Cardiovascular-targeted pharmacotherapy continues to rapidly evolve as newer agents are sought to fill in gaps in care or to lower adverse reactions of existing therapies. With newer agents, benefits are accompanied with new potential reactions, which can have adverse consequences on patients. This chapter covers important aspects of adverse drug reactions and reviews pharmacokinetics and pharmacodynamics of commonly used drugs with an emphasis on mechanisms. Finally, specific syndromes or cardiac disease states are presented, with focused discussion on newer pharmacologic agents than can present challenges to the clinicians faced with the plethora of choices.
Adverse drug reactions (ADRs) are the fourth leading cause of death in patients hospitalized in the United States.1-3 ADRs are responsible for approximately 1 of every 16 hospital admissions and occur in as many as 20% of hospitalized patients.1,4 The cost of these events in financial terms is staggering; estimates of the financial burden of ADRs in the United States range from $30 billion to more than $130 billion annually.2,3
The World Health Organization defines an ADR as "a response to a drug that is noxious and unintended and occurs at doses normally used in man for the prophylaxis, diagnosis and therapy of disease, or for modification of physiological function."5 ADRs are commonly classified as either type A (augmented) or type B (bizarre) reactions.6 Type A reactions are predictable based on the pharmacologic characteristics of the agent(s) (ie, drug). In contrast, type B reactions are idiosyncratic and unpredictable. This simple classification system remains in use throughout the literature.7 Most of the ADRs discussed in this chapter are type A reactions because they are fairly common, predictable, and often preventable. In this regard, it is absolutely critical that clinical providers including both prescribers and dispensers of drugs remain vigilant of the potential for dangerous, even lethal, ADRs in their treated patient populations, particularly if the patients have cardiovascular disease.
Patients with heart disease represent a population who are at particularly high risk for ADRs. Certain cardiovascular disease states such as heart failure can influence drug metabolism and elimination by altering end-organ perfusion.8 Patients with heart disease are often elderly. Advanced age is associated with higher ADR risk due to age-related alterations in renal and hepatic function, the presence of multiple medical comorbidities, and a high prevalence of polypharmacy.9 Dementia may influence medication compliance, and confusion regarding the indications and doses of prescription drugs is common among older patients, particularly when they receive care from multiple providers.10-12 ADR risk has been shown to increase exponentially with the number of medications prescribed and correlates closely with the total number of drugs taken by an individual patient.13 For example, a patient taking seven medications has the potential for 6 + 5 + 4 + 3 + 2 + 1 = 21 possible drug-drug interactions. The average nursing home patient takes seven medications, and most of these ...