Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology > Drugs acting on bone metabolism > Flashcards

Drugs acting on bone metabolism Flashcards

(51 cards)

Start Studying
1
Q

What are the main minerals in bone?

A

Calcium and phosphates

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

What are the main cells in bone homeostasis?

A

osteoblasts,

osteoclasts and osteocytes.

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

What are osteoblasts?

A

Osteoblasts are bone-forming
cells: they secrete important
components of the extracellular
matrix-the osteoid.

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

What are Osteoclasts?

A

Osteoclasts are multinucleated

bone-resorbing cells.

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

What are osteocytes?

A 
Osteocytes are derived from the
osteoblasts, which, during the
formation of new bone, become
embedded in the bony matrix
and differentiate into
osteocytes. These cells form a connected cellular network that,
along with the nerve fibers in
bone has a role in the response
to mechanical loading.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is osteoid?

A

Osteoid is the organic
matrix of bone and its
principal component is
collagen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is bone remodeling?

A 
 The process of remodelling involves:
• Two main cell types: osteoblasts and osteoclasts
• Variety of cytokines
• Bone minerals-particularly calcium and phosphate
• The actions of several hormones:
 Parathyroid hormone (PTH)
 Calcitonin
 The vitamin D family
 Estrogens
 Growth hormone
 Steroids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the action of cells and cytokines?

A

The osteoblast expresses a surface ligand, the RANK ligand (RANKL):
• Expression is stimulated by calcitriol, parathyroid hormone (PTH), cytokines
and glucocorticoids

RANKL interacts with a receptor on the
osteoclast termed RANK (receptor
activator of nuclear factor kappa B). The
result is:
• Differentiation and activation of the
osteoclast progenitors to form mature
osteoclasts;
• Fusion of osteoclasts occurs to give giant
multinucleated bone-resorbing cells.

The osteoblast also releases ‘decoy’ molecules of osteoprotegerin (OPG),
which can bind RANKL and prevent activation of the RANK receptor.

 Bisphosphonates inhibit bone resorption
by osteoclasts.

 Anti-RANKL antibodies (e.g.
denosumab) bind RANKL and prevent
the RANK-RANKL interaction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the hormones involved in bone metabolism?

A 
The actions of several hormones:
 Parathyroid hormone (PTH)
 Calcitonin
 The vitamin D family
 Estrogens
 Growth hormone
 Steroids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the function of Parathyroid hormone?

A

 Mobilises Ca2+ from bone
 Promotes its reabsorption by the
kidney
 Stimulates the synthesis of calcitriol,
which in turn increases Ca2+
absorption from the intestine and synergises with PTH in mobilizing bone Ca2+
 Promotes phosphate excretion

• Net effect – to increase the concentration of Ca2+ in the
plasma and lower that of
phosphate

 But given therapeutically in a low intermittent dose, PTH and
fragments of PTH
paradoxically stimulate
osteoblast activity and
enhance bone formation.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is calcitonin and what is its function?

A

 Calcitonin is a peptide
hormone secreted by
the specialized ‘C’ cells
in the thyroid follicles.

 The main action of
calcitonin is on bone:
• Inhibits osteoclasts
• In the kidney:
 Decreases of the
reabsorption of both Ca2+
and phosphate
• Its overall effect:
 Decrease of the plasma
Ca2+ concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the sources of vitamin D?

A

Two sources of vitamin D:
 Dietary ergocalciferol (D2)
 Cholecalciferol (D3) is generated in the skin by the action of ultraviolet irradiation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What occurs in the conversion of cholecalciferol?

A

 In the liver to calcifediol (25-hydroxy-vitamin D3)
 Further in the kidney to calcitriol (1,25-
dihydroxy-vitamin D3) – the active form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the function of calcitriol?

A

Calcitriol
 Stimulates the absorption of Ca2+ and phosphate
in the intestine
 Mobilizes Ca2+ from bone
 Increases Ca2+ reabsorption in the kidney
tubules
 Promotes the maturation of osteoclasts and
stimulates their activity
 Decreases collagen synthesis by osteoblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What function does estrogen have on bone metabolism?

A

• Inhibit the cytokines that
recruit osteoclasts

• Oppose the bone resorbing, Ca2+-
mobilizing action of PTH

• Increase osteoblast
proliferation and inhibit
apoptosis

• Withdrawal of estrogen,
as happens at the
menopause, can (and
usually does) lead to
osteoporosis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do glucocorticoids play a role in bone metabolism?

A 
Glucocorticoids
• Physiological
concentrations are
required for osteoblast
differentiation.

• Excessive
pharmacological
concentrations:
 Inhibit osteoblast
differentiation and activity
 Stimulate osteoclast action
 Result:
 Osteoporosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some examples of bone diseases?

A

Rickets
osteoporosis
paget’s disease of bone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How are the drugs used in bone disorders classified?

A 
1. Bisphosphonates
а. I generation
Clodronic acid
b. II generation
Alendronic acid
Ibandronic acid
Zoledronic acid
  1. Estrogens, SERM
    Raloxifene
  2. Parathormone analogs
    Teriparatide
  3. Monoclonal antibodies
    against RANKL
    Denosumab
  4. Strontium
    Strontium ranelate
  5. Calcitonin
    Calcitonin
  6. Vit. D and analogs
    Calcitriol
    Cholecalciferol
    Calcipotriol
  7. Calcimimetics
    Cinacalcet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the PK of bisphosphonates?

A 
 PK
• Applied orally or i.v.
• Poorly absorbed
• Accumulate at the sites of bone mineralisation (50% of the dose)
• Remain in bone potentially for
months or years
• The free drug is excreted
unchanged by the kidney.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the PD of Bisphosphonates?

A

 PD
• They inhibit bone resorption by
an action mainly on the
osteoclasts
• They form tight complexes with calcium in the bone matrix
• Osteoclasts are exposed to high concentrations of the drugs during bone resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the unwanted effects of bisphosphonates?

Study These Flashcards
A 
 Unwanted effects
• Oesophagitis (alendronate)
• Bone pain – occasionally
• Given intravenously –
osteonecrosis of the jaw
(zoledronate)
22
Q

What are the clinical uses of bisphosphonates?

Study These Flashcards
A 
 Clinical uses of
bisphosphonates
• Osteoporosis
 Prevention of fractures in
high-risk individuals
 Alendronate – by mouth,
daily or once weekly in
addition to calcium with
vitamin D3.
 Zoledronate – annually by
intravenous infusion,
expensive

• Malignant disease involving
bone (e.g. metastatic breast
cancer, multiple myeloma)
 To reduce bone damage, pain
and hypercalcaemia

• Paget’s disease of bone
 Intermittent administration

23
Q

What is the mechanism of action, clinical use, and ADRs of Estrogens and SERM?

Study These Flashcards
A

Raloxifene

 Mechanism of action – SERM
• Agonist activity on bone, stimulating osteoblasts and
inhibiting osteoclasts
• Agonist actions on the cardiovascular system
• Antagonist activity on mammary tissue and the uterus

 Clinical use
• An alternative to a bisphosphonate for secondary
prevention in postmenopausal women who cannot
tolerate a bisphosphonate

 Adverse drug reactions
• Hot flushes, leg cramps, and peripheral edema
• Less common are thrombophlebitis and
thromboembolism

24
Q

What are PTH and teriparatide?

Study These Flashcards
A 
 Teriparatide – the
peptide fragment (1-
34) of recombinant
PTH:
• Given in small doses
subcutaneously once
daily
• Paradoxically stimulates
osteoblast activity and
enhances bone
formation
• Used to treat selected
patients with
osteoporosis
• Well tolerated
25
What is the mechanism of action of Monoclonal antibodies against RANKL (Denosumab)?
```  Mechanism of action • Monoclonal antibody (IgG2 ), which targets and binds with high affinity with RANKL • Inhibits osteoclastogenesis and activity ```
26
What is the clinical use of Monoclonal antibodies against RANKL (Denosumab)?
Clinical use • Treatment of postmenopausal osteoporosis and some cancers (prostate and breast)
27
What is the administration of Monoclonal antibodies against RANKL (Denosumab)?
Administration • S.c. once every 6 months together with Calcium and vitamin D
28
What is the ADR of Monoclonal antibodies against RANKL (Denosumab)?
``` ADR: • Infections (airways and urinary tract) because a number of cells in the immune system also express RANKL • Rarely – osteonecrosis of the jaw ```
29
What is strontium rantelate?
Strontium ranelate • Inhibits bone resorption and also stimulates bone formation • An alternative to a bisphosphonate in prevention of osteoporotic fractures, when a bisphosphonate is not tolerated • The precise mechanism of action is not clear  Strontium atoms are adsorbed onto the hydroxyapatite crystals  Remain in the bone for many years  Eventually they exchange for calcium in the bone minerals • The drug is well tolerated.
30
What are cholecalciferol and calcitriol used for?
 Given orally  Deficiency states: prevention and treatment of rickets and osteomalacia (cholecalciferol).  Osteodystrophy of chronic renal failure (calcitriol).
31
What is calcipotriol used for?
Calcipotriol  Ointment  Psoriasis (inhibits cell proliferation; has effects on immunologic markers that are thought to play a role in the etiology of the disease)
32
What is calcitonin used for?
Synthetic salmon calcitonin Given by subcutaneous or intramuscular injection. Clinical use: • Hypercalcaemia (e.g. associated with neoplasia) • Paget's disease of bone (to relieve pain and reduce neurological complications)
33
What is cinacalet?
 A calcimimetic agent – mimics the action of calcium in the body by: • Mimics the stimulatory effect of Ca2+ on the calcium-sensing receptor to inhibit PTH secretion by the parathyroid glands. • The reduction in PTH levels also leads to a decrease in blood calcium levels.
34
what are the clinical uses of cinalcet?
 Clinical uses: • In secondary hyperparathyroidism in patients with serious kidney disease who need dialysis • To reduce hypercalcemia in patients with parathyroid carcinoma or with primary hyperparathyroidism who cannot have their parathyroid glands removed
35
Which are the hormones secreted by the thyroid gland?
* Thyroxine (T4) * Tri-iodothyronine (T3) * Calcitonin
36
Which hormone regulates hormone synthesis and secretion?
``` Hormone synthesis and secretion are regulated by thyroid-stimulating hormone (thyrotrophin) and influenced by plasma iodide. ```
37
What is the functional unit of the thyroid?
```  The functional unit of the thyroid is the follicle.  The follicle: • A single layer of epithelial cells (1) • A cavity (*) filled with a thick colloid containing thyroglobulin. ```
38
How are thyroid hormones synthesized?
• Uptake of plasma iodide by the follicle cells • Oxidation of iodide and iodination of tyrosine residues of thyroglobulin to MIT and DIT (thyroperoxidase) • Coupling in pairs: either MIT with DIT to form T3, or two DIT molecules to form T4. • Endocytosis of the thyroglobulin molecule into the follicle cell • Proteolysis of thyroglobulin and releasing T4 and T3 • Secretion of T4 and T3 into the plasma.
39
What are the actions of thyroid hormones?
Two categories: • Affecting metabolism:  General increase in the metabolism of carbohydrates, fats and proteins, T3 being three to five times more active than T4 • Affecting growth and development – a critical effect on growth:  Partly by a direct action on cells  Indirectly by influencing growth hormone production and potentiating its effects on its target tissues
40
What is the mechanism of action of thyroid hormones?
 Genomic actions – a specific nuclear receptor, TR ``` • T4 may be regarded as a prohormone, because when it enters the cell, it is converted to T3 • T3 then binds with high affinity to a member of the TR family • Activation of transcription, resulting in generation of mRNA and protein synthesis ```  Non-genomic actions
41
What are some abnormalities of thyroid function?
 Hyperthyroidism (thyrotoxicosis); either diffuse toxic goiter or toxic nodular goiter  Hypothyroidism; in adults this causes myxoedema, in infants cretinism ```  Simple non-toxic goitre caused by dietary iodine deficiency, usually with normal thyroid function ```
42
Which are the drugs used for thyroid and thyroid activity?
1. Drugs with the activity of thyroid hormones Levothyroxine 2. Thyreostatic agents Thiamazol Propylthiouracil 3. Iodides Potassium iodide
43
What is levothyroxine?
Levothyroxine: Synthetic compound Given orally Unwanted effects may occur with overdose: • Severe overdose:  Signs and symptoms of hyperthyroidism  Precipitating of angina pectoris, cardiac dysrhythmias or even heart failure • Less severe overdose  Increased bone resorption leading to osteoporosis
44
What is the action of thyreostatic agents? (Thiamzol, Propylthiouracil)
Mechanism of action: • Inhibition of the iodination of tyrosil residues in thyroglobulin • Inhibition of the thyroperoxidase-catalysed oxidation reactions • Reduction of the deiodination of T4 to T3 in peripheral tissues (Propylthiouracil)
45
What is the clinical response of thyreostatic agents? (Thiamzol, Propylthiouracil)
The clinical response: • After several weeks (the thyroid may have large stores of hormone) • Propylthiouracil is thought to act somewhat more rapidly because of the reduction of the deiodination of T4 to T3
46
What is the ADR of thyreostatic agents? (Thiamzol, Propylthiouracil)
Adverse drug reactions: • Neutropenia and agranulocytosis (the most dangerous unwanted effect with an incidence of about 1%, reversible on cessation of treatment} • Rashes (more common up to 25%)
47
What are the indications of thyreostatic agents? (Thiamzol, Propylthiouracil)
 Indications: • Hyperthyroidism (diffuse toxic goitre) – long treatment (at least 1 year) • In very severe hyperthyroidism (thyroid storm) – propylthiouracil is preferred. The β-adrenoceptor antagonists (e.g. propranolol) are also used.
48
What is the mechanism of action of Potassium iodide?
Mechanism of action – not entirely clear: • It may inhibit iodination of thyroglobulin, possibly by reducing the H2O2 generation that is necessary for this process
49
What are the effects of potassium iodide?
Effects: • Temporary inhibition of the release of thyroid hormones (10-14 days) • Reduction in vascularity of the gland
50
What are the clinical uses of potassium iodide?
Clinical use: • For the preparation of hyperthyroid subjects for surgical resection of the gland • As part of the treatment of thyroid storm
51
What are the ADRs of potassium iodide?
Adverse drug reactions (iodide in tears and saliva): • Lacrimation, conjunctivitis • Pain in the salivary glands

Pharmacology (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions