OTC Pain Relievers and Fever Reducers

Pain is the most common reason for people to seek medical advice, and doctors will most often recommend over-the-counter (OTC) pain medication to help. Fever is one of the most common reasons that children visit the doctor. Moreover, one in five emergency room visits for children is due to a high fever. Since OTC medicines that are effective in treating pain also are effective at reducing fever, they will be considered together in this article.

Pain can be classified as acute, chronic non-malignant, or chronic malignant. Headaches are the most common cause of pain and can be considered a separate class of pain.

Acute pain

Acute pain is experienced by everyone; it is usually short in duration with an identifiable pathology, a predictable prognosis, and treatment that usually includes analgesics. Acute pain is most often due to injuries. Examples of injuries include:

• muscle soreness due to overuse, sprains or strains, or viral infections,
• tears of the ligaments,
• broken bones,
• bruises, and
• cuts.

Acute pain from such injuries can respond well to OTC pain medication. Muscle soreness also may respond well to heat and massage.

Chronic non-malignant pain

Chronic non-malignant pain often begins as acute pain, but it continues beyond the typical time expected for resolution of the problem or persists or recurs for other reasons. It is a type of pain associated with progressive, debilitating diseases such as arthritis. Treatment for chronic non-malignant pain can include OTC medications . However, because of the chronic nature of the pain, regular use of OTC medications can lead to side effects.

Chronic malignant pain

Chronic malignant pain is pain associated with advanced, progressive diseases (often fatal) such as cancer, multiple sclerosis, AIDS, and terminal kidney disease. OTC medications for pain may be useful for the management of chronic malignant pain. However, stronger prescription medications are usually necessary.

Headaches are the most common reason that pain medications (analgesics) are taken. Headaches can be classified into three types:

1. muscle contraction,
2. migraine or vascular, and
3. sinus.

Muscle contraction headache

A muscle contraction headache, the most common type, results from the continuous tightening of the muscles in the upper back, neck, or scalp. This type of headache often is described as a tight, pressing, or throbbing sensation of the head. It can be brought on by emotional stress and anxiety ("tension headaches"). Acute muscle contraction headaches generally respond well to OTC analgesics, but chronic muscle contraction headaches can require physical therapy or relaxation techniques.

Migraine or vascular headaches

Migraine or vascular headaches are due to dilation (widening) of blood vessels in the head. An estimated 28 million people in the United States (about 12% of the population) will experience migraine headaches. Migraine headaches affect children as well as adults. Before puberty, boys are affected more than girls by migraine headaches. However, as a child nears adolescence, girls are affected more than boys. An estimated 6% of men and up to 18% of women will experience a migraine headache. Although many patients use the expression "migraine" to describe any particularly painful headache, many of these are actually muscle contraction headaches. OTC medications for pain may be quite effective for treating migraine headaches. However, prescription medications that are specifically formulated for treating or preventing migraines are often necessary.

Sinus headache

A sinus headache is caused by inflammation or an infection or blockage of one or more sinuses. The pain often is limited to the area around the eyes or the forehead. The pain may occur upon awakening, and may decrease in intensity after the person stands or sits up for a period of time. In addition to analgesics, OTC decongestants can be effective to help drain the sinuses.

Most fevers last only a few hours or days and are not dangerous; however, they may cause a great deal of discomfort. A rectal temperature of greater than 101.8 F (38.8 C), an oral temperature of more than 100 F (37.8 C), or an armpit temperature of greater than 99 F (37.2 C) is considered significantly abnormal. Fevers are usually due to viral or bacterial infections; however, they also can be due to cancers, injury to tissue (for example, heart attacks), hyperthyroidism, other illnesses in which there is inflammation, and dehydration. Additionally, many different drugs have been reported to cause "drug fever."

Harmful effects of fever (for example, dehydration, changes in consciousness, seizures, or coma) are likely to occur at temperatures above 106 F. Lower fevers can be dangerous in persons with heart disease, since fever increases the effort required by the heart to pump blood.

Two percent to four percent of children between the ages of 6 months and 5 years (usually before age 3) with high fevers will experience febrile seizures; though these seizures generally last no more than 15 minutes. Moreover, children who experience febrile seizures have a higher risk of developing epilepsy later in life.

The three classes of OTC analgesic/antipyretic medications are:

• Salicylates: aspirin (also called acetylsalicylic acid or ASA), choline salicylate, magnesium salicylate, and sodium salicylate;
• Acetaminophen
• Nonsteroidal antiinflammatory drugs (NSAIDs): ibuprofen, naproxen sodium, and ketoprofen. (Aspirin is also an NSAID, but it is considered separately from the other NSAIDs because it has some unique properties.) Each of these drugs is discussed in detail below.

In most circumstances, these medications all have very similar abilities to relieve pain and fever. Their onset of action (the interval from the time of ingestion to the start of pain relief) also are similar. Naproxen sodium may have a somewhat longer duration of pain relief (analgesia) than the other NSAIDs or aspirin. At high doses, salicylates and NSAIDs suppress inflammation and are, therefore, particularly useful in treating inflammatory diseases, such as arthritis. Acetaminophen does not have anti-inflammatory actions.

Many OTC analgesics are available in combination with other drugs. There is some evidence that caffeine and antihistamines enhance the effects of analgesics. Thus, caffeine increases the pain-relieving effects of aspirin and ibuprofen, and the antihistamines orphenadrine and phenyltoloxamine enhance the pain-relieving effects of acetaminophen. Combinations of decongestants with analgesics are logical only when nasal or sinus congestion are present, such as with sinus headaches.

Aspirin can damage the lining of the stomach and duodenum, thereby causing abdominal pain, bleeding, and/or ulcers. As a result, 1 in 5 persons who take aspirin in a dose of 2.5 grams per day or more develops ulcers and about 1 in 6 will lose enough blood from gastrointestinal bleeding to develop anemia. In an attempt to reduce the potential for these complications, some aspirin-containing tablets have been coated with a special coating that prevents the tablet from dissolving until it is past the stomach and duodenum. These "enteric-coated" aspirin products may reduce the frequency of abdominal pain, but not the bleeding or ulcers. Moreover, the onset of pain relief is delayed with enteric-coated aspirin because it takes more time for the tablets to dissolve.

Other attempts to prevent complications have included aspirin-containing products that release the aspirin slowly over time (for example, Zorprin, Measurin, Verin). Like enteric-coated products, these products are not ideal when prompt relief of pain is needed. They also do not prevent ulcers or bleeding. Buffered (for example, Bufferin) and effervescent (such as Alka-Seltzer) aspirin products are absorbed more quickly from the stomach and intestine than aspirin, but they do not act more rapidly than regular aspirin and do not reduce the risk of bleeding or ulcers. Furthermore, effervescent aspirin products contain large amounts of sodium (salt) and should be avoided in persons with high blood pressure, heart failure, or certain kidney diseases.

Side effects of aspirin

Aspirin prevents platelets from their natural ability to stick together and form blood clots. On the one hand, this effect can be used beneficially, such as to prevent the blood clots that cause heart attacks or strokes. On the other hand, by preventing blood clots, aspirin can have the detrimental effect of promoting bleeding. Therefore, aspirin should not be used by people who have diseases that cause bleeding (such as hemophilia and severe liver disease) or diseases in which bleeding may occur as a complication (such as stomach ulcers). Moreover, since the effect of aspirin on platelets lasts for many days, people should not take aspirin for at least seven days before surgical or dental procedures because of the increased risk of bleeding after the procedures.

In patients at risk for bleeding, acetaminophen can be an excellent alternative to aspirin since acetaminophen does not have an effect on platelets, blood clots, or bleeding.

Like aspirin, other NSAIDs affect platelets, but the duration of the effect is less than with aspirin. Two aspirin-related, salicylate-containing products (salsalate and choline magnesium trisalicylate) have no effect on the platelets, but they are available only by prescription.

Serious side effects of aspirin occur infrequently. However, they may occur and generally tend to be more frequent with higher doses. Therefore, it is advisable to use the lowest effective dose to minimize side effects.

The most common side effects of aspirin involve the gastrointestinal system. Aspirin can cause ulcers of the stomach and duodenum (first part of the small intestine), abdominal pain, nausea, gastritis (inflammation of the stomach), and even serious gastrointestinal bleeding from ulcers. Sometimes, ulcers of the stomach and bleeding occur without any abdominal pain, and the only signs of bleeding may be bloody or dark stools or weakness.

Although many people claim to be "allergic" to aspirin, most describe their "allergy" as abdominal pain or heartburn. These common side effects are not allergies, but rather reflect the irritating effects of aspirin on the lining of the stomach. True allergy to aspirin is a rare and serious condition in which a patient can develop swelling of tissues, spasm of the airways (bronchospasm) that causes difficulty breathing, and even anaphylaxis, a life-threatening condition. Clearly, patients with a history of allergy to aspirin should not take aspirin. Since aspirin is related chemically to the other NSAIDs, patients who are allergic to the other NSAIDs, such as ibuprofen (Motrin) and naproxen (Aleve), should also not take aspirin.

Pregnancy/breastfeeding and aspirin

Regular aspirin consumption during pregnancy has been associated with side effects in the pregnant mother, including bleeding and complications during labor. It is unclear if aspirin taken in the first two trimesters poses a risk to the fetus. However, when taken during the third trimester, aspirin may increase the risk of bleeding in the newborn. Nevertheless, for certain mothers with diseases that are associated with a high risk for blood clotting during pregnancy and miscarriage, aspirin is actually recommended in low doses for prevention. Although very little aspirin is secreted into breast milk, most authorities recommend that nursing mothers avoid using aspirin. A woman should consult with her health care practitioner before taking any medications while pregnant or breastfeeding.

Viral infections in children and aspirin

Because aspirin causes Reye's syndrome (a potentially fatal liver disease that occurs almost exclusively in persons under the age of 15 years), aspirin should not be given to children when a viral infection is suspected.

Drug interactions and aspirin

Aspirin may interact with other medications and cause undesirable side effects. For example, high doses of aspirin can increase the activity of valproic acid (Depakene; Depakote), an effect which can cause drowsiness or behavioral changes.

High doses of aspirin also can enhance the effect of some blood sugar-lowering medications used to treat diabetes, including glyburide (Diabeta), glipizide (Glucotrol), and tolbutamide (Orinase), which can possibly lead to hypoglycemia (low blood sugar). Blood sugar levels may need to be more closely monitored in this setting.

Aspirin, when taken together with an anti-coagulant such as warfarin or enoxaparin (Lovenox), can greatly impair the body's ability to form blood clots, resulting in excessive bleeding spontaneously, from ulcers, or related to a procedure. Therefore, patients on such combinations must be closely monitored by a doctor.

Low dose aspirin can raise levels of uric acid in the blood and may need to be avoided in patients with increased uric acid levels or gout.

Certain NSAIDs, particularly ibuprofen (Motrin, Advil), if taken just before aspirin or in multiples doses each day, can reduce the anti-platelet effects of aspirin treatment and theoretically render aspirin less effective in preventing heart attacks and ischemic strokes.

Salicylates other than aspirin

Choline salicylate (Arthropan) is available as a liquid. It is absorbed more quickly, but its onset of action is no different than that of aspirin. Some people find choline salicylate fishy tasting. Fortunately, it can be mixed with juice or soda prior to ingestion. It is less effective at reducing fevers in children than either aspirin or acetaminophen.

Magnesium salicylate (Arthriten; Backache) is as effective as aspirin at reducing pain. Patients with chronic kidney disease should avoid magnesium salicylate, since the magnesium may accumulate in the body.

Sodium salicylate (Scot-Tussin Original) and aspirin are equally effective in the long-term treatment of rheumatoid arthritis, but sodium salicylate is less effective at reducing pain or fever.

Acetaminophen comes in various oral formulations, including different types (elixirs or syrups) and flavors of liquids, capsules, tablets, caplets, and suppositories. The capsules contain tasteless granules that can be emptied onto a teaspoon containing a small amount of drink or soft food, and can then be swallowed. However, the granules should not be mixed in a glass of liquid since the granules will stick to glass itself. The amount of acetaminophen that is absorbed from rectal suppositories is about half that of the oral formulations.

Side effects of acetaminophen

Acetaminophen generally is safe to use, and few people develop side effects. In high doses, however, it can cause liver damage and doses of 4000 mg (4 grams) per day should not be exceeded.

Pregnancy/breastfeeding and acetaminophen

Acetaminophen has no known harmful effects on the mother, fetus, or infant and, therefore, can be used safely during pregnancy and breastfeeding.

Drug interactions and acetaminophen

It has been reported that patients with HIV-related diseases (such as AIDS) who take AZT (zidovudine; Retrovir) and acetaminophen are at an increased risk of developing suppression of their bone marrow. Such patients develop lower white and red blood cell and platelet counts and, therefore, are more susceptible to infection, anemia, and bleeding.

There are three OTC NSAIDs; ibuprofen, naproxen sodium, and ketoprofen. All have pain relieving (analgesic), fever reducing (antipyretic), and anti-inflammatory properties. Additionally, NSAIDs are more effective than aspirin or acetaminophen for menstrual cramps.

Preparations of NSAIDs

Ibuprofen is available in tablets as well as in a pediatric suspension. Naproxen sodium is available in tablets. Ketoprofen is available as tablets and capelets.

Side effects and NSAIDs

The most frequent side effect of NSAIDs is damage to the lining of the stomach and duodenum that can lead to abdominal pain, nausea, and loss of appetite. NSAIDs also can cause ulcers and bleeding from the stomach and duodenum, but less frequently and less severely than occurs with aspirin use. NSAIDs, like aspirin, affect platelets and can inhibit the formation of blood clots, and, therefore, they should be discontinued at least 3 days before surgery or dental procedures.

Because alcohol intensifies the effect of NSAIDs on bleeding, alcohol should not be taken with NSAIDs. NSAIDs also can cause kidney damage, particularly in the elderly or patients with high blood pressure, diabetes, atherosclerosis, or who take diuretic medications ("water pills").

Patients who are allergic to aspirin should not take NSAIDs since they are likely to be allergic to NSAIDs as well. NSAIDs may cause fluid retention in persons with congestive heart failure.

The most serious side effects are kidney failure, liver failure, ulcers, and prolonged bleeding after an injury or surgery.

Pregnancy/breastfeeding and NSAIDs

NSAIDs are safe for use during the first or second trimesters of pregnancy, but should not be taken during the third trimester because they can:

• prolong labor and delay birth,
• increase bleeding in the mother following birth, and
• can cause cardiac (heart) and vascular (blood vessels) complications in the newborn.

Nevertheless, use of NSAIDs during any portion of pregnancy should be approved by the treating doctor. Ibuprofen and naproxen sodium also are safe for use by nursing mothers. Due to insufficient data, ketoprofen is not recommended for use by nursing mothers.

Drug interactions and NSAIDs

NSAIDs reduce the blood pressure-lowering effects of certain high blood pressure (antihypertensive) medications, including:

• thiazide diuretics such as hydrochlorothiazide (Dyazide, Maxzide);
• beta-blockers such as propranolol (Inderal, Inderal LA), atenolol (Inderal, Tenormin), and metoprolol (Lopressor);
• angiotensin receptor antagonists such as enalapril (Vasotec), lisinopril (Zestril; Prinivil), benazepril (Lotensin), quinapril (Accupril), ramipril (Altace), and captopril (Capoten); and
• some medications that act on the brain, such as clonidine (Catapres).

NSAIDs reduce blood flow to the kidneys and reduce the action of diuretics and decrease the elimination of lithium (Eskalith) and methotrexate (Rheumatrex).

NSAIDs also decrease the ability of the blood to clot and can increase the risk of bleeding. When used with other drugs that also increase bleeding risk (for example, warfarin), there is an increased likelihood of serious bleeding or complications of bleeding. Therefore, individuals who are taking drugs that reduce the ability of blood to clot should avoid the prolonged use of NSAIDs.

The American Association of Poison Control Centers reported that of all overdoses of OTC products, 66% involved acetaminophen, 19% involved ibuprofen, and 15% involved aspirin.

Aspirin overdose can occur with as little as 150 mg/kg (10,000 mg or 10 grams in the average sized male) as a single dose, or 90 mg/kg per day for at least two consecutive days. Symptoms of toxicity due to aspirin include:

• tiredness,
• ringing in the ears,
• rapid breathing,
• seizures, vomiting,
• bleeding, and
• coma.

Large doses of acetaminophen rarely cause serious problems in children. In adults, as little as 10 grams can damage the liver and the kidneys.

Overdoses of ibuprofen rarely produce important problems. Nausea, vomiting, stomach pain, tiredness, and dizziness are the most common symptoms of large doses of ibuprofen. Rarely, coma may occur.