Transcript Substance abuse in pregnancy

Substance abuse in pregnancy
Tom Archer, MD, MBA
UCSD Anesthesia
Prevalence of substance abuse
during pregnancy
• Perhaps 5% of pregnant women in US use
illicit drugs.
• Perhaps 19% use alcohol.
Abel EL Am J Obstet Gynecol 2002;186:768-72.
Substances abused
•
•
•
•
•
•
•
•
Alcohol
Tobacco
Cocaine
Opioids
Methamphetamine
Ecstasy
Benzodiazepines
Solvents
Substance abuse
is associated with:
• +HIV (particularly with amphetamine use)
• Suicide attempts
• Lack of prenatal care
Ethical problem
• Drug or alcohol- abusing mother may be
subject to child abuse laws
• This is a disincentive for her to self-report.
• What is our role?
Mandatory testing of pregnant
women for drugs and alcohol?
• Would it protect children?
• Would it discourage prenatal care?
• Would it discourage women from seeking treatment?
• 1997 criminal prosecution in South Carolina for exposing
fetus to cocaine.
• Health care personnel attitudes are relevant to enforcement
of any laws to be enacted.
Should society punish / treat women
who drink or use drugs during pregnancy?
• Michigan study shows predominant opinion of
MDs is in favor of defining drug and alcohol use
during pregnancy as “child abuse” and requiring
testing and / or compulsory treatment or
punishment.
• National organizations of peds, OBs and FPs are
more “politically correct” (less punitive and
intrusive).
• What is the right mix of punishment vs. treatment?
• How will this affect our dealing with these
patients?
Abel EL Am J Obstet Gynecol 2002;186:768-72.
Reporting maternal drug use
• Pediatricians more likely to report than
OBs?
• Pediatricians see less of a problem with
“patient confidentiality.”
Evidence of fetal withdrawal syndrome at birth or
fetal alcohol syndrome
• Grounds for removal of infant from
maternal custody?
Dangers of drug use to fetus
•
•
•
•
Brain damage
Teratogenesis (e.g. fetal alcohol syndrome)
Behavioral disorders
Growth restriction d/t chronic placental
insufficiency
• Placental abruption
• Infection (e.g. HIV).
Short term effect
of glucose uptake
into muscle
Long term
anabolic effects
http://casestudies.med.utah.edu/med1/diabetes2/images/web/Insulin_signalling_pathways.jpg
Cell does
some
thing fast
with
existing
machinery
Epinephrine
Signal Transduction Pathways
mRNA
Thyroid hormone
Protein
Cell makes new
machinery
Perinatal testing
• Maternal / fetal hair for cocaine / other
drugs.
• Meconium for fatty acid ethyl esters
(FAEEs) from heavy ETOH use.
Alcohol
• Fetal alcohol syndrome (high doses)
• Alcohol related neurodevelopmental
disorder (ARND) (lower doses)
Cocaine
• Placental abruption, IUGR, prematurity,
neurodevelopmental problems, IUFD.
• Fetal exposure varies widely at same
maternal dosage (placental metabolism?)
• Cocaine in fetal hair IDs mothers taking
cocaine in last trimester (addicted?), since
hair forms only in last trimester.
Cocaine
• Diagnosis is hard– patients are loathe to
report.
• Urine testing
• Hair testing.
MAC and cocaine /
methamphetamine
• Chronic use may decrease MAC
• Acute intoxication may increase MAC.
Cocaine
• Local anesthetic – blocks sodium channels
• Blocks reuptake of dopamine, norepinephrine and
serotonin in CNS.
• Euphoria, hypertension, tachycardia,
vasconstriction, coronary vasospasm, thrombosis.
• Associated vasculitis?
Cocaine
• Increases vascular cell adhesion molecules
(promoting white cell infiltration into
tissues)
• Promotes thrombosis
• Cocaine is like obesity and hyperglycemia
in this respect!
Hyperglycemia, sepsis and pre-eclampsia all
“activate” (damage) endothelium.
WBC
WBC
Platelet
Hyperglycemia, sepsis
or pre-eclampsia
Platelets
Protein (edema)
Archer TL 2006 unpublished
Anesthesia for cocaine abusers
• GA may cause severe hypertension.
• If GA is chosen, ? Labetalol, +/- NTG to
avoid hypertension. Labetalol better than
hydralazine d/t maternal tachycardia with
hydralazine.
• RA probably anesthetic of choice.
Risks of anesthesia for cocaine
abusers
• GA may cause severe hypertension.
• RA probably anesthetic of choice.
• RA dangers: platelet dysfunction, severe
hypotension, lack of response to ephedrine.
• Uncooperative, unhappy patient
Cocaine, endothelium and MI
• Direct hemodynamic effects (inc HR, BP)
• Coronary vasospasm
• Endothelial effects (increased tissue factor
and decreased tissue factor pathway
inhibitor)
– Increased thrombotic tendency
CART– cocaine and amphetamine
regulated transcript (peptide)
• Constricts arterioles by an Endothelin A
mechanism
Hypertension in pregnancy
•
•
•
•
•
•
•
Pre-eclampsia
Cocaine use
Methamphetamine use
Alcohol, opioid withdrawal
Pheochromocytoma
Hyperthyroidism
MH
Smoking
• Carbon monoxide administration to fetus
• Placental vascular constriction
Nicotine
• Maternal use in pregnancy affects birth weight,
infant cognition, behavior.
• Perhaps 25% of women smoke during pregnancy.
• Fetal brain has nicotine receptors.
• Fetal exposure to nicotine may predispose to
attention deficit disorder, conduct disorder and
substance abuse.
Ecstasy
• “MDMA” increases serotonin and (less)
dopamine in brain.
• Brain damage
• Hyperthermia
The End
•
16036808
AuthorsFiala M. Eshleman AJ. Cashman J. Lin J. Lossinsky AS. Suarez V. Yang W. Zhang J. Popik W. Singer E.
Chiappelli F. Carro E. Weinand M. Witte M. Arthos J.
Authors Full NameFiala, Milan. Eshleman, Amy J. Cashman, John. Lin, Justin. Lossinsky, Albert S. Suarez,
Vannina. Yang, Wendy. Zhang, Jun. Popik, Waldemar. Singer, Elyse. Chiappelli, Francesco. Carro, Eva. Weinand,
Martin. Witte, Marlys. Arthos, James.
InstitutionDepartment of Medicine, West Los Angeles VA Medical Center and UCLA School of Medicine, Los
Angeles, CA 90095, USA. [email protected]
TitleCocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular
endothelial cells.
SourceJournal of Neurovirology. 11(3):281-91, 2005 Jul.
Local Messages*UTHSCSA LIBRARIES DO NOT OWN THIS TITLE*
AbstractCocaine is a suspected cofactor in human immunodeficiency virus (HIV)-associated dementia but cocaine's
effects are not clear. Herein the authors describe investigations of the mechanisms by which cocaine increases HIV-1
invasion through brain microvascular endothelial cells (BMVECs). Cocaine binds to a site on BMVECs, which is not
a biogenic amine transporter, a binding site for estrogen, or a muscarinic receptor and for which benztropine and
tamoxifen have the highest affinity. Cocaine treatment of BMVECs disrupts intercellular junctions and induces cell
ruffling, which could account for their increased permeability and decreased electrical resistance. HIV-1 enters
BMVECs by macropinocytosis and is transported to lysosomes and inactivated. In cocaine-treated BMVECs, the
virus enters and persists in large cytoplasmic "lakes." Cocaine exposure of BMVECs up-regulates transcription of
genes important in cytoskeleton organization, signal transduction, cell swelling, vesicular trafficking, and cell
adhesion. The toxicity of cocaine for the blood-brain barrier may lead to increased virus neuroinvasion and
neurovascular complications of cocaine abuse.
Publication TypeJournal Article. Research Support, N.I.H., Extramural. Research Support, U.S. Gov't, P.H.S..
•
15637118
AuthorsChen Y. Ke Q. Xiao YF. Wu G. Kaplan E. Hampton TG. Malek S. Min JY. Amende I. Morgan JP.
Authors Full NameChen, Yu. Ke, Qingen. Xiao, Yong-Fu. Wu, Guifu. Kaplan, Emel. Hampton, Thomas G. Malek, Sohail. Min, JiangYong. Amende, Ivo. Morgan, James P.
InstitutionCardiovascular Division, Department of Medicine, The Charles A. Dana Research Institute and Harvard-Thorndike Laboratories,
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
TitleCocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion
molecules.
SourceAmerican Journal of Physiology - Heart & Circulatory Physiology. 288(5):H2323-31, 2005 May.
Local Messages*UTHSCSA LIBRARIES OWN JOURNAL. CLICK LIBRARY HOLDINGS FOR VOLS OWNED*
AbstractCocaine treatment of mice with viral myocarditis significantly increases neutrophil infiltration into the myocardium and exacerbates
the inflammatory response. The mechanisms of these effects are unknown; however, it may be that cocaine increases circulating
catecholamines and consequently increases inflammatory cell adhesion to the coronary endothelium. Here, we examined the hypothesis that
cocaine enhances inflammatory cell infiltration via catecholamine-induced upregulation of cell adhesion molecule (CAM) expression in adult
BALB/c mouse hearts. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte
adhesion molecule-1 (E-selectin), and leukocyte adhesion molecule-1 (L-selectin) were detected by gene array analysis, RT-PCR, Western
blotting, and immunohistochemical staining. CAMs were significantly upregulated in cocaine-treated mouse hearts. beta-Adrenergic
stimulation with epinephrine also upregulated CAM expression, confirming the effects obtained with cocaine. Beta-adrenergic blockade with
propranolol inhibited epinephrine-induced CAM expression. In hearts infused with polymorphonuclear neutrophils (PMN), an increased
adhesion of PMN to the coronary endothelium was observed in cocaine-treated and epinephrine-treated mouse hearts compared with control
hearts. Blocking antibodies against ICAM-1, E-selectin, and L-selectin significantly inhibited epinephrine-enhanced PMN adhesion, whereas
anti-VCAM-1 had lesser effects. Our findings suggest that cocaine-induced neutrophil infiltration is mediated by beta-adrenergic stimulation
through upregulation of CAM expression, which enhances PMN adhesion. Conversely, beta-adrenergic blockade with propranolol inhibits the
effects of cocaine and epinephrine on CAM expression and decreases PMN adhesion to the coronary endothelium. These observations may
be of significance for the development of preventative and therapeutic approaches to patients with cocaine- or catecholamine-induced
myocarditis.
Publication TypeJournal Article. Research Support, Non-U.S. Gov't. Research Support, U.S. Gov't, P.H.S..
•
14738173
AuthorsMastrogiannis DS. O'Brien WF.
Authors Full NameMastrogiannis, D S. O'Brien, W F.
InstitutionDepartment of Maternal Fetal Medicine, Good Samaritan Hospital, West Islip, New York,
USA.
TitleCocaine affects prostaglandin production in human umbilical cord cell cultures.
SourceJournal of Maternal-Fetal & Neonatal Medicine. 14(4):261-6, 2003 Oct.
Local Messages*UTHSCSA LIBRARIES OWN JOURNAL. CLICK LIBRARY HOLDINGS FOR
VOLS OWNED*
AbstractOBJECTIVE: To investigate the possible effects of cocaine on prostacyclin and
prostaglandin (PG) E2 production from endothelial cells derived from human umbilical cord.
STUDY DESIGN: First-passaged endothelial cells derived from the umbilical vein were incubated
with various doses of cocaine, procaine and lidocaine and 24 h later the supematants were assayed
for prostacyclin metabolites 6-keto-PGF1alpha and PGE2. Cocaine concentrations tested were 0, 10,
100, 500 and 1000 microg/ml. RESULTS: Cocaine produced a dose-dependent reduction in
prostacyclin and PGE2 production from endothelial cells (p) < 0.05). Acetylcholinesterase (a possible
detoxifier of cocaine) abolished the effect of cocaine on prostacyclin production. Procaine, an esteroltype anesthetic, produced a similar effect on prostacyclin production, an effect not observed with
lidocaine. CONCLUSION: It is speculated that, when present in high concentrations, cocaine may
affect vascular tone by inhibition of endothelial cell prostacyclin and PGE2 release.
Publication TypeJournal Article.
•
12757774
AuthorsTogna GI. Togna AR. Graziani M. Franconi M.
Authors Full NameTogna, Giuseppina I. Togna, Anna Rita. Graziani, Manuela. Franconi, Matteo.
InstitutionDipartimento di Fisiologia Umana e Farmacologia, Istituto di Farmacologia Medica,
Universita di Roma La Sapienza, P.le A. Moro, 5-00185 Rome, Italy. [email protected]
TitleTestosterone and cocaine: vascular toxicity of their concomitant abuse.
SourceThrombosis Research. 109(4):195-201, 2003 Feb 15.
Local Messages*UTHSCSA LIBRARIES OWN JOURNAL. CLICK LIBRARY HOLDINGS FOR
VOLS OWNED*
AbstractOver the last few years, several studies have described an increase in the use of anabolicandrogenic steroids (AAS). More important, frequency of AAS use was significantly associated with
frequency of psychotropic drug use, such as cocaine. Since information is not available on the effects
of their concomitant abuse, and taking into account that cocaine and testosterone, when singly
abused, are known to induce severe adverse effects on vascular system, our purpose was to evaluate
in vitro the combined effect of these drugs on platelet and endothelial functions. Results show that
testosterone, at concentrations not exerting any appreciably acute effects on their own, is capable of
potentiating the cocaine effect on endothelial and platelet functions, indicating that concomitant use
of testosterone and cocaine could result in enhancement of the thrombotic risk ascribed to these
drugs.
Publication TypeIn Vitro. Journal Article.
•
16341998
AuthorsWu YW. Lynch JK. Nelson KB.
Authors Full NameWu, Yvonne W. Lynch, John K. Nelson, Karin B.
InstitutionDepartment of Neurology, University of California San Francisco, San Francisco, California 94117, USA.
TitlePerinatal arterial stroke: understanding mechanisms and outcomes. [Review] [103 refs]
SourceSeminars in Neurology. 25(4):424-34, 2005 Dec.
Local Messages*UTHSCSA LIBRARIES OWN JOURNAL. CLICK LIBRARY HOLDINGS FOR VOLS OWNED*
AbstractArterial ischemic infarction occurring around the time of birth is an increasingly recognized cause of
neurological disability in children. The rate of arterial infarction in neonates is as high as the annual incidence of
large-vessel ischemic stroke in adults. Factors contributing to this increased risk of stroke among neonates include
complications that occur before, during, and after delivery. Maternal conditions that have been associated with
perinatal stroke in the fetus include prothrombotic disorders, cocaine abuse, and placental complications such as
chorioamnionitis and placental vasculopathy. In many cases, the placenta is suspected to be the underlying embolic
source for perinatal stroke, although data on placental pathology is often lacking. During the delivery process, an
infant may develop a cervical arterial dissection that leads to stroke. Several conditions in the neonatal period
predispose to perinatal stroke including prothrombotic disorders, congenital heart disease, meningitis, and systemic
infection. Perinatal stroke may present with neonatal seizures during the first weeks of life or may be asymptomatic
until months later when the infant is first noted to have pathological handedness. The outcome of perinatal stroke is
variable and depends on severity, anatomic localization, and other factors not yet well characterized. As many as 50%
of infants with documented stroke recognized in the newborn period do not develop a hemiparesis. The incidence,
clinical presentation, pathogenesis, risk factors, and outcome of this increasingly recognized disorder are reviewed.
[References: 103]
Publication TypeJournal Article. Review.
•
15027587
AuthorsFoidart JM. Seak-San S. Emonts P. Schaaps JP.
Authors Full NameFoidart, Jean-Michel. Seak-San, Sonteara. Emonts, Patrick. Schaaps, Jean-Pierre.
InstitutionMaternite Universitaire, CHR Citadelle, boulevard du 12e-de-Ligne, 1, B-4000 Liege, Belgique. [email protected]
Title[Vascular placental pathology in high-risk groups: definition and synopsis]. [Review] [89 refs] [French]
SourceAnnales de Medecine Interne. 154(5-6):332-9, 2003 Sep-Oct.
Local Messages*UTHSCSA LIBRARIES OWN JOURNAL. CLICK LIBRARY HOLDINGS FOR VOLS OWNED*
AbstractThe vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or
acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some
others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental
hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three
categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is
sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk
factors. The risk factors of VPP classified as moderate include age (> or = 35 years), increased blood pressure during the second trimester of
pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic
diseases. Risk is significantly elevated among obese (BMI > or = 25), primiparous women, women with a past familial history (first degree)
of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin
pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients
with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with
antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria,
hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It
remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated
with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events
outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious
placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia
(antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique
heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the
multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental
vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight
heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous
thromboembolism or vascular placental pathology remains controversial. [References: 89]
Publication TypeEnglish Abstract. Journal Article. Review.
Cocaine inh