The challenge of managing drug interactions in elderly people

Mallet, Louise; Spinewine, Anne; Huang, Allen

doi:10.1016/s0140-6736(07)61092-7

Cited by 464 publications

(327 citation statements)

References 56 publications

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“…A large proportion of drugs are metabolised or excreted by the kidney and thus CKD patients have an increased risk of druginduced encephalopathy. In addition to filtration and half-life considerations, 24 protein binding and drug interactions 25 may also be important factors in managing drug toxicity in CKD.…”

Section: Encephalopathy and Deliriummentioning

confidence: 99%

Neurological complications of chronic kidney disease

2009

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Patients with chronic kidney disease (CKD) are frequently afflicted with neurological complications. These complications can potentially affect both the central and peripheral nervous systems. Common neurological complications in CKD include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic neuropathies. These conditions have significant impact not only on patient morbidity but also on mortality risk through a variety of mechanisms. Understanding the pathophysiological mechanisms of these conditions can provide insights into effective management strategies for neurological complications. This review describes clinical management of neurological complications in CKD with reference to the contributing physiological and pathological derangements. Stroke, cognitive dysfunction and dementia share several pathological mechanisms that may contribute to vascular impairment and neurodegeneration. Cognitive dysfunction and dementia may be differentiated from encephalopathy which has similar contributing factors but presents in an acute and rapidly progressive manner and may be accompanied by tremor and asterixis. Recent evidence suggests that dietary potassium restriction may be a useful preventative measure for peripheral neuropathy. Management of painful neuropathic symptoms can be achieved by pharmacological means with careful dosing and side effect considerations for reduced renal function. Patients with autonomic neuropathy may respond to sildenafil for impotence. Neurological complications often become clinically apparent at end-stage disease, however early detection and management of these conditions in mild CKD may reduce their impact at later stages.

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Section: Encephalopathy and Deliriummentioning

confidence: 99%

Neurological complications of chronic kidney disease

2009

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“…Pharmacodynamic interactions can lead to amplification or reduction in the therapeutic effects or adverse effects of a specific drug. 28 A pharmacodynamic interaction may be due to irrational prescribing, such as initiation of TCA (with anticholinergic effect) in a patient with Alzheimer disease treated with an acetylcholinesterase inhibitor, which may lead to deterioration of the cognitive status. Even with rational polypharmacy, a combination of 2 drugs 30 Life-threatening opioid intoxication has been reported in association with codeine use in a UM.…”

Section: Adrs Associated With the Treatment Of Npmentioning

confidence: 99%

Treatment Considerations for Patients With Neuropathic Pain and Other Medical Comorbidities

Haanpää¹,

Gourlay

Kent

et al. 2010

Mayo Clinic Proceedings

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The efficacy of drugs for neuropathic pain has been established in randomized controlled trials that have excluded patients with comorbid conditions and those taking complex medications. However, patients with neuropathic pain frequently present with complex histories, making direct application of this evidence problematic. Treatment of neuropathic pain needs to be individualized according to the cause of the pain, concomitant diseases, medications, and other individual factors. Tricyclic antidepressants (TCAs), gabapentinoids, selective noradrenergic reuptake inhibitors, and topical lidocaine are the first-line choices; if needed, combination therapy may be used. When a new drug is added, screening for potential drug interactions is recommended. The TCAs have anticholinergic adverse effects and may cause orthostatic hypotension. They should be avoided or used cautiously in patients with cardiac conduction disturbances or arrhythmias. Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol. A combination of several serotoninergic drugs may lead to serotonin syndrome. Risk of gastrointestinal tract bleeding is increased in patients taking selective serotonin reuptake inhibitors or venlafaxine, especially when combined with nonsteroidal anti-inflammatory drugs. Dose adjustment may be needed in patients with renal or hepatic impairment. Depending on the drug, the dose is reduced or the dosage interval lengthened. Slow titration and careful follow-up are needed. No drug is absolutely safe during pregnancy and lactation. Particular care must be exercised during the first trimester when drug dose should be as low as possible. Individual weighing of benefits and risks should guide therapeutic decisions.Mayo Clin Proc. 2010;85(3)(suppl):S15-S25 ADR = adverse drug reaction; BP = blood pressure; CKD = chronic kidney disease; CYP = cytochrome P450; ECG = electrocardiogram; EM = extensive metabolizer; GFR = glomerular filtration rate; MI = myocardial infarction; NP = neuropathic pain; NSAID = nonsteroidal anti-inflammatory drug; OR = odds ratio; PM = poor metabolizer; RCT = randomized controlled trial; SNRI = selective noradrenergic reuptake inhibitor; TCA = tricyclic antidepressant; UM = ultrarapid metabolizer From Rehabilitation ORTON,

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“…Studies may be conducted in silico, in vitro or in vivo, the latter comprising formal pharmacokinetic interaction studies in animals and humans, or as reports of clinical observations.The assessment of these studies is seldom explicit, and there is lack of consistency and considerable disparity between resources [2][3][4][5][6]. For example, in a recent study of four international drug interaction compendia, between 14% and 44% of the interactions classified as major in any one compendium were not listed in other compendia [4].Thus, interpreting the clinical relevance of a given perpetrator is often difficult, particularly for healthcare providers subject to 'information overload' and 'alert fatigue' [7,8]. Computerized DDI checkers at the point of prescribing appear no better, delivering alerts that are frequently irrelevant to clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

Polasek

Lin

Miners

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Many drugs inhibit or induce cytochrome P450 enzymes (CYP) to cause clinically significant changes in the concentrations of other drugs, i.e.'perpetrate' pharmacokinetic drug-drug interactions (PK-DDIs).• Tables that list the substrates, inhibitors and inducers of CYP are common, but they lack consistency and are constructed from evidence of variable quality. WHAT THIS STUDY ADDS• This is the first study to catalogue important perpetrators of PK-DDIs using objective criteria and clinical pharmacokinetic drug interaction studies. This information is intended to inform clinical decisions on PK-DDIs.• Existing tables of CYP inhibitors and inducers have low sensitivity and low positive predictive value in identifying the major perpetrators of PK-DDIs. • Several drugs were identified which potentially perpetrate CYP-mediated PK-DDIs, but quality clinical pharmacokinetic interaction studies are lacking. This information may be used to inform future research. AIMSTo catalogue the perpetrators of CYP-mediated pharmacokinetic drug-drug interactions (PK-DDIs) using clinically relevant criteria, and to compare this with an analogous catalogue. METHODSCandidate inhibitors and inducers of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A ('perpetrators') were evaluated using published clinical pharmacokinetic interaction studies. Studies were selected on the basis of Նsix human subjects, use of a validated in vivo probe substrate for the CYP enzyme, and clinically relevant dosing. Inhibitors were described according to the FDA classifications of strong, moderate or weak, whereas inducers were classified as major (Նtwofold decrease in AUC) or weak (

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The challenge of managing drug interactions in elderly people

Cited by 464 publications

References 56 publications

Neurological complications of chronic kidney disease

Neurological complications of chronic kidney disease

Treatment Considerations for Patients With Neuropathic Pain and Other Medical Comorbidities

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

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