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Digoxin dosing in obesity articles: Antiarrhythmic and DOAC Dosing in Obesity

Because availability of reliable coagulation assays is limited, testing of DOAC levels in the real-world setting remains to be widely implemented.

Matthew Cox
Saturday, April 10, 2021
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  • The hypotension and bradycardia noted in patients receiving single, large i.

  • Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Share via:.

  • Given the relatively narrow therapeutic index for theophylline and the potential for serious dose-related toxicity e.

  • The onset of action occurs 30 minutes to 2 hours after oral ingestion and 15 to 30 minutes after intravenous administration [ 20 ].

  • J Clin Pharm Ther ;

All not clear

This article is intended to help the clinician arrive at dosing regimens based on extrapolations from the information that is available. Anticoagulants Heparin Weight-based nomograms have been developed for regular heparin [ 14 ], but the appropriateness of such nomograms for dosing the morbidly obese patient is unknown. One of these reports listed medications that had been prescribed to patients who suffered adverse drug events in medical or surgical ICUs during a 6-month monitoring period 2 tertiary care hospitals with 11 ICUs [ 2 ]. The V area before and after was unchanged 0. Critical revision of the manuscript for important intellectual content : Bauman, DiDomenico, Viana, and Fitch.

In addition to the pharmacokinetic studies of cephalosporins in morbidly obese patients, there are studies looking at clinical end points, particularly infectious complications associated with different dosing regimens for surgical prophylaxis. Thromb Res — Citations By continuing to use our site, you are agreeing to the use of cookies as set in our privacy policy. Subsequently, the digoxin concentration should be monitored and the dose of digoxin adjusted to ensure that the chronic steady state dose results in trough concentrations of 0. If DOAC therapy is desired in these morbidly obese patients, peak and trough drug-specific levels should be drawn in accordance with ISTH guidelines until further evidence is available to support use. Elucidating the underlying mechanisms for the differential response to sodium channel blocker antiarrhythmic drugs in obese patients with atrial fibrillation.

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Dosing of medications commonly used in the intensive care unit Analgesics Opioids While there are no pharmacokinetic studies involving an opioid analgesic agent that limited enrollment to morbidly obese patients, there are studies that odsing looked at other end points e. The impact of body weight on rivaroxaban pharmacokinetics. There are case reports of obese patients requiring very large doses of heparin e. The lower limit of detection for this assay is 0. Susceptibility testing i. Since there are no studies of the LMWHs in morbidly obese patients, information concerning dosing in this population must be extrapolated from studies in which the LMWHs were given to patients with a range of weights [ 16 ].

The laboratory records of hospitalized adult patients who had a digooxin concentration determined over a 6-month period were used to screen for suitable patients. The impact of body weight on rivaroxaban pharmacokinetics. Although the Jelliffe method was originally designed to result in a concentration of about 1. One additional point in this regard could be made.

Privacy Policy. Spironolactone does not interfere with the obesuty of digoxin concentration by this method; patients receiving concurrent therapy with this agent were therefore not digoxin dosing in obesity articles from the analysis. Table 1. Our results and the need to perhaps be more precise in tailoring chronic dosing regimens to obtain therapeutic concentrations should prompt the availability of new strengths, such as 0. Eur J Clin Pharmacol — Based on this information, it was concluded that the 2 g dose of i.

Same food—but metabolism was speeded up

Wilson SJ, Wilbur K, Burton E, Anderson DR Effect of patient weight on the anticoagulant response to adjusted therapeutic dosage of low-molecular-weight heparin for the treatment of argicles thromboembolism. In addition, the variance of the expected digoxin concentration as a function of the dose of digoxin, the creatinine clearance, and the IBW was estimated from the present data. In the 0. Djouder credited this to the fact that cardiovascular disease of patients using digoxin causes high liquid retention, which masks the weight-loss effect of digoxin.

Kirchhof P. Since digoxin dosing in obesity articles are no studies of the LMWHs in morbidly obese patients, information concerning dosing in this population must vosing extrapolated from studies in which the LMWHs were given to patients with a range of weights [ 16 ]. Second, the articles focused on medications prone to causing adverse effects or requiring interventions by pharmacists. These data suggest a disproportionate distribution into the excess body weight.

There are two studies involving the administration of cephalosporins in morbid obesity, one in otherwise healthy subjects and one in patients undergoing gastric bypass surgery [ 30boesity ]. There is some data that demonstrates that the type of prophylactic dosing regimen may further influence postoperative infection rates in patients with morbid obesity. This finding is similar to Koup and Jusko's original observations in which their method performed better than a method similar to Jelliffe's, which gives us a degree of confidence in our data set despite the retrospective nature of the data collection. Additional searches for the same period were then performed using the search headings morbid obesity combined with drugand morbid obesity limited by clinical trial.

Definitions

Usual loading and maintenance dose regimens should be instituted in morbidly obese patients receiving digoxin, procainamide and propranolol and probably other beta-blocking agents using IBW for weight-based regimens. Drafting of the manuscript : Bauman, DiDomenico, and Viana. Patient selection.

While the published studies have somewhat disparate pharmacokinetic results, propranolol does not appear to have substantial distribution into adipose dlgoxin. Third, the documentation periods were over a prolonged period of time i. One of these reports listed medications that had been prescribed to patients who suffered adverse drug events in medical or surgical ICUs during a 6-month monitoring period 2 tertiary care hospitals with 11 ICUs [ 2 ]. Kido K, Ngorsuraches S. The emphasis was on studies involving morbidly obese patients but, in the absence of such data, investigations involving lesser forms of obesity were extracted. An update.

Visualization of adipocytes from an obese mouse left and from a lean obesity articles treated with digoxin rightshowing a better response to nutrient excess and burning of fat. JAMA — There are very few studies relative to medication dosing in morbidly obese patients and no studies specific to the ICU setting. For those medications for which therapeutic drug monitoring is possible, this can be a valuable adjunct to other clinical markers of appropriate dosing. There is clearly a need for more investigations involving dosing regimens of medications in the morbidly obese population.

1. Introduction

A final search was performed using the heading obesity combined with each of the medications chosen for discussion in this paper. You can also search for this author in PubMed Google Scholar. References 1.

While there is no reason to suspect that once daily dosing regimens using obesity articles adjusted body weight would not work in morbidly obese patients, there are reasons to be concerned until studies in this population have been performed. The medical records of these patients were then reviewed for the following entry criteria: patients had to be older than 18 years with a presumed steady state digoxin concentration ie, a concentration determined in the postdistributive state [at least 6 hours after oral digoxin administration] when receiving a stable dose of digoxin for a suitable time period to reach steady state. Digoxin plasma concentrations were measured by a turbidimetric inhibition immunoassay method using digoxin-specific antibodies Synchron LX; Beckman Coulter, Fullerton, Calif. Furthermore, total healthcare costs were significantly lower in the rivaroxaban group. The V ss corrected for TBW remained higher in obese subjects 0. There is no statistical distinction between the method proposed here and the Koup and Jusko method based on these confidence intervals.

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Background The therapeutic range for digoxin in heart failure has recently changed dosihg become lower and narrower, and the new obesity is associated with improved mortality. The V ss corrected for TBW remained higher in obese subjects 0. The bibliographies of retrieved publications and textbooks were reviewed for additional references. The peripheral volume of distribution V peripheral and inter-departmental clearance normalized to TBW were smaller in the obese compared to the normal weight patients For example, the incidence of wound infections with or without prophylaxis was evaluated in a double-blind randomized investigation involving 53 patients undergoing gastric bypass surgery [ 32 ]. Original Investigation.

  • In patients with multiple digoxin concentrations, only a single digoxin level that best represented steady state conditions ie, the last trough concentration determined during hospitalization was used in the analysis.

  • As obesity levels rise, pharmacists are finding they need new tools to ensure they adequately tailor the amount of medicine patients receive.

  • Figure 1. Based on this study, a conservative approach is to administer procainamide loading and maintenance doses based on IBW in moderately obese patients.

  • Ciprofloxacin mg i. The effect of digoxin on mortality and morbidity in patients with heart failure.

  • MacLeod-Glover N.

Source: CNIO. With rising levels of obesity, pharmacists find themselves in a quandary. Apr 27, Health. Digoxin artciles mortality in patients with atrial fibrillation. While patients receiving conventional multiple daily dose schedules presumably received the same product, the problem was not noted until the large, once daily doses had been given.

Compared to the historical wound infection rate of Digoxin dosing in obesity articles pharmacokinetics of diazepam have doaing studied in 17 obese mean Amjad W. However, the shorter half-lives found in the morbidly obese compared to normal patients 3. Yet for many approved drugs, no specific guidance for treating those with obesity appears on the label.

The ‘first causal link between obesity and inflammation’

Wang Z. In pharmacokinetic studies, the clearance of medications is determined since this parameter is often useful in estimating maintenance dose requirements. Given the lack of literature available concerning dosing in patients heavier than kg and, for this article, morbidly obese patientsa variety of regimens are being used.

There is no statistical digoxin dosing in obesity articles between the method proposed here and the Koup and Jusko method based on these confidence intervals. Current guidelines recommend DOACs over warfarin in articlew patients with NVAF due to similar, if not superior, efficacy in prevention of stroke and thromboembolism combined with lower risks of serious bleeding. While patients receiving conventional multiple daily dose schedules presumably received the same product, the problem was not noted until the large, once daily doses had been given. With the availability of antimicrobials that have similar or improved effectiveness relative to the aminoglycosides, it is often possible to avoid the potential ototoxicity and nephrotoxicity concerns associated with the aminoglycosides.

J Clin Psychopharmacol ;38 3 obexity Google Scholar. Since lidocaine clearance is primarily a function of hepatic blood flow i. However, given the lack of studies in morbidly obese patients as well as concerns associated with large i. Keywords: Digoxin, serum level, toxicity, mortality, heart failure, chronic atrial fibrillation. There were no significant differences between the obese and normal patients for V ss and clearance based on IBW 0.

Expert Analysis

If a continuous infusion of a medication is administered until steady sosing concentrations are reached, the total apparent volume of distribution is V ss. The clearance was decreased in the obese patients, suggesting that extended dosing intervals might be possible Although there is no supportive data, a similar approach would seem reasonable when using i. While both V and clearance were significantly reduced in another trial of morbidly obese patients receiving propranolol Table S1 [ 44 ], the overall conclusions from both studies are similar; initial propranolol dosing should be based on IBW with subsequent titration according to clinical effects.

  • This article should also serve as a reminder of the importance of stating which weight was used for dosing in published studies and why that weight was chosen assuming a weight-based approach to therapy was used.

  • The fact that no side effects were observed in animals suggests that, in humans, the dose at which weight loss could be observed may not be harmful. Introduction Digoxin has been used for more than years in the treatment of patients with Heart Failure HF [ 1 ].

  • In addition, the variance of the expected digoxin concentration as a function of the dose of digoxin, the creatinine clearance, and the IBW was estimated from the present data. There is clearly a need for more investigations involving dosing regimens of medications in the morbidly obese population.

  • Points clustering tightly around that line correspond to a smaller RMS. Download PDF.

In patients with multiple digoxin concentrations, only a single digoxin level that best represented steady state conditions ie, the last trough concentration determined during hospitalization was obeeity in the analysis. The idgoxin indicate that DOACs provide consistent efficacy and safety compared with warfarin across all categories of BMI, but weight categories vary among trials, with small representations of the morbidly obese population. The other option would be to use an adjusted weight in conjunction with once daily dosing regimens, but arbitrarily limit the total daily dose e. Recommendations Given the limited data concerning heparin dosing in morbidly obese ICU patients, the ready accessibility of the appropriate laboratory test e. The researchers suggest that their study offers up a possible therapeutic strategy based on a novel approach: fighting obesity by targeting its inflammatory component. The benefits of prophylaxis with anti-infective agents in morbidly obese patients have been known for some time. While the opioids are considered to be lipophilic compounds, there are differences in their pharmacokinetics and clinical effects that preclude dosing based solely on predicted distribution into adipose tissue [ 11 ].

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An update. Presuming the patient needs a continuous i. Usual loading and maintenance dose regimens should be instituted obesity articles morbidly obese patients receiving digoxin, procainamide and propranolol and probably other beta-blocking agents using IBW for weight-based regimens. Haemostasis — There is one study involving propofol in obese patients, the majority of whom appeared to be morbidly obese based on the information presented in the article Table S1 [ 58 ]. Purchase access Subscribe to JN Learning for one year. Maintenance doses should be started with conventional daily doses, or IBW if using weight-based regimens, with subsequent titration based on therapeutic drug monitoring and clinical effectiveness.

  • Obviously, a more evidence-based approach would be preferred, if the evidence becomes available. Alternatively, recent guidelines 2 suggest the digoxin concentration should be less than 1.

  • McCauley et al. The V ss was higher in the obese subjects

  • Elucidating the underlying mechanisms for the differential response to sodium channel blocker antiarrhythmic drugs in obese patients with atrial fibrillation. Similar to lidocaine, there are no pharmacokinetic studies of procainamide in morbidly obese patients but there is information on subjects with moderate obesity mean

  • For prophylaxis, whether using conventional heparin or LMWHs, the regimen should err on the higher end of the suggested range when a range of doses are provided.

The need for caution is exemplified by the finding of apparent pyrogen-mediated toxicity in patients receiving once daily aminoglycoside dosing with one particular product [ 28 ]. Proarrhythmia and sudden cardiac death are significant risks associated with use of select AADs and, in most cases, dose dependent. Jelliffe RW An improved method of digoxin therapy. Slowing the rate of infusion may also attenuate this problem. The sum of V c and all V p yields V ss.

Antimicrob Agents Chemother — These are the types of questions that arise with respect to medication dosing in the ICU setting. Procainamide Similar to lidocaine, there digoxin dosing in obesity articles no pharmacokinetic studies of procainamide in morbidly obese patients but there is information on subjects with moderate obesity mean Devine BJ Case number gentamicin therapy. Comparison with other methods. Due to minimal representation of morbidly obese patients in the pivotal DOAC trials, as well as limited pharmacokinetic and pharmacodynamic data in this population, several retrospective studies have been conducted to determine whether DOACs are a safe and effective alternative compared with warfarin in this population.

Publications

JAMA Intern. Access provided by. Presuming this is the case, each dose becomes, in essence, a loading dose, unless prolonged administration and accumulation occur.

  • The purpose of this article is to review the literature with respect to medication dosing in morbidly obese patients in the ICU setting.

  • In the last two decades, several studies have correlated therapeutic use of digoxin with increased mortality. Growth hormone prescribing and initial BMI SDS: Increased biochemical adverse effects and costs in obese children without additional gain in height.

  • Based on the lack of pharmacokinetic differences based on IBW and the similar blood concentrations associated with percent neuromuscular blockade, it was recommended that dosing of vecuronium be based on IBW. In cases in which a medication distributes more slowly into peripheral body fluids or tissues e.

  • Citations Some institutions such as ours are electing to cap the dose at the kg weight for patients weighing more than this amount due to many of the same concerns as noted for the LMWHs.

Source: Courtesy of Trevor Johnson Trevor Johnson is a principal scientist and former pharmacist who now works at Certara UK Limited, which develops technology for understanding obesity articles diigoxin in different populations, including obese people. Google Scholar. Kido and Ngorsuraches also showed no difference in ischemic stroke or major bleeding in DOACs compared with warfarin in morbidly obese patients with AF. J Thromb Haemost ; For example, a recent analysis of AF patients, including individuals with and without HF, found no association between digoxin treatment and mortality, even after adjustment for confounding factors with different models and propensity scores [ 29 ].

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These studies with diazepam and midazolam suggest that maintenance doses should be based on IBW. Electronic Supplementary Material. Immunomodulators Corticosteroids Corticosteroids are frequently used in the ICU setting and many of the dosing regimens are weight-based, despite the lack of studies in morbidly obese patients. On the other hand, the most up-to-date meta-analysis on the subject grouped approximately 40 studies and more thanpatients. Scalese M. Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Media Center ACC.

Similarly, if a non-weight-based method of loading were used, it would be expected that morbidly obese patients would be more likely to require repeated doses to maintain therapeutic effectiveness. There is one study involving propofol in obese patients, the majority of dosibg appeared to be morbidly obese based on the information presented in the article Table S1 [ 58 ]. Acquisition of data : Bauman and Fitch. As displayed in the nomogram, digoxin dose increases linearly with increasing creatinine clearance and increasing IBW or increasing height. They further noted that in addition to the potential clinical relevance of their findings, the study has added value in that it identifies a causal link between inflammation and weight gain. Create an account. However, they noted the potential hemodynamic concerns related to single, large i.

Although limited by retrospective healthcare claims data, which innately pose risk for inaccuracies, this study included a large population and supported the use of rivaroxaban in morbidly obese patients with AF. J Psychosom Res — Ahmed A.

N Engl J Med ; Since supplemental doses could always be given if needed, it seems reasonable to use a similar approach in morbidly obese patients in conjunction with therapeutic drug monitoring. PLoS One. For example, in one study involving surgical patients in an ICU setting, a mean dobutamine infusion rate of 8. Eur J Clin Pharmacol — Similarly, clearance was not significantly different between the two groups Until more research has been conducted in morbidly obese patients in the ICU setting, anti-Xa monitoring should be available when the decision is made to use treatment doses of LMWHs.

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Digitalis toxicity: Mechanisms, diagnosis, and dlgoxin. However, given the lack of digoxin dosing in obesity articles in morbidly obese patients as well as concerns associated with large i. More importantly, once a weight has been chosen for dosing a medication, the same weight should be used to maintain consistency in subsequent dosing adjustments. With regards to maintenance doses, for the majority of medications discussed in this article, IBW should be used when weight-based dosing is desirable. Since there are no studies of the LMWHs in morbidly obese patients, information concerning dosing in this population must be extrapolated from studies in which the LMWHs were given to patients with a range of weights [ 16 ]. Similar variability is seen in pharmacokinetic investigations involving dobutamine.

The level with the 2 dugoxin dose in the extremely obese patients was Aust Prescr ; Relevant articles were identified through a computerized literature review using MEDLINE for the years to January with the search heading obesity combined with drug and subsequently limited by clinical trial. Am J Cardiol ;

BMC Res. J Clin Pharmacol — Renard D. Hallberg P. Introduction Digoxin has been used for more than years in the treatment of patients with Heart Failure HF [ 1 ].

Reprints and Permissions. Digoxin dosing in obesity articles J Clin Pharmacol Ther — The term V c represents the articlew of the compartment into which the medication rapidly distributes. In other words, a series of smaller i. Evaluation of initial dofetilide dosing recommendation based on actual body weight in overweight and obese patients. There is a case report in which the clinicians used this dosing recommendation in a kg patient mg i. Drug Saf.

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Initial maintenance infusions should also be based on IBW with subsequent titration by clinical effect and peripheral nerve stimulation. For example, the incidence of wound infections with or without prophylaxis was evaluated in a double-blind randomized investigation involving 53 patients digoxin dosing in obesity articles gastric bypass surgery [ 32 ]. Patients were excluded from the analysis for the following reasons: 1 the presence of significant drug-drug interactions eg, amiodarone, quinidine, verapamil, or macrolide antibiotics2 documentation in the patient's record of a history of poor medication adherence, or 3 the presence of end-stage renal dysfunction requiring dialysis or of unstable renal function ie, acute renal failure. Recommendations The weight for the initial infusion rate should be based on the indication and urgency of the particular situation, with subsequent adjustments based on clinical response. Recommendations The substantial inter-individual analgesic requirements noted in normal and moderately obese patients precludes the use of a single calculation for estimating dosing requirements. While the most appropriate initial loading dose and infusion rate for the morbidly obese patient has not been established, dose adjustments of regular heparin can be made relatively quickly using common assay techniques e. Infect Control Hosp Epidemiol —

  • Creation of a dosing nomogram.

  • Clinical trials of experimental drugs largely exclude obese people, opting for subjects who weigh closer to an outdated standard of 70kg. When analyzing data from studies with new users of digoxin i.

  • The jointly estimated articles based on 51 complete joint observations between dose and clearance, dose and IBW, and clearance and IBW were, respectively, 5. If the medication is used in such patients, should TBW be used for determining the appropriate dose since TBW was used in all other patients in the original study?

  • This review will focus on the intravenous i.

Furthermore, many medications used in the ICU do not have dosage forms other than those intended for i. Vancomycin There are two studies of vancomycin in morbidly obese patients Table S1 [ 3637 ]. Details of the obesity articles of such fluid changes on the pharmacokinetics of medications have not been well studied, particularly in morbidly obese patients. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Furthermore, all of the studies in morbidly obese patients were conducted prior to the clinical use of large e. Furthermore, there were only a small number of studies investigating the pharmacokinetics of medications in otherwise healthy, morbidly obese patients summarized in Table S1although additional information can be gleaned from pharmacokinetic studies of less obese patients discussed in text. Thrombolytics Given the widespread use of thrombolytics and the weight-based dosing employed in many of the clinical trials, the lack of studies in patients with moderate to severe obesity is somewhat surprising.

N Engl J Med ; Anticoagulants Heparin Weight-based nomograms have been developed for regular heparin [ 14 ], but the appropriateness of such nomograms for dosing the morbidly obese patient is unknown. Jerry L. The widespread availability of APTT measurements and the i. Devine BJ Gentamicin therapy.

Publication types

There are two studies involving the administration of cephalosporins in morbid obesity, one in otherwise healthy subjects and one in patients undergoing gastric bypass surgery [ 3031 ]. A digoxin dosing in obesity articles approach would be to use an adjusted weight for initial dosing, albeit this recommendation is not based on any published data. View Large Download. Anticoagulants Heparin Weight-based nomograms have been developed for regular heparin [ 14 ], but the appropriateness of such nomograms for dosing the morbidly obese patient is unknown. The point at which these lines intersect is the recommended digoxin dose.

While the opioids are considered to be lipophilic compounds, there ddigoxin differences in their pharmacokinetics and clinical effects that preclude dosing based solely on predicted distribution into adipose tissue [ 11 ]. All studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients. The emphasis was on studies involving morbidly obese patients but, in the absence of such data, investigations involving lesser forms of obesity were extracted. NIH Publication No. These neurohumoral actions are evident at low digoxin concentrations; further decreases in norepinephrine concentrations are not observed as the concentration of digoxin increases, that is, from 0. Another study involving cimetidine i.

They further noted that in addition to the potential clinical relevance of their findings, the study has added value in that it identifies a causal link between inflammation and weight gain. Front Physiol ; Similarly, clearance was not significantly different between the two groups And the fact that no side effects were observed in animals suggests that, in humans, the dose at which weight loss could be observed may not be harmful. Vecuronium 0. Some institutions such as ours are electing to cap the dose at the kg weight for patients weighing more than this amount due to many of the same concerns as noted for the LMWHs. After the nomogram was constructed, we compared the prescribed digoxin dose with that recommended by our dosing nomogram and, in turn, analyzed the resultant serum digoxin concentrations.

Study supervision : Bauman and DiDomenico. In the clinical setting, issues related to weight definitions are further complicated by temporary changes in body water such as third-spacing of fluids, which may or may not influence the distribution and elimination of medications. Some institutions such as ours are electing to cap the dose at the kg weight for patients weighing more than this amount due to many of the same concerns as noted for the LMWHs. Save Preferences. The advantage to this supplemental dosing approach is that it is more likely to avoid problems such as hypotension that may occur with single large i. Drug Intell Clin Pharm —

Clin Pharmacokinet — Our results and the need to perhaps be more precise in tailoring digoxin dosing in obesity articles dosing regimens to obtain therapeutic concentrations should prompt the availability of new strengths, such as 0. New York, NY Dover; Other anti-infectives Other anti-infectives such as aztreonam, which have relatively few serious adverse effects, should be dosed at the upper end of ranges for treating serious infections in morbidly obese patients.

Drug disposition in obese humans. Increased risk of influenza among vaccinated adults who are obese. For example, according to one study, obese women are more likely to become pregnant than non-obese women after taking the emergency contraception pill Levonelle [2]. N Engl J Med ;

With longer courses of therapy, and particularly when dose-related corticosteroid adverse effects are of major concern, IBW could be used based on the limited pharmacodynamic information cited earlier. Its action on sinus automaticity promotes heart rate reduction and lengthens atrioventricular conduction by reduction of the conduction velocity of electrical impulses through the atrioventricular node [ 19 ]. Pharmacotherapy — Further complicating this, each drug has its own chemical properties, such as lipid solubility, that affect its behaviour in an obese body. Djouder ascribes this to the fact that the cardiovascular disease of patients using digoxin causes high liquid retention, which masks the weight-loss effect of digoxin.

Since lidocaine clearance is primarily a function of hepatic blood flow i. Front Physiol ; In digoxin dosing in obesity articles, lipophilic drugs will readily diffuse into fat tissue, which would call for dosing based on total body weight for an obese person because their extra weight is largely fat. This makes it important to monitor drug levels after an initial dose. Quinolones The pharmacokinetics of ciprofloxacin have been studied in 17 moderately obese subjects

  • In other words, K and half-life are determined by the relationship of volume and clearance. Log in to leave a comment.

  • Tipping the scales: the problem of drug dosing in obese patients As obesity levels rise, pharmacists are finding they need new tools to ensure they adequately tailor the amount of medicine patients receive.

  • There was a tenfold variation in dosing requirements Each of the invariant plots shown here plots the mean digoxin plasma concentration between observed Cp o and expected Cp e on the x-axis and the difference between observed and expected divided by 2 on the y-axis.

  • Given the potential toxicity of atracurium with dosing based on TBW, as well as the small number of patients in this study, it seems that a more conservative initial dosing approach would be advisable in morbidly obese patients, using either IBW or, possibly, an adjusted weight somewhere between IBW and TBW. Pharmacotherapy —

  • Cheymol G Effects of obesity on pharmacokinetics.

While the mechanism requires further elucidation, the seizures are related to blood dosong of imipenem and are of particular concern in patients with renal dysfunction who have impaired elimination of the drug. Similarly, clearance was not significantly different between the two groups For example, in one study involving surgical patients in an ICU setting, a mean dobutamine infusion rate of 8. Correspondence: Jerry L.

In 3 patients, 1 variable ie, height to estimate IBW was unavailable could not be gleaned from digoxkn patient's medical records, leaving a complete set of 51 observations. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. However, given the lack of studies in morbidly obese patients as well as concerns associated with large i. Although the pharmacodynamics of remifentanil was not studied, the pharmacokinetic data and the adverse effect information suggest that IBW should be used for dosing remifentanil in morbidly obese patients.

Definitions

Am J Cardiol FF. Save Preferences. However, to many this is a confusing regimen that could lead to dosing errors and possibly digoxin toxicity.

  • With regards to the carbapenems, meropenem would appear to be a better choice than imipenem given the need to give larger doses in morbidly obese patients and the associated concerns related to seizures.

  • However, they noted the potential hemodynamic concerns related to single, large i.

  • Download PDF.

  • On the other hand, the most up-to-date meta-analysis on the subject sigoxin approximately 40 studies digoxin dosing in obesity articles more thanpatients. This article should also serve as a reminder of the importance of stating which weight was used for dosing in published studies and why that weight was chosen assuming a weight-based approach to therapy was used.

  • Given the relatively narrow therapeutic index for theophylline and the potential for serious dose-related toxicity e. Privacy Policy.

Purchase access Subscribe to JN Learning for one year. Other anti-infectives such as aztreonam, which have relatively few serious adverse effects, should be dosed digoxin dosing in obesity articles the upper end of ranges for treating serious infections in morbidly obese patients. The patients were given cefazolin 1 g i. Recommendations With the availability of antimicrobials that have similar or improved effectiveness relative to the aminoglycosides, it is often possible to avoid the potential ototoxicity and nephrotoxicity concerns associated with the aminoglycosides.

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First, the information digoxin dosing in obesity articles in the articles was relatively current. Kido and Ngorsuraches also showed no difference in ischemic stroke or major bleeding in DOACs compared with warfarin in morbidly obese patients with AF. Pastori D. Intramuscular use is not recommended since creatinine phosphokinase levels can increase considerably [ 2022 ] and this route has great pharmacokinetic variability. Trevor Johnson is a principal scientist and former pharmacist who now works at Certara UK Limited, which develops technology for understanding drug action in different populations, including obese people.

MacLeod-Glover N. Thus, the cardiac action potential atticles shorten, promoting negative chronotropism and positive inotropism due to increased calcium for the sarcomeric excitation-contraction coupling [ 1 ]. The V ss was not significantly different between the obese and normal weight patients Procainamide Similar to lidocaine, there are no pharmacokinetic studies of procainamide in morbidly obese patients but there is information on subjects with moderate obesity mean Furthermore, all of the studies in morbidly obese patients were conducted prior to the clinical use of large e. Rohde L.

Different doses for different folks

Am J Gastroenterol — Although doding is some evidence to suggest that the dosing of at least one of the non-depolarizing neuromuscular blocking agents i. The V ss was not significantly different between the obese and normal weight patients The volume of distribution V or Vd is a proportionality constant that has no direct physiological equivalent, but rather it specifies the volume in which the medication would be contained if the concentration throughout the body were the same as the plasma or serum concentration.

However, the investigators concluded that the minimal risk of cefamandole accumulation with a 6 hourly dosing schedule, along with the increased V, argues for a larger dose in the digoxin dosing in obesity articles obese patients to insure adequate blood and tissue concentrations. Ann Pharmacother The clearance was Recover your password. However, there are no pharmacokinetic studies of amiodarone in morbidly obese patients and, if such were performed, the information would need to be interpreted with caution considering the marked inter-patient variability of pharmacokinetic parameters in normal weight patients [ 38 ].

All patients had normal renal and hepatic function. Articles sum of V c and all V p yields V ss. Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. Therefore, maintenance dose increases of phenytoin need to be conservative e. The need for caution is exemplified by the finding of apparent pyrogen-mediated toxicity in patients receiving once daily aminoglycoside dosing with one particular product [ 28 ]. Pharm Res ;32 12 — Virgadamo S.

Similarly, clearance was not significantly different between the two groups Dosing of histamineblockers in morbidly obese patients should be based on either the usual recommended daily doses or IBW if using weight-based dosing. Until more research has been conducted in morbidly obese patients in the ICU setting, anti-Xa monitoring should be available when the decision is made to use treatment doses of LMWHs. To derive recommendations for the dosing of commonly used medications in the morbidly obese patient in the ICU. The medications selected for discussion in this article were based on two published reports.

Digoxin: The good and the bad. Cao et al. In this regard, there is at least one report in the literature describing that hemodialysis patients who had their digoxin dose increased from 0. Erstad View author publications. The ECG monitoring that was performed in the study seemed to reinforce this recommendation, at least when verapamil is being used for its anti-arrhythmic activity. The V ss corrected for TBW remained higher in obese subjects 0. Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban BAY in healthy subjects.

All patients had normal renal and hepatic un. Interestingly, an childhood obesity paradox" has been observed, in which increased BMI has been associated with better overall outcomes. This Issue. Purchase access Subscribe to JN Learning for one year. Dosing of medications in morbidly obese patients in the intensive care unit setting. However, the investigators concluded that the minimal risk of cefamandole accumulation with a 6 hourly dosing schedule, along with the increased V, argues for a larger dose in the morbidly obese patients to insure adequate blood and tissue concentrations.

Expert Analysis

Table 1. Also, for cefazolin in particular, there is evidence to recommend the use of higher doses e. Recommendations Although there is some evidence to suggest that the dosing of at least one of the non-depolarizing neuromuscular blocking agents i. Interestingly, an "obesity paradox" has been observed, in which increased BMI has been associated with better overall outcomes. Privacy Policy.

Erstad Authors Brian L. Cordarone amiodarone Prescribing Information Pfizer, Inc. The medications selected for discussion in this article were based on two published reports. Media Center ACC.

Correspondence: Jerry L. However, the clearance digoxin dosing in obesity articles unchanged, which translated into a prolonged elimination half-life in the obese compared to aricles weight patients Similar trough edoxaban plasma concentrations and anti-Factor Xa activity were demonstrated among normal and obese cohorts, indicating that obesity may not alter the pharmacokinetic or pharmacodynamic activity of edoxaban despite the observed clinical differences. Remifentanil 7. The hypotension and bradycardia noted in patients receiving single, large i.

  • Digitalis Investigation Group, The effect of digoxin on mortality and morbidity in patients with heart failure.

  • Recommendations These studies with diazepam and midazolam suggest that maintenance doses should be based on IBW. As obesity levels rise, pharmacists are finding they need new tools to ensure they adequately tailor the amount of medicine patients receive.

  • The hypotension and bradycardia noted in patients receiving single, large i.

  • Until such studies are available, the clinician must try to derive the best dosing regimens for medications based on the limited pharmacokinetic data available for some agents and clinical judgement.

  • The safety of digoxin as a pharmacological treatment of atrial fibrillation.

The main electrophysiological and electrocardiographic effects of digoxin are summarized in Fig. When analyzing data from studies with new articles of digoxin i. The results are startling: underweight children were not getting enough rhGH, and obese children were getting more than enough [1]. Third, the documentation periods were over a prolonged period of time i. In a scenario that is poor in well-designed evidence i. Accepted : 02 June

Tipping the digoxin dosing in obesity articles the problem of drug dosing in obese patients As obesity levels rise, pharmacists are finding they need new tools to ensure they adequately tailor the amount of medicine patients receive. Vecuronium 0. Infect Control Hosp Epidemiol — Ziff O. Get help. Source: Courtesy of Trevor Johnson Trevor Johnson is a principal scientist and former pharmacist who now works at Certara UK Limited, which develops technology for understanding drug action in different populations, including obese people. Support Center Support Center.

Eur J Anaesthesiol — Other drug dowing properties such as ionization, blood-to-plasma ratio and protein binding must also be taken into account, and combined with the physiological changes in obesity, he says. Conclusions There is clearly a need for more investigations involving dosing regimens of medications in the morbidly obese population. Elucidating the underlying mechanisms for the differential response to sodium channel blocker antiarrhythmic drugs in obese patients with atrial fibrillation. Drug disposition in obese humans.

Comparative effectiveness, safety, and costs of rivaroxaban and warfarin among morbidly obese patients with atrial fibrillation. Sedative use in the two groups was comparable. AAD Dosing in Obesity Although the pharmacokinetics and pharmacodynamics of AAD therapies can be quite complex and altered by body composition, there is limited guidance on dosing and management specific to the obese population. Although the authors have not studied the possible causes for this outcome, the toxicity of digoxin is well-known and may lead to malignant arrhythmias that increase mortality in these patients [ 32 ]. Sign in Join. For short courses of therapy e.

Of these 54, 30 were men and 24 were women mean [SD] age, 68 [15] years. One notable exception to the last two generalizations is the low molecular weight ovesity LMWHswhich have primarily been studied by s. Historically, 2 methods have been used to estimate the initial dose of digoxin: the Jelliffe method 910 and the Koup et al 11 and Jusko et al 12 method, hereafter the Koup and Jusko method. There are studies in moderately obese patients that suggest that doses of rocuronium and vecuronium should be based on IBW and, unless additional data to the contrary becomes available, this recommendation should be applied to morbidly obese patients undergoing sustained blockade in the ICU setting. Slowing the rate of infusion may also attenuate this problem.

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