Chapter outline

Acetaminophen

Chronic acetaminophen overdose can occur with regular daily consumption of higher than recommended doses and is discussed earlier in this section (see Chapter 6). Acute acetaminophen toxicity is generally the result of taking a single dose that is significantly higher than the recommended dose and is considered a medical emergency because untreated acute acetaminophen toxicity can cause fatal hepatic necrosis. Hepatotoxicity can also occur with a single dose of the recommended amount of acetaminophen (e.g., 1000 to 1500 mg in adults) under certain conditions, such as malnutrition, fasting, or heavy alcohol consumption (Burke, Smyth, FitzGerald, 2006).

Prompt diagnosis and treatment of acute acetaminophen overdose will optimize outcome. Approximately 10% of individuals who overdose and do not receive treatment develop severe liver damage. Damage occurs when plasma concentrations are 300 mcg/mL or more at 4 hours or 45 mcg/mL at 15 hours after ingestion of acetaminophen (Burke, Smyth, FitzGerald, 2006). If the dose is not fatal, liver damage can be reversible over a period of weeks or months (Burke, Smyth, FitzGerald, 2006).

Early symptoms of acute acetaminophen overdose occur within 2 days of ingestion and include nausea, vomiting, drowsiness, confusion, and abdominal pain. Plasma transaminase levels become elevated within 12 hours. Clinical signs of hepatic damage are evident within 4 days of overdose by increasing jaundice, right subcostal pain, tender hepatomegaly, and coagulopathy (prolonged prothrombin time) (Burke, Smyth, FitzGerald, 2006). Toxicity may be accompanied by renal impairment. Poor prognosis is associated with hepatic encephalopathy or worsening coagulopathy.

A Cochrane Collaboration Review concluded that the evidence for support of any one method of acetaminophen overdose treatment is weak; activated charcoal, gastric lavage, and ipecac administration within 2 hours of acetaminophen ingestion reduce absorption, but the clinical implications are not clear (Brok, Buckley, Gluud, 2006). Others recommend initial administration of activated charcoal but do not recommend gastric lavage (Burke, Smyth, FitzGerald, 2006). N-acetylcysteine (NAC) (Mucomyst, Mucosol) should be given orally to individuals at risk of hepatic injury (Brok, Buckley, Gluud, 2006; Burke, Smyth, FitzGerald, 2006). The underlying mechanism of hepatic damage as a result of acetaminophen overdose is conversion of acetaminophen to the toxic metabolite N-acetyl-p-benzo-quinone imine (NAPQI), and NAC detoxifies NAPQI. Administration of NAC should not be delayed or avoided if activated charcoal has already been given; interaction between the two is not a concern (Burke, Smyth, FitzGerald, 2006).

Aspirin and Other Salicylates

Toxicity related to aspirin and other salicylates is also generally a result of taking higher than recommended doses. Symptoms of toxicity from chronic use (referred to as chronic salicylism) include headache, dizziness, ringing in the ears, difficulty hearing, dim vision, confusion, drowsiness, and sweating (Burke, Smyth, FitzGerald, 2006). Toxicity may go undetected because some of these symptoms mimic the disease being treated. All are reversible by lowering the dose.

Acute salicylate overdose, on the other hand, is considered a medical emergency, and prognosis depends on prompt diagnosis and treatment. The American Association of Poison Control Centers recommends that any suspected or confirmed salicylate overdose in the outpatient setting be immediately referred to an emergency department for treatment (Chyka, Erdman, Christianson, et al., 2007). Fatal doses vary significantly and depend on the aspirin formulation; however, death has been reported with doses of 10 to 30 gm in adults (Burke, Smyth, FitzGerald, 2006).

Symptoms of acute toxicity include lethargy, ringing in the ears, nausea and vomiting, and convulsions. Gastric irritation may not be evident. Hyperventilation and tachycardia are sometimes mistaken for anxiety (O’Malley, 2007). However, co-ingestion of CNS-depressant drugs, such as opioids, can blunt respiratory symptoms. Serum aspirin levels may be normal or modestly elevated, and blood gas analysis will likely demonstrate respiratory alkalosis. Patients in the late stages of salicylate toxicity are often misdiagnosed as having sepsis, myocardial infarction (MI), or a psychiatric disturbance (O’Malley, 2007). Postmortem examination has shown myocardial necrosis, pulmonary congestion, hemorrhagic gastritis and ulceration, cerebral edema, and muscle rigidity.

There is no specific antidote for salicylate overdose. Emesis should not be induced (Chyka, Erdman, Christianson, et al., 2007). A combination of gastric irritation, nausea, and lethargy places the patient at high risk for vomiting, which can result in aspiration; therefore, the benefits and risks of gastric decontamination must be weighed. The most commonly used method for gastric decontamination consists of administering multidose activated charcoal (25 mg without sorbitol every 3 hours) to prevent further absorption of the drug from the GI tract (O’Malley, 2007). Doses are repeated if bowel sounds are absent when the next dose is due. Administration of activated charcoal is particularly important if enteric-coated aspirin, which has delayed absorption, has been ingested (Burke, Smyth, FitzGerald, 2006). Alkanized IV fluids (sodium bicarbonate + potassium chloride) are infused rapidly to counteract acidity and prevent hypokalemia (O’Malley, 2007). Maintaining high urine alkalinity (i.e., pH greater than 8) will facilitate salicylate excretion. Supplemental glucose should be administered to patients with altered mental status as this may indicate decreased CNS glucose despite normal plasma glucose levels. Hemodialysis is required if these simpler methods are ineffective (Burke, Smyth, FitzGerald, 2006; O’Malley, 2007).

Other NSAIDs

An overdose of a proprionic acid derivative, such as ibuprofen, ketoprofen, or naproxen, usually produces minimal symptoms of toxicity and is rarely fatal. However, there are case reports of multisystem organ failure and death after consumption of massive amounts of ibuprofen (e.g., 105-gm sustained-release ibuprofen) (Holubek, Stolbach, Nurok et al., 2007; Wood, Monaghan, Streete, et al., 2006). Management of suspected ibuprofen overdose accounts for 5% of the calls to poison control centers in the United Kingdom, and the fatalities associated with ibuprofen overdose are often complicated by comorbidities and co-ingestion of other drugs (Volans, Monaghan, Colbridge, 2003). There have been single reports of acute pancreatitis induced by an overdose of ibuprofen (Magill, Ridgway, Conlon et al., 2006) and naproxen (Aygencel, Akbuga, Keles, 2006).

Common symptoms of mild NSAID (e.g., ibuprofen, naproxen) overdose include nausea, vomiting, and abdominal pain. However, many patients are completely asymptomatic (Volans, Monaghan, Colbridge, 2003). Acute massive overdose produces severe metabolic acidosis, hypotension, hypothermia, and reduced level of consciousness, or the patient may be unresponsive. Treatment of acute toxicity includes gastric decontamination with activated charcoal, vasopressors, correction of metabolic acidosis, and dialysis (Wood, Monaghan, Streete, et al., 2006). Overdose of other NSAIDs appears to be similar to that seen with the proprionic acid derivatives.

Conclusion

Chronic nonopioid overdose can occur with regular daily intake of higher than recommended doses. Acute toxicity usually occurs when a single dose that is significantly higher than the recommended dose is consumed. Prognosis depends on prompt and appropriate treatment dependent on the type of nonopioid involved.

Section III Conclusion

USE of acetaminophen and NSAIDs for pain relief is usually on an outpatient basis. Patients are often discharged from the hospital with nonopioids, and they are frequently prescribed or recommended to patients during an office or clinic visit. Because many are available without a prescription, the patient may decide independently to use them.

A review of the literature revealed numerous reasons why patients do not adhere to a variety of medications prescribed for pain (Monsivais, McNeil, 2007). In addition to an introductory review of the literature, these authors examined 42 abstracts and 17 full-text articles. Some of the concerns revealed are pertinent to nonopioid analgesics and may be diminished by providing the patient with written information about their medications. (See patient education forms for selected medications on pp. 250-255.) A common reason for nonadherence was a high level of concern about the medication, such as adverse effects, “dependency,” and questions about the real need for the medication. Patients also had misconceptions about how long it should take for the drug to be effective, and they would stop taking it if no benefits occurred by the expected time. Patients also feared tolerance, that is, that the medication might cease to work if taken on a regular basis.

Nonopioids can cause serious adverse effects underscoring the need to provide accurate and complete information to patients and their families regarding safe use. The usual teaching about drug, name, dose, timing, and adverse effects is important. Written information may be particularly helpful because it reminds the patient of what was said. It can be shared with interested family members and any health care providers the patient may see. Forms III-1 to III-3 are teaching tools specific to ibuprofen, naproxen, and celecoxib. Forms III-4 and III-5 (pp. 256-259) are teaching tools for prescription and nonprescription products containing acetaminophen and NSAIDs, respectively.

The information in the Patient Medication Information forms that follow is based on content from this chapter and the following five references:

References