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ADAMS, CHAPTER 47
Drugs for Bone and Joint Disorders
ROLE OF CALCIUM IN
MAINTAINING
HOMEOSTASIS
Critical to proper functioning of the nervous,
muscular, and cardiovascular systems
Adequate levels in body necessary to:
• Transmit nerve impulses
• Prevent muscle spasms
• Provide stability and movement
ROLE OF CALCIUM IN
MAINTAINING
HOMEOSTASIS
Also important for blood coagulation and
myocardial activity
To maintain homeostasis:
• Calcium balance in the body is regulated by
parathyroid hormone (PTH)
ROLE OF CALCIUM IN
MAINTAINING
HOMEOSTASIS
Parathyroid—Secretes PTH
•
•
•
•
•
Stimulates osteoclasts
Accelerates bone resorption
Causes breakdown of bone
Consequently, calcium increases in blood
Calcium ion influences the excitability of all neurons
RECOMMENDED DIETARY
ALLOWANCE (RDA) OF
CALCIUM
For adults RDA is 800–1200 mg/day
Increased amounts of calcium required for:
• Pregnant women
• Growing children
• Menopausal women
RECOMMENDED DIETARY
ALLOWANCE (RDA) OF
CALCIUM
Normal serum calcium range is 4.5–5.5 mEqL or
8.5–10.mg/dl.
Serum calcium levels exceeding 5.5 mEq/L result in
hypercalcemia.
Hypocalcemia results from serum calcium levels
below 4.5 mEq/L
ROLE OF CALCIUM IN
MAINTAINING
HOMEOSTASIS
Too high (hypercalcemia) calcium levels lead to:
• Decreased sodium permeability across cell
membranes—a dangerous state
Too low (hypocalcemia) calcium levels cause:
• Cell membranes to become hyperexcitable
• Convulsions or muscle spasms
ROLE OF PARATHYROID
HORMONE IN CALCIUM
BALANCE
Control of calcium by the endocrine system begins
in the parathyroid gland
The parathyroid secretes parathyroid hormone
(PTH)
PTH stimulates osteoclasts and accelerates bone
resorption
As a result, calcium increases in the blood
CALCITONIN
Increases bone density and reduces the risk of
vertebral fractures
ROLES OF PARATHYROID HORMONE AND
CALCITONIN IN CALCIUM BALANCE
Calcitonin, secreted by the thyroid gland,
stimulates bone deposition
This removes calcium from the blood
Together PTH and calcitonin control calcium
homeostasis
PTH and calcitonin influence three targets: bones,
kidneys, and gastrointestinal tract
FIGURE 47.1
(A) PARATHYROID HORMONE (PTH)
continued on next slide
FIGURE 47.1
(B) CALCITONIN ACTION
ROLE OF VITAMIN D IN
CALCIUM BALANCE
Vitamin D is necessary for effective absorption of
calcium
Vitamin D is synthesized from precursor molecules
Cholecalciferol is converted to an intermediate
form, calcifediol
Then it is metabolized to calcitriol (the active form
of vitamin D)
FIGURE 47.2
PATHWAY FOR VITAMIN D ACTIVATION AND ACTION
OSTEOPOROSIS
Most common metabolic bone disease
Responsible for 1.5 million fractures per year
Related to bone deterioration—bone resorption
outpaces bone deposition
• Lack of dietary calcium and vitamin D
• Disrupted bone homeostasis
FIGURE 47.3
CALCIUM METABOLISM IN OSTEOPOROSIS
RISK FACTORS FOR
OSTEOPOROSIS
Onset of menopause: most common risk factor
High alcohol or caffeine consumption
Anorexia nervosa
Tobacco use
Physical inactivity
Testosterone deficiency
Lack of vitamin D or calcium
Drugs that lower calcium in blood
• Corticosteroids, anticonvulsants, immunosuppressants
PHARMACOTHERAPY OF
OSTEOPOROSIS
Calcium supplements and vitamin D
Bisphosphonates
Estrogen receptor modulators
Calcitonin
Slow-release calcium fluoride
Statins
Hormone replacement therapy (HRT) no longer
recommended
BISPHOSPHONATES FOR
OSTEROPOROSIS
Most common treatment
Block bone resorption by inhibiting osteoclast
activity, increase bone density
BISPHOSPHONATES
Prototype drug: alendronate (Fosamax)
Mechanism of action: Lowers serum alkaline
phosphate, an enzyme important to bone turnover
Primary use: for prevention and treatment of
osteoporosis in postmenopausal women; for
corticosteroid-induced osteoporosis; for
osteoporosis in men; for Paget's disease
Adverse effects: diarrhea, nausea, vomiting, GI
irritation, metallic- or altered-taste perception;
pathologic fractures with long-term use
CALCIUM SALTS
Prototype drug: calcium salts
Mechanism of action: to return serum calcium
levels to normal
Primary use: used to prevent and treat mild
hypocalcemia; for osteoporosis; Paget's disease;
chronic hypoparathyroidism, rickets, pregnancy,
lactation, and rapid childhood growth
Adverse effects: hypercalcemia
• IV administration of calcium may cause hypotension,
bradycardia, dysrhythmias, cardiac arrest
ROLE OF THE NURSE:
CALCIUM SUPPLEMENT
THERAPY
Assess for signs and symptoms of hypercalcemia
such as:
• Drowsiness, lethargy, weakness, headache,
• Anorexia, nausea, vomiting, thirst, and increased
urination
ROLE OF THE NURSE:
CALCIUM SUPPLEMENT
THERAPY
Obtain baseline and periodic vital signs, labs, and
ECG
Assessment signs for hypocalcemia are facial
twitching, muscle spasms, paresthesias, and
seizures
Contraindicated in patients with a history of renal
calculi, digoxin toxicity, dysrhythmias, or
hypercalcemia
Investigate for history of fracture
VITAMIN D THERAPY
Primary use: for impaired kidney function or
hypoparathyroidism
• Also useful in treating rickets
Adverse effects: hypercalcemia
• Headache, weakness, dry mouth, thirst
• Increased urination, muscle or bone pain
VITAMIN D THERAPY
Prototype drug: calcitriol (Calcijex, Rocaltrol)
Mechanism of action: as active form of vitamin D
• Promotes intestinal absorption of calcium
• Reduces bone resorption
• Elevates serum levels of calcium
ROLE OF THE NURSE:
VITAMIN D THERAPY
Obtain a thorough history of current medications,
vital signs
Complete a physical examination
Assess intake of fat-soluble vitamins, and current
medications
Assess sclera, skin pigment, and bowel movements
ROLE OF THE NURSE:
VITAMIN D THERAPY
Provide education related to the prescribed drug
treatment
Monitor lab studies:
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•
•
•
CBC, platelets, liver- and renal-function studies
Uric acid levels, and urinalysis
Magnesium and phosphate levels
Calcium and phosphate levels
SELECTIVE ESTROGEN RECEPTOR MODULES
(SERM) FOR OSTEOPOROSIS
Decrease bone resorption and increase bone
density
May be either estrogen agonists or antagonists,
depending on the drug or tissue involved
SELECTIVE ESTROGEN RECEPTOR
MODULATORS (SERMS)
Prototype drug: raloxifene (Evista)
Mechanism of action: Decreases bone resorption
• Increases bone mass and density by acting through
estrogen receptor
Primary use: prevention of osteoporosis in
postmenopausal women
Adverse effects: hot flashes, migraine headache,
flu-like symptoms; endometrial disorder, breast
pain, vaginal bleeding; may cause fetal harm when
administered to pregnant women
OSTEOMALACIA
MBD characterized by softening of bones due to
demineralization
Most frequent cause of osteomalacia is deficiency
of vitamin D and calcium in the diet
Most prevalent in the elderly, in premature infants,
and in individuals on strict vegetarian diets
If it occurs in children it is called rickets
OSTEOMALACIA
Signs and symptoms of osteomalacia include:
• Hypocalcemia, muscle weakness, muscle spasms
• Diffuse bone pain, especially in the hip area
Classic signs of rickets in children include bowlegs
and a pigeon breast.
• Children may also develop a slight fever and become
restless at night.
PHARMACOTHERAPY OF
OSTEOMALACIA
Calcium supplements and vitamin D
• Calcitriol is useful in treating rickets.
• Calcitriol usually prescribed in combination with
calcium supplements.
Recommendations
• Daily calcium and vitamin D
• Adequate exposure to sunlight
OSTEOARTHRITIS
Degenerative, age-onset disease
Characterized by wearing away of cartilage at
articular joint surfaces
Symptoms
• Muscle spasms
• Localized pain and stiffness
• Joint and bone enlargement
OSTEOARTHRITIS
Etiology poorly understood
• Thought to be due to excessive wear of weightbearing joints
• Hip, knee, spine
Considered by some a normal part of aging
PHARMACOTHERAPY OF
OSTEOARTHRITIS
Goal is reduction of pain and inflammation
• Topical medications (capsaicin cream)
• NSAIDs (including aspirin)
• Acetaminophen
PHARMACOTHERAPY OF
OSTEOARTHRITIS
If OTC drugs don't succeed:
• Tramadol (Ultram)
• Opiods with acetominophen
• Sodium hyaluronate (Hyalgan) injections into joint
RHEUMATOID
ARTHRITIS
Systemic autoimmune disorder
Characterized by inflammation of multiple joints
Autoantibodies (rheumatoid factors) activate
inflammatory response in joints
RHEUMATOID
ARTHRITIS
Other extra-articular systemic manifestations may
develop: infections, pulmonary disease,
pericarditis, blood abnormalities, metabolic
dysfunction
PHARMACOTHERAPY FOR
RHEUMATOID ARTHRITIS
NSAIDs initially
Corticosteroids for severe inflammation
Disease-modifying antirheumatic drugs
Several months may be needed before therapeutic
results are achieved
DISEASE-MODIFYING
ANTIRHEUMATIC DRUGS
Prototype drug: hydroxychloroquine sulfate
(Plaquenil)
Mechanism of action: Relieves severe inflammation
of arthritis and lupus
• Mechanism of action not known
DISEASE-MODIFYING
ANTIRHEUMATIC DRUGS
Primary use: for rheumatoid arthritis and lupus
erythematosus
• For patients who have not responded well to other
anti-inflammatory drugs
Adverse effects: anorexia, GI disturbances, loss of
hair
• Possible ocular effects, headache
• Mood and mental changes
GOUT
A form of acute arthritis characterized by buildup
of uric acid in blood or joint cavities
Primary gout—hereditary defect in uric acid
metabolism
GOUT
Secondary gout due to certain drugs or diseases
that affect uric acid metabolism (diabetic
ketoacidosis, kidney failure, leukemia, hemolytic
anemia, others)
GOUT
Symptoms of acute attacks
• Red, swollen tissue
• Often in big toes, ankles, fingers, wrists, knees,
elbows
Triggered by diet, injury, or other stress
Attacks often occur at night
PHARMACOTHERAPY OF
GOUT
Goals: termination of acute attacks; prevention of
future attacks
NSAIDs for pain and inflammation
Corticosteroids for more severe pain and
inflammation
Uricosurics increase excretion of uric acid by
blocking reabsorption in the kidney
PHARMACOTHERAPY OF
GOUT
Prophylactic therapy:
• Drugs that inhibit formation of uric acid
• Drugs that convert uric acid into a less toxic form
URIC ACID INHIBITOR
Prototype drug: alllpurinol
Mechanism of action: Inhibits synthesis of
microtubules
• Subcellular structures responsible for helping white
blood cells infiltrate area
Primary use: to reduce inflammation associated
with acute gouty arthritis
URIC ACID INHIBITOR
Adverse effects: rashes, Stevens–Johnson
syndrome, hypersensitivity syndrome, drowsiness,
headache, vertigo, nausea, vomiting, abdominal
discomfort, malaise, diarrhea, retinopathy,
thrombocytopenia
ROLE OF THE NURSE:
DRUGS FOR GOUT
Obtain thorough history including current
medications, vital signs
Complete a physical examination
Monitor lab studies
• CBC, platelets
• Liver- and renal-function studies
• Uric acid levels, urinalysis