Health and Prostate

Benign prostatic hyperplasia (BPH) is highly prevalent among middle aged and elderly males. Although BPH is rarely life-threatening, it is associated with bothersome lower urinary tract symptoms (LUTS) that affect quality of life by interfering with normal daily activities and predispose to erectile dysfunction (ED). The prevalence of these genitourinary disorders is age dependent, with initial development beginning around age 40. Thereafter, approximately 50% of males 60 years old and 90% of males older than 85 will suffer from BPH. Unfortunately, 50% of males with benign prostatic hyperplasia will suffer from moderate to severe LUTS. Recent studies show that LUTS may affect erectile and ejaculatory function and diminish the ability to have pleasurable intercourse. Recent studies found that lower urinary tract symptoms interferes with sexual pleasure in about 90% of patients and LUTS produces sexual dysfunction in 50% of males.

Because sexuality is one of the most important aspects of quality of life in males, the widespread prevalence of BPH and LUTS makes these conditions the targets of pharmacotherapy. The vasoactive drugs used to treat BPH, LUTS, and ED raise the specter of clinically significant adverse drug­drug interactions. This article examines the mechanisms and prevalence of clinically relevant drug interactions in patients treated for these genitourinary conditions.

Introduction

Lower urinary tract symptoms is a descriptive term rather than a pathological term because LUTS may involve BPH, benign prostatic obstruction, or a combination of these conditions. Patients with LUTS often seek medical help for complaints of urinary frequency, hesitancy, weakening stream, urgency, or nocturia. The etiology of lower urinary tract symptoms varies with the individual; in some, LUTS may result from an enlarged prostate exerting pressure on the urethra and obstructing urinary outflow. In others, LUTS may result from increased contraction of prostatic smooth muscle and from bladder dysfunction. Urinary flow rates and prostate size do not correlate with the frequency or severity of lower urinary tract symptoms.

Although LUTS may wax and wane, severity of symptoms increases over time as the prostate enlarges with aging. Studies indicate that lower urinary tract symptoms influences sexual pleasure in approximately 90% of patients, and LUTS produces sexual dysfunction in 50% of males. Sexuality is significant to the quality of life in males; therefore, prevailing benign prostatic hyperplasia and LUTS are targets for medical attention and drug therapy. The use of vasoactive drugs indicated for BPH, LUTS, and ED elevates the clinically significant adverse drug­drug interactions, especially in patients with coexisting hypertension or heart disease. Today, the lifetime risk of patients ages 55 to 65 years to receive antihypertensive drugs approaches 60%. Yet, recent trials suggest that hypertension is not adequately controlled in the majority of patients. The prevalence of hypertension increases with advancing age, as does the prevalence of comorbid conditions and total number of medications taken. Multidrug therapy, advancing age, and comorbid conditions are also key risk factors for adverse drug reactions and drug interactions. As the spectrum of drugs prescribed is constantly changing, safety in the past does not imply safety today, and safety today does not imply safety tomorrow.

By virtue of the mechanisms of action of the medications used to treat benign prostatic hyperplasia, lower urinary tract symptoms, and erectile dysfunction, along with the prevalence of heart and hypertension conditions in these males, drug interactions are of paramount concern in these patients. However, therapeutic efficacy should not be neglected over concerns regarding drug interactions. Many patients are at risk of clinically relevant drug intera ctions involving antihypertensive drugs but, presently, even more patients may be at risk of suffering from the consequences of their inadequately treated hypertension. Therefore, informed decision-making by clinicians regarding the risk-to-benefit ratio of potential drug­drug interactions could enhance the quality of life of patients with bothersome, yet non­life-threatening, genitourinary tract problems. This article examines the mechanisms and potential clinical relevance of drug interactions with medications used commonly to treat BPH, LUTS, and ED, i.e., selective alpha-1-adrenergic receptor blockers, 5-alpha-reductase inhibitors, and selective inhibitors of cyclic guanosine monophosphate (cyclic GMP)-specific phosphodiesterase 5 (PDE-5) enzymes.

Drug interactions are a major factor in the etiology of common and potentially fatal adverse drug reactions. Frequent use of complex drug regimens increases the likelihood of multiple drug interactions in the same individual. Furthermore, the significance of an interaction depends on the effect of a given drug in a specific patient. Drug interactions that cause noticeable side effects (e.g., hypotension with subsequent syncope or myocardial ischemia [MI]) are readily detectable and potentially life-threatening. Other interactions that might alter the bioavailability or the pharmacokinetics may be more subtle or insidious (e.g., effect of food on oral bioavailability). Because drug interactions should be viewed as preventable side effects, clinicians must be proactive and vigilant. This requires a thorough understanding of the potential interactions and their mechanism of interaction. However, before we proceed with a detailed discussion of clinically relevant, potential drug­drug interactions, it is important to review the mechanisms of action and pharmacokinetic profiles of the drugs commonly used to treat benign prostatic hyperplasia, lower urinary tract symptoms, and erectile dysfunction to better appreciate the potential for clinically relevant drug interactions.