Nonprescription analgesics and their use in solid-organ transplantation: a review

Progress in Transplantation, Sep 2004 by Gabardi, Steven, Luu, Linh

Objective-To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Study Selection and Data Extraction-Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. Englishlanguage studies were selected for inclusion.

Data Synthesis-Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction.

Conclusion-A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

(Progress in Transplantation. 2004; 14:182-190)

Pain has been described as an objectionable sensory and emotional experience associated with actual or potential tissue injury1; it is the most common complaint that result in patients seeking pharmacologie treatment.2 Nonprescription analgesics are purchased by more consumers than any other type of over-thecounter (OTC) medication.2 These agents are readily accessible to all patients; however, just because they are available OTC, does not mean they are harmless. Patients often perceive nonprescription analgesics as completely safe and may not realize the risks associated with these medications. In general, the nonprescription analgesics are safe for occasional use; nevertheless, the long-term use of these agents may result in several important toxicities. This is especially true for solid-organ transplant recipients.

Currently in the United States, 8 oral analgesics are available without a prescription, including aspirin; nonacetylated salicylates (choline salicylate, magnesium salicylate, and sodium salicylate); nonsalicylate, nonsteroidal anti-inflammatory drugs (NSAIDs; ibuprofen, ketoprofen, and naproxen sodium); and acetaminophen. Aspirin and nonacetylated salicylate drugs are often referred to collectively as salicylates. This review will focus on the pharmacology, adverse events, and use of the nonprescription analgesics in solid-organ transplant recipients.

Salicylates

Mechanism of Action

The salicylates work by blocking prostaglandin, prostacyclin, and thromboxane synthesis via the inhibition of cyclooxygenase (COX; both isoforms COX-1 and COX-2) in the arachidonic acid pathway. Prostaglandins have many physiologic properties, including acting as initiators and propagators of pain impulses, inflammatory mediators, and vasodilators. A reduction in prostaglandin synthesis often leads to a decreased sensitivity of pain receptors to pain impulses (analgesia), as well as a reduction in inflammation. These agents are also beneficial for the treatment of pyrexia, because of their ability to act on the hypothalamus heat-regulating center to reduce fever.2-4 Unlike other nonprescription analgesics, aspirin irreversibly acetylates platelets, resulting in decreased platelet aggregation.1 This unique mechanism of action provides an additional benefit of aspirin therapy in the prevention of cardiovascular and cardiocerebral events.2 Table 1 presents a list of common nonprescription analgesic brand names and doses.

Common Indications

Aspirin is indicated for the relief of mild to moderate pain, such as headache, dysmenorrhea, myalgia, arthralgia, and neuralgia,2-4 and is effective as an antipyretic for the temporary relief of fever. In patients with a history of myocardial infarction or unstable angina pectoris, aspirin is indicated for secondary prevention of further myocardial infarctions. Aspirin is also effective in reducing the risk of recurrent transient ischemic attacks or stroke and graft occlusion following aorta coronary bypass surgery.2-4 Table 2 shows a complete list of aspirin indications and associated doses.

Choline salicylate, magnesium salicylate, and sodium salicylate are indicated for the temporary relief of pain, inflammation, and fever. Rheumatoid arthritis, rheumatic fever, osteoarthritis, dysmenorrhea, and myalgias are some common ailments that respond to the nonacetylated salicylates.2,4