Re: Query, re Re: Fwd: Contraception - Birth control for drug addicts

[Yoshie Furuhashi <furuhashi.1@xxxxxxx>]

> There is such a condition as fetal alcolhol syndrome -- but *is* there any
> such result from cocaine. I once read that this was an urban legend because
> cocaine cannot pass through the placenta lining. Does anyone know? I mean
> *know*: New York Times, Time Magazine, etc. not accepted as source.
>
> Carrol

I don't know, but I've found many interesting articles that suggest
that the placenta protects the fetus from cocaine exposure.  Here are
some sample abstracts, which I found through a database called
Medline.   Yoshie


Authors: Potter S. Klein J. Valiante G. Stack DM. Papageorgiou A.
Stott W. Lewis D. Koren G. Zelazo PR.
Institution: Department of Psychology and Research Institute, McGill
University, Montreal, Canada.
Title: Maternal cocaine use without evidence of fetal exposure.
Source: Journal of Pediatrics. 125(4):652-4, 1994 Oct.
Abstract: We report a case of lack of fetal exposure to cocaine and
benzoylecgonine as evidenced by meconium and hair analysis, but
exposure to nicotine and its metabolite cotinine, after extensive
maternal use of cocaine and nicotine. These data suggest that the
mode of maternal use of cocaine and individual differences in
placental handling of the drug may protect some fetuses, and
highlight the need to address interpatient variability.


Authors: Simone C. Derewlany LO. Oskamp M. Johnson D. Knie B. Koren G.
Institution: Division of Clinical Pharmacology and Toxicology,
Hospital for Sick Children, Toronto, Ontario, Canada.
Title: Acetylcholinesterase and butyrylcholinesterase activity in the
human term placenta: implications for fetal cocaine exposure.
Source: Journal of Laboratory & Clinical Medicine. 123(3):400-6, 1994 Mar.
Abstract: The characterization of the enzymes responsible for drug
metabolism in the human placenta is of great importance in
determining the possible role the placenta plays in protecting the
fetus from potentially fetotoxic drugs. We speculate that the
placenta metabolizes cocaine, serving to protect the fetus from the
drug's ill effects. Cholinesterase, the principle enzyme that
metabolizes cocaine, has been hypothesized to be present yet is not
well characterized in the human placenta. The purpose of this study
was to quantify human placental acetylcholinesterase (AChE) and
butyrylcholinesterase (BChE) activity. Human placentas were obtained
from elective cesarean sections, and several lobules were thoroughly
perfused with cold buffer to ensure minimal contamination from
erythrocyte AChE. Subcellular fractions were then prepared from these
lobules by using standard differential centrifugation techniques.
Microsomes and cytosol were assayed for AChE and BChE activity by
using a spectrophotometric assay. BChE activity was found in the
cytosolic fraction of the placental villous tissue, whereas AChE
activity was measured in the microsomal fraction. By demonstrating
that BChE activity is present in human term placenta we have shown
that this organ has the capacity to metabolize cocaine and may
therefore serve as a metabolic barrier to fetal exposure to cocaine.


Authors: Simone C. Derewlany LO. Oskamp M. Knie B. Koren G.
Institution: Division of Clinical Pharmacology and Toxicology,
University of Toronto, Ontario, Canada.
Title: Transfer of cocaine and benzoylecgonine across the perfused
human placental cotyledon.
Source: American Journal of Obstetrics & Gynecology. 170(5 Pt
1):1404-10, 1994 May.
Abstract: OBJECTIVE: Our aim was to measure the transfer of cocaine
and its major metabolite benzoylecgonine across the human term
placenta. STUDY DESIGN: By means of in vitro perfusion of the human
term placental cotyledon the transfer of these compounds was
measured. RESULTS: The steady-state maternal-to-fetal transfer of
cocaine (0.18 +/- 0.05 microgram/ml/min) was significantly greater
than benzoylecgonine transfer (0.02 +/- 0.01 microgram/ml/min) (p <
0.05). When the perfused tissue was analyzed 32% +/- 7% of the
maternal cocaine dose was retained by the placental tissue, whereas
only 12% +/- 12% of the maternal benzoylecgonine dose was retained by
the placental compartment. CONCLUSIONS: These results suggest (1) the
placenta may serve as a depot for large amounts of cocaine, thus
offering some degree of fetal protection after bolus administration;
(2) fetal exposure may be prolonged by placental retention and
subsequent release of cocaine and benzoylecgonine; and (3)
benzoylecgonine does not cross the placenta as readily as does
cocaine. Variability in placental handling of cocaine and
benzoylecgonine may therefore determine fetal exposure to these
agents.


Authors: Shearman LP. Meyer JS.
Institution: Department of Psychology, Neuroscience and Behavior
Program, Tobin Hall, University of Massachusetts, Amherst, MA
01003-7710, USA.
Title: Cocaine up-regulates norepinephrine transporter binding in the
rat placenta.
Source: European Journal of Pharmacology. 386(1):1-6, 1999 Dec 10.
Abstract: We investigated the influence of 3 days of continuous
cocaine exposure on norepinephrine transporter binding in the rat
placenta. On gestational day 17, pregnant rats were implanted
subcutaneously with two cocaine-containing Silastic capsules. There
were two control groups, one that received capsules with vehicle only
and was pair-fed to the cocaine-treated females, and a second group
that was untreated and fed ad libitum. Placentas and fetal brains
were harvested and frozen on gestational day 20, and subsequently
subjected to saturation analyses for norepinephrine transporter
binding using the selective ligand [3H]nisoxetine. There was a marked
increase in the density (B(max)) of norepinephrine transporter
binding sites in the placentas of the cocaine-treated animals
compared to both control groups, but no change in the fetal brain.
The mechanism underlying this up-regulation of the placental
norepinephrine transporter is not yet known, but it could involve a
beta-adrenoceptor- and cAMP-mediated induction of transporter gene
expression.


Authors: Morishima HO. Whittington RA. Zhang Y. Cooper TB.
Institution: Departments of Anesthesiology, Obstetrics and
Gynecology, and Psychiatry, College of Physicians and Surgeons,
Columbia University, New York, USA.
Title: The disposition of cocaethylene in rat maternal, placental,
and fetal compartments.
Source: American Journal of Obstetrics & Gynecology. 180(5):1289-96, 1999 May.
Abstract: OBJECTIVE: The aim of this project was to examine the
disposition of maternally administered cocaethylene in the fetus.
STUDY DESIGN: Pregnant rats with long-term catheter placement
received an intravenous infusion of cocaethylene during a period of
30 minutes. At either the completion of the infusion or 6 hours after
the infusion the fetuses were delivered by hysterotomy. Maternal and
fetal blood and major tissue samples were obtained for assays of
cocaethylene and its metabolites. RESULTS: Cocaethylene was present
in all samples obtained at the end of the infusion, but after 6 hours
it was no longer detectable in the maternal and fetal systemic
circulations. However, a substantial amount of cocaethylene was still
present in the placenta on both the maternal and fetal sides, with
the concentration on the maternal side being higher, indicating that
the placenta stores cocaethylene. At the end of the infusion
benzoylecgonine was found in all samples and the maternal
concentrations were higher than the corresponding fetal
concentrations. This order was reversed 6 hours after infusion.
Extremely high concentrations of cocaethylene and benzoylecgonine
were found in the amnion. CONCLUSIONS: These results suggest that the
placenta limits the transfer of cocaethylene to the fetus. The high
affinity of this compound for extraplacental sites cannot be ignored.


Authors: Bailey B. Morris P. McMartin KI. Klein J. Duhart HM. Gillam
MP. Binienda Z. Slikker W. Paule MG. Koren G.
Institution: Division of Clinical Pharmacology and Toxicology, The
Hospital for Sick Children, Toronto, Ontario, Canada.
Title: Transplacental pharmacokinetics of cocaine and benzoylecgonine
in plasma and hair of rhesus monkeys.
Source: Reproductive Toxicology. 12(5):517-23, 1998 Sep-Oct.
Abstract: There is large variability in the rate and extent of fetal
damage from cocaine in humans; however, the sources of such
variability are not presently known. In order to study the
relationship between maternal cocaine pharmacokinetics at the end of
pregnancy and maternal or infant cocaine and benzoylecgonine hair
concentrations at birth, ten rhesus monkeys were administered cocaine
intramuscularly throughout pregnancy. Cocaine and benzoylecgonine
hair concentrations were determined at birth and correlated with
maternal pharmacokinetics during pregnancy. There were no
correlations between either maternal cocaine Cmax or AUC0-infinity
and maternal and infant hair cocaine or benzoylecgonine
concentrations. There were no significant correlations between
maternal hair benzoylecgonine concentrations and either maternal
benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax
(r = 0.60; P = 0.07). No correlations existed between infant hair
benzoylecgonine concentrations and either maternal benzoylecgonine
AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P =
0.40). Also, no correlation was found between maternal cocaine dose
and maternal or infant cocaine and benzoylecgonine hair
concentrations. In comparison to toxicants such as nicotine and
carbon monoxide for which there is a good correlation between
maternal systemic exposure and neonatal concentrations, the lack of a
similar relationship for cocaine is consistent with the role of the
placenta in contributing to the variability in the amounts of cocaine
reaching the fetus and hence, potentially to the risk of adverse
fetal outcome.