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PHARMACOLOGY > Endocrine Module > Flashcards

Endocrine Module Flashcards

1
Q

Osteoporosis

A

Systemic skeletal disorder characterized by decreased bone mass density leading to diminished stature, bone fragility, increased risk of bone fracture

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2
Q

After what age in women do bone strength and density begin to decline?

A

35

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3
Q

What fraction of men/women have osteoporosis?

A

1/4 women

1/8 men

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4
Q

Where is the body’s calcium located?

A

99% in teeth and bones

1% in extracellular fluid and soft tissue

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5
Q

Metabolic processes calcium is involved in

A

Cell membrane function and permeability
Neuronal excitability and transmission of electrical impulses
Contraction of muscle
Conduction of electrical impulses in the heart
Blood coagulation
Platelet adhesion
Hormone secretion
Enzymatic activity
Catecholamine release from adrenal medulla
Release of chemical mediators

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6
Q

Bone

A

Mineralized connective tissue that provides structural support and acts as reservoir for calcium, phosphorus, magnesium, sodium, carbonate

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7
Q

Two main forms of calcium in bone tissue

A

Calcium phosphate
Calcium carbonate
A small amount exists in an unbound, unionized form that moves from bone to bloodstream when serum calcium is low

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8
Q

What % of consumed calcium is absorbed in the intestine?

A

30-50% - the rest is lost in feces

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9
Q

Absorption of calcium is increased by

A

Presence of vitamin D, lactose, moderate amounts of fat, high protein intake, physiologic need

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10
Q

Absorption of calcium is impaired with

A

Vitamin D deficiency, high fat diet, diarrhea

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11
Q

How much calcium should adults consume?

A

1000 mg/day

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12
Q

How much calcium should growing children, pregnant/lactating women and postmenopausal women (no HRT) consume?

A

1200 mg/day

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13
Q

What is the best source of calcium?

A

Milk and milk products (also contain vitamin D and lactose which increase calcium absorption)

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14
Q

What are good sources of calcium besides milk?

A

Broccoli, spinach, kale, shellfish such as clams and oysters

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15
Q

Which 3 hormones regulate calcium and bone metabolism?

A

Parathyroid hormone
Calcitonin
Calcitriol

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16
Q

Parathyroid hormone

A

Secreted from parathyroid gland when serum calcium falls
Stimulates activity of osteoclasts to increase bone resorption
Increases reabsorption of calcium in tubules of kidneys
Activates calcitriol (active form of vitamin D) in the intestines

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17
Q

Calcitonin

A

Secreted from thyroid gland when serum calcium rises
Inhibits activity of osteoclasts to stimulate rate of deposition
Inhibits reabsorption of calcium in tubules of kidneys to increase amount excreted in urine

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18
Q

2 forms of vitamin D

A

Ergo-calciferol obtained from diet

Cholecalciferol - synthesized from cholesterol in skin when exposed to UV light

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19
Q

Calcifediol

A

Intermediate metabolite of vitamin D (formed in liver)

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20
Q

Calcitriol

A

Active form of vitamin D (formed in kidneys)

Enhances intestinal absorption of calcium

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21
Q

2 types of receptors calcitriol works on

A
  1. Membrane level - activates L-type calcium channels to modulate calcium influx across cell borders
  2. Intracellular protein - calcitriol protein complex enters nucleus and causes nuclear DNA to generate an mRNA specific for production of a calcium binding protein that intermediates in the system effects of calcitriol
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22
Q

Action of calcitriol at the tissue/system level

A

Stimulates intestinal calcium and phosphate transport
Increases serum calcium and phosphate from bone resorption through inducing differentiation of osteoclasts
Decreases renal excretion of calcium and phosphate

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23
Q

What is indicative of undetected osteoporosis?

A

Shortened stature
Back pain
Spinal deformity

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24
Q

Causes of osteoporosis

A

Inadequate dietary calcium
Inadequate calcium absorption
Vitamin D deficiency
Disruption of calcium and bone metabolism (hypersecretion of PTH, hyposecretion of calcitonin)

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25
Q

Which body areas are particularly vulnerable to osteoporosis related fracture?

A

Vertebrae of lower dorsal and lumbar spines
Wrists
Hips

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26
Q

When to osteoporotic fractures often occur?

A

After bending or lifting movements, slips, trips, falls

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27
Q

Alterable/minor risk factors

A
  • Smoking - increases calcium excretion via kidneys
  • Calcium and vitamin D deficiency - increases bone resorption
  • Increased sodium or protein intake - increases calcium excretion via kidneys and increases bone resorption
  • Caffeine and alcohol - cause diuresis leading to increased calcium excretion
  • Lack of exercise - exercise helps retain calcium and increases bone mass density
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28
Q

Major risk factors

A

Female gender (esp. with advanced age, prolonged amenorrhea, menopause because estradiol limits activity of osteoclasts and progesterone stimulates osteoblasts to build new bone)
Fragility fractures (less than 40 y/o)
Ancestry - Asian or Caucasian
Small frame - smaller bones, less mass
Family history - especially maternal
Glucocorticoid therapy for more than 3 months - inhibits bone deposition and increases resorption

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29
Q

Who should be assessed for presence of risk factors for osteoporosis?

A

All adults over 50

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30
Q

Anyone over 50 should undergo bone mass density testing if…

A 
They are over 65
Fragility fractures after age 40
Family history of osteoporotic fracture
Use of high dose systemic glucocorticoid therapy for 3 months
Current smoking or alcohol
Low body weight
Rheumatoid arthritis
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31
Q

Anyone under 50 should undergo bone mass density testing if…

A

History of fragility fractures
Premature menopause
Primary hyperparathyroidism
Hypogonadism

32
Q

How are bone mass density tests performed?

A

Dual energy x-ray absorptionmetry
Test scans lumbar region and one hip
Takes about 10 minutes
Low radiation exposure, high sensitivity for diagnosis

33
Q

If bone mass density is normal and they are deemed low risk for fracture…

A

Repeated testing every 5 years

34
Q

Recommended calcium/vitamin D intake for postmenopausal women

A

1200 mg calcium

800-2000 IU vitamin D

35
Q

If a client is deemed moderate risk for fracture…

A

Preventative strategies such as lifestyle change and pharmacotherapy initiated

36
Q

In cases of severe bone mass density loss…

A

Pharmacological treatment for osteoporosis is required to increase bone mass density and mediate high risk of fragility fracture

37
Q

In cases of moderate/high risk for fracture…

A

Bone mass density tests every 1-3 years

38
Q

Recommended calcium/vitamin D intake for people with osteoporosis

A

1000 mg/day calcium
800 IU/day vitamin D
Insufficient to prevent fracture, used as adjunct

39
Q

Pharmacological treatment option

A 
Hormone replacement therapy
Selective estrogen receptor modulators
Bisphosphonates
RANKL inhibitors
Parathyroid hormone
40
Q

Hormone therapy

A

Estrogen and progesterone which have a positive effect on bone mass density - prevents loss in menopausal women and increase density in patients with existing osteoporosis

41
Q

Who is HRT recommended in?

A

Women with moderate-severe symptoms due to risk of breast cancer, heart disease, stroke - hot flashes, night sweats, disrupted sleep pattern, fatigue

42
Q

HRT should not be prescribed for

A

Solely for treatment of osteoporosis

43
Q

Routes of admin for HRT

A

Oral and transdermal

44
Q

Selective estrogen receptor modulators

A

Act as an estrogen agonist at beta-estrogen receptors in bone to inhibit osteoclast activity and reduce rate of bone resorption
Act as an estrogen antagonist at alpha-estrogen receptors in breast and endometrial tissue - no risk of breast or uterine cancer

45
Q

What are SERMs recommended for?

A

Prevention and treatment in asymptomatic menopausal and post-menopausal women

46
Q

Adverse effects of SERMs

A

Leg cramps
Hot flashes
Venous thromboembolism

47
Q

Tissue selective estrogen complexes

A

Combine SERMs with one or more synthetic estrogens, effective for relief of menopausal symptoms and prevention of bone loss
Protect breast and endometrium from oncogenic effects of unopposed estrogen

48
Q

What are TSECs recommended for?

A

Prevention of postmenopausal osteoporosis

49
Q

Bisphosphonates

A 
Drug class of choice to prevent and treat osteoporosis
Inhibit osteoclast activity and reduce bone resorption, increase bone mass density and overall bone strength
50
Q

How soon are results seen in bisphosphonate therapy?

A

1-3 months

51
Q

How should alendronate and risedronate be administered

A

Orally, daily
Empty stomach with full glass of water to minimize risk of esophageal irritation and improve absorption
No other food or meds 30 minutes post-admin and remain upright
Adverse effects related to abdominal pain and dysphagia

52
Q

Most potent bisphosphonate

A

Zoledronic acid

53
Q

How should zoledronic acid be administered and for what scenario?

A

IV annually for treatment of postmenopausal osteoporosis

Less frequent dosing (increased adherence) and reduced risk of GI effects

54
Q

Atypical femur fractures are associated with

A

Long term use of bisphosphonates (5-7 years)

55
Q

AFFs are often preceded by

A

Pain in thigh or groin weeks-months before fractuer

56
Q

If clients report pain in thigh or groin, what tests should be performed and why?

A

AFF risk - radiography, bone scans, MRI

57
Q

If any evidence of AFF is present…

A

Bisphosphonate therapy should be discontinued

58
Q

Drug holidays from long term bisphosphonate therapy

A

Reduce AFF risk

59
Q

Long term skeletal retention and stable bone mass density are shown after how many years of bisphosphonate therapy?

A

5

60
Q

Discontinuation after 5 years of bisphosphonate therapy is appropriate for…

A

Those at moderate risk of fracture

In high risk, benefit of continuation of therapy outweighs risks

61
Q

How are bisphosphonates cleared?

A

Renally - only 50% is deposited in bone

62
Q

What is the drug of choice with renal dysfunction?

A

Denosumab

63
Q

Receptor activator of nuclear factor kappa-B ligand inhibitors

A

RANKL - binds to RANK receptor on osteoclasts to promote removal of calcium from bone
Estrogen deficiency stimulates upregulation of RANKL, increasing osteoclast function

64
Q

How are RANKLs administered?

A

SC injection twice yearly

65
Q

First drug of choice in postmenopausal women at high risk of fracture or in those that do not tolerate or respond to bisphosphonate therapy

A

RANKL inhibitors

66
Q

Clients taking RANKL inhibitors should seek medical attention for

A

Signs of infection
Allergic reaction
Skin damage
AFF

67
Q

Common adverse effects of RANKL inhibitors

A

Hypocalcemia, fatigue, GI disturbance, MSK pain, skin lesions, increased risk for infection
Increased risk for AFF

68
Q

Parathyroid hormone (teriparatide)

A

Builds new bone

69
Q

PTH is recommended for use in…

A

Cases of severe osteoporosis or those who do not respond to other treatments

70
Q

How is PTH administered?

A

Daily SC for no longer than 24 months - osteosarcoma risk

Intermittent administration increases osteoblast activity and promotes deposition

71
Q

What adverse effects are associated with PTH therapy?

A

Nausea, dizziness, leg cramps

72
Q

Antiresorptive therapies include

A

HRT
Bisphosphonates
SERMs
Calcitonin

73
Q

Is combination resorptive therapy recommended?

A

No

74
Q

Risk of hip fracture compared to breast cancer

A

1/6 fracture hip, 1/9 develop breast cancer

Death rate for hip fracture is higher

75
Q

Long term effects of hip fracture

A

50% do not return to previous functional state

20% require LTC

PHARMACOLOGY (27 decks)

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