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Recent estimates suggest that each year more than 1 million patients are injured while in the hospital and approximately 180,000 die because of these injuries. Furthermore, drug-related morbidity and mortality are common and are estimated to cost more than $136 billion a year. The most common type of drug-induced disorder is dose-dependent and predictable. Many adverse drug events occur as a result of drug-drug, drug-disease or drug-food interactions and, therefore, are preventable.

Clinicians' awareness of the agents that commonly cause drug-induced disorders and recognition of compromised organ function can significantly decrease the likelihood that an adverse event will occur. Patient assessment should include a thorough medication history, including an analysis of all prescribed and over-the-counter medications, vitamins, herbs and "health-food" products to identify drug-induced problems and potentially reversible conditions. An increased awareness among clinicians of drug-induced disorders should maximize their recognition and minimize their incidence.

Drug-induced disorders, in the form of adverse drug events or drug interactions, occur daily in all health care environments. Unfortunately, significant morbidity and mortality are often the consequence of these reactions. Several studies have reported that an average of 10 percent of all hospital admissions may be attributable to drug-induced disorders; this percentage may be a significant underestimate. (Manasse HR Jr. Medication use in an imperfect world: drug misadventuring as an issue of public policy, Part 1. Am J Hosp Pharm 1989.)

Furthermore, an evaluation of a large sample of 30,195 randomly selected hospital records revealed that 1,133 patients (3.7 percent) experienced a disabling injury caused by medical treatment while hospitalized. (Leape LL, Brennan TA, Laird N, Lawthers AG, Localio AR, Barnes BA, et al. The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med 1991.) Other studies report that hospitalized patients have a 1.5 to 43.5 percent chance of having a drug-induced disorder. (Manasse HR Jr. Medication use in an imperfect world: drug misadventuring as an issue of public policy, Part 1. Am J Hosp Pharm 1989.)

Using the conservative figure, that 4 percent of hospitalized patients have an adverse event due to medical treatment, and extrapolating to the United States, each year over 1 million patients are injured while in the hospital, and approximately 180,000 die as a result of these injuries. (Bates DW, Cullen DJ, Laird N, Petersen LA, Small SD, Servi D, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. JAMA 1995.)

In the ambulatory care environment, the incidence of drug-induced disorders not causing hospitalization or death is less well known because different, less effective methods are used to collect data. Reported rates have ranged from 2.6 to 50.6 percent, depending on the source of the data. (Schneider JK, Mion LC, Frengley JD. Adverse drug reactions in an elderly outpatient population. Am J Hosp Pharm 1992.) The lower rates generally reflect data collected from physicians, and the higher rates come from patient surveys.

Drug-related morbidity and mortality are estimated to cost more than $136 billion a year in the United States. (Johnson JA, Bootman JL. Drug-related morbidity and mortality. A cost-of-illness model. Arch Intern Med 1995.) A recent study (Classen DC, Pestotnik SL, Evans RS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. JAMA 1997.) of hospitalized patients demonstrated that adverse drug events extended the hospital stay by nearly two days and increased the cost of hospitalization by about $2,000. Furthermore, patients experiencing an adverse drug event had an increased risk of death that was nearly two-fold greater.

The definition of a drug-induced disorder varies considerably, depending on the source used. Many clinicians rely on a combination of the definitions of the World Health Organization (WHO) and the American Society of Health-System Pharmacists (ASHP). (Requirements for adverse drug reaction reporting. Geneva: World Health Organization, 1975 - American Society of Hospital Pharmacy. ASHP guidelines on adverse drug reaction monitoring and reporting. Am J Health Syst Pharm 1995.)

This commonly used definition states that an adverse drug reaction (ADR) is an adverse drug event (ADE) or drug interaction that results in an undesirable or unexpected event that requires some change in the clinician's care of the patient; such as discontinuing a drug, modifying a dosage, prolonging hospitalization or administering supportive treatment. ADRs do not include drug withdrawal, drug-abuse syndromes, accidental poisonings or complications of drug overdose.

Although not all adverse drug reactions conform neatly to a simple classification system, drug-induced disorders have historically been classified as type A and type B reactions.10,11

Type A reactions are the normal pharmacologic effects of a drug that are exaggerated to the point of being undesirable. These reactions are usually dose-dependent and are fairly predictable. They may also be caused by drug-drug, drug-disease or drug-food interactions. Although their incidence and morbidity are high, these reactions are rarely life-threatening. Type A reactions are the most common type of drug-induced disorders. Clinicians should be aware that these reactions may occur at any time during drug therapy.

Type B reactions are effects of a drug that are unrelated to its known pharmacologic actions. These reactions may or may not be dose-related. They are unpredictable and include idiosyncratic, immunologic and allergic reactions, and carcinogenic and teratogenic events. The incidence of type B reactions is relatively low, but the mortality is high.

Adverse drug events that involve extension of the agent's pharmacologic activity are common. For example, a patient who develops pancytopenia following the administration of an antineoplastic agent and then develops bleeding, hypoxia and an opportunistic infection has experienced several adverse drug events while, hopefully, halting the growth of the cancer. Even though many chemotherapeutic agents predictably produce these events, the events are certainly undesirable and force the clinician to alter the care of the patient by discontinuing the chemotherapy, hospitalizing the patient, and administering blood products, antibiotics and oxygen, or administering alternative therapy.

Many other examples of adverse drug events that are extensions of the agent's pharmacologic action may be found. For example, pseudoparkinsonism and other extrapyramidal symptoms related to a relative dopamine deficiency are common adverse drug events occurring in patients taking antipsychotics such as haloperidol (Haldol), prochlorperazine (Compazine), fluphenazine (Prolixin, Permitil), and thiothixene (Navane). Other examples of adverse drug events are the proarrhythmic effects of all antiarrhythmic agents, including quinidine (Quinidex), procainamide (Pronestyl), lidocaine (Xylocaine) and amiodarone (Cordarone).

With nonsteroidal anti-inflammatory drugs (NSAIDs), the anti-inflammatory action occurs as a result of inhibition of production of prostaglandins. Because the formation of the prostaglandin responsible for protecting the gastric mucosa is also inhibited, an increased incidence of peptic ulcer disease is a common adverse drug event in patients taking NSAIDs.

Many adverse drug reactions are caused by drug interactions. An interaction between some nonsedating antihistamines (i.e., astemizole [Hismanal], terfenadine [Seldane]) and certain antimicrobials (i.e., erythromycin, clarithromycin [Biaxin], ketoconazole [Nizoral]) resulting in a potentially fatal cardiac arrhythmia is an example of a preventable adverse drug reaction. The ability of amiodarone to inhibit the metabolism of warfarin (Coumadin, Panwarfin), resulting in a significantly increased INR (international normalized ratio) and a higher risk of bleeding, is another preventable adverse drug reaction caused by a predictable drug interaction.

Some adverse drug reactions are idiosyncratic and unpredictable. Stevens-Johnson syndrome and toxic epidermal necrolysis are potentially fatal dermatologic reactions that may occur following the administration of a variety of drugs, including allopurinol (Zyloprim), sulfa-containing antibiotics, NSAIDs and phenytoin (Dilantin).

1 - Antibiotic agents  
2 - Chemotherapeutic agents 
3 - Anticoagulant agents
4 - Cardiovascular agents   5 - Anticonvulsant agents   
6 - Antidiabetic agents
7 - Antihypertensive agents   
8 - Analgesic agents    
9 - Antiasthma agents
10 - Sedative-hypnotic agents    
11 - Antidepressant agents    
12 - Antipsychotic agents
13 - Antiulcer agents       

Below lists the most common clinical manifestations of drug-induced disorders. Approximately 60 percent of drug-induced disorders present as bone marrow suppression, bleeding, central nervous system effects and dermatologic reactions. (Leape LL, Brennan TA, Laird N, Lawthers AG, Localio AR, Barnes BA, et al. The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med 1991.) Careful attention to and evaluation of these toxicities, along with a high degree of suspicion, may enable the clinician to detect drug-induced problems early, before significant morbidity and mortality occur.

 Listed from Most Frequest to Less Frequent

1 - Bone Marrow Supression    
2 - Bleeding    
3 - Central Nervous System Effects
4 - Allergic / Cutaneous Reactions    
5 - Metabolic Effects    
6 - Cardiac Effects
7 - Gastrointestinal Effects    
8 - Renal Effects    
9 - Respitory Effects