This chapter includes the medications helpful in treating problems affecting the bones, joints, muscles, and ligaments. There are many musculoskeletal disorders that cause pain, stiffness, and boney deformity. Powerful drugs are used for the more serious problems; safer over-the-counter (OTC) drugs are used for less serious conditions. Many acute problems, such as sprains, fractures, or tears, require only short-term therapy. Some disorders, such as arthritis, may require long-term therapy with simpler drugs used initially, advancing to advanced drugs as the pain and mobility problems increase. Most of these products—even the drugs sold OTC have serious adverse reactions, and patient response to therapy must be monitored closely.

This chapter is divided into four sections. The first section deals with antiinflammatory and analgesic medications such as the salicylates and nonsteroidal antiinflammatory drugs (NSAIDs), which are used to treat both minor and severe pain and common orthopedic problems. The second section presents skeletal muscle relaxants. The third section introduces a variety of medications used to treat arthritis, the disease-modifying antirheumatic medications (DMARDS) and immune modulators. Agents used to treat high uric acid levels found in gout are presented in the fourth section. These are all common conditions that licensed practical and vocational nurses see and medicines they use frequently.

Muscular and Skeletal Systems

The muscular and skeletal systems work together to provide support and movement for the body (Figures 18-1 and 18-2). The skeletal system is made up of the bones, cartilage, ligaments, and joints, and the muscular system is those muscles attached to the skeleton.

The skeleton protects, supports, and allows body movement, produces blood cells in the long bones, and stores minerals. The muscular system helps the body parts move, holds the body upright, and produces body heat.

Disease may attack just a small part of the body or the whole muscular and skeletal system. Injuries are often due to trauma, wear over many years, or overuse. Although some traumatic skeletal injuries heal well, some injury sites may continue to have pain and deformity.

The Inflammatory Response

The inflammatory response is necessary for the body’s survival when faced with stress or injury. A number of things can trigger the inflammatory response. These include infectious agents, ischemia (lack of blood supply to a tissue), antigen-antibody interactions, and thermal (heat or cold) or other injury. The inflammatory response has three phases:

1. Acute, brief, local vasodilation (opening up of the blood vessels) and increased capillary permeability

2. A delayed, subacute infiltration (movement) of leukocytes and phagocytic cells into the tissue

3. Chronic proliferative tissue degeneration (breakdown) and fibrosis

The inflammatory response of the body produces the symptoms of erythema (redness or irritation), edema (fluid buildup in the body tissues), tenderness, and pain. This happens when the affected blood cells release a variety of inflammatory mediators (substances that continue the inflammatory response). The inflammatory mediators act to increase blood flow to the area and increase capillary permeability, allowing movement of large molecules across cell walls into the site. One of the most important inflammatory mediators is histamine, which causes vasodilation to increase blood flow to the area. Cytokines help control the inflammatory process. Prostaglandins also have a role in the inflammatory reaction.

Prostaglandins have several actions in the body. The useful functions of prostaglandins have to do with “housekeeping” actions in the tissues, especially in protecting the mucosa of the gastrointestinal (GI) tract. They also maintain normal renal function, platelet aggregation (clumping together), consciousness and mental functions in the brain, and temperature. Prostaglandins also cause erythema and an increase in local blood flow, and they can remove the vasoconstrictor effects of substances such as norepinephrine and angiotensin. These actions of prostaglandins are controlled by a series of reactions at sites of tissue injury and inflammation. Prostaglandins are helpful when they are kept in check, but harmful when they are not.

The housekeeping functions of prostaglandins are controlled by cyclooxygenase-1 (COX-1). Cyclooxygenase-2 (COX-2) is created where there is inflammation caused by cytokines and other inflammatory mediators. It is also found in the brain, where it plays a role in fever and perception of pain. COX-2 is an active participant in the inflammatory process and produces harmful results in the body if not controlled.

Although it is important to have medications that can block the harmful actions of prostaglandins, the important physiologic functions of prostaglandins that are helpful in the body must be preserved. Most antiinflammatory drugs block the actions of both COX-1 and COX-2. A group of drugs known as COX-2 inhibitors or blockers was developed to reduce the inflammatory response in some tissues without destroying the tissue of the GI tract (Figure 18-3). Although these drugs reduce the incidence of gastric bleeding, current research suggests that they may do so at the expense of the heart. All but one of these drugs have been removed from the market because of this problem.

FIGURE 18-3 Model for nociceptive pain. A, Tissue injury triggers cyclooxygenase-2 (COX-2) in peripheral tissue to convert arachidonic acid to prostaglandin E2 (PGE2), resulting in stimulation of the nociceptor in peripheral nerve to send a signal for pain to the central nervous system. B, Nonsteroidal antiinflammatory drug (NSAID) interfering with COX-2–mediated prostaglandin synthesis.

Antiinflammatory and Analgesic Agents

Overview

Aspirin is one of the most commonly taken medications. The ease with which it can be bought and the fact that people decide when and if they need it should not decrease the importance given to this drug in treating common and significant musculoskeletal problems. Aspirin (acetylsalicylic acid [ASA]) has greater antiinflammatory action than other salicylates and is preferred in the treatment of many problems. Acetaminophen is also used for analgesia in generalized pain and arthritis because of its safety. Acetaminohen is an analgesic but not an NSAID because it has no antiinflammatory properties. The NSAIDs are powerful agents to help decrease pain and inflammation. Prostaglandins may make peripheral pain receptors more sensitive to painful stimuli. Both salicylates and NSAIDs are thought to limit the production of prostaglandins.

Salicylates

Action

Salicylates have analgesic (pain-reducing), antipyretic (temperature-reducing), and antiinflammatory effects. It also has growing use as an emergency antiplatelet drug in patients who are having a myocardial infarction (MIs) or to prevent other MIs or strokes in men. Salicylates stop the production of prostaglandins, which affects the pain and inflammatory processes through a depressant effect on the central and peripheral pain receptors. They do this by blocking the production of cyclooxygenase, an enzyme that is necessary for the production of prostaglandins.

Uses

Aspirin is stronger or more potent in stopping prostaglandin synthesis than are other salicylates, and it has greater antiinflammatory effects. Aspirin is used in the treatment of mild to moderate pain. Aspirin is the only drug in this category to slow the clumping of platelets for the life of the platelet (7 to 10 days). It also interferes with factor III of the clotting mechanism. This makes it useful in reducing the risk for strokes or for treating transient ischemic attacks (TIAs) in patients who have had some types of TIAs. However, it is of no benefit for men who have already had strokes. Research shows that aspirin does not seem to prevent TIAs or strokes in women.

Small daily doses of aspirin are also used to reduce the risk of death or nonfatal MI in patients with previous infarction or unstable angina pectoris. Lower doses are just as effective and have fewer side effects than higher doses for this purpose. Unlabeled uses of aspirin in low doses also include prevention of colorectal cancer and preeclampsia.

Salicylates are used as first-line therapy to treat various forms of arthritis (rheumatoid arthritis, osteoarthritis, degenerative joint disease) through inhibition of cyclooxygenase (COS). The inflammatory and analgesic effects of aspirin are roughly equivalent to those of many other NSAIDS. Their use has declined somewhat with the option of NSAIDS. They are used to treat fever produced by bacterial illnesses and in therapy for pain from trauma to soft tissue or muscle. Pain in the muscles, nerves, and joints (myalgias, neuralgias, and arthralgias), as well as headache and dysmenorrhea, are also treated with salicylates. The antiinflammatory effects are useful in treating systemic lupus erythematosus, acute rheumatic fever, and similar conditions. An aspirin should be chewed immediately by any patient suspected of having an acute MI to help limit tissue damage.

Adverse Reactions

The greatest concern in use of aspirin for chronic disease is the production of GI distress and bleeding. Bleeding may often occur suddenly and without pain. It is estimated that a normal person taking Aspirin loses 10 mL of blood every day from minor GI irritation. Hypersensitivity (allergy) is also common and may produce anaphylaxis. In those with allergy, there may also be cross-sensitivity to other medications, including NSAIDS and acetaminophen. Other adverse reactions to antiinflammatory analgesics include tinnitus (ringing in the ears), visual disturbances, edema, urticaria (hives), rashes, anorexia (lack of appetite), epigastric discomfort, and nausea. Aspirin has been associated with the occurrence of Reye syndrome when given to children with varicella (i.e. chickenpox) or influenza. In Reye syndrome, symptoms may affect all organs of the body, but most seriously affects the brain and liver. Rapid development of severe neurological symptoms, including lethargy, confusion, seizures, and coma, make Reye syndrome a life-threatening emergency. Most authorities advise against the use of aspirin in these and other viral infections. In overdosage, symptoms may progress from mild to severe, beginning with hyperventilation, diaphoresis (sweating), thirst, headache, drowsiness, skin eruptions, and electrolyte imbalance, and progressing to central nervous system (CNS) depression, stupor, convulsions and coma, tachycardia (rapid heartbeat), and respiratory insufficiency. Respiratory and metabolic acidosis are most often seen in children.

Drug Interactions

Alcohol taken with any of the antiinflammatory analgesics increases the chance of GI bleeding. There is an increased effect of anticoagulants, sulfonylureas, and sulfonamides if they are used at the same time as salicylates. Ascorbic acid increases the effect of salicylates by increasing renal tubular reabsorption. Salicylates interact with other NSAIDs to increase effects, side effects, and toxicities. Salicylates also increase or potentiate the effects of phenytoin (Dilantin) and inhibit hyperuricemia produced by pyrazinamide. Salicylates can affect the results of many laboratory test results.

Nursing Implications and Patient Teaching

n Assessment

Learn all possible details about the patient’s health history. Check for the presence of allergy to aspirin or other NSAIDs, history of asthma or nasal polyps, GI problems or ulcer disease, current use of other drugs that may cause interactions, or other hepatic or renal disease. These conditions are precautions or contraindications to the use of salicylates.

The health care provider may ask the nurse to get a stool specimen to check for occult blood before beginning the medication. This will help decide whether or not the patient had bleeding in the stool before the medication was started.

n Diagnosis

Careful attention should be paid to other medications and disease processes of the patient. Are there conditions that would make the use of NSAIDs or salicylates dangerous? What is the risk for GI bleeding in this patient? How much caffeine, alcohol, or tobacco does this patient use? Are there other problems related to weight, mobility, safety, or nutrition?

n Planning

Antiinflammatory analgesics should not be used in patients with hepatic (liver) disease. Patients on anticoagulant therapy or with blood clotting problems must be very careful when they use these products. These drugs also should not be used before surgery (because of their effect on platelet aggregation) or before labor (because bleeding may increase). They should be used with caution in patients with symptoms suggesting TIAs. In patients with musculoskeletal pain that persists for more than 10 days, further evaluation of the pain is needed.

Antiinflammatory analgesics should not be used during pregnancy, especially during the third trimester, because they may have adverse effects on the fetus. Salicylates are excreted in breast milk.

These drugs should be used carefully if the patient has gastric irritation, especially in patients with a past history of upper GI problem, blood dyscrasias, or decreased renal function.

Hydration (supply of fluids) should be monitored carefully in children, because they seem to be more likely to get salicylate intoxication or overdose.

Reye syndrome is an acute, life-threatening problem seen in children that produces vomiting and lethargy that may go on to delirium and coma with permanent brain damage and possible death. Use of aspirin after influenza, chickenpox, or other viral conditions in children seems to be closely related to the development of Reye syndrome and should be avoided.

Many salicylate products are not recommended for use in children younger than 12 years of age. When salicylates are ordered for children, check the specific drug to make certain that the product is safe for children.

Clinical Pitfall

Reye Syndrome

Children who have repeated instances of viral upper-respiratory-tract infections within a short time or who have disorientation due to high fever should not be given salicylates. These drugs have been linked to the development of Reye syndrome post viral infection.

n Implementation

The administration and dosage for each of the salicylate products vary. There are tablets, capsules, drops, chewable preparations, suppositories, and injectable forms of these products. Aspirin is the most active agent and has the greatest amount of salicylate per unit. Individual products should be checked for dosing specifics by age.

Patients (particularly poorer patients or immigrants) with diabetes who are testing their urine with Benedict’s Clinitest may get incorrect readings. They may need to switch to another form of urine testing while using salicylate products. Salicylates also increase the action of oral hypoglycemic agents, and patients with diabetes should be alert to signs of hypoglycemia (low blood sugar level).

A summary of dosing information for the salicylates is provided in Table 18-1.

Table 18-1

Antiinflammatory Analgesics

GENERIC NAME	TRADE NAME	COMMENTS
Salicylates and Acetaminophen
acetaminophen	Acephen Aceta Acetaminophen Apacet FeverAll Panadol Tempra 3 Tylenol	Used as an analgesic-antipyretic in the presence of aspirin allergy and for patients with blood coagulation disorders being treated with oral anticoagulants, bleeding diatheses, upper GI disease, gastritis, hiatal hernia, and gouty arthritis. Also used for a variety of soft-tissue injuries and for acute pain relief.
acetylsalicylic acid (ASA, aspirin)	Aspergum Bayer Ecotrin Empirin	The most commonly used antiinflammatory agent. Standard against which all other agents are compared. Hypersensitivity often exists.
acetylsalicylic acid (ASA) buffered choline salicylate	Alka-Seltzer Ascriptin Bufferin	Aspirin-antacid combinations are used in patients who experience GI distress from plain aspirin. Dosage and administration are the same as for plain aspirin.
diflunisal	Dolobid	Salicylic acid nonsteroidal derivative.
magnesium salicylate	Doan’s caplets	Sodium-free salicylate with lower incidence of GI problems than ASA.
salsalate	Amigesic Salflex	Take in divided doses.
sodium salicylate	Sodium Salicylate	Comes in an enteric-coated pill.
Nonsteroidal Antiinflammatory Drugs
diclofenac	Cataflam Voltaren	Used for chronic long-term therapy. Also comes in a delayed-release tablet.
fenoprofen	Nalfon	Administer medication 30 min before or 2 hr after meals; food interferes with absorption.
flurbiprofen	Ansaid	Used in rheumatoid arthritis and osteoarthritis.
ibuprofen	Advil Motrin Nuprin	Approved for use in the treatment of dysmenorrhea. Used in acute, chronic pain and for inflammatory processes.
indomethacin	Indocin	A potent prostaglandin synthesis inhibitor with significant toxic side effects; many adverse reactions (including blood dyscrasias) and drug interactions. Acute gouty arthritis. Take for 5 days, then reduce dosage. Patient should be weaned off medication as soon as possible.
ketorolac	Toradol	Given IM for short-term management of pain and orally for short duration. Do not use longer than 5 days.
meclofenamate		Has ability to block action of prostaglandins and inhibit their synthesis, whereas other NSAIDs only inhibit prostaglandin synthesis.
mefenamic acid	Ponstel	Recommended for treatment of dysmenorrhea rather than arthritis or other acute musculoskeletal problems.
meloxicam	Mobic	Take with or without food.
naproxen	Aleve Anaprox Naprosyn	Used for mild to moderate pain, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis. Long-term therapy may require the higher dosage range. If no symptomatic effect in 2 wk, trial should be continued for 2 more wk before drug discontinued. Used to treat acute gout.
piroxicam	Feldene	Indicated in the treatment of acute exacerbations and long-term management of rheumatoid arthritis and osteoarthritis.
sulindac	Clinoril	Used for arthritis and ankylosing spondylitis, acute painful shoulder or gout.
Cyclooxygenase-2 Inhibitor
celecoxib	Celebrex	Used in osteoarthritis, rheumatoid arthritis, acute pain, and dysmenorrhea. Long-term use may damage heart. Do not use in patients allergic to sulfa.

GI, Gastrointestinal; IM, intramuscular; NSAID, nonsteroidal antiinflammatory drug.
Indicates “Must-Know Drugs,” or the 35 drugs most prescribers use.

n Evaluation

The patient should be monitored to see that symptoms resolve (i.e., pain is gone and temperature is reduced to 101° F or lower). The dosage should be reduced or the drug stopped if tinnitus (ringing in ears) develops. Observe for fever that does not fall or other symptoms that suggest the patient is getting worse, and notify the health care provider.

For arthritis, higher dosages are usually needed to control pain and stiffness. The dosage should be slowly increased as necessary while the patient is watched not only for pain relief, but for improvement in such things as increased strength of grip, increased mobility, and improved ability to carry on normal activities of daily living. Patients taking medication over a long time should be monitored for signs of occult (hidden) bleeding with regular blood counts and stool checks. Check for signs of aspirin toxicity, especially tinnitus. Periodic checks of serum salicylate levels may be helpful if the dosage is reaching maximum levels or if there is a question of patient compliance.

n Patient and Family Teaching

Tell the patient and family the following:

• These drugs may cause stomach upset because they are so strong. This symptom may be reduced by taking medicine with food, milk, or a full glass of water. Patients should never take the medication without adequate liquid, because it may lead to GI distress and pain.

• The patient should contact the health care provider right away if ringing in the ears; abnormal bleeding or bruising; or bloody or black, tarry stools are noted.

• Chronic problems may require taking the medicine for more than a week before the patient notices any decrease in symptoms.

• The medication should be taken regularly to reduce inflammation. If the medication is taken regularly, a stable serum level is kept in the blood, and symptoms can be reduced more easily.

• The patient should not take any other medications at the same time without the knowledge of the health care provider. This includes drugs the patient may purchase OTC.

• The health care provider should be contacted if the patient is taking the medicine for a fever and: (1) the fever does not come down in 24 to 48 hours, or (2) the patient becomes lethargic (sleepy) or hard to awaken.

• This medication should be kept out of the reach of children and all others for whom it is not prescribed. Even small doses may be fatal to small children.

• If the patient is unable to take the medication in the form prescribed, the health care provider should be contacted so another form may be ordered. Medication is available in chewable tablets and suppositories to make it easier for some patients to take.

Acetaminophen

Overview

Acetaminophen (Tylenol) is an OTC medication commonly used to decrease fever and mild pain. It can be used in patients who have experienced gastric irritation with aspirin or other NSAIDs. Acetaminophen is similar to aspirin in its effectiveness in treating fever and pain. It is the drug of choice for relief of minor pain in children. Acetaminophen is different from aspirin in that it does not have an antiinflammatory effect or an effect on platelet aggregation.

Acetaminophen is a metabolite of phenacetin, a product that was taken off the market because of a link with nephropathy (kidney damage). It is also linked to hepatotoxicity (liver damage) when dosage is increased. Acetaminophen may be included with other OTC drugs used to treat common illnesses.

Clinical Pitfall

Safety with Acetaminophen

Parents frequently do not realize that acetaminophen is in many products and miscalculate the dosage of acetaminophen given to young children, exceed the dosage, or give the dose too often. This may produce liver toxicity and death due to liver failure. Always remind parents to be careful in giving this drug. Drug manufacturers voluntarily removed many children’s cough and cold OTC products containing acetaminophen to help avoid this problem.

Action and Uses

Acetaminophen works as an antipyretic by direct action on the hypothalamic heat-regulating center, lowering the temperature to a normal level. It does this by blocking the action of pyrogenic cytokines on the heat-regulating center. This helps get rid of body heat via vasodilation and sweating.

The mechanism of analgesic action is not clear. It may be due to inhibition of prostaglandin synthetase in the CNS. Acetaminophen differs from aspirin in that it does not inhibit peripheral prostaglandin synthesis. This may account for the absence of inflammatory and platelet-inhibiting effects. Acetaminophen is a very effective medication for treating chronic pain of both malignant and nonmalignant origin. Other medications are often combined with acetaminophen to enhance their effectiveness.

Acetaminophen is the initial drug of choice for treatment of osteoarthritis. It is effective in pain relief and has fewer adverse reactions than aspirin or NSAIDs.

Adverse Reactions

If used as directed, adverse reactions are rare. The symptoms of hypersensitivity are skin eruptions, urticaria, erythema, and fever. Extremely rare hematologic reactions include hemolytic anemia, leukopenia, neutropenia, and pancytopenia. Other reactions are hypoglycemia, liver toxicity, and jaundice (yellow color of skin, eyes, and mucous membranes). Overdosage is possible and may be fatal. This is particularly a problem in young children and older adults.

Drug Interactions

Use of acetaminophen with the following drugs may increase the risk of hepatotoxicity (damage to the liver): barbiturates, hydantoins (Dilantin), carbamazepine (Tegretol), rifampin, and ethanol.

Activated charcoal reduces acetaminophen absorption. Acetylcysteine (Mucomyst) is used as an antidote in acetaminophen overdose.

Nursing Implications and Patient Teaching

n Assessment

Learn as much as possible about the patient’s health history. Ask questions to learn about other problems the patient may have that might have produced pain. Does the patient have any risk factors for drug interactions?

n Diagnosis

What other products does that patient take for symptoms of common colds or minor pains at the same time as using it for treatment of osteoarthritis? If so, do the products contain acetaminophenen that might place them at risk for overdose or developing toxicity.

n Planning

Acetaminophen is available OTC, and many patients decide when and how much medicine to take. Ask specifically about acetaminophen use when taking a medication history to include all OTC medications, herbal medicine, and prescription drugs. Generic acetaminophen is equally effective and less expensive than brand-name products.

n Implementation

Acetaminophen is the drug of choice for reduction of fever. Treatment of minor fever is not indicated unless the fever is making the patient uncomfortable. Symptomatic relief of a temperature greater than 40° C is usually required. Treatment of a temperature higher than 41° C or 105° F to 106° F is a medical emergency. Caution the patient against overdosing.

Dosing information for acetaminophen is provided in Table 21-1.

n Evaluation

Monitor fever or pain control. Watch for symptoms of gastric distress, nausea, or bleeding.

n Patient and Family Teaching

Tell the patient and family the following:

• The patient should not exceed the recommended dosage.

• Have the patient look at or bring in all of their medications to assess for the drugs that may have acetaminophen.

• This medication should be kept out of the reach of children.

• The patient should stop using this medication if a sensitivity reaction occurs.

• Severe pain or high fever may indicate serious illness. If symptoms persist, the patient should contact the health care provider.

• The patient should avoid consumption of excessive alcohol while taking this medication because of increased risk of liver damage.

Nonsteroidal Antiinflammatory Drugs

Action

Nonsteroidal antiinflammatory drugs ((NSAIDs) have analgesic, antiinflammatory, and antipyretic effects and are used to treat rheumatic diseases, degenerative joint disease, osteoarthritis, and acute musculoskeletal problems. The exact mode of action of NSAIDs is not known, although it is believed that the analgesic and antiinflammatory effects of NSAIDs are largely the result of their ability to stop the production of prostaglandins. All NSAIDs inhibit cyclooxygenase, thus blocking the production of prostaglandins. One NSAID celecoxib (Celebrex) specifically works to inhibit COX-2, the chemical created at sites of inflammation by cytokines and inflammatory mediators. These agents also inhibit platelet clumping or aggregation, but this effect appears to be dose related.

Uses

Use of NSAIDs may be indicated for acute or chronic musculoskeletal pain.

Most NSAIDs are used in the treatment of both rheumatoid arthritis and osteoarthritis. They are used specifically in the relief of arthritic signs and symptoms, in treatment of acute inflammatory flare-ups and worsening of symptoms, and for long-term management of arthritis. NSAIDs are also used in treatment of pain from dental extraction, minor surgery, and soft-tissue athletic injuries. Ibuprofen (Advil, Motrin) has been approved for use in dysmenorrhea because of its inhibition of prostaglandin production.

Adverse Reactions

Adverse reactions to NSAIDs include asthma, fluid retention, hypertension (high blood pressure), confusion, dizziness, blurred or decreased vision, malaise (weakness), sleepiness, tinnitus, pruritus, skin irritation or rash related to sun exposure, abdominal pain, anorexia, bloating, constipation, diarrhea, dyspepsia (stomach discomfort after eating), excessive gas in the GI tract, GI bleeding (upper or lower), heartburn, nausea, vomiting, hematuria (blood in the urine; occurs with some NSAIDs or with worsened renal failure), and many forms of blood-cell changes.

Drug Interactions

Because the various NSAIDs are somewhat different structurally, their specific drug interactions vary. Therefore each agent should be checked for drug interactions that should be monitored. Most products have many significant drug interactions.

Lifespan Considerations

Older Adults

NSAIDs

The incidence of perforated peptic ulcers or bleeding is more common in older adult patients taking an NSAID than in younger adults. Serious consequences occur more often in this age group.

Older adult patients with renal impairment may be at higher risk for NSAID-induced hepatotoxicity or nephrotoxicity (damage to the kidney) and often require a lower dose to prevent drug levels from building up in the blood.