Drugs that Affect Bone and Mineral Homeostasis Flashcards by Jamaira Belmes

Actions of PTH

(-) calcium excretion – increased serum calcium

promotes phosphate excretion – decreased serum phosphate

stimulates production of active vit. D metabolites
promotes bone turnover

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Signs and Symptoms of Excess PTH

painful bones
renal stones
abdominal groans
psychiatric overtones

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Regulates synthesis and secretion of Parathyroid Hormone (PTH)

Free Ionized Calcium

decreased free ionized calcium stimulates PTH release

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Regulates gene transcription via the vitamin D receptor

Vitamin D (INACTIVE)
Ergocalciferol
Cholecalciferol

Vitamin D (ACTIVE)
Calcitriol
Doxercalciferol
Paricalcitol
Calcipotriene

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Used for management of secondary hyperparathyroidism in patients w/ CKD and management of hypocalcemia

Calcitriol

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Used for management of secondary hyperparathyroidism in patients w/ CKD

Doxercalciferol

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An analog of Calcitriol used for management of secondary hyperparathyroidism in patients w/ CKD

Paricalcitol

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An analog of calcitriol approved for PSORIASIS

Calcipotriene

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Suppresses the activity of osteoclasts and (-) bone resorption

BISPHOSPHONATES

Alendronate
Risedronate
Ibandronate
Pamidronate
Zoledronate (Zoledronic acid)

Osteoporosis, Paget’s disease

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Side effects of Bisphosphonates

GI irritation
esophagitis

take lots of water and keep patient in an upright position for 30 mins after intake of bisphophonates

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Acts through PTH receptors to produce a net increase in bone formation

PTH ANALOG

Teriparatide
Natpara

osteoporosis

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Acts through calcitonin receptors to (-) bone resorption

osteoporosis
Paget’s disease
TUMOR MARKER - thyroid cancer

Calcitonin
Salcatonin

SE:
rhinitis
N/V
facial flushing
tingling

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Actions of Calcitonin

(-) bone resorption and renal excretion –> decrease serum calcium and phosphate

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Estrogen agonist effect - BONE

Estrogen antagonist - BREASTS and ENDOMETRIUM

for osteoporosis

SERMS

Raloxifene

SE:
increased risk of VTE

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Monoclonal antibody

Binds to RANKL and prevents it from stimulating osteoclast differentiation and function

for osteoporosis

RANK LIGAND INHIBITORS

Denosumab

SE - increase risk of infection, osteonecrosis

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Activates the calcium sensing receptor –> (-) PTH secretion

for hyperparathyroidism

CALCIMIMETIC

Cinacalcet

SE - nausea, hypocalcemia, adynamic bone

MINERALS

osteoporosis
osteomalacia

Strontium
Calcium
Phosphate

SE - ectopic calcification

Binds to dietary phosphate and prevents its absorption

for
hyperphosphatemia (CKD)
hypoparathyroidism
vitamin D intoxication

PHOSPHATE BINDING RESIN

Sevelamer

Which of the following drugs is routinely added to calcium supplements and milk for the purpose of preventing rickets in children and osteomalacia in adults?

(A) Cholecalciferol
(B) Calcitriol
(C) Gallium nitrate
(D) Sevelamer
(E) Plicamycin

(A) Cholecalciferol

The 2 forms of vitamin D—cholecalciferol and ergocalciferol— are commonly added to calcium supplements and dairy products

Which of the following drugs is most useful for the treatment of hypercalcemia in Paget’s disease?

(A) Fluoride
(B) Hydrochlorothiazide
(C) Pamidronate
(D) Raloxifene
(E) Teriparatide

Paget’s disease is characterized by excessive bone resorption, poorly organized bone formation, and hypercalcemia.

Bisphosphonates and calcitonin are first-line treatments.

Pamidronate is a powerful bisphosphonate used parenterally to treat hypercalcemia

The active metabolites of vitamin D act through a nuclear receptor to produce which of the following effects?

(A) Decrease the absorption of calcium from bone
(B) Increase PTH formation
(C) Increase renal production of erythropoietin
(D) Increase the absorption of calcium from the gastrointestinal tract
(E) Lower the serum phosphate concentration

(D) Increase the absorption of calcium from the gastrointestinal tract

The active metabolites of vitamin D increase serum calcium and phosphate by promoting calcium and phosphate uptake from the gastrointestinal tract, increasing bone resorption, and decreasing renal excretion of both electrolytes.

They inhibit, rather than stimulate, PTH formation

A 59-year-old female was referred to your clinic for evaluation of osteopenia. She was diagnosed with adult-onset cystic fibrosis (CF). She reported being treated with prednisone 2 times in the past for CF exacerbations. Since menopause at 52 years of age, she had been treated with raloxifene for osteoporosis prevention. She also was on daily calcium and
vitamin D supplementation. Her bone mineral density test revealed a T score of –1.6 at the lumbar spine, –2.2 at the left femoral neck, and –1.6 at the total left hip.

Which of the following drugs can be used to reduce the fracture risk by further stimulating bone formation in this patient?

(A) Cholecalciferol
(B) Ergocalciferol
(C) Furosemide
(D) Tamoxifen
(E) Teriparatide

(E) Teriparatide

Teriparatide increases bone formation and bone resorption; during the first 6 months, it causes a net gain in bone.

Teriparatide should not be used longer than 2 years due to risk of osteosarcoma

A 58-year-old postmenopausal woman was sent
for dual-energy x-ray absorptiometry to evaluate the bone mineral density of her lumbar spine, femoral neck, and total hip. The test results revealed significantly low bone mineral density in all sites.

Chronic use of which of the following medications is most likely to have contributed to this woman’s osteoporosis?

(A) Lovastatin
(B) Metformin
(C) Prednisone
(D) Propranolol
(E) Thiazide diuretic

Long-term therapy with glucocorticoids such as prednisone is associated with a reduction in bone mineral density and an increased risk of fractures

If this patient began oral therapy with alendronate, she
would be advised to drink large quantities of water with the tablets and remain in an upright position for at least 30 min and until eating the first meal of the day.

These instructions would be given to decrease the risk of which of the following?
(A) Cholelithiasis
(B) Diarrhea
(C) Constipation
(D) Erosive esophagitis
(E) Pernicious anemia

(D) Erosive esophagitis

The patient’s condition was not sufficiently controlled with alendronate, so she began therapy with a nasal spray containing a protein that inhibits bone resorption. The drug contained in the nasal spray was which of the following? ``` (A) Calcitonin (B) Calcitriol (C) Cinacalcet (D) Cortisol (E) Teriparatide ```

(A) Calcitonin

A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH concentration and a low serum concentration of 25-hydroxyvitamin D. He was successfully treated with ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH concentration became markedly elevated Which of the following drugs is most likely to lower this patient’s serum PTH concentration? ``` (A) Calcitriol (B) Cholecalciferol (C) Furosemide (D) Gallium nitrate (E) Risedronate ```

(A) Calcitriol In patients with chronic kidney disease that requires dialysis, the impaired production of active vitamin D metabolites compounded with elevated serum phosphate due to renal impairment leads to secondary hyperparathyroidism. Administration of the active vitamin D metabolite calcitriol acts directly on the parathyroid to inhibit PTH production

Although the drug therapy was effective at lowering serum PTH concentrations, the patient experienced several episodes of hypercalcemia. He was switched to a vitamin D analog that suppresses PTH with less risk of hypercalcemia. Which drug was the patient switched to? ``` (A) Calcitriol (B) Cholecalciferol (C) Furosemide (D) Paricalcitol (E) Risedronate ```

(D) Paricalcitol Paricalcitol is an analog of 1,25-dihydroxyvitamin D3 (calcitriol) that lowers serum PTH at doses that rarely precipitate hypercalcemia. The molecular basis of this selective action is poorly understood but is of value in the management of hyperparathyroidism and psoriasis

In the treatment of patients like this with secondary hyperparathyroidism due to chronic kidney disease, cinacalcet is an alternative to vitamin D-based drugs. Cinacalcet lowers PTH by which of the following mechanisms? (A) Activating a steroid receptor that inhibits expression of the PTH gene (B) Activating the calcium-sensing receptor in parathyroid cells (C) Activating transporters in the GI tract that are involved in calcium absorption (D) Inducing the liver enzyme that converts vitamin D3 to 25-hydroxyvitamin D3 (E) Inhibiting the farnesyl pyrophosphate synthase found in osteoclasts

(B) Activating the calcium-sensing receptor in parathyroid cells Cinacalcet is a member of a novel class of drugs that activate the calcium-sensing receptor in parathyroid cells. When this receptor is activated by cinacalcet or free ionized calcium, it activates a signaling pathway that suppresses PTH synthesis and release.

Net effect of elevated PTH at high doses

increased bone resorption hypercalcemia hyperphosphatemia

Net effect of intermittent doses of PTH

net increase in bone formation

Vitamin D (INACTIVE) added to dairy products and other food products for PSORIASIS

Ergocalciferol | Cholecalciferol

Vitamin D (ACTIVE)

Calcitriol Doxercalciferol Paricalcitol Calcipotriene

Preferred in patients with CKD, chronic liver disease and hyperparathyroidism

Calcitriol

Analogs of calcitriol and used topically for psoriasis

Paricalcitol | Calcipotriene

SE of Vitamin D

hypercalcemia hyperphosphatemia hypercalciuria

BISPHOSPHONATES Suppresses the activity of osteoclasts in part via (-) of Farnesyl Pyrophosphate synthesis (-) bone resorption and secondarily bone formation by acting on hydroxyapatite crystal structure for Paget's disease of bone hypercalcemia (malignancies) osteoporosis bone metastases

BISPHOSPHONATES -DRONATE ``` Alendronate Zoledronic acid (prototype) Etidronate Ibandronate Pamidronate Risedronate Tiludronate ``` ``` SE: adynamic bone esophagitis osteonecrosis of the jaw renal impairment GI irritation ```