Patterns of multiple substance abuse during pregnancy: implications for mother and fetus

This paper describes patterns of drug use such as choice of drug, other substances abused, and route of administration in 174 women who reported methamphetamine, cocaine, heroin, or "Ts and blues" abuse during pregnancy. Seventy-five percent (130/174) reported using more than one drug. Other than tobacco, alcohol and cocaine were the drugs most frequently used in combination with other drugs (7% to 53% and 12% to 54% of the time, respectively). The extent of polydrug use observed in this study emphasizes (1) the difficulty in ascribing adverse maternal or fetal health effects to single substances, and (2) the potential for interaction effects due to multiple substance abuse.     

Taking the Pissoir – a novel and reliable way of knowing what drugs are being used in nightclubs

Background: The epidemiology on recreational drug use is based on self-reported user surveys. The scope of this is limited as users are often not aware of exactly what drug(s) they are using. Waste water (sewage plant) analysis has been used to identify “regional” recreational drug use but is limited by a lack of understanding of the metabolism and stability of novel recreational drugs. Aims: The feasibility of collecting pooled urine samples from a sub-population attending a night-club using a portal urinal to confirm the classical and novel recreational drugs being used. Design and Methods: Urine samples were collected from a nightclub over one weekend for analysis by various chromatographic techniques involving mass spectrometry. Results: Classical recreational drugs and novel psychoactive substance, including mephedrone, 3-trifluoromethylphenylpiperazine and 2-aminoindane were found. Parent drug/metabolites were also detected for amphetamine, cocaine, ketamine, MDMA, mephedrone and 3-trifluoromethylphenylpiperazine. Conclusion: Anonymous pooled urine samples from within a nightclub can be used to confirm the actual drugs being used by some individuals within this sub-population. Metabolite detection indicates drugs were being used and not simply discarded into the urinal. This methodology could be used to monitor recreational drug trend in other environments, e.g. schools, geographical regions/areas and compare drug use over time.     

Diastolic alterations in infants exposed to intrauterine cocaine: a follow-up study by color kinesis.

BACKGROUND: During the first 48 hours of life, newborn infants exposed to cocaine in utero have left ventricular diastolic segmental abnormalities. It is unknown whether these abnormalities are transient because of short-term effects or persist in older infants, possibly reflecting a teratogenic effect of cocaine. METHODS: This study prospectively evaluated global and segmental systolic and diastolic cardiac parameters by color kinesis. The patients were 2- to 6-month-old infants who were exposed to cocaine in utero (N = 56). Their data were compared with normal control patients with no intrauterine drug exposure (N = 60) and newborns exposed to drugs other than cocaine (N = 72). RESULTS: At the age of 2 to 6 months, there was no significant difference in the measured color kinesis parameters among the cocaine-exposed and the 2 control groups (infants prenatally exposed to other drugs and no drugs). Infants exposed to heavy cocaine prenatally, as compared with the noncocaine-exposed group, had a significant (P =.007) increase in septal fractional area change during left ventricular filling. CONCLUSIONS: At 2 to 6 months of age, infants have recovered from initial left ventricular diastolic segmental alterations seen in the first 48 hours of life except for the septal wall in the heavily cocaine-exposed group.     

Cocaine: effects of in utero exposure on the fetus and neonate

In North America, an increasing number of babies are prenatally exposed to cocaine, yet the implications of cocaine use during pregnancy are not fully understood. The effects of cocaine are exerted primarily by its influence on aminergic receptors in the central and peripheral nervous systems. Developmental, physiological, and behavioral problems in infants and children are likely outcomes of maternal cocaine abuse, but these findings are confounded by concomitant use of other drugs such as marijuana and cocaine and by factors such as time, dosage, and route of cocaine intake. Different screening options exist for cocaine and its metabolites, including sampling of neonatal urine, hair and meconium need to be considered, as do the sensitivity and the ethical implications of such testing. Clinical management of cocaine-exposed infants requires attention to several issues, including: central nervous system irritation, cardiac anomalies, apnea, and feeding difficulties, as well as infant safety and follow-up postdischarge. Early detection and intervention remain the primary objectives of caring for cocaine-exposed infants.     

Cardiovascular effects of recreational cocaine abuse

Deaths related to the recreational use of cocaine in the United States have increased to epidemic proportions within the last decade. Frequently, persons with cocaine toxicity present to the emergency room, require critical care nursing, and are admitted to the intensive care unit. This article outlines the cardiovascular effects of recreational cocaine abuse. Initially, the historical perspective of the drug is outlined. The mechanism of action, administration, absorption, and excretion are discussed. Details regarding the cardiovascular effects of cocaine are described. Although no uniform treatment plan has been developed for every complication of cocaine overdose, the current therapeutic modalities are outlined. Finally, the clinical implications for clinical practice are addressed. The recreational abuse of cocaine presents new patient care challenges for the critical care nurse. With increased knowledge, the health care provider may assist in meeting the clinical needs of this emerging patient population.     

Mephedrone: a designer drug of recent use in France

Designer drugs are currently marketed as substitutes for stimulant drugs as cocaine, amphetamine, MDMA...Unlike compounds listed as narcotics, these new substances are deliberately synthesized to avoid anti-drug laws. Among them, mephedrone (4-methylmethcatinone) that belongs to cathinone family, has been recently introduced in France. Users report positive euphoric and entactogenic effects. They also describe negative effects such as increased dependence towards the drug itself and larger craving for tobacco and alcohol. The numerous and various described adverse effects include psychoactive, digestive, cardiovascular... effects. Some fatality cases have been reported in scientific literature or in press and attributed to mephedrone often in association with other substances. Mephedrone has been listed as narcotic in several European countries and more recently in France.     

Recreational drugs. Societal and professional issues

Recreational drug use presents a challenge to society and, in particular, the profession of nursing. Recreational drug use must be appreciated for the implications it presents for the episodes of abuse and development of chronic health problems. The effects and recreational use of volatile substances, cannabis, opioids, barbiturates, benzodiazepines, amphetamines, cocaine, psychedelics, and designer drugs as well as alcohol, caffeine, and nicotine must be acknowledged and understood if options for change are to be considered. The resultant cost of recreational drug use as well as health care implications, public safety, and prevention are significant issues society is faced with today. These issues will continue to be significant unless the current posture toward recreational drug use and abuse is addressed. The profession of nursing continues to be faced with the problems associated with recreational drug use not only through caring for clients, but immediately by the effects of recreational drug use on individual professional nurses. To respond effectively, nursing education and nursing research must be challenged to create an emphasis on this focus. Only through this type of multifocal approach will long-term substantial change be affected for the betterment of future generations.     

Cocaine abuse: an expanding healthcare problem for the 1990s.

Cocaine, the most addictive recreational drug available, has increased in popularity and widespread use in the past decade. Crack, a new form of cocaine that is smoked, is purer and more rapidly absorbed into the vascular system, greatly increasing the risk of overdose. Cocaine produces many physiologic effects on the body systems. This case report focuses on two cardiovascular responses related to cocaine use: cardiomyopathy and coronary vasospasm. Cocaine abusers may present with complaints of chest pain or other nonspecific symptoms that require diligent assessment skills to be recognized as cocaine-related. Therefore, it is essential that nurses be knowledgeable about the effects of cocaine and the symptoms of cocaine abuse.     

Substance abuse and the kidney

Substance abuse has been increasing steadily in the UK and some other countries. Recent evidence suggests more than 40% of young people have tried illicit drugs at some time. There are numerous medical consequences to recreational drug use, and a physician should always consider substance abuse in any unexplained illness. The renal complications of drug abuse are also becoming more frequent, and may encompass a spectrum of glomerular, interstitial and vascular diseases. Although some substances are directly nephrotoxic, a number of other mechanisms are also involved. These effects are often chronic and irreversible, but occasionally acute with possible recovery. The rapid growth of illicit drug use is clearly a major public health problem. We review the commonly used substances of abuse and their associations with renal disease.     

Evaluation of herbal dietary supplements marketed on the internet for recreational use

BACKGROUND: The Internet is a popular tool for marketing and purchasing herbal dietary supplements (DS). Various Web sites sell these products purely for recreational use. OBJECTIVE: To describe the content of Web sites that advertise and market herbal DS for recreational use (ie, for the purpose of altering mood/behavior/or perception, "getting high," or as a substitute for a drug of abuse). METHODS: Four major search engines and the search terms "buy herbal high" and "buy legal high" were used to identify Web sites selling herbal DS for recreational use. Web sites were evaluated for their country of origin and for compliance with the Dietary Supplement Health and Education Act (DSHEA). Products were evaluated for their ingredient lists, effect claims, comparisons with illicit drugs, adverse effects, drug interactions, and contraindications. RESULTS: Twenty-eight unique Web sites with 119 products were evaluated. Most sites were in the US (54%) and were in compliance with DSHEA. Forty-seven percent of the products were likened to illicit drugs, typically marijuana (48%) or 3-,4-methylene dioxyamphetamine (Ecstasy; 23%). The most common product ingredients were ephedra alkaloids (27%), Salvia divinorum (17%), kava (10%), guarana (10%), Acorus calamus (10%), and damiana (10%). Effect claims frequently involved the products' use as a hallucinogen (51%) or stimulant (39%). Sixty-four percent of the sites mentioned adverse effects, and 54% mentioned drug interactions. CONCLUSIONS: This study demonstrates that herbal DS are being marketed for use as legal alternatives to illicit drugs of abuse. Healthcare professionals need to be aware of this trend and the products that are involved.     

Interactions of phytotherapeutic drugs,foods and drinks with medicines

Phytotherapeutic preparations contain a large number of pharmacologically active components. Protective systems have evolved to detoxify and eliminate these xenobiotics. Among them is the cytochrome P450 system and the transporter p-glycoprotein in intestine and liver that control the absorption, biotransformation and elimination of drugs. Components of phytotherapeutic preparations can interfere with the function of these systems and lead to interactions with drugs. St John's wort, for example, induces the expression of p-glycoprotein and CYP3A4 in liver and intestine and thereby decreases the activity of other drugs. Garlic extracts as well may decrease the activity of drugs that are substrates for CYP3A4. In contrast, grapefruit juice inhibits intestinal CYP3A4. This results in a higher bioavailability of some drugs and possibly more adverse effects. Some relevant interactions were only detected after many years of widespread use, indicating that the treating physician should not only inquire about a change in co-medication but also about the use of alternative medicines or a change in dietary habits when a patient presents with unexpected and unusual adverse effects or a sudden loss of drug efficacy. It would be desirable if more information regarding the potential for interactions with commonly used drugs was available prior to registration of new phytotherapeutic preparations in order to document their safety for patients who require continuous treatment with a drug because of a chronic disease.     

Assessing abuse liability during drug development: changing standards and expectations

As public health concerns have changed, regulatory expectations for assessing abuse liability of new central nervous system (CNS) drugs have increased. All CNS-active drugs with any properties indicating stimulant, depressant, hallucinogenic, or mood-elevating effects will require an evaluation of abuse liability. Abuse liability assessment involves the collection, analysis, and interpretation of data on chemistry and tampering, animal behavioral pharmacology, clinical trial adverse events (AEs), diversion and overdose, and potentially reinforcing (subjective) effects in recreational drug users.     

Cannabis can augment thrombolytic properties of rtPA: Intracranial hemorrhage in a heavy cannabis user

Cannabis is one of the most commonly used illicit drugs in the United States and is considered to have several adverse health effects. There is evidence suggesting that its recreational use is associated with both increased cardio- and cerebrovascular events. Recently, multiple cases of ischemic and hemorrhagic strokes associated with cannabis use were reported in the literature (Goyal et al., 2017). It has been suggested that cannabis can affect cerebral auto-regulation and vascular tone leading to vasoconstriction and acute ischemic stroke. However, hemorrhagic strokes, which are often seen with sympathomimetic illicit drugs (e.g. cocaine and amphetamines), have rarely been reported due to cannabis. Many cellular mechanisms within non-ischemic tissue post stroke may be augmented by heavy cannabis use. Here, we describe a rapid development of hemorrhage following thrombolytic therapy in a patient with heavy cannabis use with an ischemic stroke.     

Maternal cocaine use during breastfeeding

Question In my practice several patients have struggled with cocaine abuse during their pregnancies. One woman, now postpartum, wants to breastfeed her infant. Despite being abstinent for the final few months of her pregnancy, I am concerned about the potential adverse effects on her child if she happens to relapse. What is the current evidence about the risks of cocaine exposure during breastfeeding?Answer Given the substantial benefits of breastfeeding for infant health and development, there is no reason for mothers who previously abused cocaine to avoid breastfeeding. It is important for the health care team to counsel patients both on the serious potential risks of cocaine exposure for babies and on the benefits of breastfeeding, to allow for an informed choice. Additionally, attempts should be made to estimate maternal commitment to breastfeeding and discontinuation of cocaine use, and to offer addiction counseling to mitigate the potential risks of infant cocaine exposure. It is paramount to minimize the risk to the infant, which would certainly include mothers ceasing use of cocaine while breastfeeding. For mothers who elect to breastfeed and use cocaine intermittently, breastfeeding should be delayed sufficiently after cocaine use to allow for drug elimination (approximately 24 hours).     

Accuracy of current clinical diagnosis in recreational drug‐related attendance to the emergency department

Objective: To determine the accuracy of current clinical diagnosis in recreational drug‐related attendances to emergency by blood analysis. Methods: A prospective convenience sample of 103 patients who attended hospital with suspected recreational drug‐related presentations was collected. Doctors' clinical impression of drugs responsible for presentation was compared with a detailed forensic blood analysis for recreational drugs. Results: Among 103 samples, 80 (78%, 95% confidence intervals [CI] 70–86%) were found to have correct clinical suspicion of the recreational drug responsible for clinical presentation confirmed by laboratory analysis. Clinical diagnosis was most accurate for gamma‐hydroxy butyrate (GHB) (sensitivity 97%, specificity 91%) and less accurate for amphetamines (sensitivity 61%, specificity 79%), alcohol (sensitivity 42%, specificity 84%) and opiates (sensitivity 46%, specificity 100%). Multiple drug ingestion was found in 70% (95% CI 61–79%) of samples. Sensitivity and specificity of clinical impression for prediction of multiple drug ingestion presence is 75% (95% CI 66–83%) and 85% (95% CI 78–92%), respectively. Conclusion: Clinical diagnosis in recreational drug‐related attendances to the ED was correct in most cases. Drugs, such as GHB, were the most accurately diagnosed. Inaccuracy in recognizing other drugs, like amphetamines, opiates and alcohol, occurs where a coingestant produces a more profound clinical picture. Multiple drug ingestion is a common scenario in recreational drug presentations to emergency.     

Ethical and Regulatory Considerations of Placental Therapeutics

PurposePlacental therapeutics aim to treat placental disease; however, ethical and regulatory issues should be considered if the drug also potentially affects the fetus. Drugs that might transfer or edit genes carry a specific challenge because currently fetal gene editing and fetal gene therapy are considered unethical.MethodsThis article reviews the literature on ethical and regulatory considerations for placental therapeutics.FindingsProposals for maternal gene therapy, directed to the maternal side of the placenta, have been discussed with patients and stakeholders. No absolute ethical, legal, or regulatory barriers to this potential treatment were identified. Patients who have experienced placental disease, such as fetal growth restriction, are interested in these therapies; some would participate in first-in-human trials. Such trials need careful regulatory considerations, such as the steps required to indicate tolerability and efficacy in preclinical models and the optimal animals for reproductive toxicology studies. Ex vivo dual human placenta perfusion experiments and villous explant in vitro studies allow drugs to be tested in normal and diseased human placenta, providing short-term tolerability and toxicologic assessment. Testing drugs in nonhuman primates is an option but carries ethical and feasibility considerations. Selection of inclusion and exclusion criteria for clinical trial participants is important to ensure that the most suitable patients are exposed to a first-in-human drug. These patients will almost certainly be pregnant women with a high risk of perinatal loss and/or perinatal and maternal morbidity. Criteria should identify sufficient numbers of patients to make a trial feasible as well as a phenotype that will respond to the mechanism of action. How to dose escalate and to capture information on adverse events are also key to optimal clinical trial design.ImplicationsDeveloping placental therapeutics requires input from scientists, practitioners, and regulators and close liaison with patients to ensure that new drugs are tested as carefully as possible.     

Relative reinforcing effects of cocaine, remifentanil, and their combination in rhesus monkeys

Human polydrug abusers often take combinations of opioids and stimulants, but it is not clear why. Behavioral economics with demand curve analysis is uniquely able to separate two of the possibilities: that the drug combination increases the reinforcing potency of the component drugs or that the drug combination is a more effective reinforcer than either drug alone. Rhesus monkeys self-administered a range of doses of cocaine, remifentanil, and combinations of the drugs through indwelling intravenous catheters; the number of responses required for each drug infusion increased across drug-availability sessions. Combining small doses of cocaine and remifentanil that by themselves resulted in very low rates of responding yielded rates of responding that were higher than the maximum maintained by any dose of the constituent drugs. Nevertheless, demand curve analysis demonstrated that the drug combination was equally elastic as the component drugs, indicating that it was not more effective as a reinforcer than either cocaine or remifentanil alone. This suggests that enhanced self-administration of this particular drug combination is due primarily to the drug enhancement of the potency of the other drug.     

Characterization of the effects of cocaine and GBR 12909, a dopamine uptake inhibitor, on behavior in the squirrel monkey.

The behavioral effects of cocaine and GBR 12909, a highly selective dopamine uptake inhibitor, were compared in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus termination and a second-order schedule of drug self-administration. Both drugs exhibited similar pharmacological profiles; intermediate doses increased response rates markedly and higher doses decreased response rates below control values. The magnitude of the rate-increasing effect was similar for cocaine and GBR 12909, although cocaine was approximately 3 times more potent. In contrast, the direct-acting dopamine agonists, SKF 38393 and quinpirole, produced only decreases in response rates. When cocaine and GBR 12909 were studied in combination with dopamine antagonists, the effects of either on fixed-interval performance were attenuated in a similar manner by a D1-selective antagonist (SCH 23390) and a D2-selective antagonist (spiperone), indicating the involvement of both D1 and D2 receptor subtypes. In contrast, an alpha 1-selective antagonist (prazosin) did not alter the dose-effect curve for cocaine or GBR 12909 in a manner that indicated a pharmacological antagonism. When doses of cocaine were administered in combination with GBR 12909, the effects on behavior were additive. However, the combined effects of cocaine and SKF 38393 or cocaine and quinpirole were more complex and did not appear to be additive. When the cocaine or GBR 12909 was self-administered under a second-order, fixed-interval schedule of drug injection, schedule-appropriate responding was maintained and the potency difference between the two drugs was comparable to that observed under the stimulus-termination schedule.(ABSTRACT TRUNCATED AT 250 WORDS)