Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrinological Pharmacology > 15. Agents affecting bone mineral homeostasis (calcium, vitamin D, parathyroid hormone, calcitonin, etc.). Pharmacotherapy of osteoporosis. > Flashcards

15. Agents affecting bone mineral homeostasis (calcium, vitamin D, parathyroid hormone, calcitonin, etc.). Pharmacotherapy of osteoporosis. Flashcards

1
Q

primary hormonal modulators

A

parathyroid hormone (PTH) - Teriparatide

  • kidney: Ca2+ excretion–, Phosphate excretion++, synthesis of Vit-D (stimulates renal 1alpha-hydroxylase)
  • osteoblast and -clast are activated:
    1. continious high stimulation -> net bone resorption
    2. intermittend low concentration: net bone formation
  • Intestine: Ca2+ and Phosphate absorption++, (indirect by Vit D)

VitD2 (ergocalciferol)+ VitD3 (Cholecaciferol) = liver and kidney = calcitriol (1,25-dihydroxy-VitD)
- kidney: Ca2+ and Phosphate reabsorption++
- Bone: direct bone reabsorption++ Ca2+ and Phosphate, indirect effect is mineralisation by ++Ca2+ and ++Phosphate
Intestine: Absorption of Ca2+ and Phosphate
- inhibits PTH release
- Intestine and bone effect are more potent than kidney
-(Ergocalciferol,) Cholecalciferol, (Doxercalciferol) -> Prodrug
- calcitriol
(-Paricalcitol)
(-Calcipotriene)- topical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Analogues of primary hormonal modulators

A

parathyroid hormone (PTH) - Teriparatide

VitD2 (ergocalciferol)+ VitD3 (Cholecaciferol) = liver and kidney = calcitriol (1,25-dihydroxy-VitD)
-(Ergocalciferol,) Cholecalciferol, (Doxercalciferol) -> Prodrug
- calcitriol
(-Paricalcitol)
(-Calcipotriene)- topical

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

secondary hormonal modulator

A

Calcitonin: (calcitonin as medication itself?)

  • kidney: Ca2+ and Phosphate excretion++
  • bone: inhibits osteoclast activity (bone reabsorption– )
  • NET: Ca2+ – (loss)

Estrogens:

  • Inhibition of PTH induced bone reabsorption
  • inhibits osteoclast activity
  • SERM as medication: RALOXFEN

Glucocorticoids:

  • intestinal and renal Ca2+ reabsorption– (down)
  • RANK-Receptor suppression
  • RANKL stimulation
  • inhibitory effect on osteoblast and collagen synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Non-hormonal modulators

A

Bisphosphonates:

  • direct suppression of Osteoclast (fornesyl pyrophosphonate synthase)
  • BMU– ??
  • Ca2+ – ??
    1. Alendronate!!
    2. Zoledronate!!

RANK-Ligand inhibitor :

  • RANK-L also plays a role in the immune response
  • Denosumab!!

Calcimimetics:
- activating Ca+-sensing receptors in Parathyroid gland
(- Cinacalcet)

(Flouride: )
- stabilizes hydroxy-apatide crystals

(strontium ranelate)
- promotes osteoclast apoptosis and osteoblast activity ++

Thiazide diuretic:

  • increases ca2+ level
  • Hydrochlorothiazid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Parathyroid hormone (PTH)

A
  • Kidney: Ca2+ excretion ↓, P excretion ↑, synthesis of active vitamin D (PTH stimulates renal 1α-hydroxylase enzyme)
  • Bone: (both osteoclast and osteoblast are stimulated) continuous high concentration → net bone resorption; intermittent low concentration → net bone formation
  • Intestine: Ca2+ and P absorption ↑ (indirect effect, mediated by vitamin D)
  • Net effect on serum levels: Ca2+ ↑, P ↓

analogue:
Teriparatide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Teriparatide

A

Parathyroid hormone (PTH)-analogue

  • Kidney: Ca2+ excretion ↓, P excretion ↑, synthesis of active vitamin D (PTH stimulates renal 1α-hydroxylase enzyme)
  • Bone: (both osteoclast and osteoblast are stimulated) continuous high concentration → net bone resorption; intermittent low concentration → net bone formation
  • Intestine: Ca2+ and P absorption ↑ (indirect effect, mediated by vitamin D)
  • Net effect on serum levels: Ca2+ ↑, P ↓

Teriparatide

  • PTH analogue (recombinant form; consists of N-terminus – 34 amino acids of parathyroid hormone)
  • Subcutaneous injection
  • Osteoporosis (promotes bone formation in low, intermittent doses)
  • Side effects: hypercalcemia, hypercalciuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Vitamin D

A

Vitamin D2 (ergocalciferol) + vitamin D3 (cholecalciferol) from skin and/or intestinal absorption → converted by the liver and kidney to the biologically active metabolite calcitriol (1,25 dihydroxy-vitamin D)

  • Kidney: Ca2+ and P reabsorption ↑; urinary Ca2+ may be elevated as the effects of vitamin D are more potent on bone and GI
  • Bone: direct effect is bone resorption (↑ of serum Ca2+ and P); indirect effect is promoting mineralization by increasing the availability of Ca2+ and P
  • Intestine: Ca2+ and P absorption ↑
  • Inhibitory effect on PTH release
  • Net effect on serum levels: Ca2+ ↑, P ↑
  • Vitamin D cannot be used to treat primary hyperparathyroidism; only the secondary form! For primary disease → surgical and bisphosphonate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Ergocalciferol (vitamin D2)

Cholecalciferol (vitamin D3)

A

Vitamin D2 (ergocalciferol) + vitamin D3 (cholecalciferol) from skin and/or intestinal absorption → converted by the liver and kidney to the biologically active metabolite calcitriol (1,25 dihydroxy-vitamin D)

  • Kidney: Ca2+ and P reabsorption ↑; urinary Ca2+ may be elevated as the effects of vitamin D are more potent on bone and GI
  • Bone: direct effect is bone resorption (↑ of serum Ca2+ and P); indirect effect is promoting mineralization by increasing the availability of Ca2+ and P
  • Intestine: Ca2+ and P absorption ↑
  • Inhibitory effect on PTH release
  • Net effect on serum levels: Ca2+ ↑, P ↑
  • Oral
  • Require metabolism in liver and/or kidney to active forms
  • Vitamin D deficiency – rickets disease, osteomalacia (nutritional deficiency, intestinal osteodystrophy, hypoparathyroidism, nephrotic syndrome)
  • Side effects: hypercalcemia, hyperphosphatemia, hypercalciuria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Calcitriol

1,25 dihydroxy-vitamin D

A
  • Oral
  • Drug in active form, does not require metabolism
  • Secondary hyperparathyroidism in patients with
    chronic kidney disease → vitamin D inhibits PTH release, corrects hypocalcemia, and improves bone disease
  • Management of hypocalcemia in patients with hypoparathyroidism
  • Vitamin D cannot be used to treat primary hyperparathyroidism; only the secondary form! For primary disease → surgical and bisphosphonate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Doxercalciferol

not on the list

A
  • Analogue of calcitriol
  • Prodrug
  • Oral or parenteral
  • Secondary hyperparathyroidism in patients with chronic kidney disease
  • Side effects are milder compared to calcitriol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Paricalcitol

not on the list

A

Paricalcitol

  • Analogue of calcitriol
  • Oral
  • Secondary hyperparathyroidism in patients with chronic kidney disease
  • Side effects are milder compared to calcitriol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Calcipotriene (Calcipotriol)

not on the list

A
  • Analogue of calcitriol
  • Topical
  • Psoriasis (vitamin D inhibits keratinocyte proliferation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Calcitonin

A

Kidney: Ca2+ and P excretion ↑

  • Bone: inhibits osteoclast activity (bone resorption ↓)
  • Net effect on serum levels: Ca2+ ↓
  • Analogue of biological source
  • Subcutaneous injection, nasal spray
  • Osteoporosis
  • Paget’s disease
  • Acute management of hypercalcemia
  • Side effects:
    rhinitis with the nasal spray,
    hypocalcemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Raloxifene

A

Estrogens
- Inhibition of PTH-induced bone resorption (inhibit osteoclast activity)

  • Oral

SERM – Selective estrogen receptor modulators

  • Estrogen antagonist activity → breast, CNS, uterus
  • Estrogen agonist activity → liver, bone
  • Osteoporosis in post-menopausal women
  • Side effects: hot flushes, increased risk of venous
    thromboembolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Glucocorticoids

A
  • Intestinal and renal Ca2+ absorption ↓
  • RANK-L stimulation, RANK receptor suppression
  • Inhibitory effects on osteoblast activity and collagen synthesis

Net effect → risk of osteoporosis if systemic therapy is used for prolonged time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Alendronate

Zoledronate

(Risedronate)

A

Bisphosphonates
- Direct suppression of osteoclast activity (inhibit farnesyl pyrophosphate synthase enzyme, which plays a critical role in osteoclast survival) → prevent bone
turnover by decreasing the number of the basic multicellular (remodelling) units - BMU
- Result in rapid increase of bone mineral density in the first year; later, a new equilibrium between bone metabolism and resorption is established

  • Oral or parenteral administration
    (oral bioavailability < 10%; absorption further impaired by food)
  • Eliminated by the kidneys with no prior metabolism
  • Effect may persist for up to 2 years following treatment cessation
  • Osteoporosis (1st line treatment → cost, efficacy, long- term beneficial effects)
  • Paget’s disease
  • Bone metastasis
  • Hypercalcemia due to hyperparathyroidism

Side effects:
- hypocalcemia,
- upper GI irritation
(may be prevented by administration with large quantities of water, and avoidance of gastric reflex),
- osteonecrosis of the jaw (rare, more likely with IV use)

*Bisphosphonate is used as the carrier molecule for radio-active isotope (99mTc) during bone scintigraphy, binding hydroxyapatite in areas on increased bone turnover

17
Q

Denosumab

A

RANK-Ligand inhibitors

RANK-L stimulates osteoclast differentiation and function → bone resorption

  • Human monoclonal antibody (IgG)
  • Subcutaneous injection, every 6 months
  • Post-menopausal osteoporosis
  • Side effects:
    increased risk of infection
    (role of RANK-L in the immune response)
18
Q

Cinacalcet

not on the list

A

Calcimimetics
Lowers PTH levels by activating the Ca2+-sensing receptor in the parathyroid gland

  • Oral
  • Secondary hyperparathyroidism due to chronic kidney disease
  • Management of parathyroid carcinoma
  • Side effects: nausea, hypocalcemia, adynamic bone
    disease (decreased bone activity)
19
Q

Fluoride

not on the list

A
  • Accumulates in bones and teeth, stabilizes the hydroxyapatite crystals
  • Promotes new bone growth
    Fluoride
  • Oral or in drinking water and toothpaste
  • Effect is doubtful
  • Side effect (acute toxicity): GI and neurological
    symptoms
20
Q

Strontium ranelate

not on the list

A
  • Promotes osteoclast apoptosis, enhances osteoblast activity
  • Not in clinical use due to financial reasons
  • Osteoporosis
21
Q

Thiazide diuretics

A
  • Increases Ca2+ serum level
  • Osteoporosis

Inhibit Na+/Cl- transporter in distal convoluted tubule

Hydrochlorothiazide

  • Oral
  • Duration of action 8-12 h’
  • Hypertension
  • Congestive heart failure
  • Mild edema
  • Sulfonamide derivative

Drug interactions

  • Digoxin (enhanced toxicity due to electrolyte disturbances)
  • Avoid in patients with diabetes mellitus

Inhibition of Na+/Cl- transporter (NCC) in the distal convoluted tubule

  • Natriuresis (loss of NaCl) – effect is moderate but sustained
  • Hypercalcemia (opposite effect to the one achieved by loop diuretics)
  • K+ wasting (excess Na+ is reabsorbed in the collecting tubule) – hypokalemic metabolic alkalosis
  • Hypertension
  • CHF (adjunct to loop diuretics)
  • Nephrolithiasis (urine Ca2+ ↓)
  • Nephrogenic diabetes insipidus
  • Osteoporosis (serum Ca2+ ↑ promote bone formation)
  • Side effects: sulfonamide hypersensitivity, hypokalemic
    metabolic alkalosis, hyponatremia, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, Lithium level ↑

Thiazide diuretics and other thiazide derivatives may also act a potent openers of K+-channels, resulting hyperpolarization:
􏰀 Vasodilation (smooth muscle cell effects)
􏰀 Insulin release ↓ (pancreatic β-cell effects)

22
Q

Osteoporosis – definition

A

Reduction in the strength of bone that leads to an increased risk of fractures; loss of bone tissue is associated with deterioration in skeletal microarchitecture. Main clinical manifestations are vertebral and hip fractures, although fractures can occur at almost any skeletal site.

23
Q

etiology of osteoporosis

A

Primary → post-menopausal, senile (age-associated)

Secondary (all are risk -
factors for developing primary osteoporosis) →

Endocrine:

  • Hyperparathyroidism
  • Hypothyroidism
  • Hyperthyroidism
  • Hypogonadism
  • Pituitary tumors
  • Type 1 D.M

GI:

  • Malnutrition
  • Malabsorption
  • Hepatic insufficiency
  • Vitamin C, D deficiencies

Drug-induced:

  • Anticoagulants
  • Chemotherapy
  • Corticosteroids
  • Anticonvulsants
  • Alcohol
24
Q

Bone mineral density (BMD)

A

Diagnosis by dual energy X-ray absorptiometry (DEXA) scan, graded based on the T-score.

Classification T-score:
Normal:
-1.0 or greater

Osteopenia:
Between -1.0 to -2.5

Osteoporosis:
-2.5 or less

Severe osteoporosis:
-2.5 or less with a pathologic fracture

25
Q

Pharmacological management of osteoporosis

A

I. Inhibit bone resorption:

  • Hormonal replacement therapy* : Estrogen (with/without progestin)
  • SERM (selective estrogen receptor modulator) : Raloxifene
  • Bisphosphonate
  • RANK-L inhibitors – Denosumab
  • Calcitonin analogues

*Estrogen replacement therapy in post-menopausal women has shown to increase the risk of breast cancer and cardiovascular events.
Currently not recommended as a chronic treatment of osteoporosis!

II. Promote bone formation:

  • PTH analogues – Teriparatide
  • Ca2+ supplementation
  • Vitamin D supplementation
  • Thiazide diuretics

Endocrinological Pharmacology (6 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions