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The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics.

Although a statement on Neonatal Drug Withdrawal was published in 1998 by the American Academy of Pediatrics, pharmacologic management of neonatal abstinence syndrome (NAS) remains a challenge. Published clinical trials are limited, restricting treatment decision making to practitioner's experience and preference rather than evidence-based medicine. To optimize withdrawal symptom prevention, drug selection is often based on the offending agent (opioids versus polysubstance exposure), clinical presentation, mechanism of action (agonist versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters and available drug formulations. This review addresses risk factors and pathophysiology of NAS, summarizes parameters of common drugs used for the management of NAS, and reviews published literature of standard therapies as well as newer agents. Based on the current literature, paregoric is no longer recommended and oral morphine solutions remain the mainstay of therapy for opiate withdrawal. Other potential therapies include methadone, buprenorphine, phenobarbital and clonidine with the latter two agents as adjunctive therapies.

Chronic pain (CP) is a very common problem in elders, due to bodily degenerations, worldwide. Studies carried out in various countries have shown that CP is associated with the elders’ quality of life, significantly limiting their activities and hampering them to maintain an independence lifestyle. What’s worse, elderly suffering from CP mostly also experience mental problems. Yet, there have been only a few such research done and reported on this topic, concerning the elderly ethnic montagnards in the rural southwest Guangxi of China. This study aimed to explore the statement and self-management of rural dwelling elders with CP. First, cross-sectional surveys were conducted and then interviews were carried out. 150 elder people experiencing CP -- pain suffered at least 4 to 5 days a week during the past 3 months, according to the criteria of the international Association for the study of Pain (IASP) -- were enrolled in this study by convenience sampling. They were asked to fill in 3 questionnaires; the first related to participants’ mental status, the second related to participants’ perception of pain intensity, and the third related to pain’s impact on participants’ daily life. Following the completion of questionnaires, individual interviews were conducted, with the help of some students who are fluent in local native languages as well as in Chinese. The results show that CP significantly affected participants’ quality of life. The prevalence of suffering from multifocal CP was 90%. In the management of CP, 64% people mainly relied on paregoric means; a wide range self-management techniques were mentioned such as hot compress application for which some plant material was used, collected from the surrounding environment; only a few people went to seek professional treatment. Moreover, most of them said that they had reconciled to the pain or consider it as part of their fate. Encourage older people to seek different ways to manage their pain, not just traditional but complementary and professional approaches. In such severely lacking professional high-level medical resource environment, the elder people should change their cognition of CP and choose pertinence approaches and instruments based on their own condition.

Drugs and sexual function are intimately linked, and drug history and sexual history are essential components of psychosocial assessments. Obtaining a history of drug use, however, can be as complex as eliciting a sexual history. The complexity stems in part from associated taboos and the stigmatization of drug users across cultures. Drugs can be used ritualistically as part of sexual activity, perpetuating sexual taboos. Psychoactive substance use can be defensive in persons with preexisting sexual dysfunction or co-morbid mental disorders. Drug use can also generate or worsen sexual dysfunction. Psychoactive drugs are believed to have aphrodisiacal properties. They have been used as an instrument in religious practices and as a way to lift the taboos associated with sex and aggression. Descriptions of the behavioral effects of psychoactive drugs can be dated to 4000 B.c. Ethanol, opium, and derivatives of the Erythroxylum coca and Cannabis sativa plants are among the oldest psychoactive drugs known to man. As noted by Musto [1], opium was one of the earliest drugs imported to North America. The distribution of laudanum and paregoric, alcohol extracts of crude opium, became widespread. Morphine, a naturally occurring alkaloid, was isolated from Papaver somniferum, the opium poppy plant, in 1806. Codeine was isolated in 1832 and was marketed as a cough suppressant Heroin, or diacetylmorphine, was synthesized in 1898. At the

Americans have something to learn from our extensive consumption of opium, heroin, and cocaine, that oc curred before World War I. Forgetting this era, we commonly act as if the heroin "epidemic" of the 1960s or the current cocaine "epidemic" is a new phenomenon in the United States. Some of us assume that the widespread use of a drug implies that legalization or "decriminalization" is the only reasonable response. The history of legislative con= trol in the United States suggests that other courses may be effective and that alternatives to legalization ap pear to have reduced opiate and co caine consumption in the United States earlier in this century. In spite of a heavy national addiction rate in 1920, the United States did reduce its number of addicts to a relatively small number. Clearly the social and legal factors affecting drug use are complex. There is no single influ ence that determines a particular level of drug use and abuse. Legislative control over dangerous drugs may be dated from attempts in the nineteenth century to prevent acute poi soning by certain substances that might be purchased in ignorance of their lethal po tential or might be too easily available to the suicidal. Opium was sold in a crude form containing about 10 percent mor phine, as well as in concoctions derived from crude opium: paregoric, laudanum, and a solution in acetic acid known as "black drop." Morphine had been isolated from opium in the first decade of nine teenth century. Consumption of opium in the United States rose steadily before and after the Civil War. Before the war, such prominent and progressive physicians as Oliver Wendall Holmes had complained about "opium drunkards." In the second half of the century, many more physicians, as well as the general public, widely deplored

The Efficacy of Paregoric Versus Tincture of Opium in the Treatment of Neonatal Abstinance Syndrome (NAS)

Background: Although the number of cases of passively-addicted newborns is increasing, there has been scant development of treatment alternatives for these infants. Evidence from in vitro cell culture and in vivo animal studies by S. Crain and associates suggests that Naltrexone, an opiate antagonist, can inhibit opiate excitatory activity when given in microdoses. Naltrexone has also been used successfully in the treatment of adult addiction, but there are no reported studies using Naltrexone in the treatment of passively addicted newborns. The aims of this study were to test the hypothesis that Naltrexone microdose supplementation of paregoric treatment for neonatal withdrawal could reduce the duration of treatment required and to examine the safety of Naltrexone for these infants.

Our cohort (N=68) consisted of newborns treated for narcotic withdrawal with paregoric at University Hospital in Newark, NJ in 1994. Overall mean length of treatment, i.e., mean (standard deviation) was 18.5 (13.4) days. Scoring with the Finnegan Narcotic Abstinence Scale (FNAS) was initiated on average at 0.7 (1.2) days of life. Maximum FNAS score was obtained at a 3.6(5.1) days of life. Starting dose was given at mean 4.0 (4.9) days. Infants dosed initially with fewer than 6 drops (n=30) required a mean of 14.7 (13.3) days of treatment while those receiving 6 or more drops (n=37) needed 21.6(12.8) days, p=.03 by unpaired t-test, (i.e.), requiring an extra week of treatment). Contrary to expectation, there was, in general, little correlation between beginning or maximum FNAS vs beginning or maximum dosage of paregoric. For example, r=.15 between maximum FNAS and maximum dosage (p=.44 by Pearson correlation analysis). Starting FNAS was 4.9 (3.1) and maximum FNAS was 11.4(1.9). Starting paregoric dose was 5.5 (1.5) and maximum dose was 6.0 (1.7). In fact, the starting and maximum dose was the same for 47 infants (70.1%), indicating essentially little or no change in dosing regimen during a period of escalating withdrawal symptoms as measured by FNAS. Length of treatment was related to starting dose, maximum dose and maximum FNAS score, with correlations of r=.30 (P=.01), re=.58 (p=.0001) and r=.33 (p=.006) respectively.

A partition chromatographic method for the determination of morphine in paregoric and other opium preparations was subjected to collaborative study. The morphine is separated from associated opium alkaloids by successive elution through consecutive acidic and alkaline columns and is measured by UV absorbance. The isolated morphine was shown to have a high degree of purity. The method is rapid and the results of the collaborative study show good precision and accuracy. The method is recommended for adoption as official, first action.

An ultraviolet absorption spectrophotometric method is described for the determination of morphine in paregoric. Morphine is isolated from a 5 ml paregoric sample by a modification of the USP XVII extraction procedure and then measured by ultraviolet absorption spectrophotometry. Factors affecting the precision and accuracy of the method are discussed.

[Read in the Section on Diseases of Children, June, 1883.] Many of our most successful practitioners of medicine amongst the adult population have made signal failures when called upon to exhibit their skill in the treatment of tender children. We have often been pained by the remarks dropped from the lips of some physicians whom we were endeavoring to regard as sample practitioners, on account of the indifference manifested, and the slight degree of importance attached to their practice among the children, such as, “Well, you may give a few drops of ‘paregoric,’ or some ‘catnip tea,’ or most anything of that kind you may find convenient, as we cannot do much for children so young;” or, “Your mothers or ‘old women’ can treat young children as well as I or any physician can;” or, “I don't like to treat children, it is so unsatisfactory. They cannot tell how they

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Newborns exposed in-utero to opiates and/or nonopiates frequently undergo NAS. This study evaluated:1)the relationship between the type of maternal drug use and the incidence of NAS and 2)which of 3 treatment drugs was most effective-- paregoric, phenobarbitol, or diazepam. NAS was assessed by a scoring system related to drug dose. Successful treatment was considered when one drug controlled the NAS. Of the 300 infants, 176(59%) were treated for NAS and 124(41%) required no treatment. Maternal drug use consisted of opiates(33%), non-opiates(14%)and varying combinations of both(53%). Infants exposed to non-opiates in-utero were less likely to undergo abstinence(36%) than those exposed to opiates(58%) or both(70%). The mean number of days to control symptoms of NAS was 7.6, and duration of treatment averaged 38,6 days, The efficacy of treatment drug for NAS depended upon the type of drug exposure in-utero. If maternal drug use included opiates alone, paregoric was the drug most successful in controlling NAS (87% of infants). In maternal non-opiate use, phenobarbital was most effective(100%). In maternal opiate and non-opiate use, paregoric was most effective(88%). Treating an infant with diazepam indicated the need for a second treatment drug in 70% of cases, regardless of maternal drug use (p=.001). These data suggest that:1)effective NAS treatment is related to the type of maternal drug use, 2)there is a higher incidence of NAS in infants prenatally exposed to opiates alone or in combinnation with non-opiates, and 3)diazepam is Ineffective as a treatment agent for NAS.

Measures of newborn sucking behavior were used to study effects on the infant's state of CNS arousal induced by maternal addiction. The sucking performance of 38 infants diagnosed and treated for narcotic withdrawal by a new symptom scoring system (Neonatal Abstinence Score) was compared with that of 50 infants whose withdrawal was regulated by acceptable clinical methods. The findings indicate the value of the scoring system in prescribing the dosage of drug therapy which resulted in better levels of CNS arousal and improved sucking performance. Also, using sucking performance as a criterion, it was found that paregoric was superior to phenobarbital in treating neonatal withdrawal. In addition, the severity of withdrawal as measured by sucking was directly related to the mother's length of time in the methadone maintenance program and her average dose of methadone. This finding may reflect the fact that patients enrolled in a maintenance program are assured of a continued supply of a long-acting narcotic drug, as compared to street addicts, whose supply is highly variable in quality and availability, and, that addicts who enter the methadone program during pregnancy tend to be given smaller doses than those who are not pregnant.

The majority of infants born to drug-dependent women undergo neonatal abstinence syndrome (NAS) and often require pharmocotherapy for the treatment of withdrawal symptoms. Phenobarbitol, paregoric, and diazepam have been recommended for the treatment of the syndrome. While some investigators have examined the efficacy of these agents in treating NAS, there are no data regarding the use of specific pharmacologic agents and developmental outcome. This study evaluated 85 infants bom to drug-dependent women who were maintained on methadone during pregnancy. Severity of infant withdrawal was assessed with the Neonatal Abstinence Scoring system (Pediatric Research 7:319, 1973). Infants who required pharmacotherapy were randomly assigned to one of four treatment regimens: paregoric, phenobarbitol (titration), phenobarbitol (loading), and diazepam. When treatment was not successful with the assigned agent, one of the other agent(s) was used. At 6 months of age, the developmental status of infants was assessed with the Bayley Scales of Mental Development. Based on NAS treatment, four groups were delineated: I) paregoric (n=21); II) phenobarbitol (n=17); III) more than one agent (n=31); and IV) no treatment. (Data for the phenobarbitol loading and titration groups were combined since analysis revealed no differences between groups. All infants who initially received diazepam were included in Group III since diazepam as a single agent was not successful). Results of one way analysis of variance revealed no differences in developmental status between groups (p =

Infants undergoing neonatal abstinence due to maternal drug use are commonly treated with paregoric, phenobarbital or diazepam. This study was designed to test the effectiveness of each of these agents as the first treatment drug in the control of abstinence symptomatology. The relationship of the type of maternal drug use to the effectiveness of treatment was also examined. Subjects were 134 infants treated for abstinence at Thomas Jefferson University Hospital between 1979 and 1983. Infants with serious medical complications were eliminated from the study. A series of least squares linear regression analyses was performed using the treatment drug, type of maternal drug use (opiates, non-opiates, or both), and the interaction of treatment and maternal drugs as predictors of whether or not a second pharmacotherapeutic agent was needed to bring the infant under control. Results revealed that if maternal drug use was limited to non-opiates, phenobarbital therapy was a significant predictor of successful treatment with one drug. Treating an infant with diazepam, however, significantly predicted the need for a second agent, regardless of maternal drug use. Paregoric was a significant predictor of successful treatment if maternal drug use included opiates or a combination of opiates and other drugs, and was a significant predictor of unsuccessful treatment if the mother abused only non-opiates. These results emphasize the ineffectiveness of diazepam for the treatment of neonatal abstinence as well as the relationship of maternal drug use to effective pharmacotherapy.

Man and animals generally seek escape from discomfort. Man today seems more prone to do so than ever before and, as will be seen, has acquired a considerable variety of means to that end. No one knows when man learned that there were natural agents available, the poppy among them, to ease his pains; but he did acquire that knowledge, and there the history of narcotics begins. Legally and otherwise, narcotic has a broader connotation than opiate. Practically, however, the major part of the narcotics problem centers around the opiates and their synthetic substitutes, and this account of historical development will deal with these only. Chopra suggests that the food value of the seeds of the opium poppy was recognized much earlier than the somniferous property of the capsule or poppy head,' but the capsules were used in the preparation of soporific drugs and soothing beverages from time immemorial. Poppies were grown for the capsules in Asia Minor many centuries ago, and the Arabs carried the dried poppy heads to eastern countries at a very early date. Eventually, someone discovered that at one stage in the development of the poppy plant, Nature seemed to concentrate its soporific properties-that is, the ingredients responsible for them-in the plant juice which would exude from the lanced ripe poppy head. This juice, collected and dried, is crude opium. Opium became a household remedy and the mainstay of the physician in its crude form, in pills, and in various liquid preparations-laudanum, paregoric, etc.whatever the symptomatic need. It also became a medium of social exchange and self indulgence as a confection and, in modified form, for smoking. Even into the latter half of the nineteenth century, there was little recognition of and less attention paid to overindulgence in or abuse of opium. It was the panacea for all ills. When a person became tolerant to its action and dependent upon it so that abstinence symptoms developed if a dose or two were missed, more was taken for the aches and pains and other discomforts of abstinence, just as it was taken for similar symptoms from any other cause. In the first decade of the last century, just about 150 years ago, the curiosity of Sertiirner, a German pharmacist, brought about the separation and recognition of