Subject(s)
Analgesics, Opioid/administration & dosage , Opioid-Related Disorders/epidemiology , Pediatrics , Prescription Drug Misuse/statistics & numerical data , Adolescent , Adolescent Behavior , Adolescent Medicine , Awareness , Humans , Mass Screening , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/therapyABSTRACT
Drug testing is often used as part of an assessment for substance use in children and adolescents. However, the indications for drug testing and guidance on how to use this procedure effectively are not clear. The complexity and invasiveness of the procedure and limitations to the information derived from drug testing all affect its utility. The objective of this clinical report is to provide guidance to pediatricians and other clinicians on the efficacy and efficient use of drug testing on the basis of a review of the nascent scientific literature, policy guidelines, and published clinical recommendations.
Subject(s)
Alcoholism/diagnosis , Drug Evaluation, Preclinical/methods , Illicit Drugs/analysis , Substance-Related Disorders/diagnosis , Adolescent , Alcoholism/rehabilitation , Child , Emergency Service, Hospital , Ethanol/adverse effects , Ethanol/pharmacokinetics , Humans , Illicit Drugs/adverse effects , Illicit Drugs/pharmacokinetics , Infant, Newborn , Marijuana Abuse/diagnosis , Marijuana Abuse/rehabilitation , Metabolic Clearance Rate/physiology , Predictive Value of Tests , Specimen Handling , Substance-Related Disorders/rehabilitationABSTRACT
One strategy for isolating neuronal L-type calcium (Ca(2+)) currents, which typically comprise a minority of the whole cell current in neurons, has been to use pharmacological agents that increase channel activity. This study examines the effects of the benzoyl pyrrole FPL 64176 (FPL) on L-type Ca(2+) currents and compares them to those of the dihydropyridine (+)-202-791. At micromolar concentrations, both agonists increased whole cell current amplitude in PC12 cells. However, FPL also significantly slowed the rate of activation and elicited a longer-lasting slow component of the tail current compared to (+)-202-791. In single channel cell-attached patch recordings, FPL increased open probability, first latency, mean closed time and mean open time more than (+)-202-791, with no difference in unitary conductance. These gating differences suggest that, compared to (+)-202-791, FPL decreases transition rates between open and closed conformations. Where examined, the actions of FPL and (+)-202-791 on whole cell L-type currents in sympathetic neurons appeared similar to those in PC12 cells. In contrast to its effects on L-type current, 10 microM FPL inhibited the majority of the whole cell current in HEK cells expressing a recombinant N-type Ca(2+) channel, raising caution concerning the use of FPL as a selective L-type Ca(2+) channel agonist in neurons.
