Principles of clinical pharmacology applied to analgesics in children

2021 ◽  
pp. 441-448
Author(s):  
Karel Allegaert ◽  
Sinno H.P. Simons ◽  
Dick Tibboel
Keyword(s):  
Clinical Pharmacology ◽  
Critical Illness ◽  
Objective Assessment ◽  
Developmental State ◽  
Time Profile ◽  
Therapeutic Window ◽  
Preterm Neonates ◽  
Individual Child ◽  
Pharmacological Management ◽  
Dosing Regimens

Analgesic dosing regimens should take into account the severity and type of pain, the therapeutic window of the drug, and also the age or developmental state of the child. Translation of these concepts to safe and effective pharmacological management of pain in neonates, infants, and children necessitates a thorough understanding of the principles of clinical pharmacology of analgesics in children. Growth, weight or size, and maturation or age evolve in children and profoundly affect the pharmacokinetics (concentration–time profile, absorption, distribution, metabolism, and excretion) and pharmacodynamics (concentration–effect profile, objective assessment) of drugs, and this is also the case for analgesics. This will result in extensive variability in dosing and effects throughout childhood, and this variability is most prominent in infancy. In addition to maturational changes, there are also nonmaturational aspects (preterm neonates and critical illness, obesity, pharmacogenetics) that should be considered to further improve dosing in every individual child.

Principles of pain pharmacology in paediatrics

2013 ◽  
pp. 429-435 ◽  
Author(s):  
Kim Chau ◽  
Gideon Koren
Keyword(s):  
Clinical Response ◽  
Growth And Development ◽  
Genetic Factors ◽  
Developmental State ◽  
Infants And Children ◽  
Therapeutic Window ◽  
Pharmacological Management ◽  
Interindividual Differences ◽  
Paediatric Patients ◽  
Dosing Regimens

Changes during growth and development may profoundly alter the pharmacokinetic and pharmacodynamics profile of medications in children of different ages, and in comparison to adults. Genetic factors can also influence the disposition and action of a drug, and contribute to interindividual differences in clinical response. Safe and effective pharmacological management of pain in neonates, infants, and children requires a thorough understanding of the principles of analgesic pharmacology in paediatric patients. Analgesic dosing regimens should take into account the severity of pain, the age or developmental state of the infant, and the therapeutic window of the drug.

The Pharmacological Management of Delirium in Critical Illness

2008 ◽  
Vol 3 (2) ◽  
pp. 148-157 ◽  
Author(s):  
Alessandro Morandi ◽  
Max Gunther ◽  
E. Ely ◽  
Pratik Pandharipande
Keyword(s):  
Critical Illness ◽  
Pharmacological Management

scholarly journals P26 Pilot on harmonising dosing recommendation for term and preterm neonates in the Netherlands (Neodose project)

2019 ◽  
Vol 104 (6) ◽  
pp. e27.2-e28
Author(s):  
MA de Hoop-Sommen ◽  
TM van der Zanden ◽  
K Allegaert ◽  
RB Flint ◽  
SHP Simons ◽  
...  
Keyword(s):  
The Netherlands ◽  
Neonatal Intensive Care ◽  
Scientific Evidence ◽  
Local Treatment ◽  
Pilot Project ◽  
Total Daily Dose ◽  
Preterm Neonates ◽  
Treatment Protocols ◽  
Term Neonates ◽  
Dosing Regimens

BackgroundMany drugs are used off-label in term and preterm neonates, and dosing recommendations for many drugs are lacking in the Dutch Paediatric Formulary (DPF). This results in widely varying dosing regimens used across neonatal intensive care units (NICUs) in the Netherlands. The Neodose pilot project aimed to develop best-evidence national dosing recommendations for (pre)term neonates. Because scientific evidence is scarce, a consensus-based approach was used.MethodsA priority drug list, containing the most frequently used drugs for neonates, was drafted. From this list 22 drugs were selected for further research within the Neodose pilot project. The pilot utilized a two-step approach: First, consensus was established with all Dutch NICUs for neonatal dosing recommendations. Local treatment protocols were retrieved, compared and discussed, leading to consensus-based dosing recommendations. Secondly, we aimed to develop best-evidence dosing recommendations for the following five drugs: acyclovir, ganciclovir, ibuprofen, hydrocortisone and dexamethasone.ResultsFor 21 of 22 drugs, local dosing guidelines differed significantly. Mostly concerning total daily dose, dosing frequency and route of administration. Little or no distinction is made between treatment of preterm and term neonates. Approximately half of the consensus-based dosing recommendations (45%) differ in some degree from all local protocols. Comparing the consensus-based dosing recommendations with the available evidence, almost half of the consensus doses were adjusted. The grounds on which dosing recommendations were adjusted differed. Acyclovir-dosing adjustment was based on pharmacokinetics. Hydrocortisone-dosing was adjusted due to new insights after the evidence has been put together. For dexamethasone-dosing, the consensus dose was eventually chosen, because every available trial used a different dosing regimen.ConclusionThis pilot showed that, when evidence is inconclusive, consensus on dosing regimens in neonates can be obtained by comparing local regimens and analysing the available evidence. For more uniform use, these new recommendations will be published in the DPF.Disclosure(s)This project was funded by the federation of medical specialists for qualitative improvement (Stichting Kwaliteitsgelden Medisch Specialisten (SKMS).

The Pharmacological Management of Epilepsy Associated with Psychological Disorders

1982 ◽  
Vol 141 (6) ◽  
pp. 549-557 ◽  
Author(s):  
E. H. Reynolds
Keyword(s):  
Clinical Pharmacology ◽  
Seizure Control ◽  
Psychological Disorders ◽  
Psychosocial Problems ◽  
Mental Function ◽  
Careful Monitoring ◽  
Chronic Patients ◽  
Pharmacological Management ◽  
Anticonvulsant Treatment ◽  
Modern Knowledge

SummaryThe anticonvulsant treatment of epilepsy associated with psychological disorders is reviewed in the light of modern knowledge of the clinical pharmacology and adverse mental effects of the drugs. Careful monitoring of individual drug therapy from the onset of treatment improves compliance and seizure control and avoids unnecessary and harmful polypharmacy, and some of the neurological and psychosocial problems of chronic epilepsy. In chronic patients on polypharmacy cautious rationalization may improve mental function but can be hazardous due to withdrawal seizures. A clearer perception of the limits of anticonvulsant therapy will allow more attention to appropriate psychosocial measures.

CRISPR-based gene editing is presently being tried in many clinical trials

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Clinical Trials ◽  
Cell Function ◽  
Therapeutic Window ◽  
Development Environment ◽  
Drug Dosing ◽  
Protein Levels ◽  
Cell Tissue ◽  
Rnp Complex ◽  
Dosing Regimens

CRISPR is a bacterial host defense system that may work as "molecular scissors" in eukaryotic cells to permanently modify genetic coding. Some barriers to using CRISPR as a therapeutic include guaranteeing adequate delivery of the RNP complex to the proper cell/tissue and showing safe and effective editing. Off-target editing (i.e., unwanted modification in a non-target DNA location) may result in a range of safety problems impacting normal cell function. The degree of cell editing events, including off-target modifications, is known to be altered by in vitro dosage and time of exposure to active RNP complexes. The safety of these drugs relies heavily on preventing unwanted mutations, off-target mutations, and any genomic rearrangements, all of which may have harmful implications.In some illnesses, a slight general adjustment of positive and negative protein levels may be sufficient to have a therapeutic impact. Understanding this therapeutic window will enable researchers to modify drug dosing regimens, especially for in vitro use, to obtain optimum pharmacodynamics with the fewest potential adverse effects. Most of the bioanalytical endpoints outlined for CRISPR are simple methods performed in most labs. Development teams will need to manage resources by selecting key exposure endpoints that deliver the greatest value from pharmacokinetics/PD and safety evaluations. Two in vitro delivery strategies have entered clinical trials in immune-privileged locations. The drug development environment will have to be altered in close coordination with regulatory agencies to construct need-to-know endpoints and pivotal trials to successfully move medicines forward in a safe and controlled way.

Comparative Clinical Pharmacology of Rocuronium, Cisatracurium, and Their Combination 

1998 ◽  
Vol 89 (5) ◽  
pp. 1116-1124 ◽  
Author(s):  
Mohamed Naguib ◽  
Abdulhamid H. Samarkandi ◽  
Adel Ammar ◽  
S. R. Elfaqih ◽  
Salem Al-Zahrani ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Time Course ◽  
Time Profile ◽  
Neuromuscular Blocking ◽  
Combination Group ◽  
Onset Of Action ◽  
Recovery Times ◽  
Train Of Four ◽  
American Society ◽  
American Society Of Anesthesiologists

Background The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs. Methods Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 microg/kg and 100-300 microg/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction. Results The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 26.2 (25.8-26.5) microg/kg [corrected] for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups. Conclusions Cisatracurium is four to five times more potent than rocuronium. Rocuronium had a faster onset of action, a shorter clinical duration, and a faster spontaneous recovery rate compared with equipotent doses of cisatracurium.

scholarly journals Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 174
Author(s):  
Samira Samiee-Zafarghandy ◽  
Tamara van Donge ◽  
Karel Allegaert ◽  
John van den Anker
Keyword(s):  
At Risk ◽  
Umbilical Cord ◽  
Gestational Age ◽  
Early Identification ◽  
Drug Exposure ◽  
Early Initiation ◽  
Preterm Neonates ◽  
Dosing Regimen ◽  
Optimal Care ◽  
Dosing Regimens

In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure–response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure). We applied early (12 h after birth) vs. typical (36 h after birth) initiation of treatment. We observed that use of universally recommended dosing regimens in preterm neonates can result in under- or over-exposure. Use of a PK-guided dosing regimen resulted in effective target exposures within 24 h after birth with early initiation of treatment (12 h after birth). Future prospective studies should explore the incorporation of umbilical cord methadone concentrations for early identification of preterm neonates at risk of developing severe NAS and investigate the use of a PK-guided methadone dosing regimen, so that treatment failure, prolonged length of stay and opioid over-exposure can be avoided.

scholarly journals Evaluation of Jaundice meter in the assessment of jaundice among Nigerian preterm neonates

1970 ◽  
Vol 42 (3) ◽  
pp. 194-198
Author(s):  
BO Kayode-Adedeji ◽  
JA Owa ◽  
GO Akpede ◽  
SO Alikah
Keyword(s):  
Birth Weight ◽  
Gestational Age ◽  
Serum Bilirubin ◽  
Objective Assessment ◽  
Total Serum Bilirubin ◽  
Preterm Neonates ◽  
Total Serum ◽  
Transcutaneous Bilirubin ◽  
The Mean ◽  
Transcutaneous Bilirubinometry

Background: The objective assessment of the severity of neonatal jaundice is Total Serum Bilirubin (TSB) determination, which requires multiple blood sampling. This has inherent problems, including risks of anaemia and infection. Transcutaneous Bilirubinometry (TcB) is a reliable, non-invasive alternative, however there is paucity of data on its performance in black preterm neonates.Objectives: To evaluate the correlation between transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) among Nigerian preterm neonates, and to determine the parameters affecting the relationship.Method: Jaundiced preterm neonates delivered between 28 and 36 weeks of gestation admitted at the Irrua Specialist Teaching Hospital (ISTH), Nigeria were recruited . The TSB levels were determined by spectrophotometry while the corresponding TcB levels were obtained using Jaundice Meter (JM-103). The neonates were stratified into gestational age and birth weight groups.Results: A total of 189 paired TcB and TSB levels were obtained from 60 neonates. The Mean (sd) TcB level of 11.4 (3.1) mg/dl was significantly higher than the mean TSB level of 10.2 (2.8)mg/dl (p= 0.028). The overall correlation coefficient between TcB and TSB was 0.98 and it was not significantly affected by the gestational age, birth weight and bilirubin levels.Conc lusion: Transcutneous bilirubin strongly correlates with total serum bilirubin levels among Nigerian preterm neonates, irrespective of gestational age, birth weight and the degree of jaundice.Keywords: hyperbiliruinaemia, jaundice meter, Nigerian, preterm, neonates, transcutaneous bilirubinometry

Sign in / Sign up

Export Citation Format

Share Document