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Drug–Disease Interactions

A drug–disease interaction occurs when an administered drug exacerbates an underlying disease in a patient. Drug–disease interactions are one type of inappropriate prescribing. However, drug–disease interactions can be a potential result of both inappropriate and appropriate medication use. Table 1 provides an abbreviated list of potential drug–disease interactions.

Table 1 Examples of Potential Drug–Disease Interactions
Congestive heart failure (systolic dysfunction)
  • First-generation calcium channel blockers Type 1A antiarrhythmics
Chronic obstructive pulmonary disease
  • Noncardioselective β-blockers Sedative hypnotics
Arrhythmias
  • Tricyclic antidepressants
Chronic renal failure
  • Non-aspirin, nonsteroidal anti-inflammatory drugs
Parkinson's disease
  • Acetylcholinesterase inhibitors
  • Antipsychotics (except clozapine and quetiapine)
  • Metoclopramide
Diabetes
  • Atypical antipsychotics
  • β-Blockers
  • Corticosteroids
  • Thiazide diuretics
Depression
  • α-Blockers
  • Barbiturates
  • Corticosteroids
  • Digoxin
  • Lipophilic β-blocker benzodiazepines
  • Water-soluble β-blockers
Benign prostatic hyperplasia
  • Anticholinergics
  • Bethanechol
  • Opioid analgesics
  • Pseudoephedrine
  • Skeletal muscle relaxants
  • Tricyclic antidepressants
Hypertension
  • Central nervous system stimulants
  • Non-aspirin, nonsteroidal anti-inflammatory drugs
  • Pseudoephedrine
Falls
  • Conventional antipsychotic benzodiazepines
  • Sedative hypnotics
  • Selective serotonin reuptake inhibitors
  • Tricyclic antidepressants
Constipation
  • Anticholinergics
  • Calcium channel blockers
  • Iron supplements
  • Opioid analgesics
  • Tricyclic antidepressants
Heart block
  • Digoxin
  • Tricyclic antidepressants
Peptic ulcer disease
  • Aspirin
  • Corticosteroids
  • Non-aspirin, nonsteroidal anti-inflammatory drugs
  • Potassium supplements
Peripheral vascular disease/Raynaud's
  • β-Blockers
Urge incontinence
  • Acetylcholinesterase inhibitors
  • β-Blockers
  • Bethanechol
  • Diuretics
  • Lithium
  • Selective serotonin reuptake inhibitors
Stress incontinence
  • α-Blockers
  • Anticholinergics
  • Conventional antipsychotics
  • Long t½ benzodiazepines
  • Tricyclic antidepressants
Source: Lindblad CI, Hanlon JT, Gross CR, et al. Clinically serious drug–disease interactions in the elderly: Opinion of a consensus panel. Unpublished poster, 2005.

Epidemiology

The elderly are well known to be a small section of the population, yet they consume at least one third of prescription medications in the United States. The elderly also often have multiple comorbidities that lead to their increased drug use. An increase in the number of medications increases the risk of a drug–disease interaction in the elderly. Furthermore, as people age, physiological changes in their bodies decrease their ability to compensate for drug-related injury. The combination of increased medications and decreased homeostatic reserve is magnified in those patients considered to be frail or at increased risk (e.g., low body weight, age 85 years and older, decreased renal function, use of narrow therapeutic range drugs, history of prior adverse drug reaction).

Research on drug–disease interactions is just beginning to commence. Multiple studies have documented that approximately 6% to 30% of elderly patients have evidence of one or more drug–disease interactions. The prevalence of drug–disease interactions has been difficult to measure because we do not have a single source of information about drugs that may exacerbate diseases. The most commonly used list of inappropriate medications is Beer's criteria. Beer's criteria contain only a subset of all possible drug–disease interactions. A thorough review of the literature recently identified more than 60 possible drug–disease interactions. Furthermore, little overlap exists between studies examining drug–disease interactions, and guidelines differ on severity and prevalence. Despite the relatively high prevalence of drug–disease interactions, there is a paucity of information on their association with health outcomes. Inappropriate prescribing, which includes drug–disease interactions, may increase hospitalizations and mortality. Risk factors for drug–disease interactions include, but are not limited to, advanced age, being married, multiple medication use, and comorbidities. Finally, poorer health has been associated with increased use of inappropriate medications that may include medications with the potential to cause a drug–disease interaction.

Interventions

Pharmacists can play a major role in identifying potential drug–disease interactions in the elderly. Our lack of a single source to identify common drug–disease interactions (only drug–drug interactions) underscores the need to examine each patient closely and determine any risks associated with his or her medications. Also, the importance of asking about which nonprescription medications are used cannot be overstressed. One third of all medications used by the ambulatory elderly are sold without prescriptions. Health care professionals should also inquire about the use of dietary supplements, including vitamins and herbal agents. Furthermore, the appropriateness of each prescribed medication should be assessed using a variety of methods. If the patient's medical history and medication list are not screened, a drug–disease interaction may be more likely to occur. Interventions could be targeted for community-dwelling elderly because they often do not have the benefits of regular medication reviews, as do patients in nursing home or hospital settings.

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