DRUGS THAT EFFECT THE MUSCULOSKELETAL SYSTEMCHAPTER 21 PHARMACOLOGY

A variety of drugs are used in the treatment of musculoskeletal (bone and muscle) disorders. Examples of the musculoskeletal disorders discussed in this chapter include osteoarthritis, rheumatoid arthritis, gout, and Paget’s disease. The drug selected is based on the musculoskeletal disorder being treated, the severity of the disorder, and the patient’s positive or negative response to past therapy. For example, early cases or rheumatoid arthritis may respond well to the salicylates, whereas advanced rheumatoid arthritis may require the use of one of the gold compounds.

The salicylates and nonsteroidal and anti-inflammatory druds (NSAIDs) are important in the treatment of arthritic conditions. For example, the salicylates and NSAIDs are used in the treatment of rheumatoid arthritis (a chronic disease characterized by inflammatory changes within the body’s connective tissue) and osteoarthritis (a noninflammatory joint disease resulting in degeneration of the articular cartilate and changes in the synovial membrane), as well as a relief of pain or discomfort resulting from musculoskeletal injuries such as sprains.

GOLD COMPOUNDSEXAMPLE MEDS & THEIR CLASSIFICATION:gold sodium thiomalate ANTIRHEUMATIC & GOLD COMPOUNDaurothioglucose ANTIRHEUMATIC & GOLD COMPOUNDauranofin ANTIRHEUMATIC & GOLD COMPOUNDACTIONSThe exact mechanism of the gold compounds in the suppression or prevention of inflammation is unknown. Gold compounds decrease synovial inflammation andretard cartilage and bone destruction. Gold decrease the concentration of rheumatoid factor and immunoglobulins.USESGold compounds are used to treat active juvenille and adult rheumatoid arthritis not controlled by other anti-inflammatory drugs. It is important to note thatwhen cartilage and bone damage has already occurred, gold cannot reverse structural changes to the joints. The greatest benefits appears to occur in patients in the earlystages of disease.

ADVERSE REACTIONSAdverse reactions to the gold compounds may occur any time during therapy, as well as many months afther therapy has ended. Dermatitis (inflammation of theskin) and stomatitis (inflammation of mucosa of the mouth, gums and possibly the tongue) are the MOST COMMON adverse reaction seen. Pruritus often occurs before the skin eruption becomes apparent. Photosensitivity reactions may also occur. Chrysiasis (grey to blue pigmentation of the skin) may occur and is caused by gold depositsin tissues. Gold dermatitis is exacerbated by exposure to sunlightCONTRAINDICATIONSContraindicated in patients with unknown hypersensitivity to any component of the drug. Parenteral administration is contraindicated inpatients with uncontrolled diabetes, hepatic disease, uncontrolled hypertension, uncontrolled congestive heart failure, sustemic lupus erythematosus, and blood dyscrasias and in those with recent radiotherapy. Oral administration in contraindicated in patientswith necrotizing enterocolitis, pulmonary fibrosis and hematologic disorders and during pregnancy (category C) and lactation.INTERVENTIONAurothioglucose and gold sodium thiomalate are given IM, preferably in the upper outer quadrant of the gluteus muscle. Auranofin given orally. Observe closely for adverse reaction, dermatitis. Itching should be reported to the primary health careprovider immediately. If itching occurs apply soothing lotion on ananti-septic cream. Keep environment free of irritants that can aggravate itching such as rough fabrics, excessive warmth or excessive dryness. Inspect pts mouth daily for ulceration of the mucous membranes. Teeth should be brushed after every meal and the mouth should be rinsed. If platelet count fails below 100,000/mm3 or if the pt experiences signs and symptoms of thrombocytopenia (easy brusing, bleeding gums, epistaxis, melena) notify physician immediately

DRUGS USED IN THE TREATMENT OF GOUT

EXAMPLE MEDS & CLASSIFICATIONAllopurinol (Zyloprim) ANTIGOUT DRUGColchicine ANTIGOUT DRUGSulfinpyrazone ANTIGOUT, ANTIPLATELET, URICOSURIC AGENTProbenecid (Benemid) ANTIGOUT, URICOSURIC AGENT

ACTIONSAllopurinol (Zyloprim) reduces the production of uric acid, therefore decreasing serum acid levels and the deposits of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. Therefore it relieves the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. Sulfinpyrazone increase the excreation of uric acid by the kidney, which lowers serum acid levels and consequently retards the deposits of urate crystals in the joints. Probenecid (Benemid) works in the same manner and maybe given alone or with colchicine as combination therapy when there are frequent, recurrent attacks for gout. Probenecid also has been used to prolong the plasma levels of the penicillins and cephalosporins.USESDrugs indicated for treatment of gout may be used to manage acute attacks of gout or in preventing acute attacks of gout (prophylaxis).

ADVERSE REACTIONSOne adverse reaction associated with allopurinol is skin rash, which in some cases may be followed by serious hypersensitivity reactions such as exfoliativedermatitis and Stevens-Johnson syndrome. Nausea, vomiting, diarrhea, abdominal pain and hematologic changes can also be noted. Colchinine administration may result in nausea, vomitin, diarrhea, abdominal pain, and bone marrow depression. When this drug is given to patients with an acute attack of gout, the primary health care provider may order the drug given at frequent intervals until gastrointestinal symptoms occur. Probenecis administration may cause headache, gastrointestinal symptoms, urinary frequency and hypersensitivity reactions. Upper GI disturbance may be seen with the

administration of sulfiinpyrazone. When the drug is given with food, milk or antacis, GI distress may persist and the drug therapy may need to be discontinued.CONTRAINDICATIONSContraindicated in pt with known hypersensitivity. Probenecid is contraindicated in paties with blood dyscrasias or uric acid kidney stones and in children younger than 2 yrs.Sulfinpyrazone is contraindicated win patients with peptic ulcer disease and GI inflammation. Colchicine is contraindicated in patients with serious GI, renal, hepatic, or cardiac disorders and those with blood dyscrasias.INTERVENTIONSAllopurinol, probenecid, and sulfinpyrazone should be with or immediately after meals to minimize gastic distress. Colchicine usually can be given with food ormilk. When drug is used to treat an acute gout attack, it may be given every 1 to 2 hours until the pain is relieved. Increase fluid intake, Monitor I&O Report immediately the presence of any rash.

SKELETAL MUSCLE RELAXANTSEXAMPLE MEDS & CLASSIFICATIONScarisoprodol (Soma) CENTRAL ACTING SKELETAL MUSCLE RELAXANTbaclofen (Lioresal) CENTRAL ACTING SKELETAL MUSCLE RELAXANTchlorzoxazone (Paraflex) CENTRAL ACTING SKELETAL MUSCLE RELAXANTCyclobenzaprine (Flexeril) CENTRAL ACTING SKELETAL MUSCLE RELAXANT

diazepam (Valium) CENTRAL ACTING SKELETAL MUSCLE RELAXANT, BENZODIAZEPINE, ANXIOLYTIC, ANTIEPILEPTICACTIONSThe mode of action of many skeletal muscle relaxants such as carisoprodol (Soma), baclofen (Lioresal), and chlorzoxazone (Paraflex), is not clearly understood. Many of these drugs do not directly relax skeletal muscles, but their ability to relieve acute painfulmusculoskeletal conditions may be due to their sedative action. Cyclobenzaprine (Flexeril) appers to have an effect on muscle tone, thus reducing muscle spasm. The exact mode of action of diazepam (Valium), an antianxiety drug in the relief of painfulmusculoskeletal action, which may account for some of its ability to relieve muscle spasms and pain.USESSkeletal muscle relaxants are used in various acute, painful musculoskeletal conditions, such as muscles strains and back pain.

ADVERSE REACTIONSDrowsiness is the MOST COMMON seen. Dizziness, light-headedness, confusion,rash, blurred vision, weakness, diarrhea, nausea, vomiting, dry mouth,Hypotension, tachycardia to name a few.CONTRAINDICATIONSContraindicated in patients with known hypersensitivity. Baclofen in contraindicated inskeletal muscle spasms caused by rheumatic disorders. Carisoprodol is contraindicatedin patients with known hypersensitivity to meprobamate. Cyclobenzaprine is contraindicated in patients with a recent myocardial infarction, cardiacconduction disorders, and hyperthyroidism. Cyclobenzaprine is also contraindicated within 14 days of the administration of a monoamine oxidase inhibitor. Oral dantrolene iscontraindicated in patients with active hepatic disease and during lactation.INTERVENTIONS

Given with food to minimize GI distress. Rest, Physical therapy, drug therapy and other measures should be maintained as part of the treatment. Monitor for adverse reaction, drowziness, risk for injury, assisstance with ambulatory, etc. If drowziness is severe, notify the primary health care provider before the next dose is due.

CLASSIFICATION: BISPHOSPHONATESEXAMPLE MEDSAlendronate, etidronate, and risedronateACTIONSAlendronate, etidronate, and risedronate act primarily on the bone by inhibiting normal and abnormal hone resorption. This results in bone mineral density,Reversing the progression of osteoporosisUSESBisphosphonates are used to treat osteoporosis in postmenopausal women, Paget's disease of the bone, and postoperative treatment after total hip replacement(etidronate).

ADVERSE REACTIONNausea, vomiting, diarrhea, increased or recurrent bone pain, headache, dyspepsia, acid regurgitation, dysphagia and abdominal pain.CONTRAINDICATIONSContraindicated in patients who are hypersensitive to the bisphosphonates. Alendronate and risedronate are contraindicated in patients with hypocalcemia. Alendronate is a pregnancy Category C drug ad is contraindicated during pregnancy. These drugs arecontraindicated in patients with renal impairment with serum creatinine less than 5 mg/dL. Concurrent use of these drugs with hormone replacement therapy is notrecommended.INTERVETIONSWhen administering alendronate or risedronate the nurse gives the drug orally in the morning before the first food or drink of the day. Both are administeredonce a day. Etidronate is not administered within 2 hours of food, vitamin and mineral supplements or antacids. When using Alendronate for treatment of osteoporosisin postmenopausal women, the dosage is 70 mg/weekly or 10 mg/day. When using drug for prevention of osteoporosis, 5 mg of the drug is given daily or 35 mg once a week. When alendronate and riserdronate are administered, serum calcium levels are monitored before, during and afther therapy. To facilitate delivery of the drug tothe stomach and minimize adverse GI effects, administer the drug with 6 to 8 oz. of water while the patient is in an upright position. Instruct pt to remain upright for atleast 30 minutes after takin the drug.

CLASSIFICATION: CORTICOSTEROIDSEXAMPLE MEDSBudesonide, hydrocortisone, prednisone, cortisone, flunisolide, fluticasoneACTIONSCorticosteroids are hormones secreted from the adrenal cortex. These hormones arise from the cortex of the adrenal gland and are made from the crystallinesteroid alcohol cholesterol. Synthetic forms of the natural adrenal cortical hormones are available. The potent anti action of the corticosteroids makes these drugs useful in the treatment of many types of musculoskeletal disorders.USESThe cortisteroids may be used to treat rheumatic disorders such as anklosing spondylitis, rheumatoid arthritis, gout, bursitis (inflammation of the bursa, usually the bursa ofthe shoulder) and osteoarthritis

ADVERSE REACTIONCortisteroids may be given in high doses for some arthritic disorders. Many adverse reactions are associated with high-dose and long-term cortisteroidstherapy. Muscle weakness, loss of muscle mass, tendon rupture, osteoporosis, aseptic syncopal episodes, cardiac arrhythmias, aggravation of hypertension.INTERVENTIONSWhen the patient is receiving one of these drugs on alternate days, the drugs must be given before 9am. It is important because that these drugs shoult not beomitted or discontinued suddenly.

MISCELLANEOUS DRUGSEXAMPLE MEDS & CLASSIFICATIONPenicillamine CHELATING AGENT, ANTIRHEUMATICMTX (methotrexate) ANTIMETABOLITE, ANTINEOPLASTIC, ANTIPSORIATIC, ANTIRHEUMATICHydroxychloroquine ANTIMALARIAL, ANTIRHEUMATIC, 4-AMINOQUINOLINEACTIONSThe mechanism of action of penicillamine, MTX, and hydroxychloroquine in the treatment of rheumatoid arthritis is unknown.

USESPenicillamine, MTX, and hydoxychloroquine are used in the treatment of rheumatoid arthritis. The administration of MTX is reserved for severe,disabling disease that is not responsive to other treatment.

ADVERSE REACTIONHydroxychloroquine administration may result in irritability, nervousness, anorexia, nausea, vomiting, and diarrhea. This drug also may have adverse effectson the eye, including blurred vision, corneal edema, halos around lights, and retinal damage. Hematologic effects, such as aplastic anemia and leukopenia, may also be seen.The adverse reactions seen with penicillamine include pruritus, rash, anorexia, nausea, vomiting, epigastric pain, bone marrow depression, proteinuria, hematuria,increase skin friability, and tinnitus. Penicillamine is capable of causing severe toxic reactions. MTX is a potentially toxic drug that is also used in the treatment of malignancies and psoriasis. Nausea, vomiting, a decreased platelet count, leukopenia,stomatitis, rash, pruritus, dermatitis, diarrhea, alopecia, and diarrhea may be seen with theadministration of this drug.CONTRAINDICATIONSContraindicated in patients with known hypersensitivity. Hydroxychloroquine iscontraindicated in patients with porphyria (a group of serious inherited disoders affecting the bone marrow or the liver), psoriasis and retinal disease (irreversible). MTX is contraindicated during pregnancy because it is a Pregnancy category X drugand may cause birth defects in the developing fetus. Penicillamine is contraindicated in patients with a history of allergy to penicillin.INTERVENTIONSHydroxychloroquine should be administered with food or milk to help prevent GI upset. MTX is administered orally. Peniciallamine must be given to a patient withan empty stomach, 1 hour before or 2 hours after a meal. Report immediately for adverse reactions. Particular attention is paid to visual changes. Observe for easily brusing and infection. Decrease platelet count may cause the patient to bleed easily. Avoid IM injections. Observe stood for diarrhea or signs of GI bleeding