The Skeletal System and Drug Therapy Chapter 6 The Skeletal System and Drug Therapy © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Topics Anatomy and Physiology of Bones and Joints Osteoporosis Arthritis Herbal and Alternative Therapy © Paradigm Publishing, Inc.

Anatomy and Physiology of Bones and Joints 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 © Paradigm Publishing, Inc.

Anatomy and Physiology of Bones and Joints Anatomy of the Skeletal System © Paradigm Publishing, Inc.

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 © Paradigm Publishing, Inc.

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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Osteoporosis Screening Tests for Osteoporosis 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 bone mineral density (BMD) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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.

© Paradigm Publishing, Inc. 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 gastroenterology (GI) international units (IU) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 intravenous (IV) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 selective estrogen receptor modulators (SERMs) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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. © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 osteoarthritis (OA) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 rheumatoid arthritis (RA) erythrocyte sedimentation rate (ESR) rheumatoid factor (RF) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 nonsteroidal anti-inflammatory drugs (NSAIDs) cyclooxygenase I (COX-1) cyclooxygenase II (COX-2) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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.

© Paradigm Publishing, Inc. 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 disease-modifying antirheumatic drugs (DMARDs) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 subcutaneous (SC) © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. 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 © Paradigm Publishing, Inc.

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 Side Effects: nausea, heartburn, diarrhea, constipation Side Effects (rare): eyelid swelling, lower limb swelling, hair loss, and allergic reaction © Paradigm Publishing, Inc.

© Paradigm Publishing, Inc. Summary 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.