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Chronic morphine of beta-endorphin during chronic naltrexone maintenance treat- induces visible changes in the morphology of mesolimbic dopa- ment in ex-opiate addicts buy levitra soft 20mg. Psychopharmacology: the third gen- istration induces a sustained increase of prodynorphin mRNA eration of progress levitra soft 20 mg on line. Rationale for maintenance pharmacotherapy of op- administration and correlation with preprodynorphin mRNA purchase 20 mg levitra soft otc. Dopamine receptor antagonists prevent Acad Sci 2000;909:186–216 effective 20 mg levitra soft. Beta-endorphin levels during J Pharmacol 1995;14:235–244 levitra soft 20 mg otc. Abnormal metyrapone accumbens using both mu 1 and delta opioid receptors. Ann tific meeting of the College on Problems of Drug Dependence. Altered HPA axis responsivity elevation of serum levels of prolactin through an opioid receptor to metyrapone testing in methadone maintained former heroin mechanism in humans: gender differences and implications for addicts with ongoing cocaine addiction. Neuropsychopharmacol- modulations of dopaminergic tone in the treatment of addic- ogy 2001;24:568–575. Culpepper-Morgan JA, Inturrisi CE, Portenoy RK, et al. Dynorphin A1-13 administration ment of opioid induced constipation with oral naloxone: a pilot causes elevation of serum levels of prolactin in human subjects. Reliability of se- ings of the 55th annual scientific meeting of the College on quential naloxone challenge tests. Am J Drug Alcohol Abuse Problems of Drug Dependence. Arch naloxone in opioid dependence: a case of naloxone induced Intern Med 1966;118:304–309. Medical safety, side effects and toxicity of metha- 108. Proceedings of the fourth national conference on methadone hypothalamic-pituitary-adrenal axis activation than naloxone in 1506 Neuropsychopharmacology: The Fifth Generation of Progress normal volunteers: implications for the treatment of alcoholism. Methadone disposition during the perinatal period Alcohol Clin Exp Res 1998;22:1430–1436. Thrombocytosis in factor and CRF-R1 mRNAs in rat brain and pituitary during the offspring of female mice receiving dl-methadone. Proc Soc 'binge' pattern cocaine administration and chronic withdrawal. Effects of chronic 'binge' for the quantitative determination of methadone in human pattern cocaine administration on plasma ACTH and cortico- plasma and urine. Stereoselective disposition adrenal activity and pro-opiomelanocortin mRNA levels in the of methadone in man. Transition from moderate to excessive lated by acute intermittent morphine with or without water drug intake: change in hedonic set point. Steady-state methadone toward homeostatic dysregulation in rats. Psychopharmacology in rats does not change mRNA levels of corticotropin-releasing 2000;148:289–298. POMC and anterior pituitary CRF1 receptor mRNA levels after 130. Persistent increase in the acute, but not chronic, daily 'binge' intragastric alcohol admin- motivation to take heroin in rats with history of drug escalation. Effects of dynor- rats under opioid maintenance: the effects of stress, heroin prim- phin A(1-13) on opiate withdrawal in humans. Dynorphin A(1- but not corticosterone, is involved in stress-induced relapse to 13) analgesia in opioid-treated patients with chronic pain: a heroin-seeking rats. Increase of extracellular emission computerized tomography (SPECT).

Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study cheap 20 mg levitra soft with amex. Alcohol Clin Exp Res 1992;16:1078–1089 buy levitra soft 20 mg visa, with permission purchase levitra soft 20mg with mastercard. There is a limited understanding of the extent populations cheap levitra soft 20mg line. Thus levitra soft 20 mg generic, atrophy may not be detectable in young to which these studies also reflect genetic or alcohol-related healthy ethanol-dependent populations (220). Studies of ethanol intoxication ethanol-dependent adolescents show hippocampal volumet- suggest that it reduces cortical metabolism in humans (233). The study in adolescents raises the possibility that or following medications for detoxification, predominately adolescents show disruptive effects on brain development or describe reductions in regional cerebral perfusion or glucose an increased sensitivity to the neurotoxic effects of ethanol. More Over the initial years of sobriety, there is recovery in the pronounced deficits were observed in patients with evidence volumes of gray and white matter and reductions in sulcal of cortical atrophy based on structural neuroimaging (236), and ventricular volume (222). There are differences in the years of ethanol use, age (237), and multiple ethanol detoxi- rate of particular brain regions and particular tissue types fications (238). Cerebral perfusion and metabolic deficits with regard to the rate of recovery (222,223). The relatively may attenuate over the initial months of sobriety (237), rapid recovery of white matter volume with sobriety does and improvement may continue over several years (239). Ethanol with- cal perfusion and metabolic rate is associated with reduced drawal seizures have been linked to neurotoxicity in these performance on cognitive tests that engage the frontal cortex patients (225). Similarly, cerebellar metabolic deficits are associated white matter loss was particularly associated with ethanol with behavioral evidence of cerebellar dysfunction (236). Although cortical atrophy has been described in ethanol-dependent patients with good nutritional status (227), the Wernicke-Korsakoff syndrome Behavioral Studies and hepatic cirrhosis are generally associated with more prominent MRI volumetric deficits in cortical and limbic The most profound cognitive deficits associated with alco- structures than ethanol-dependent patients who are other- holism are the memory impairments arising from nutri- wise healthy (228). Although the factors that might predispose individuals to develop alcohol- most severe consequences of alcoholism for cognition may ism. One risk factor, antisocial personality disorder, appears not reflect the direct toxic effects of ethanol on the brain, to be independently associated with reductions in frontal many patients exhibit cognitive deficits independent of cortex gray matter volume (229). Thus, the observation that these factors that reflect the combined impact of age, famil- frontal gray matter volume loss is present in young ethanol- ial vulnerability for alcoholism, adaptations to ethanol dependent patients could reflect a combination of the vul- effects on the brain, perhaps degree of liver injury (244), nerability to alcoholism and atrophic effects of ethanol de- presence of comorbid depression, and ethanol-related neu- pendence (214). Cognitive function is further compromised in those patients who continue to drink, due to the direct effects of ethanol on cognition (246). The familial vulnerability to alcoholism and traits associ- Magnetic Resonance Spectroscopy ated with that vulnerability are associated cognitive deficits Magnetic resonance spectroscopy (MRS) has been applied and educational achievement (247). Although reductions to the evaluation of structural deficits in alcoholic patients in attention, planning, visual-spatial learning, and impulse in a limited fashion. Proton-MRS ([1H]MRS) enables the control have been described in children of alcoholics (248), measurement of N-acetyl-aspartate (NAA), a constituent of these findings are not universal (249). One study found reductions in the NAA/ be largely accounted for by comorbid traits such as antisocial creatine ratio in the frontal cortex and cerebellum of personality, similar to both MRI and event-related potential ethanol-dependent patients (230,231). A phosphorus-MRS (ERP) findings in alcohol dependent patients (250,251). Familial his- these effects contribute to its complex array of behavioral tory of alcoholism appears to compound the negative conse- effects in animals and humans. Direct effects of ethanol on quences of social drinking on cognitive function (253). Further, the cellular consequences of exposure to a familial alcoholism history (254). Thus it is possible that ethanol are modulated by ethanol-sensitive regulatory en- cognitive responses to ethanol may also contribute to the zymes, such as PKA and PKC. In this regard, there is growing evidence that the in patients (255). Ethanol-dependent patients show many interplay of the prefrontal cortex (PFC) and limbic struc- impairments in cognitive function. Deficits in the level of tures including the nucleus accumbens (NAc) and amygdala performance and efficiency of verbal skills, learning and generally plays an important role in reward (266,267).

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In reality discount levitra soft 20 mg amex, cerebral edema in many situations buy levitra soft 20mg with mastercard, usually exhibit a combination of vasogenic and cytotoxic edema levitra soft 20mg cheap. Interstitial (hydrostatic or hydrocephalic) edema is associated with hydrocephalus order levitra soft 20 mg amex, in which there is increased tension of CSF across the ependyma discount levitra soft 20mg overnight delivery. Interstitial edema, or transependymal flow, is radiographically seen with hypodense areas surrounding the ventricular system and is associated with increased CSF volume or pressure. In cytotoxic edema, osmotic therapy with mannitol and hypertonic saline may not reduce edema in the Cerebral Edema | 83 lesion itself, but may reduce the volume of normal brain allowing for some increased margin of safety by decreasing intracranial pressure (Raslan 2007). Steroids are of no value in cytotoxic edema due to stroke, and may be harmful in the settings of brain trauma. Surgical decompression of cytotoxic edema with decompressive craniectomy may be therapeutic, and life-saving (Hofmeijer 2009). Vasogenic edema responds to steroids and surgical resection of the lesion, and may also benefit from osmotic therapy with mannitol or hypertonic saline (Oddo 2009). Hydrostatic edema is treated surgically with CSF removal or shunting, and it is treated medically with agents to decrease production of CSF, such as acetazolamide and furosemide. General Neurological Treatment Strategies Magdy Khalaf, Nabil Kitchener The concept of neurocritical care has been developed to coordinate the management of critically ill neurological patients within a single specialist unit and to include clinical situations such as swallowing disturbances, respiratory problems management in neurocritical care, infection control in the unit, pain relief and sedation in some patients, as well as diagnosing brain death. Acute rehabilitation is important in securing improved long-term neurological outcomes after many brain insults, trauma, ischemia or hemorrhage. Intervention from neurophysiotherapists, as part of the neurocritical care multiprofessional team, must occur as early as possible. Respiratory muscle impairment is the most common reason for admission to the ICU in patients with neuromuscular disorders. Objective measures of respiratory muscle function are necessary because significant respiratory muscle impairment may exist despite a paucity of symptoms. Analgesia in the neurocritical care unit is indicated in many situations such as postoperative pain, traumatic injury, and subacute or chronic pains. Although it is mandatory and beneficial in many situations, precautions must be taken before General Neurological Treatment Strategies | 85 applying many agents; e. Some agents may cause decreased level of consciousness or obtundation leading to impairment of neurological exam. This chapter will cover management of these issues in the neurocritical care setting. Swallowing Disturbances Weakness, spasticity or both of the pharynx and tongue cause dysphagia and tendency for aspiration. A feeding tube through a percutaneous endoscopic gastrostomy (PEG), cervical esophagostomy or jejunostomy is a reliable method of patient feeding when prolonged deficit is expected. Nutrition support by enteral feeding through either a nasogastric or an orogastric tube should be maintained in all intubated patients whenever possible. In patients with a normal baseline nutritional state, support should be initiated within 7 days. In malnourished patients, nutritional support should be initiated within 72 h. Delayed gastric emptying is common in critically ill patients on sedative medications but often responds to promotility agents such as domperidone, and metoclopramide (Gomes 2010). Parenteral nutrition is an alternative to enteral nutrition in patients with severe gastrointestinal pathology. When patients improve the gastrostomy is easy to close. It is better to try to provide adequate and safe nutrition by mouth in an alert patient before placing a feeding tube. Nasogastric tubes have been used temporarily for feeding but they are uncomfortable, cause pressure necrosis of the nares when used chronically, and allow aspiration, so it should not be used for long. In ambulatory patients with severe dysphagia, cervical esophagostomy may be useful, as a patient can insert the tube during feedings and the ostium can be covered with a dressing at other times. Patients with severe weakness or ataxia of the upper extremities are usually unable to feed themselves, so percutaneous endoscopic gastrostomy is the method of choice (Wanklyn 1995). Tube 86 | Critical Care in Neurology feeding needs high caloric diet (1200 to 2400 Kcal/day) for active patients, and liquid foods are usually concentrated to deliver 1 Kcal/ml. To avoid clogging of the tube, each feeding is followed with water. Tube feeding is best started with about one half the total desired calories diluted in water, with gradual increase in concentration and calories, to avoid diarrhea and malabsorption, reaching a maximum volume of about 200 ml (150 ml food and 50 ml of water). If aspiration of saliva and nasal secretions is a problem, a cuffed endotracheal tube is necessary and the use of tricyclic antidepressants or anticholinergic drugs (if there is no absolute contraindication for its use) might reduce salivation and prevent drooling (Fjærtoft 2011).

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Mrs E benefited from the rest and was happy to continue to support her husband at home discount levitra soft 20mg with mastercard. This case illustrates the paradox of some OCD patients who are concerned about cleanliness buy 20mg levitra soft, but who are themselves generic 20mg levitra soft otc, quite unclean buy cheap levitra soft 20mg. It seems that their concerns and the anxiety are so great and preoccupying that they are unaware of the facts of their actual situation order levitra soft 20mg with visa. Case history, 3 Mr F was a 54-year-old divorced, unemployed former clerk, living alone in a Housing Department unit. His marriage had ended 20 years previously and he one child, a daughter living in a distant part of the country. He stated that he would not have been able to come alone because leaving his home was anxiety provoking. He had two friends from the distant past and had maintained contact with them by telephone. He reported that there had been a problem with his kitchen tap and he had not been able to turn it on for 7 years. Mr F could afford a plumber, but the stress of having another person in his flat was too much to contemplate. He had tried a vast range of medications over the years. He said that none had helped in the slightest and he had experienced severe side effects with most of them. His reluctance to leave the house appeared to be agoraphobia. He was disabled by an obsession that he may lose letters from his letter-box. When he approached his letter-box he first searched the small, concrete front drive (about the size of a room) to make sure that the post-man had not dropped a letter before putting it into the box. This searching of a blank flat surface could take half an hour. Mr F would then slowly open the door of his letter-box by one or two centimetres and peep in over the top to see if there were any letters. Irrespective, he would then open the door completely, take out any letters and then feel around inside the box for some minutes to make sure there were no letters left. The most difficult stage then followed: he would again have to search the concrete drive to make sure that no letters had dropped out when he had opened the door. The process of checking his letter-box could take one hour or more. He knew that he was behaving illogically, and this caused him distress. At the time of presentation he had given up all resistance. He said it was less anxiety provoking to comply with this compulsion than to resist, and he would not co-operate with ERP or any other form of behaviour therapy. Mr F believed he may get some help from a particular SSRI and asked for it to be prescribed. Supportive psychotherapy was provided and attempts were made (unsuccessful) to encourage Mr F to participate in pleasurable activities. He appeared to enjoy his meetings with the psychiatrist and would always bring word and number puzzles. After one year Mr F described what may have been a depressive episode which lasted a month. He was already taking a sufficient dose of an effective antidepressant and as change was almost impossible, Mr F and his psychiatrist decided to wait for natural remission. He began bringing the psychiatrist up to 4 plastic shopping bags of old belongings, old magazines and broken electrical equipment. The opinion was formed that Mr F had been hoarding for years and that with the assistance of medication and supportive therapy he was now able to discard some of this material.

This temperature decline may promote slow-wave azepine type I receptors cheap 20 mg levitra soft fast delivery. Finally generic levitra soft 20 mg on line, these during the early evening also increases slow-wave sleep in agents differ in terms of active metabolites buy 20mg levitra soft fast delivery, which may have both young and older individuals generic 20mg levitra soft with amex, and improves sleep conti- longer half-lives than the parent compound levitra soft 20mg visa. For each of these outcomes, the effect size d ranged between. For instance, treatment with zopiclone for both 14 days and 8 weeks of treatment was associated Several medication classes are used for the treatment of in- with greater improvements in quality of life measures, social somnia, although the strength of evidence regarding their activities, and professional activities compared to placebo efficacy and tolerability varies considerably. In particular, For instance, zaleplon, with its very short half-life, has not prescriptions for trazodone increased sixfold. Some patients clearly developed tolerance studies failing to show such improvement (72). In particu- studies show continued efficacy over several nights of con- lar, risk seems to be increased with the use of long-acting tinued nightly administration. For instance, triazolam, zol- agents, high doses, multiple agents, and cognitive impair- pidem, and zaleplon have shown continued efficacy over a ment in patients (73,74). Data regarding automobile crashes period of 4 to 5 weeks in double-blind, placebo-controlled are somewhat mixed. Other studies have shown risk associated with stance, double-blind studies have shown continued efficacy long half-life drugs and recent initiation of treatment, but for up to 24 weeks with no evidence of tolerance according not with longer-term treatment (76). In fact, examination of two specific benzo- common of these is a continuation of their desired therapeu- diazepine agents in this cohort did not show an elevated tic effect, sedation during the daytime. The behavioral aspect of taking a pill may contribute of the drug is more controversial, with some studies noting to rebound insomnia. Venlafaxine Cognitive and behavioral treatments can help patients dis- Trazodone, to to ↑ continue chronic benzodiazepine use (83). Recurrence is another potential discontinuance syndrome ↑, Increase. Although data are difficult to obtain, Studies with small numbers of subjects and diverse inclu- benzodiazepines may be used by. A over time as well as a tendency to intermittent rather than more recent 2-week double-blind placebo-controlled study consistent dosing (86). This study showed improvements in subjective sleep latency and sleep duration with both active drugs, although there was some evidence for superiority of zolpidem during Antidepressant Drugs the second treatment week. Finally, somnia include trazodone, tertiary tricyclic agents, and mir- a recent open-label trial of paroxetine for primary insomnia tazapine. These drugs clearly have diverse effects on neuro- in the elderly showed significant improvement in a multi- transmission, as reviewed in Chapter 79. In general, the variate measure of sleep quantity based on both diary and sedating properties of antidepressants are related to antago- polysomnographic sleep measures (96). For instance, fluvoxamine the treatment of insomnia. Some antidepressant drugs also has a relatively alerting effect relative to desipramine that can cause or exacerbate insomnia problems. Selective seroto- in turn is more alerting than amitriptyline (97,98). In addition, serotonergic specific antide- comparison of fluoxetine with trazodone showed that the pressants can lead to anomalous sleep stages characterized later drug was associated with more improvements in in- Chapter 133: Current and Experimental Therapeutics of Insomnia 1939 somnia symptoms, but also with a greater percentage of specific receptors in the suprachiasmatic nucleus of the hy- sedating events during the daytime (100). In addition, melatonin shifts circadian parisons between fluoxetine and nefazodone has consis- rhythms according to a phase response curve (110,111). Doses greater than 1 mg are likely to induce supraphysiologic concentrations. Clinical trials have Antihistamines employed doses ranging from. Antihistamines such as diphenhydramine and doxylamine During daytime administration, melatonin causes sleepi- are the most widely available over-the-counter preparations ness in fatigue and healthy subjects (112,113). The mechanism of action of these drugs in- ministered at night to healthy subjects, melatonin decreases volves inhibition of histamine H1 receptors. Histaminic sleep latency (114) and the number of awakenings, and neurons in the posterior hypothalamus promote wakeful- improves sleep efficiency in an experimental insomnia para- ness through interactions with ascending cholinergic nuclei digm (115).

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