1. ADAMS, CHAPTER 47 Drugs for Bone and Joint Disorders

2. 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

3. 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)

4. 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

5. 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

6. 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

7. 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

8. 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

9. CALCITONIN Increases bone density and reduces the risk of vertebral fractures

10. 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

11. FIGURE 47.1 (A) PARATHYROID HORMONE (PTH) continued on next slide

12. FIGURE 47.1 (B) CALCITONIN ACTION

13. 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)

14. FIGURE 47.2 PATHWAY FOR VITAMIN D ACTIVATION AND ACTION

15. 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

16. FIGURE 47.3 CALCIUM METABOLISM IN OSTEOPOROSIS

17. 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

18. 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

19. BISPHOSPHONATES FOR OSTEROPOROSIS Most common treatment Block bone resorption by inhibiting osteoclast activity, increase bone density

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. ROLE OF THE NURSE: VITAMIN 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

28. 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

29. 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

30. 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

31. 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.

32. 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

33. 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

34. OSTEOARTHRITIS 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

35. PHARMACOTHERAPY OF OSTEOARTHRITIS Goal is reduction of pain and inflammation Topical medications (capsaicin cream) NSAIDs (including aspirin) Acetaminophen

36. PHARMACOTHERAPY OF OSTEOARTHRITIS If OTC drugs don't succeed: Tramadol (Ultram) Opiods with acetominophen Sodium hyaluronate (Hyalgan) injections into joint

37. RHEUMATOID ARTHRITIS Systemic autoimmune disorder Characterized by inflammation of multiple joints Autoantibodies (rheumatoid factors) activate inflammatory response in joints

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

39. PHARMACOTHERAPY FOR RHEUMATOID ARTHRITIS NSAIDs initially Corticosteroids for severe inflammation Disease-modifying antirheumatic drugs Several months may be needed before therapeutic results are achieved

40. DISEASE-MODIFYING ANTIRHEUMATIC DRUGS Prototype drug: hydroxychloroquine sulfate (Plaquenil) Mechanism of action: Relieves severe inflammation of arthritis and lupus Mechanism of action not known

41. 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

42. 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

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

44. 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

45. 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

46. PHARMACOTHERAPY OF GOUT Prophylactic therapy: Drugs that inhibit formation of uric acid Drugs that convert uric acid into a less toxic form

47. 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

48. URIC ACID INHIBITOR Adverse effects: rashes, Stevens–Johnson syndrome, hypersensitivity syndrome, drowsiness, headache, vertigo, nausea, vomiting, abdominal discomfort, malaise, diarrhea, retinopathy, thrombocytopenia

49. 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