Adverse drug reactions (adverse effects) are any unwanted effects of drugs (medications). There are several different types:
Dose-related
Allergic
Idiosyncratic
Dose-related adverse drug reactions represent an exaggeration of the drug's therapeutic effects. For example, a person taking a medication to reduce high blood pressure may feel dizzy or light-headed if the medication reduces blood pressure too much.
A person with diabetes may develop weakness, sweating, nausea, and palpitations if insulin or another antidiabetic medication reduces the blood sugar level too much.
This type of adverse drug reaction is usually predictable but sometimes unavoidable. It may occur if a medication dose is too high (overdose reaction), if the person is unusually sensitive to the medication, or if another drug slows the metabolism of the first drug and thus increases its level in the blood (see Drug Interactions). Dose-related reactions may or may not be serious, but they are relatively common.
Allergic drug reactions are not dose-related but require prior exposure to a drug. Allergic reactions develop when the body's immune system develops an inappropriate reaction to a drug (sometimes referred to as sensitization). After a person is sensitized, later exposures to the drug produce one of several different types of allergic reaction. Sometimes doctors do skin tests to help predict allergic drug reactions.
Idiosyncratic adverse drug reactions are not well understood. This type of adverse drug reaction is unpredictable. Examples of idiosyncratic adverse drug reactions include rashes, jaundice (yellowing of the skin), anemia, a decrease in the white blood cell count, kidney damage, and nerve injury that may impair vision or hearing. These reactions tend to be more serious but typically occur in a very small number of people. Affected people may have genetic differences in the way their body metabolizes or responds to medications.
Some adverse drug reactions are not related to the medication's therapeutic effect but are usually predictable, because the mechanisms involved are mostly understood. For example, stomach irritation and bleeding often occur in people who regularly use aspirin or other Some adverse drug reactions are not related to the medication's therapeutic effect but are usually predictable, because the mechanisms involved are mostly understood. For example, stomach irritation and bleeding often occur in people who regularly use aspirin or othernonsteroidal anti-inflammatory drugs (NSAIDs). The reason is that these medications reduce the production of prostaglandins, which help protect the digestive tract from stomach acid.
Severity of Adverse Drug Reactions
Adverse drug reactions (adverse effects) are any unwanted effects of medications. There is no universal scale for describing or measuring the severity of an adverse drug reaction. The U.S. Food and Drug Administration (FDA) classifies adverse drug reactions as serious or nonserious. Assessment is largely subjective.
Mild nonserious adverse drug reactions do not necessarily mean that people must stop taking a medication, especially if no suitable alternative is available. However, doctors are likely to reevaluate the dose, frequency of use (number of doses a day), and timing of doses (for example, before or after meals; in the morning or at bedtime). Other medications may be used to control the adverse drug reaction (for example, a stool softener to relieve constipation).
Nonserious adverse drug reactions may include digestive disturbances (nausea, constipation, diarrhea), headaches, fatigue and malaise, vague muscle aches, rashes, difficulty with urination, change in mood, or temporary changes in some blood components (such as a reversible decrease in the white blood cell count).
Serious reactions include those that may be life threatening (such as liver failure, abnormal heart rhythms, certain types of allergic reactions), those that result in persistent or significant disability or hospitalization, and those that cause birth defects. These reactions are relatively rare. People who develop a severe reaction usually must stop using the medication and must be treated. However, doctors must sometimes continue giving high-risk medications (for example, chemotherapy to people with cancer or immunosuppressants to people undergoing organ transplantation). Doctors use every possible means to prevent or control a severe adverse drug reaction.
Lethal reactions are those in which a drug reaction directly or indirectly caused death. Lethal reactions can be the reasons that some medications are withdrawn from the market.
In the United States, suspected adverse drug reactions may be voluntarily reported to the FDA via the MedWatch safety reporting program. Reporting can help the FDA assess risk on an ongoing basis.
Risk Factors for Adverse Drug Reactions
Many factors can increase the likelihood of an adverse drug reaction (any unwanted effects of a medication). They include:
Hereditary factors
Certain preexisting diseases
Very young or old age
Pregnancy
Breastfeeding
Decreased renal or hepatic function
Hereditary factors make some people more susceptible to the toxic effects of certain medications. Various genes have been identified that affect how the body responds to medications. For example, differences in certain genes can affect metabolism of medications in the liver, allowing medications levels to rise and increase the chances of an adverse drug reaction. However, testing for these differences is complex and is not yet used routinely in clinical practice.
Certain preexisting diseases can alter drug absorption, metabolism, and elimination and the body's response to drugs (see Drug-Disease Interactions), increasing the risk of adverse drug reactions.
How mind-body interactions, such as mental attitude, outlook, belief in self, and confidence in health care professionals, influence adverse drug reactions remains largely unexplored.
Use of Several Medications
Taking several medications, whether prescription or over-the-counter, contributes to the risk of having an adverse drug reaction (see Drug-Drug Interactions). The number and severity of adverse drug reactions increase as the number of medications taken increases.
The use of alcohol also increases the risk of an adverse drug reaction.
Asking a doctor or pharmacist to periodically review all the medications a person is taking and to make appropriate adjustments can reduce the risk of an adverse drug reaction.
Age
Infants and very young children are at high risk of adverse drug reactions, primarily for one of two reasons: because their capacity to metabolize drugs is not fully developed and because they are still growing and developing new tissue. For example, because tooth enamel is forming, if the antibiotic tetracycline is given to infants and young children (up to about age 8), it may permanently discolor tooth enamel. Infants and very young children are at high risk of adverse drug reactions, primarily for one of two reasons: because their capacity to metabolize drugs is not fully developed and because they are still growing and developing new tissue. For example, because tooth enamel is forming, if the antibiotic tetracycline is given to infants and young children (up to about age 8), it may permanently discolor tooth enamel.
Children under age 18 are at risk of Reye syndrome if they are given aspirin while they have influenza or chickenpox.Children under age 18 are at risk of Reye syndrome if they are given aspirin while they have influenza or chickenpox.
Older adults are at high risk of having an adverse drug reaction for several reasons (see Aging and Medications). They are likely to have many health problems and thus to be taking several prescription and over-the-counter medications.
Also, as people age, the liver is less able to metabolize many drugs, and the kidneys are less able to eliminate drugs from the body, increasing the risk of kidney damage and other adverse drug reactions. These age-related problems are often made worse by undernourishment and dehydration, which tend to become more common as people age.
Older adults are also more sensitive to the effects of many medications. For example, older adults are more likely to experience light-headedness, loss of appetite, depression, confusion, and impaired coordination, putting them at risk of falling and fractures. Medications that can cause these reactions include many antihistamines, sleep aids, antianxiety medications, antihypertensives, antihyperglycemics and antidepressants (see table Some Medications Particularly Likely to Cause Problems in Older Adults).
Pregnancy and Breastfeeding
Many medications—for example, antihypertensive medications such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)—pose a risk to the health and normal development of a fetus. Many medications—for example, antihypertensive medications such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs)—pose a risk to the health and normal development of a fetus.
To the extent possible, pregnant people should not take any medications, especially during the first trimester (see table Some Medications and Risk of Problems During Pregnancy). The developing fetus is especially vulnerable to effects of medications during the first trimester of pregnancy and only essential medications (as recommended by the treating health care provider), and prenatal vitamins, should be taken. However, for some medications, including ACE inhibitors and ARBs, risk increases during the second and third trimesters of pregnancy.
Use of any prescription medications, over-the-counter medications, and dietary supplements (including medicinal herbs) during pregnancy requires a doctor's supervision.
Social drugs (alcohol and nicotine) and illicit drugs (cocaine and opioids such as heroin) also pose risks to the pregnancy and the fetus and therefore should be avoided.Social drugs (alcohol and nicotine) and illicit drugs (cocaine and opioids such as heroin) also pose risks to the pregnancy and the fetus and therefore should be avoided.
Medications and medicinal herbs may be transmitted through breast milk to an infant (see Medication and Substance Use During Breastfeeding). Some medications should not be taken by women who are breastfeeding, whereas others can be taken but require a doctor's supervision.
People who are breastfeeding should consult with a health care professional before they take any medications. Social and illicit drugs may harm a breastfeeding infant.
Overdose Toxicity
Overdose toxicity refers to serious, often harmful, and sometimes fatal toxic reactions to an accidental overdose of a medication (because of an error on the part of the doctor, pharmacist, or person taking the medication) or to an intentional overdose (homicide or suicide).
A lower risk of overdose toxicity is often the reason doctors prefer one medication over another when both medications are equally effective. For example, if a sleep aid is needed, doctors may recommend melatonin or prescribe zolpidem as a safer choice over a benzodiazepine (such as temazepam or triazolam) as benzodiazepines have the potential to cause dependence and are dangerous in overdose. Safety is also the reason that newer antidepressants, such as fluoxetine and paroxetine, have largely replaced older but equally effective antidepressants, such as imipramine and amitriptyline (see table A lower risk of overdose toxicity is often the reason doctors prefer one medication over another when both medications are equally effective. For example, if a sleep aid is needed, doctors may recommend melatonin or prescribe zolpidem as a safer choice over a benzodiazepine (such as temazepam or triazolam) as benzodiazepines have the potential to cause dependence and are dangerous in overdose. Safety is also the reason that newer antidepressants, such as fluoxetine and paroxetine, have largely replaced older but equally effective antidepressants, such as imipramine and amitriptyline (see tableMedications for Treatment of Depression).
Young children are at high risk of overdose toxicity. Brightly colored tablets and capsules, most of which are adult-dose formulations, can attract the attention of young children. In the United States, federal regulations require that all prescription medications taken by mouth be dispensed in childproof containers unless a person signs a waiver to the effect that such a container presents a handicap.
Most metropolitan areas in the United States have poison control centers that provide information about chemical and drug poisoning, and most telephone directories list the number of the local center. This number should be copied and placed near a telephone or programmed into an automatic-dialing telephone or cellular phone.
