China
Africa
Explore chapters and articles related to this topic
Medicines in neonates
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
The concentration-dependent bactericidal activity of aminoglycosides, their high volume of distribution and the finding that their binding to the brush membrane of the proximal tubule, as well as the cochlear cell, is a saturable process, has given rise to the concept that relatively larger doses with much longer intervals between doses should be used in neonates, as has been demonstrated in adults [10–16]. Initial results are encouraging. Therapeutic drug monitoring is recommended. The optimal trough blood levels are as follows: amikacin: <5 mcg/dl; netilmicin: <2 mcg/dl; gentamicin: <2 mcg/dl: tobramycin: <2 mcg/dl. Lower trough concentrations are probably indicated if the dosing intervals are prolonged. The concentration dependent killing effect of metronidazole allows once daily administration (Table 4).
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Gerry Davies, Charles Peloquin
Aminoglycosides are associated with nephrotoxicity and ototoxicity which is related to the duration of dosing but not to dose size or interval.153 High tone hearing loss is common in treatment of MDR-TB154,155 and is permanent in about two-thirds of cases. A recent systematic review suggested that co-administration of N-acetylcysteine may reduce the risk of ototoxicity.156 Nephrotoxicity is less common and usually reversible. Hypokalemia and hypomagnesemia due to tubular dysfunction may occur independently of changes in GFR.157 Therapeutic drug monitoring is helpful where available.158 Neuromuscular blockade is a rarer side effect, most marked in patients undergoing anesthesia or with myasthenia gravis.
Prophylaxis and treatment of invasive fungal infections in neutropenic cancer and hematopoietic cell transplant patients
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Daniel R. Richardson, Marcie L. Riches, Hillard M. Lazarus
Prolonged antifungal prophylaxis may be associated with the emergence of multiple resistant fungal species, such as Zygomycetes, C. kruzei, Cunninghamella, Rhizopus, disseminated Aspergillus ustus, and breakthrough Candida glabrata fungemia [87–91]. The emergence of resistant organism simply may be related to selection pressure, though some suggest sub-therapeutic antifungal serum concentrations are contributory. Trifilio et al. noted a weak correlation between lower plasma voriconazole levels and the emergence of resistant IFIs [92]. These and other similar observations have led to considerable discussion about the importance of monitoring voriconazole blood concentrations. A recent randomized, controlled trial investigating the effect of therapeutic drug monitoring showed a benefit, with a complete or partial response seen in 81% of monitored patients as compared to 57% response in non-monitored patients [93]. This result also is supported by observational studies correlating better drug levels with improved responses [94]. The optimal trough concentration remains controversial though most investigators support trough levels >1.0 µg/mL [94].
Treatment and biologic maintenance-dosing patterns among pediatric patients with ulcerative colitis or Crohn’s disease
Published in Current Medical Research and Opinion, 2023
Theresa Hunter, Wendy J. Komocsar, Richard B. Colletti, Chunyan Liu, Keith J. Benkov, Jennifer L. Dotson, Steven J. Steiner, Nanhua Zhang, Wallace Crandall
The development of biologics and the evidence of their efficacy and safety is continuously increasing, thereby shifting the treatment paradigm of pediatric IBD. The current pediatric UC guidelines recommend initiating infliximab in hospitalized pediatric patients with severe UC who are anti-TNF therapy naïve, after a 3- to 5-day course of intravenous corticosteroids without response35,36. Among the biologics prescribed for UC or CD, anti-TNFs (infliximab and adalimumab) were the most used in our finding, however, the doses of biologics used were observed to be higher than the standard dosing guidelines20,35,36. Therapeutic drug monitoring in clinical practice can identify patients who are receiving inadequate doses, and lead to increased dosing. Another possibility could be due to limited options available, up titrating the dose is more feasible than switching to a different biologic37. In addition, the recommended optimum doses in pediatric population may need adjustment depending on the clinical response38.
A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies
Published in Xenobiotica, 2022
Vanessa Martins, Lynsey Fazal, Aram Oganesian, Alpesh Shah, Jessie Stow, Hugh Walton, Nicola Wilsher
Polypharmacy is also inevitable with an ageing population and many diseases have common aetiologies and/or demographics, for example, smoking and obesity are risk factors for both cardiovascular disease and cancers. Patients are therefore likely to be on several medications for pre-existing conditions before presenting with new diseases. Clinical teams will be presented with the need to consider potential inadvertent drug–drug interactions alongside the deliberate effect of a pharmacoenhancer combination. An extensive review has shown that drug–drug interactions with chemotherapeutics can lead to a reduction in patient survival (Sharma et al. 2019). Furthermore, a retrospective analysis indicated that approximately 40% of drug-related deaths in a university hospital were attributable to drug–drug interactions (Montané et al. 2018). Clinical therapeutic drug monitoring has been established as an approach for dose tailoring to an individual patient, which is particularly important for drugs with a narrow therapeutic index. This activity requires a multidisciplinary team including DMPK scientists, clinicians, nurses and pharmacists to work in concert to ensure best practices are achieved (Kang and Lee 2009).
Antimicrobial safety considerations in critically ill patients: part I: focused on acute kidney injury
Published in Expert Review of Clinical Pharmacology, 2022
Foroud Shahbazi, Lida Shojaei, Fakhrossadat Farvadi, Sara Kadivarian
Transient acute kidney injury is initially defined as risk, injury, or failure in day one that is improved in the next five days [45]. However, a recent consensus report from the Acute Disease Quality Initiative (ADQI) 16 Workgroup defined transient AKI and acute kidney diseases as AKI that recovered within 48 hours and 90 days after initiation, respectively [46]. Up to 50% of patients with AKI at admission are recovered within 48 hours [47]. The GFR improves earlier than SrCr in patients with transient AKI and dose adjustment based on CrCl and eGFR is not recommended [47]. Transient AKI should be differentiated from intrinsic AKI, as the latter does not recover following renal blood flow improvement [48]. Early identification and discontinuation of nephrotoxins or initiation and reintroduction of them during transient AKI or AKD should be individualized [46,49]. Selecting non- or less nephrotoxic agents, minimizing pharmacokinetic and pharmacodynamic interactions, and medication dose adjustment are among interventions that may be helpful in transient AKI or AKD recovery [46,49]. Early dose reduction in the setting of transient AKI may lead to subtherapeutic levels and clinical failure [47]. No dose adjustment is recommended for beta-lactams during the first 72 hours [50]. Therapeutic drug monitoring is useful for optimizing pharmacodynamic/pharmacokinetics targets and minimizing treatment failure [46].