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 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ultimate objective in devising animal analogs of physical dependence on ethanol is to obtain meaningful imitations that have behavioral and biological similarities to human subjects during the ethanol withdrawal syndrome. The natural history of alcoholic disease in human subject and in experimental animals involves three periods, each characterized on the basis of temporal relationships, pattern of ethanol intake, blood ethanol concentrations, and/or a typical sequence in the onset and decay of the characteristic spectrum and continuum of overt behavioral, neurological, and biological signs and responses. These characteristics are expressions of different functional states of the central nervous system (CNS): 1) the baseline period or predrinking period reflects normal function of the CNS; 2) the induction period or drinking period is characterized by overt signs and responses of nonspecific, long-term CNS depression; and 3) the withdrawal period is characterized by a relatively rapid transition in the CNS function from depression during the prodromal detoxication phase to hyperexcitability observed during the withdrawal syndrome (dependence phase). The rapid transition from overt depression to overt hyperexcitability is a consequence of rapid removal of the drug from the system, and constitutes the basis of the reversal in the CNS function in both humans and experimental animals.
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PMID:Reversal in central nervous system function during ethanol withdrawal in humans and experimental animals. 722 62

Flupirtine is a novel non-opiate centrally acting analgesic agent with muscle relaxant properties, advocated for use in a number of pain states. Preliminary evidence suggests that flupirtine 100 to 200mg orally or 150mg rectally 3 to 4 times daily (maximum daily dose 600mg) is more effective than placebo in relieving moderate acute pain of various types. For the relief of pain due to surgery, traumatic injury, dental procedures, headache/migraine and abdominal spasms, flupirtine has proved at least as effective as the opiate analgesics codeine, dihydrocodeine and pentazocine, the nonsteroidal anti-inflammatory agents suprofen, diclofenac and ketoprofen, as well as dipyrone and paracetamol (acetaminophen). Although evidence to support a role in the treatment of chronic pain is limited, flupirtine has been found as effective as pentazocine in short term trials of patients with muscular or neuralgiform pain, dysmenorrhoea, soft tissue rheumatism or cancer pain. The safety profile of flupirtine has not yet been fully established, although initial evidence suggests that adverse reactions, while frequent, are usually minor in nature. The most common reactions are drowsiness, dizziness, dry mouth and various gastrointestinal complaints. In comparison with opiate drugs, flupirtine appears to produce fewer central nervous system effects, no respiratory or cardiovascular depression, and no overt tolerance or physical dependence on prolonged administration. If these initially favourable results are confirmed in larger long term trials, then flupirtine would appear to represent an effective analgesic for the relief of moderate pain, particularly that of musculoskeletal origin.
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PMID:Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. 768 75

Optimal pain control in the dying child often requires aggressive opioid therapy that exceeds recommended parameters and may hasten death caused by respiratory depression. For pediatric nurses caring for the dying child, the administration of potentially life-shortening analgesia gives rise to a number of ethical issues. Pediatric nurses often express concern that aggressive pain control is a form of euthanasia or fear the child will develop a drug dependence. Lack of clarity about the ethical obligations and professional responsibilities of nurses who administer potentially life-shortening analgesia may also contribute to the dilemmas surrounding such situations. If left unresolved, these issues can interfere with the nurse's ability to implement an appropriate pain regimen. To provide adequate pain control, pediatric nurses who care for dying children must accomplish the following: critically examine ethical issues and underlying principles; understand the phenomena of addiction, tolerance, and physical dependence; and identify the boundaries of acceptable nursing practice when administering potentially life-shortening analgesia to terminally ill children.
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PMID:Pain management and potentially life-shortening analgesia in the terminally ill child: the ethical implications for pediatric nurses. 781 90

Many of the symptoms of nicotine withdrawal are similar to those of other drug withdrawal syndromes: anxiety, awakening during sleep, depression, difficulty concentrating, impatience, irritability/anger and restlessness. Slowing of the heart rate and weight gain are distinguishing features of tobacco withdrawal. Although nicotine withdrawal may not produce medical consequences, it lasts for several weeks and can be severe in some smokers. Like most other drug withdrawals, nicotine withdrawal is time-limited, occurs in non-humans, is influenced by instructions/expectancy and abates with replacement therapy and gradual reduction. Unlike some other drug withdrawal syndromes, protracted, neonatal or precipitated withdrawal does not occur. Whether nicotine withdrawal is associated with tolerance, acute physical dependence, greater duration and intensity of use, rapid reinstatement, symptom stages, cross-dependence with other nicotine ligands, reduction by non-pharmacological interventions and genetic influences is unclear. Whether nicotine withdrawal plays a major role in relapse to smoking has not been established but this is also true for other drug withdrawal syndromes.
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PMID:Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities. 784 57

A review of the published case reports of adverse behavioral episodes or unexpected psychopathology in patients taking benzodiazepines was undertaken in an attempt to determine if these adverse or unexpected events are more likely to occur with alprazolam when compared with other currently marketed benzodiazepines. Adverse behavioral phenomena and unexpected psychopathology were divided into the following categories: (1) anger or violence, (2) impulsive, suicidal, or self-harming behavior, (3) depression, (4) mania, (5) schizophrenia, (6) withdrawal syndromes and (7) physical dependence and abuse liability. It is difficult to draw conclusions from this literature because of the limitations of spontaneously reported cases and the lack of epidemiologic studies. Despite these limitations, it appears that some differences between alprazolam and older benzodiazepines may exist. The older benzodiazepines are more commonly reported to have adverse events than alprazolam (with the exception of mania or hypomania). On the other hand, worsening in post-traumatic stress disorder and an increase in impulsive behavior in patients with borderline personality disorder have only been reported in patients receiving alprazolam. This is probably explained by the fact that only alprazolam has been used to any great extent in these conditions.
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PMID:Adverse behavioral events reported in patients taking alprazolam and other benzodiazepines. 826 90

Earlier work suggested that adaptive mechanisms of the hibernating brain may also block the development of morphine physical dependence. To test an alternate view that CNS depression itself might be the major factor in the failure of dependence to develop, we compared the strength of dependence produced by morphine (two 75-mg pellets, s.c.) given for 12 hr in the presence, versus in the absence, of continuous pentobarbital anesthesia in nonhibernating ground squirrels (Citellus lateralis) and, in addition, in rats. Dependence was measured by the naloxone (5 mg/kg, s.c.) evoked abstinence syndrome in the awake state. The results demonstrated that pentobarbital-induced general anesthesia does not significantly reduce the development of morphine dependence in either species. We conclude that CNS depression alone does not account for the hibernation-related reduction in morphine physical dependence.
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PMID:Morphine physical dependence in the hibernator: central nervous system mechanisms underlying the development of dependence remain functional during depression induced by pentobarbital anesthesia. 845 Jul 4

Narcotic opioid compounds are among the most widely prescribed drug interventions for individuals suffering pain. Among the unwarranted side effects of respiratory depression, constipation, and physical dependence are the immunosuppressive qualities, particularly those which affect cell-mediated immunity. The immunosuppressive characteristics of opioid narcotics (e.g., morphine) have recently come into focus with the advent of acquired immune deficiency syndrome (AIDS) and the putative causative agent, human immunodeficiency virus type 1 (HIV-1). Specifically, a vast reservoir of HIV-1-infected individuals exists among drug abusers. Moreover, experimental evidence would suggest narcotic opioids may increase viral load in infected individuals by modifying the cellular machinery of activated leukocytes. Likewise, investigators have shown that opioids modify tumor growth and development. In this review, a comparison between endogenous opioid peptides and exogenous opiates on cell-mediated immunity and its relationship to viral infection and tumors is described.
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PMID:Exogenous and endogenous opioids as biological response modifiers. 865 91

Although the incidence of anxiety disorders diminishes with age, the prevalence of anxiety symptoms among older patients is substantial. These symptoms, which include cognitive and somatic manifestations, are a source of diminished quality of life. The many potential sources of illness- and medication-induced anxiety must be excluded before instituting treatment. The general principles of antianxiety medication treatment in older patients include: (i) symptom relief with minimum sedation; (ii) improvement in sleep; (iii) freedom from autonomic and cognitive toxicities; and (iv) freedom from physical dependence and drug interactions. Older compounds such as the tricyclic antidepressants should be avoided, since more modern agents (e.g. benzodiazepines and buspirone) are well tolerated and effective. Modern antidepressants have also been used to reduce anxiety symptoms, although there is a potential for the opposite effect to occur. The selective serotonin reuptake inhibitors appear to be better suited to treating syndromes such as panic and obsessive-compulsive disorder, whereas nefazodone would be a better choice for generalised anxiety complicated by depression.
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PMID:Optimal management of anxiety in older patients. 887 13

This study investigated the effect of delta opioid receptor blockade by naltrindole on the development of physical dependence and tolerance to the antinociceptive and respiratory depressive effects of morphine in rats. Chronic morphine was delivered either by s.c. injection of increasing amounts of morphine over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated with saline or naltrindole. Antinociception and respiratory depression were assessed after administration of a challenge dose of morphine, and withdrawal signs were determined after naloxone challenge. Naltrindole significantly attenuated the development of antinociceptive tolerance after all three chronic treatment regimens. In addition, rats pretreated with naltrindole displayed significantly fewer withdrawal symptoms and less weight loss after a naloxone challenge. In contrast, naltrindole did not prevent the development of tolerance to morphine-induced respiratory depression. These results imply that tolerance to antinociception and physical dependence involves adaptations at interacting mu and delta receptor populations, whereas tolerance to respiratory depression reflects actions of independent mu and delta receptor populations. These findings suggest that delta antagonists may have potential clinical application for decreasing the rapid development of tolerance to opiate-induced analgesia, while allowing for the development of protective tolerance to respiratory depression.
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PMID:Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats. 919 Aug 71

Chronic pain represents a challenge to patients, families, employers, and the physicians who care for these individuals. Opioids remain the mainstay of the analgesic medications for the treatment of both acute and chronic pain. Controlled release preparations of morphine, oxycodone, fentanyl and long acting opioid agents such as methadone and levorphanol have been medically and ethically accepted in managing chronic cancer pain. However, the continued use of these medications for patients with chronic noncancer pain has been fiercely debated. This article attempts to reconcile the medical and ethical dilemma of using opioid medications for chronic noncancer pain. Growing clinical experience in the field of pain medicine has helped to clarify: (1) the misunderstanding of addiction, physical dependence and analgesic tolerance, (2) the misconception that chronic opioid therapy inevitably causes personality changes, depression, and impairment of cognitive and physical function, (3) the lack of information on the correct use of opioid analgesics with regard to titration and management of related side effects. The behavioral management of pain patients undergoing chronic opioid therapy is also discussed. A protocol for optimal patient management is proposed. Particular emphasis is given to the consent form, behavioral contracting, and the consequences of noncompliance. The importance of psychologic evaluation before a long-term opioid trial, to minimize future complications, is stressed. Although most patients on the opioid regimen do well, special attention must be given to patients with current addiction, a past history of addiction, or current misuse of opioid medications. Pharmacologic and conservative interventions are often warranted in those patients with significant behavioral problems. If such strategies fail, and chronic opioid therapy is deemed necessary, some treatment guidelines are offered.
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PMID:Ethical issues in the management of chronic nonmalignant pain. 931 Oct 61


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