http://evolve.elsevier.com/Edmunds/NP/
Top 100 drug; 
key drug.
Acetaminophen is a metabolite of phenacetin. Phenacetin was introduced in 1887, was used extensively for many years, and then was taken off the market because its use led to nephropathy. APAP has been in use since 1893 but has become very popular since 1949. APAP has the effectiveness of phenacetin without the adverse reactions. However, acetaminophen overdosage may still cause nephropathy.
The problem most frequently noted with APAP involves difficulty in determining proper dosing in children. The FDA continues to issue safety alerts on various preparations to state that the dosing is confusing. All cough and cold medications that contain acetaminophen and are marketed for children younger than 2 years have been withdrawn from the market. Current guidelines recommend avoiding use of these products PO in children younger than 2 years because of the risk of toxicity associated with improper dosing. For information for patients, go to www.knowyourdose.org. A new formulation of IV acetaminophen for pediatric use went on the market in 2011.
The FDA is asking manufacturers of combination products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet to decrease the risk of overdosage. This will be phased in over a course of years.
The use of acetaminophen in the management of fever is discussed in this chapter. For additional information on the use of APAP in the treatment of pain, see Chapter 43
Therapeutic Overview
Fever is an elevation of the setpoint of body temperature. The hypothalamus is the site of the heat-regulating center. The setpoint is elevated through several mechanisms. The most common of these involves the monocyte-macrophages, which, when stimulated, release pyrogenic cytokines such as interleukin-1. These stimulate the heat-regulating center to raise the setpoint. This prompts increased heat production via shivering or decreased heat loss through peripheral vasoconstriction.
Disease Process
It is essential for the clinician to identify and treat the cause of fever and not just the symptoms. Fever is a symptom with many causes, the most common of which is infection. The danger in treating a fever involves the risk that symptoms of a worsening infection may be masked. A fever may be an important indication of antibiotic resistance. Fever of unknown origin is defined as an unexplained case of fever exceeding 38.3°C on several occasions for at least 3 weeks in patients without neutropenia or immunosuppression. Causes of fever and hyperthermia are listed in Table 35-1.
TABLE 35-1
Causes of Fever and Hyperthermia
| Common Causes of Fever | Less Common Causes of Fever | Causes of Hyperthermia |
| Infections: bacteria, virus, rickettsia, fungus, parasites | Cardiovascular disease: myocardial infarction, thrombophlebitis, pulmonary embolism | Heatstroke |
| Autoimmune disease | GI disease: inflammatory bowel disease, alcoholic hepatitis, granulomatous hepatitis | Malignant hyperthermia of anesthesia |
| CNS disease, including head trauma and mass lesions | Medication: drug fever | Malignant neuroleptic syndrome |
| Malignant disease, especially renal cell, liver, leukemia, and lymphoma | Other: sarcoidosis, tissue injury, hematoma, and factitious causes |
Mechanism of Action
Acetaminophen reduces fever through direct action on the hypothalamic heat-regulating center, thereby lowering the setpoint to normal. It does this by inhibiting the action of pyrogenic cytokines on heat-regulating centers. This action increases dissipation of body heat via vasodilation and sweating.
Analgesic
Acetaminophen is a centrally acting analgesic. Its site and mechanism of analgesic action are not clear but may result from inhibition of prostaglandin synthetase in the CNS. APAP differs from ASA in that it does not inhibit peripheral prostaglandin synthesis. This may account for the weak or absence of antiinflammatory and platelet-inhibiting effects.
Treatment Principles
Evidence-Based Recommendations
For the person with osteoarthritis (OA), acetaminophen is the medication of first choice for mild pain. Little evidence suggests that acetaminophen provides any benefit when peripheral inflammation is a causative factor for the pain.
Cardinal Points of Treatment
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
