteoporosis (amongst other things). not 1st choice
33
which drugs are used to treat Paget's disease? which one is first choice?
1. bisphosphonates (dromate, zoledronic acid)- _1st choice_ 2. calcitonin - NOT first choice
34
PTH * has what key physiological affects? * how does it mediate these effects?
PTH acts at 1. **bone:** * _inc_ Ca reabsorption (via osteoclast activation) * _inc_ PO4 reabsorption (released along w/ Ca) 2. **kidney:** * _inc_ Ca reabsorption * **_dec_** PO4 reabsorption net effect: **raise plasma calcium and lower plasma phosphate**
35
**teriparatide** * what kind of drug? * MOA?
* **an anabolic hormone** * ​MOA: is a **PTH analog** - that, when **administered intermittently,** induces _osteoclast activity_ (by inducing RANK-L secretion by osteoblasts) that is _immediately followed by_ bone deposition (by osteoblasts) - having the net effect of **bone building ("anabolic effect")**
36
teriparatide - clinical uses
treatment of osteoporosis in pts with a **_high fracture risk_** **who have failed the antiresorptive agents** (bisophosphonates, denosumab, reloxifene, calcitonin)
37
teriparatide - PK
* dosing is: **_intermittent (once daily)_** - this timing is _imperative for a net anabolic effect._ * *continuous/high circulating of PTH = bone resorbption \> bone formation*
38
teriparatide - AEs/CIs
* AEs * it teraparatide is givin with _continuous administration_ then circulating PTH levels become too high and **reabsorptive effets \> anabolic effects**, and related AEs present: * hypercalcemia / hyperuricemia * dizziness / fatigue * cramps / arthralgia * CI: * **hypercalcemia / hyperparathyroidism** * **Pagets**
39
vitamin D preparations come in what forms?
oral supplements * ergocalciferol * cholecalciferol * calitriol
40
Vitamin D supplements clinical uses?
* rickets / osteomalacia * hypocalcemia (d/t hypoparathyroidism) * renal osteodystrophy d/t CDK) * osteoporosis
41
which Vitamin D supplement is especially useful in hypocalcemia due to chonic kidney disease?
calcitriol is the active form of Vit D, which is useful in patients with CDK, form whom the final step in vitamin D synthesis is impaired
42
which Vitamin D analog can be used to treat psoriasis?
calcipotriene
43
Vit D drug drug interactions
* phenobarticals/phenytoin - inc metabolism * mineral oil/resins - impair absorption
44
Vit D AEs?
* hypercalcemia / calciuria * hyperphosphatemia
45
Vitamin D C/I
* hypercalcemia * hyperparathyroidism * _pregnancy\*_ * sarcoidosis
46
contrst PK of ergocalciferol (D2) vs cholecalciferol (D3)
cholecalciferol = more potent & longer half life (6 weeks \> 1 week)
47
calcium preparations include what drugs?
various calcium carbonates: calium carbonate, calcium gluconate, ect
48
calcium supplements (preparations) * clinical uses * formulations * PK (& drug-drug interactions) * AE
Ca-carbonate, Ca-gluconate * clinical uses: given w/ Vit D for: * _prevention of osteoporosis:_ * *oral supplement* + dietary Ca + Vit D * hypocalcemia * *oral / IV supplement* + Vit D * formulations: IV & oral * PK: * requires _acidic_ environment for dissolution * drug-drug: absorption reduced by _anti-acids_ & _laxatives_ * AEs: * constipations / GI upset * kidney stone risk\*
49
calcimimetics * MOA * clinical uses
* MOA: is a Ca++ analog that binds parathyroid cells on the parathyroid gland to decrease synthesis of PTH * clinical uses: * primary hyperparathyroidism in pts who can't undergo surgery * secondary hyperparathyroidism in chronic renal dz * parathyroid carcinoma
50
romosozumab * what kind of drug? * MOA? * clinical uses? * AE?
* anabolic drug: scerlostin inhibitor * MOA: increases bone formation for 12 months * clinical uses: osteoporosis in _post meno-pausal female_s at high bone fracture risk * AE * **cardiovascular:** MI / stroke
51
what drugs can be used to treat osteoporosis in post-menopausal women? what are their individual AEs?
* estrogen - **thromboembolism / breast & uterine cancer** * raloxifene (SERM) - **thromboembolism** * calcitonin - hypersensitivity / flushing * romosuzumab (clerostin inhibitor) - **MI / stroke / CV death**

Pharmacology II (5 decks)

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