ADAMS, CHAPTER 47

Drugs for Bone and Joint Disorders

ROLE OF CALCIUM IN ROLE OF CALCIUM IN MAINTAINING MAINTAINING HOMEOSTASISHOMEOSTASIS

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 ROLE OF CALCIUM IN MAINTAINING MAINTAINING HOMEOSTASISHOMEOSTASIS

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 ROLE OF CALCIUM IN MAINTAINING MAINTAINING HOMEOSTASISHOMEOSTASIS

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 RECOMMENDED DIETARY ALLOWANCE (RDA) OF ALLOWANCE (RDA) OF CALCIUMCALCIUM

For adults RDA is 800–1200 mg/day

Increased amounts of calcium required for:

• Pregnant women• Growing children • Menopausal women

RECOMMENDED DIETARY RECOMMENDED DIETARY ALLOWANCE (RDA) OF ALLOWANCE (RDA) OF CALCIUMCALCIUM

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 ROLE OF CALCIUM IN MAINTAINING MAINTAINING HOMEOSTASIS 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 ROLE OF PARATHYROID HORMONE IN CALCIUM HORMONE IN CALCIUM BALANCEBALANCE

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

CALCITONINCALCITONIN

Increases bone density and reduces the risk of vertebral fractures

ROLES OF PARATHYROID HORMONE AND ROLES OF PARATHYROID HORMONE AND CALCITONIN IN CALCIUM BALANCECALCITONIN 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 ROLE OF VITAMIN D IN CALCIUM BALANCECALCIUM 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

OSTEOPOROSISOSTEOPOROSIS

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 RISK FACTORS FOR OSTEOPOROSISOSTEOPOROSIS

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 PHARMACOTHERAPY OF OSTEOPOROSISOSTEOPOROSIS

Calcium supplements and vitamin D

Bisphosphonates

Estrogen receptor modulators

Calcitonin

Slow-release calcium fluoride

Statins

Hormone replacement therapy (HRT) no longer recommended

BISPHOSPHONATES FOR BISPHOSPHONATES FOR OSTEROPOROSISOSTEROPOROSIS

Most common treatment

Block bone resorption by inhibiting osteoclast activity, increase bone density

BISPHOSPHONATESBISPHOSPHONATES

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 SALTSCALCIUM 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:ROLE OF THE NURSE:CALCIUM SUPPLEMENT CALCIUM SUPPLEMENT THERAPYTHERAPY

Assess for signs and symptoms of hypercalcemia such as:

• Drowsiness, lethargy, weakness, headache, • Anorexia, nausea, vomiting, thirst, and increased

urination

ROLE OF THE NURSE:ROLE OF THE NURSE:CALCIUM SUPPLEMENT CALCIUM SUPPLEMENT THERAPYTHERAPY

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 THERAPYVITAMIN D THERAPY

Primary use: for impaired kidney function or hypoparathyroidism

• Also useful in treating ricketsAdverse effects: hypercalcemia

• Headache, weakness, dry mouth, thirst• Increased urination, muscle or bone pain

VITAMIN D THERAPYVITAMIN 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:ROLE OF THE NURSE:VITAMIN D THERAPYVITAMIN 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:ROLE OF THE NURSE:VITAMIN D THERAPYVITAMIN D THERAPY

Provide education related to the prescribed drug treatment

Monitor lab studies:

• CBC, platelets, liver- and renal-function studies• Uric acid levels, and urinalysis• Magnesium and phosphate levels• Calcium and phosphate levels

SELECTIVE ESTROGEN RECEPTOR SELECTIVE ESTROGEN RECEPTOR MODULES (SERM) FOR OSTEOPOROSISMODULES (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 SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS)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

OSTEOMALACIAOSTEOMALACIA

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

OSTEOMALACIAOSTEOMALACIA

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 PHARMACOTHERAPY OF OSTEOMALACIAOSTEOMALACIA

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

OSTEOARTHRITISOSTEOARTHRITIS

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

OSTEOARTHRITISOSTEOARTHRITIS

Etiology poorly understood

• Thought to be due to excessive wear of weight-bearing joints

• Hip, knee, spine

Considered by some a normal part of aging

PHARMACOTHERAPY OF PHARMACOTHERAPY OF OSTEOARTHRITISOSTEOARTHRITIS

Goal is reduction of pain and inflammation

• Topical medications (capsaicin cream)• NSAIDs (including aspirin)• Acetaminophen

PHARMACOTHERAPY OF PHARMACOTHERAPY OF OSTEOARTHRITISOSTEOARTHRITIS

If OTC drugs don't succeed:

• Tramadol (Ultram)• Opiods with acetominophen• Sodium hyaluronate (Hyalgan) injections into joint

RHEUMATOID RHEUMATOID ARTHRITISARTHRITIS

Systemic autoimmune disorder

Characterized by inflammation of multiple joints

Autoantibodies (rheumatoid factors) activate inflammatory response in joints

RHEUMATOID RHEUMATOID ARTHRITISARTHRITIS

Other extra-articular systemic manifestations may develop: infections, pulmonary disease, pericarditis, blood abnormalities, metabolic dysfunction

PHARMACOTHERAPY FOR PHARMACOTHERAPY FOR RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS

NSAIDs initially

Corticosteroids for severe inflammation

Disease-modifying antirheumatic drugs

Several months may be needed before therapeutic results are achieved

DISEASE-MODIFYING DISEASE-MODIFYING ANTIRHEUMATIC DRUGSANTIRHEUMATIC DRUGS

Prototype drug: hydroxychloroquine sulfate (Plaquenil)

Mechanism of action: Relieves severe inflammation of arthritis and lupus

• Mechanism of action not known

DISEASE-MODIFYING DISEASE-MODIFYING ANTIRHEUMATIC DRUGSANTIRHEUMATIC 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

GOUTGOUT

A form of acute arthritis characterized by buildup of uric acid in blood or joint cavities

Primary gout—hereditary defect in uric acid metabolism

GOUTGOUT

Secondary gout due to certain drugs or diseases that affect uric acid metabolism (diabetic ketoacidosis, kidney failure, leukemia, hemolytic anemia, others)

GOUTGOUT

Symptoms of acute attacks

• Red, swollen tissue• Often in big toes, ankles, fingers, wrists, knees,

elbowsTriggered by diet, injury, or other stress

Attacks often occur at night

PHARMACOTHERAPY OF PHARMACOTHERAPY OF GOUTGOUT

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 PHARMACOTHERAPY OF GOUTGOUT

Prophylactic therapy:

• Drugs that inhibit formation of uric acid• Drugs that convert uric acid into a less toxic form

URIC ACID INHIBITORURIC 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 INHIBITORURIC 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: ROLE OF THE NURSE: DRUGS FOR GOUTDRUGS 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