The FDA has required manufacturers of propoxyphene-containing products (Darvon, and others) to strengthen boxed warnings to include the potential for overdose.1 This action followed disclosure of fatal overdoses linked to propoxyphene-containing products taken alone or concurrently with other CNS depressants, including alcohol. Many of the overdoses occurred in patients with a history of emotional instability or suicide attempts. Accumulation of metabolites of propoxyphene can lead to central nervous system, cardiac and respiratory depression; convulsions and cardiotoxicity have occurred.

A Schedule IV controlled substance, propoxyphene is a weak full agonist opioid indicated for relief of mild to moderate pain.2 It is often prescribed in combination with acetaminophen (Darvocet, and others). One reasonable alternative would be codeine with acetaminophen; 32 mg of codeine has an analgesic effect similar to that of 65 mg of propoxyphene. Another would be 400 mg of ibuprofen, which may be more effective than either propoxyphene or codeine combined with acetaminophen.

1. FDA News Release. FDA takes actions on Darvon, other pain medications containing propoxyphene. Available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm170769.html. Accessed August 23, 2010.

2. Drugs for pain. Treat Guidel Med Lett 2010; 92:25.

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Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain is generally treated with nonopioid analgesics and opioids. Antidepressants and anticonvulsants have been used to treat neuropathic pain. Combining two different types of analgesics may nprovide an additive analgesic effect without increasing adverse effects.

The physiologic changes that occur with aging can affect the pharmacokinetics and pharmacodynamics of many prescription and over-the-counter drugs, increasing the likelihood of adverse effects.

Alprazolam, a short-acting benzodiazepine, is one of the most widely prescribed drugs in the US. It is approved by the FDA for treatment of anxiety and panic disorder. An extended-release formulation, Xanax XR, which can be taken once a day, recently became available for panic disorder.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

Acute toxic reactions to drugs of abuse continue to be important problems. Some patients may have mixed intoxications with complex combinations of signs and symptoms.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Non-opioids can be given concurrently with opioids for an additive analgesic effect.

Oxcarbazepine, which is chemically similar to carbamazepine, and levetiracetam, a pyrrolidine acetamide chemically unrelated to other antiepileptic drugs, are the sixth and seventh drugs approved by the US Food and Drug Administration in the last five years for oral use in partial seizures.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, some drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain.

Acute toxic reactions to drugs of abuse continue to be important problems. Since the last Medical Letter article on this subject (volume 32, page 92, 1990), new reactions and new approaches to treating them have been reported.

Nalmefene (Revex - Ohmeda), an i methylene analog of naltrexone (Trexan), is a long-acting opioid antagonist that has been approved by the US Food and Drug Administration for reversal of postoperative opioid drug effects, including respiratory depression, sedation and hypotension and for management of known or suspected opioid overdose in the emergency department. The only other opioid antagonists available in the USA are naloxone (Narcan), which is also injectable but has a short duration of action, and naltrexone, which has a long duration of action but is marketed only for oral use.

Tramadol hydrochloride (Ultram - Ortho-McNeil), a centrally-acting analgesic marketed in Germany since 1977, was recently approved by the US Food and Drug Administration for oral treatment of moderate to moderately severe pain. Despite some opioid activity, tramadol has not been scheduled as a controlled substance.

Three types of analgesic drugs are available in the USA: first, aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. (American Pain Society, Principles of analgesic Use, 3rd ed, Skokie, illinois: American pain society, 1992).

Some commonly used systemic drugs that may cause pulmonary toxicity are listed in the table below. These adverse effects may sometimes be difficult to distinguish from the underlying disease (JAD Cooper, Jr et al, Am Rev Respir Dis, 133:321, 488, 1986). Pulmonary effects that are part of a generalized reaction or are indirect effects of drugs - on respiratory muscles, for example, or on the immune system - are not included here.