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NMSK Exam 3 > Pharmacology of Osteoporosis > Flashcards

Pharmacology of Osteoporosis Flashcards

1
Q

Treatment for Osteoporosis

A

1. Ca2+ Salts (maintains Ca2+, to treat hypocalcemia):

  • From food
  • Ca2+ carbonate, citrate, gluconate, in vitamins
  • Parenteral if severe

2. Vit D

  • Ergocalciferol from foods and vitamines
  • Cholecalciferol from sun

3. Calcitonin-Salmon

4. Teriparatide (PTH)

5. Bisphosphonates

  • Alendronate ( *other drenates)
  • IV Zoledronic acid 1x/yr

6. SERM (Selective Estrogen Receptor Modulator)

  • Raloxifene

7. RANKL inhibitor

  • Denosumab
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2
Q

In summary, how does osteoporosis affect the bone?

A

Increases the size of the spaces in bones so that the bones lose strength and density, and the outside of the bone also grows weaker and thinner ==> high risk of fractures that happens when standing, walking and out of nowhere.

  • Loss of height
  • Bent spine
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3
Q

Biggest RF for osteoporosis

A

Age

Other: F, white or AZN, low T in men

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4
Q

What drugs ↑ risk of osteoporosis?

A
  1. Anticoagulants (heparin)
  2. Anticonvulsants (CYP P450-inducers: phenobarbital, phenytoin, carbamazepine)
  3. Aromatase inhibitors (e.g., anastrazole, exemestane)
  4. Cyclosporine and tacrolimus
  5. Cancer chemotherapy drugs (Tamoxifin)
  6. Glucocorticoids (and ACTH)
  7. Gonadotropin-releasing AGO
  8. Lithium
  9. Methotrexate
  10. PPI
  11. SSRIs
  12. Thyroxine
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5
Q

MOA of calcitonin-salmon

A

Similar action to human calcitonin made by thyroid, but has a longer 1/2 life and more potent:

  • 1. Inhibits osteoclasts => ↓ bone resorption
  • 2. Inhibits reabsorption of Ca2+ in kidney to ↑ Ca2+ secretion
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6
Q

Calcitonin-Salmon

  1. Uses*
  2. Pharmacokinetics
  3. Toxicities*
A
  1. Uses
    1. Treat osteoporosis, but not prevent;
    2. Pagets disease of bone;
    3. Treat hypercalcemia, but not preferred drug
  2. Pharmokinetics
    1. Intranasal spray or parental SC/IM
  3. Toxicities
    1. Very safe
    2. Intrasal spray can dry nose and cause irritation
    3. Parental type can cause inflammatory rxn
    4. Neutralizing Ab appear in some pts over time
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7
Q

Bisphonates (Alendronate)

MOA

A
  • Structural analog of pyrophosphate that incorperates into the bone and inhibits bone resorption by ↓↓↓ # and activity of osteoclasts.
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8
Q

Bisphonates (Alendronate)

  • 1st drug of choice for…
A
  1. Postmenopausal osteoporosis
  2. Osteoporosis in men
  3. Glucocorticoid-inducted osteoporosis
  4. Paget disease of bone
  5. Hypercalcemia of malignancy
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9
Q

Bisphosphonates

Toxicities

A
  1. Esophagitis +/- ulceration; ↓ by taking with water when waking up and waiting 30 min before any other food/liquid
  2. Osteonecrosis of jaw
  3. Atypical femur fractures: simple, with thick cortices fracture pattern
  4. A-fib
  5. Ocular inflammation
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10
Q

Which bisphosphonate has been most commonly associated with osteonecrosis of the jaw AND dose-dependent kidney damage and rarely atrial fibrillation?

A

Zolendronic Acid (IV 1x/yr)

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11
Q

Name 3 other bisphosphonates and their route of administration

A
    1. Risedronate (PO)
    1. Ibandronate (PO, IV)
    1. Tiludronate (PO)
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12
Q

Name this complication and the cause

A
  • Atypical femur fracture: simple with thick cortices fracture pattern
  • Due to: Bisphosphonates
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13
Q

SERMS: Raloxifene

  1. MOA
  2. Use
A
  1. Acts as a estrogen AGO in bone, but estrogen ANT in breast and uterus.
  2. Uses
    1. Estogen AGO in bone =
      1. PREVENTS and TREATS postmenopausal osteoporosis in W at risk for developing estrogen-dependent breast cancer
    2. Antiestrogen effects in breast=
      1. Reduce risk for developing estrogen-dependent breast cancer
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14
Q

Where is the SERM, Raloxifene an estrogen AGO and ANT?

A
  1. AGO = bone
  2. ANT = breat and uterus
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15
Q

SERM: Raloxifene

Toxicity

A

Like estrogen, ↑ risk for:

  1. DVT’s
  2. PE
  3. Stroke

Thus, DQ at least 72 hours before prolonged immobilization.

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16
Q

When should you DQ the SERM, Raloxifene?

A

At least 72 hours before immobilization to prevent DVT, PE, stroke.

17
Q

What SERM is NOT used to treat osteoporosis?

A

Tamoxifen

18
Q

What is the only drug for osteoporosis that ↑↑↑ bone formation?

A

Teriparatide (PTH 1-34)

19
Q

Teriparatide (PTH 1-34)

  1. MOA
  2. Uses
A
  1. Only drug for osteoporosis that ↑↑↑ bone formation. Has 2 effects
    1. Given continuously => breaksdown bone via osteoclasts
    2. Given daily pulsed therapy => builds bone via osteoblasts
  2. Uses: treatment of
    1. Osteoporosis in post-menopausal women
    2. Osteoporosis in M
    3. Glucocorticoid-induced osteoporosis
20
Q

How and how often is Teriparatide (PTH 1-34) administered?

A

20 mcg/day by using pre-filled injectors with 28 doses.

21
Q

What is the MOA and effect of Denosumab?

A
  • Monoclonal AB that is a RANKL inhibitor
  1. Binds to RANKL =>
  2. Prevents RANKL from binding to RANK-R =>
  3. ↓ formation and function of osteoclasts –> ↓ bone resorption with ↑ bone mass density and strength.
22
Q

Denosumab (RANKL-I)

  1. Uses
  2. What should it be taken with?
A
  1. Uses: treats
  • Treats post-menopausal osteoporosis in W with high risk for fractures
  • Prevents skeletal-related events in pt’s with bone metastases from solid tumors

Take with Ca2+ and vitamin D supplement to prevent hypocalcemia

23
Q

Denosumab (RANKL-I)

  1. Pharmokinetics
  2. Toxicities
A
  1. Pharmakokinetics
    1. Osteoporosis: 60mg SQ injection q 6 months
    2. Bone metases: 120mg SQ injection q 4 weeks
  2. Toxicities: in all patients,
    1. Delays healing of fractures
    2. ↑ risk of new fractures and osteonecrosis of jaw
24
Q

What is an important part of the therapy when treating osteoporosis in men; what are the 2 agents most commonly used?

A
  1. ↑ risk of hypogonadism (d/t glucocorticoids or androgen deprivation therapy for prostate cancer) => give testosterone replacement
  2. Agent of choice = Bisphosphonates (i.e., alendronate); Denosumab is an alternative
25
Q

Drugs of choice for Hyperpercalcemia (6)

A
  1. Furosemide: via action in TAL
  2. Glucocorticoids: reduce intestinal absorption of Ca2+
  3. Gallium nitrate: prevents bone resorption, used to treat hypercalcemia of malignancy, but highly nephrotoxic
  4. Bisphosphonates: approved for use to treat hypercalcemia of malignancy
  5. Inorganic phosphates: IV use is life-threatening and limited to patients with severe hypercalcemia; oral is milder and OK provided patients do not have renal impairment or already elevated phosphate levels
  6. Edetate disodium (EDTA) = calcium chelating agent, can be dangerous since it can cause profound hypocalcemia with tetany, convulsion, dysrhythmias => death
26
Q

MOA of Cinacalet

A

↓ PTH secretion by:

  1. Binds to CaSR on parathyroid gland —> ↑ sensitivity to extracellular Ca2+
  2. => ↓ PTH secretion => ↓ serum Ca2+
27
Q

Cinacalcet

  1. Uses
  2. Pharmokinetics
  3. Toxicities
A
  1. Uses
    1. 1º hyperparathyroidism (parthyroid carcinoma)
    2. 2º hyperparathyroidism due to CKD
  2. Pharmokinetics
    1. Oral with food; highly bound to protein and metabolized by liver/excreted by kidney
    2. 1/2 life = 30-40 hours
  3. Toxicities
    1. N/V/D
28
Q

Symptoms of Osteoarthritis

A

Appear gradually over time, too sloely for onset to be recognized.

  1. Joint pain during/after movement
  2. Stiffness: MC in morning or when inactive
  3. ↓ flexability
  4. Tender when pressure is applied
  5. Grating or rubbing sensation when moving joint
  6. Bone spurs, which can break off and grow via by getting nourishment from synovial fluid & form joint mice, MC located in the gutters on the side of the joint but can be swept INTO joint and cause intense pain.
29
Q

Treatment of OA (osteoarthritis)

A

NO TX: only symptomatic treatment

30
Q

Which drugs can be used for non-inflammatory vs. inflammatory OA?

A
  • Acetaminophen = non-inflammatory OA

- NSAIDs (Aspirin, ibuprofin (motrin or advil)= inflammatory OA or if acetaminophen is inadequate for pain in non-inflammtory OA

31
Q

Dietary supplements commonly used for OA despite a ANY of evidence of any helping. However, the placebo affect is REAL.

A
  1. Glucosamine
  2. Chondroitin
  3. DMSO
  4. SAMe
32
Q

Herbal remedies commonly used for OA despite a ANY of evidence of any helping. However, the placebo affect is REAL.

A
  1. Devils claw
  2. Stinging nettle
  3. Rose hips
  4. Avocado soybean unsaponifiables
33
Q

Which topical NSAID is widely used for OA pain relief?

A
  1. 1% Diclofenec gel
  2. or capsaicin (not a topical NSAID)
34
Q

Nonpharmcological therapy for OA

A
  1. Weight management/exercises,
  2. Braces and foot orthoses
  3. Assistive devices
  4. Education
  5. OMM?
35
Q

Resistant pain therapy for OA

A
  1. Duloxetine (SNRI) => helps, but causes constipations
  2. Opioid analgesics
  3. Intra-articular
    1. Hylauronans
    2. Glucocorticoids
    3. Platelet rich plasma
36
Q

Tx for osteomyelitis; how long should tx be administered for?

A

4 - 6 weeks ABX based on pathogen, so bone can revascularize after debridement

  1. Clindamycin
  2. Rifampin
  3. TMP-SMX
  4. Fluoroquinolones

NMSK Exam 3 (17 decks)

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