Sarah F. Uroza
Lauren K. McCluggage
Carol Gullo Mest
Premium Wordpress Themes by UFO Themes
Osteoarthritis (OA), formerly known as degenerative joint disease, is the most common joint problem in the United States. Based on U.S. data from 2005, OA affects approximately 14% of adults older than age 25 and one third of adults older than age 65. Although prevalent, OA is often undiagnosed because clinical signs and symptoms are typically attributed to the normal aging process. In population-based studies in which asymptomatic patients were screened, the incidence of radiographic-defined OA was consistently higher than the incidence of symptomatic OA in the hands, knees, and hips.
OA is a progressive disease that can result in chronic pain, restricted range of motion, and muscle weakness, especially if a weight-bearing joint is affected. The joints commonly affected by OA include the knees, hips, cervical and lumbar spine, distal interphalangeal (DIP) joints, and the carpometacarpal joint at the base of the thumb.
There are two forms of OA. Primary, or idiopathic, OA arises from physiologic changes that occur with normal aging. Secondary OA usually results from traumatic injuries or inherited conditions and may present as hemochromatosis, chondrodystrophy, or inflammatory OA.
There are several modifiable and nonmodifiable risk factors that contribute to the development of OA. Of all the risk factors, obesity is the greatest in the development of OA of the knees and hips, especially in women. This is due to mechanical stress on weight-bearing joints. There may also be a metabolic effect of excess fat on articular cartilage that may account for some of the significance of obesity as a systemic risk factor. Other modifiable risk factors include prior joint injury and occupations that require excessive mechanical stress or heavy lifting. For patients with a past knee injury, the lifetime risk of knee OA is 57% compared to 45% in patients with no previous injury.
The nonmodifiable risk factors include gender, age, race, and genetics. Women have a higher overall risk for developing OA, but men tend to have disease onset at an earlier age. Increasing age is a risk factor until age 75, at which point the risk equilibrates. OA of the DIP and carpometacarpal joints is more common in White women; OA of the knees occurs more frequently in African American women. Genetics may determine approximately one fourth of knee OA cases and one half of hip and hand OA cases.
Joints commonly affected by OA include the hip, knee, hand, and cervical and lumbosacral spine. The American College of Rheumatology (ACR) published criteria for the diagnosis of OA of the knee (1986), hip (1991), and hand (1990) (Box 36.1
). Often, a thorough history and physical examination provide enough data to diagnose OA. The most common symptom is joint pain; the patient in an early stage of OA usually describes the pain as insidious, intermittent, and mild. As the disease progresses, the patient may describe the pain as more constant and more disabling. Most patients report remittance of pain with rest and exacerbation of pain with joint movement.
FIGURE 36.1 Destruction of cartilage in osteoarthritis.
Although the symptoms of OA are localized, associated pain may be referred. For example, it is common for OA of the hip to be referred to the medial knee. Another symptom associated with OA is crepitus, a painless “crackling” in the joint. Crepitus most commonly affects the knee, but it may be heard in other joints affected by OA as well. As OA progresses to later stages of articular damage, deformity of the joint may be observed. The deformity usually appears as an enlargement of the joint, which may result from either increased bone
production or synovitis. Other deformities resulting from OA of the knee include varus (bow-legged knees) and valgus (knock-kneed legs).
OA of the cervical spine may present with pain that radiates to the supraclavicular or upper trapezius areas. Depending on the level of nerve involvement, symptoms may progress to include pain in the distal upper extremities. OA of the lumbar spine may produce symptoms of neurogenic claudication.
On physical examination, decreased range of motion is the most common finding. This finding may be absent in the early stages of the disease but gradually progresses as the condition worsens. In later stages of the disease, joint contractures may occur, resulting in varus and valgus deformities. Patients with severe OA of the hip may present with gait disturbances.
Because OA is a progressive disease, complications such as joint effusion and enlargement may occur. Occasionally, radicular problems may occur secondary to changes in the cervical vertebrae.
Joint enlargement due to the formation of osteophytes may be observed. Osteophyte formation in the DIP joint is called Heberden nodes; in the proximal interphalangeal joint, it is referred to as Bouchard nodes.
Radiologic findings in OA may be used to confirm the suspected diagnosis. Narrow joint spaces with osteophyte formation are common findings.
INITIATING DRUG THERAPY
Before initiating drug therapy, the practitioner should recommend appropriate physical activity or physical therapy. The goals of physical therapy are to reduce pain, improve motion, and maintain functional ability (Box 36.2
). In addition, for hip and knee OA, overweight patients should be counseled on the need for weight loss.
The goals of pharmacotherapy for OA are to maintain function, prevent further joint damage, and diminish associated pain. The degree of joint involvement and the severity of the symptoms usually dictate proper interventions for individual patients.
First-line pharmacotherapy for OA is geared toward analgesia, specifically with acetaminophen (Tylenol). Due to acetaminophen’s cost-effectiveness and safety, it is currently the first-line treatment recommended in guidelines by the ACR, the European League Against Rheumatism (EULAR), and others.
Mechanism of Action
Acetaminophen exerts its action within the central nervous system (CNS). It is thought to inhibit central cyclooxygenase (COX), which results in decreased prostaglandin synthesis. Through this prostaglandin inhibition, acetaminophen exerts analgesic and antipyretic effects but does not have anti-inflammatory effects.
The recommended dose is 650 mg every 4 to 6 hours or 1,000 mg every 6 to 8 hours around the clock. The key to acetaminophen dosing for OA is to schedule the dose regardless of the patient’s pain. To be most effective, it must be taken regularly.
The recommended dose of up to 4 g/d is safe for patients with normal liver function. Higher doses have been associated with hepatotoxicity. Patients with a history of liver disease or who are chronic alcohol drinkers should not take more than 1,800 to 2,000 mg/d. All patients should be counseled regarding the need to avoid other products that contain acetaminophen.
Time Frame for Response
If taken as scheduled, patients can experience pain relief within 1 week of initiation.
Acetaminophen is typically well tolerated with the most common adverse events being dizziness and rash. For patients who take more than the recommended daily dose, acetaminophen can induce hepatic failure as a result of the accumulation of the hepatotoxic metabolite acetylimidoquinone. Also, patients need to be educated about the risk of accidental overdose with combination products that also contain acetaminophen. Renal toxicity has also been observed with chronic overdosages.
With chronic doses of greater than 1.3 g daily, acetaminophen can increase the international normalized ratio (INR) of a patient on warfarin. If a patient is on chronic acetaminophen and warfarin, the INR should be monitored more frequently upon initiation and discontinuation of acetaminophen. Isoniazid may increase the risk of hepatotoxicity of acetaminophen.
Nonacetylated salicylates (Box 36.3
) are especially beneficial in patients who are sensitive to the GI irritation caused by long-term aspirin use. Diflunisal (Dolobid), the most commonly used nonacetylated salicylate, is an effective COX-1 inhibitor with anti-inflammatory and analgesic properties, but its antipyretic activities are weak. In terms of symptom relief, the
nonacetylated salicylates are probably as effective as aspirin in treating inflammatory disorders.
When the pain associated with OA progresses and is no longer responsive to acetaminophen or NSAIDs, analgesics are the next option. Analgesics can also be used in patients who cannot tolerate acetaminophen or NSAIDs or in whom they are contraindicated. Analgesics only decrease pain and have no effect on inflammation. These drugs should be prescribed for a limited time because of potential dependence and withdrawal symptoms. Analgesics used for OA other than tramadol and tapentadol, detailed below, include codeine in combination with acetaminophen.
Mechanism of Action
Tramadol exerts multiple effects to induce pain relief. It is a mu opioid receptor agonist similar to other opioids such as morphine. By binding to the mu opioid receptor, ascending pain pathways are inhibited, resulting in decreased pain sensation. In addition, tramadol also inhibits the reuptake of serotonin and norepinephrine. These neurotransmitters are also involved in the ascending pain pathway.
Tramadol is available as an immediate-release tablet (Ultram), extended-release tablet (Ultram ER), and in combination with acetaminophen (Ultracet). For the immediate-release tablet, patients can take 50 to 100 mg every 4 to 6 hours as needed for pain with a maximum daily dose of 400 mg. For patients taking the extended-release tablet, the starting dose is 100 mg daily with an increase every 5 days to the maximum of 300 mg/d. All forms of tramadol need to be dose adjusted for renal and hepatic dysfunction.
Time Frame for Response
Patients may feel a decrease in pain as soon as 1 hour after taking an immediate-release tramadol dose with a maximum effect at 2 hours. The extended-release tablet takes about 12 hours for the maximum effect to be seen.
Unlike NSAIDs, tramadol does not produce serious GI adverse events nor does it aggravate existing hypertension, CHF, or renal disease. The most common side effects of tramadol include nausea, dizziness, drowsiness, and sweating. Due to the opioid receptor agonism, tramadol has the potential to exert similar adverse events as other opioids, such as constipation, dependency, euphoria, and respiratory depression.
Tramadol is metabolized by CYP2D6, and any medication that inhibits or induces this enzyme will interact with tramadol. Also, because it inhibits serotonin reuptake, tramadol has the potential to induce serotonin syndrome when used in combination with other serotonergic agents, such as selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, or linezolid.
Mechanism of Action
Similar to opioids, tapentadol is an agonist for the mu opiate receptor. In addition, tapentadol also inhibits the reuptake of norepinephrine.
For patients starting tapentadol (Nucynta), the recommended dose for the first day of therapy is 50 to 100 mg every 4 to 6 hours as needed with the option of giving the second dose as soon as 1 hour after the first dose, if needed. After the first day of therapy, the recommended dose is 50 to 100 mg every 4 to 6 hours as needed with a maximum daily dose of 600 mg. The dosing interval should be increased to every 8 hours or longer in patients with moderate hepatic impairment. Tapentadol is not recommended in patients with severe hepatic or renal impairment (clearance less than 30 mL/min).
Tapentadol is also available in an extended-release formulation. For opioid-naïve patients, the recommended starting dose is 50 mg by mouth twice daily. The dose can be increased by 50 mg per dose every 3 days to a maximum daily dose of 500 mg.
Time Frame for Response
Patients are likely to experience pain relief within 1 to 2 hours of taking the dose. The ER formulation peaks after 3 to 6 hours of ingestion.
The adverse event profile of tapentadol is similar to that of other opioids and tramadol. The most common adverse events are dizziness, somnolence, constipation, nausea, and vomiting. There is a risk of respiratory depression and CNS depression.
Tapentadol needs to be used cautiously with other CNS depressants due to additive effects. As mentioned above, tapentadol and MAO inhibitors cannot be used within 14 days of each other. Using tapentadol with serotonergic agents increases the risk of serotonin syndrome.
Ethanol may increase the tapentadol concentrations if patients are taking the extended-release product. Therefore, patients taking extended-release tapentadol need to refrain from alcohol and any medication containing ethanol.
Mechanism of Action
Duloxetine is a serotonin and norepinephrine reuptake inhibitor. By enhancing serotonin and norepinephrine, duloxetine works in the CNS to reduce pain transmission. Duloxetine is a relatively balanced serotonin and norepinephrine reuptake inhibitor.
The FDA-approved dosing for chronic musculoskeletal pain is 30 mg by mouth daily for 7 days and then increase to 60 mg by mouth daily, which is the listed maximum dose for this indication. However, the trials that resulted in duloxetine’s approval for this indication increased the dose to 120 mg by mouth daily in patients not having an adequate response to the 60 mg dose.
Time Frame for Response
The benefit of duloxetine was seen as early as 4 weeks in the clinical trials. Time points sooner than this were not assessed, so it is not known if its effect starts sooner.
Only gold members can continue reading. Log In
WordPress theme by UFO themes