Drug Interactions: Insights and Observations Cholinergic–Anticholinergic Drug Interactions John R. Horn, PharmD, FCCP, and Philip Hansten, PharmD

data are available comparing the anti- while on cholinesterase inhibitor thera- Drs. Horn and Hansten are both professors cholinergic potency of commonly used py forAlzheimer’s disease. Other agents of pharmacy at the University of Washington drugs under standard dosing condi- used for overactive bladder (trospium School of Pharmacy. For an electronic ver- tions, but it seems reasonable to assume chloride [Sanctura], solifenacin succi- sion of this article, including references if any, visit www.hanstenandhorn.com. that combinations of these drugs will nate [Vesicare], and darifenacin produce additive anticholinergic effects [Enablex]) have anticholinergic activity and possibly adverse reactions. and are likely to interact with choliner- Recently we described some of the When drugs from opposing pharma- gic drugs in a similar manner. pitfalls associated with categorizing cologic classes are coprescribed, an The concurrent use of olanzapine potential drug interactions based upon antagonistic response may occur, reduc- (Zyprexa) in patients with Alzheimer’s the pharmacologic class of the drugs ing the pharmacodynamic response of disease was associated with a dose- involved (Pharmacy Times, June 2005). one or both drugs. The coadministration dependent increase in anticholinergic Several instances exist, however, where of anticholinergic agents with choliner- activity, compared with patients taking a drug’s pharmacologic class accurately gic drugs has been shown to inhibit the risperidone (Risperdal).5 As with anti- predicts potential pharmacodynamic efficacy of the cholinergic agents. depressants, the selection of drugs to interactions. For example, many com- treat psychosis in patients with puterized drug interaction screening Alzheimer’s disease should be made programs contain algorithms to detect Pharmacists need to be alert for after consideration of potential phar- duplicative therapy that are based on potential interactions between drugs macodynamic interactions. The avoid- pharmacologic activity. The entry of that have opposing pharmacologic ance of drugs with anticholinergic an order for >1 nonsteroidal anti- properties properties (eg, bladder antispasmodics, inflammatory drug or diuretic agent sedating antihistamines, tricyclic anti- may be flagged as duplicative prescrib- depressants) minimizes the risk of cog- ing. The risk of excess pharmacody- Patients with Alzheimer’s disease being nitive impairment or other central namic response and possible toxicity is treated with cholinesterase inhibitors nervous system side effects in patients the rationale for these warnings. (eg, tacrine [Cognex], donepezil with Alzheimer’s disease. Drugs with anticholinergic activity [Aricept], rivastigmine tartrate [Exelon], Pharmacists need to be alert for can produce significant adverse re- galantamine HBr [Razadyne]), plus potential interactions between drugs sponses when administered in combi- drugs with anticholinergic activity, had that have opposing pharmacologic nation. Drugs such as atropine and a greater decline in their mental status properties because these combinations scopolamine inhibit muscarinic acetyl- when tested after taking concurrent may not be identified by some com- choline receptors and can produce both anticholinergic drugs for 2 years.2 It puter screening systems. Since these peripheral (constipation, dry mouth, would seem obvious to avoid this com- interactions may result from attempts tachycardia, urinary retention, reduced bination. Two recent studies of patients to treat drug side effects, changing or sweating) and central (cognitive and taking cholinesterase inhibitors, howev- adjusting the dose of the drug respon- memory impairment, confusion, deliri- er, found that anticholinergic drugs were sible for the side effects should be con- um, headache, blurred vision, dizziness, coadministered in 33% to 35% of the sidered when selecting a management and drowsiness) effects. The concurrent patients.3,4 While anticholinergic drugs strategy. This approach may eliminate administration of drugs with anti- may have been added to treat cho- the need for the interacting agent. cholinergic activity can cause a wide linesterase inhibitor side effects, this When opposing drugs are prescribed array of symptoms, particularly in elder- combination will likely result in reduced for unrelated reasons, a reduction in ly patients who are especially suscepti- therapeutic efficacy of the chol- the efficacy of one or both agents is P ble, due to age-related decrements in inesterase inhibitor and perhaps the likely to result. T endogenous acetylcholine. Many drugs anticholinergic drug. Various cases For a list of references, send a are noted in their labeling to have anti- have been noted of patients developing stamped, self-addressed envelope to: References Department, Attn. A. Stahl, cholinergic properties, and a few have cognitive impairment when adminis- Pharmacy Times, 241 Forsgate Drive, been compared at fixed concentrations tered tolterodine tartrate (Detrol LA) or Jamesburg, NJ 08831; or send an e-mail using in vitro receptor assays.1 Limited oxybutynin chloride (Ditropan XL) request to: [email protected].

46 Pharmacy Times August 2005