Abstract
Anticholinergics are the mainstay of pharmacotherapy for overactive bladder (OAB). The anticholinergics used to treat OAB differ in their pharmacological profiles, which may affect their propensity for causing commonly observed adverse effects. The purpose of this is review is to use published clinical data to evaluate the safety and tolerability of commonly prescribed anticholinergics for OAB, provide a context for safety and tolerability in terms of drug pharmacology, summarize the impact of adverse effects on adherence, and discuss the influence of study design on safety and tolerability outcomes. A MEDLINE search was conducted for the period 1990-2010 to identify studies evaluating mechanisms of action, pharmacological profiles, safety issues and adverse events pertaining to anticholinergics used in the treatment of OAB. Compared with immediate-release preparations, the extended-release, once daily and transdermal formulations are associated with lower rates of anticholinergic adverse effects, due to improved consistency in serum levels. The most significant adverse effects in terms of affecting the use of anticholinergics agents are CNS and cardiac disturbances. CNS issues are associated with pharmacological properties such as serum concentration, blood-brain barrier permeability and active transport, and receptor binding affinity. Cardiac safety (corrected QT interval) is more dependent on specific molecular attributes. However, more common but less bothersome adverse effects associated with systemic blockade of the muscarinic receptors include dry mouth, constipation, headache and blurred vision. A high potential for interaction between anticholinergics and drugs that compete with the same pathways for hepatic metabolism via cytochrome P450 and renal excretion increases the risk of adverse effects for both antimuscarinic and associated medications, especially in the elderly, who are more likely to be taking multiple drugs. This literature review demonstrates that all OAB anticholinergics are effective in reducing symptoms of OAB; however, important pharmacodynamic/pharmacokinetic differences between these agents may influence their efficacy and incidence of associated adverse effects. Because OAB is a chronic disease requiring long-term therapy, careful assessment of the pharmacological differences is needed in order to tailor therapy to the individual patient's clinical needs, and thereby maximize the chance of treatment success and long-term adherence to therapy. Since anticholinergic adverse effects are known to affect treatment adherence and persistence, the potential for adverse effects should be considered when selecting treatment for an individual patient.
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