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Chapter 6
The Skeletal System and Drug
Therapy
© Paradigm Publishing, Inc.
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Chapter 6
Topics
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Anatomy and Physiology of Bones and Joints
Osteoporosis
Arthritis
Herbal and Alternative Therapy
© Paradigm Publishing, Inc.
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Anatomy and Physiology of Bones and Joints
Bones
• Provide structure and support for the body
• Provide movement along with muscle and protect organs
• Long bones, such as the femur, contain marrow, the
birthplace for blood cells
• All bones store calcium and maintain its balance
Osteoclasts break down bone tissue, releasing calcium
Osteoblasts take calcium from blood and build bone
• Grow and increase in density at the greatest rate during
childhood and continue to build into the 30s
Bone density gradually decreases over time
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Anatomy and Physiology of Bones and Joints
Anatomy
of the
Skeletal
System
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Anatomy and Physiology of Bones and Joints
Microscopic
View of Bone
Osteoclasts and
osteoblasts
provide bone
homeostasis, a
continual process
that grows and
repairs bone
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Anatomy and Physiology of Bones and Joints
Anatomy of a
Joint
(Articulation)
The ends of
bones are coated
with cartilage
and cushioned
from friction by
the synovial
membrane and
synovial fluid
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Osteoporosis
Facts about Osteoporosis
• Is a reduction in bone density, resulting in weakened bones
and fractures
• Occurs when bone density decline accelerates abnormally
• Causes fractures in the hips, spine, and wrists
Hip fractures can be life threatening for older patients
• 90% of patients with osteoporosis are women
• Risk Factors: female, Caucasian, family history, small body
frame, smoking, heavy caffeine intake, low calcium intake
• Estrogen promotes bone density and estrogen levels
decreases after menopause
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Osteoporosis
Screening Tests for Osteoporosis
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Many pharmacies provide screening tests
BMD machines use x-ray and ultrasound
Usually measure the heel; good estimate of hip and spine
Pharmacists and technicians can be trained to perform test
Result of BMD provides a T-score which is estimate of risk
If at risk, patients can make lifestyle changes
Add weight-bearing exercise, eat foods high in calcium,
quit smoking, and decrease caffeine intake
• Diagnosis of osteoporosis may require drug therapy
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Osteoporosis
Drugs for Osteoporosis: Calcium
• Healthy adults should get 1,000 mg of calcium a day
• Patients with osteoporosis, people over 65, and women
after menopause should get 1,500 mg of calcium a day
• Daily calcium total obtained through diet and dietary
supplements
• Calcium dietary supplements
Various products
Routes: oral; several dosage forms
Dose: divided doses; only 500–600 mg of calcium
is absorbed at a time
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Osteoporosis
Drugs for Osteoporosis: Calcium (continued)
Side Effects (common): nausea, vomiting, and
constipation
Side Effect (severe): excess calcium can cause kidney
stones
Caution: do not take if kidney stone history
Caution: do not take with quinolone antibiotics,
tetracyclines, or iron supplements
© Paradigm Publishing, Inc.
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Osteoporosis
Drugs for Osteoporosis: Vitamin D
• Improves calcium absorption in the GI tract and helps
other osteoporosis agents work more effectively
• In fish, milk, breakfast cereals, and exposure to sunlight
• Often is a combination product with calcium
• Recommended daily requirements are 400 IU but many
physicians prescribe up to 1,100 IU a day
• Indications: osteoporosis and osteopenia (high risk for
developing osteoporosis)
• Side Effects: nausea, vomiting, and edema (swelling)
• Cautions: hypercalcemia and kidney problems
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Osteoporosis
Drugs for Osteoporosis: Bisphosphonates
• Mechanism of Action: inhibit osteoclasts from removing
calcium from bone tissue; prevent bone breakdown
• Indications: mainly osteoporosis, Paget’s disease, and
some bone and spinal injury cases
• Dosage Forms: variety of oral and infusion choices
• Side Effects: headache, nausea, vomiting, diarrhea,
constipation, abdominal pain, and indigestion
• Side Effects (severe, rare): insomnia, anemia, osteonecrosis
• Cautions: If oral, take on an empty stomach with water
• Storage for IV: refrigerate and then use within 24 hours
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Osteoporosis
Drugs for Osteoporosis: SERMs
• Available SERMs: Raloxifene (Evista), tamoxifen (Nolvadex),
and toremifene (Fareston)
• Mechanism of Action: work as estrogen receptors that
mimic the effects of estrogen on bone mineral density
Do not increase risk of breast or uterine cancer
• Side Effects of Raloxifene: hot flashes, headache, diarrhea,
joint pain, leg cramps, and flulike symptoms
Side Effects (severe): deep vein thrombosis or blood
clots
Cautions: Do not take if prolonged immobility
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Osteoporosis
Drugs for Osteoporosis: Human Parathyroid
Hormone
• Teriparatide (Forteo) is a human parathyroid hormone
• Mechanism of Action: supplements the body’s production
of parathyroid hormone
Regulates the calcium–phosphate balance and
stimulates new bone growth
• Indication: very severe osteoporosis; used short-term
• Cautions: associated with osteosarcoma; do not take if
have Paget’s or risk for bone cancer
• Patients taught how to use injector; drug kept refrigerated
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Your Turn
Question 1: What is a restriction of raloxifene, a SERM used for
osteoporosis?
Answer: Raloxifene should not be taken if prolonged
immobility is anticipated.
Question 2: What is the purpose of taking vitamin D with
calcium?
Answer: Vitamin D improves calcium absorption from the GI
tract. It also helps other osteoporosis agents work more
effectively.
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Arthritis
Arthritis and Osteoarthritis (OA)
• Arthritis
Is the most common joint disorder and it affects
millions
• OA
Is the most common type of arthritis
Caused by wear and tear on joints that comes with age;
onset is usually after age 40 or 50
Joint cartilage erodes and causes painful rubbing
Large joints such as knees, shoulder, and hips affected
first
Symmetry often not present
Morning stiffness is prominent but is relieved by
activity
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Arthritis
Rheumatoid Arthritis (RA)
• Is an abnormal process in the immune system that
destroys the synovial membrane and produces
inflammation in the joint
• Small joints (fingers, wrists, and elbows) affected first
• Symmetry often present
• Deformation of the joints can be disabling
• Morning stiffness and pain are not relieved
after an hour or by activity
• Two lab tests to help diagnose are ESR and RF
• Disease is not curable but can be slowed with drug therapy
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Arthritis
Gouty Arthritis (Gout)
• Is a condition in which excessive uric acid accumulates in
the blood and urate crystals then form in the synovial fluid
and irritate joints
• Joint pain and swelling often first occur in the big toe
Can cause kidney damage without drug therapy
• Drugs that predispose someone to gout are diuretics,
salicylates, nicotinic acid (niacin), ethanol, cytotoxic agents
• Certain foods rich in purine (amino acid), like red meat,
also implicated in gout
• Chronic preventive therapy may be prescribed
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Arthritis
Drugs for OA
• Reduce pain and inflammation but do not cure
Severe OA may require surgery or joint replacement
• Other remedies include physical therapy, cold/hot packs
massage, and rest
Drugs for OA: Acetaminophen
• First-line choice that controls pain, not inflammation
Route: oral, taken multiple times a day
Drugs for OA: NSAIDs
• Mechanism of Action: inhibit enzymes COX-1 and COX-2
from producing prostaglandins
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Arthritis
Drugs for OA: NSAIDs (continued)
• Are good when inflammation is the main cause of pain or
acetaminophen no longer works
• Indications: mild to moderate pain, including arthritis
• Side Effects: headache, diarrhea, nausea,
constipation, and occasional dizziness and drowsiness
• Side Effects of GI Tract: indigestion, heartburn, abdominal
pain, bleeding, ulcer, or anemia (from blood loss)
• Routes: all oral; some not chewed or crushed
• Cautions: renal (kidney) problems, fluid accumulation,
drug interactions; do not take with aspirin
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Arthritis
Pain Pathway
• Prostaglandins
promote
inflammation
and connect to
pain receptors
to trigger the
pain response
Protect the GI
lining against
erosion from
gastric acid
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Arthritis
Drugs for OA: COX-2 Inhibitors
• Celecoxib (Celebrex) is the only COX-2 inhibitor available
• Mechanism of Action: inhibits COX-2 from production of
prostaglandins that cause pain and inflammation
Does not inhibit COX-1 from protecting GI lining
• Indications: arthritis pain; pain with ulcers or GI bleeding
• Side Effects: headache, abdominal pain, heartburn,
nausea, and occasional GI irritation and bleeding
• Routes: oral; can be taken short- or long-term
• Cautions: monitor heart function
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Your Turn
Question 1: A patient is diagnosed with mild OA. What is the
physician likely to order?
Answer: The drug of choice for OA is acetaminophen.
Question 2: How is the function of a COX-2 inhibitor different
than the function of a NSAID?
Answer: A COX-2 inhibitor blocks COX-2, an enzyme that
promotes the production of the prostaglandins that cause
pain and inflammation. NSAIDs block both COX-1 and COX-2,
which cuts off prostaglandins that protect the lining of the
GI tract.
© Paradigm Publishing, Inc.
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Arthritis
Drugs for RA
• Goal of drug therapy is to maintain mobility and delay
disability for as long as possible
• Can improve pain and slow the disease progression
Drugs for RA: DMARDs
• Indications: slow disease progression of RA and used as
immunosuppressants used after organ transplant
• Mechanism of Action: inhibit immune system to slow
down destruction of joint tissue
• Best started within first 3 months from diagnosis; taken on
chronic basis to maintain disease and symptom control
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Arthritis
Drugs for RA: DMARDs (continued)
• Disease remission can sometimes be achieved
• Early therapy slows joint destruction
• Side Effects: vary among agents; effects can mimic those
of chemotherapy and are unpleasant
• Routes: oral (some not chewed or crushed), IM, IV, and SC
• Cautions: increased incidence of infection; avoid people
who are ill and use other precautions to prevent infection
• Cautions: many cause kidney damage
• Preparation and Storage: some DMARDs have special
mixing and storage; refrigerate injectable forms
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Arthritis
Drugs for Gouty Arthritis
• Treatment during an acute gout attack differs from
prevention of gout attacks
• Indications (chronic, low-dose therapy): a very severe
attack or repeated gout exacerbations within a year
• Mechanism of Action: lower uric acid levels in blood and
reduce inflammation within joints caused by urate crystals
• Colchicine is drug of choice to lower uric acid in acute and
chronic attacks; used in preventive therapy at a lower dose
• Triamcinolone Injection is a corticosteroid administered
directly into the joint for gout attack
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Arthritis
Drugs for Gouty Arthritis (continued)
• Allopurinol is the most frequently prescribed drug for gout
prophylaxis
• Side Effects (common): vary among agents; includes
diarrhea, nausea, rash, vomiting, and headache
• Routes: all are oral except triamcinolone
• Administration of Triamcinolone: intra-articular (injected
directly into the joint) to relieve pain and inflammation
• Cautions for Probenecid: drink plenty of water
(can harm the kidneys); do not take with aspirin
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Herbal and Alternative Therapies
• Glucosamine
Taken to improve pain and stiffness from OA
Studies do not support that it is effective
Side Effects: nausea, heartburn, diarrhea, and
constipation
Caution: do not take if allergic to shellfish
• Chondroitin
Taken with glucosamine for hip and knee OA
Studies do not support that it is effective
Side Effects: nausea, heartburn, diarrhea, constipation
Side Effects (rare): eyelid swelling, lower limb swelling,
hair loss, and allergic reaction
© Paradigm Publishing, Inc.
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Summary
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Bisphosphonates and SERMs used to treat osteoporosis
Calcium and vitamin D are taken for osteoporosis
Acetaminophen is the first-line choice of therapy for OA
Many patients with OA progress to long-term NSAIDs
DMARDs halt progression of RA, and NSAIDs are used to
treat pain
• DMARDs have many side effects and are difficult to take
• Drugs such as colchicine and allopurinol are used for gout
© Paradigm Publishing, Inc.
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