ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

S-Adenosylmethionine (SAMe; ademetionine) is a naturally occurring compound that is found in virtually all living organisms. It serves as a major source of methyl groups in the brain, donating these groups to molecules such as hormones, neurotransmitters, nucleic acids, proteins and phospholipids, and is of fundamental importance in a number of intracellular metabolic pathways.The most commonly reported effect of SAMe is mood elevation in depressed patients. A few, relatively small clinical studies have shown that parenteral SAMe is superior to placebo and at least as effective as standard antidepressants, perhaps with a relatively rapid onset of action. Furthermore, the addition of SAMe to standard antidepressants may shorten the time to treatment response compared with the use of antidepressants alone. There are also additional reports suggesting the usefulness of the compound in dementia. SAMe appears to be remarkably well tolerated and free of severe adverse effects.Further studies are needed to clearly establish the role that SAMe may play in the treatment of depressive disorders and dementia.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

The margin between the therapeutic benefit and toxic effects of lithium is small. Lithium toxicity may occur in a number of situations: (i) if lithium is taken in too large a dose; (ii) if excretion of the drug by the kidneys is inadequate; and (iii) if lithium concentrations increase in cells because of negative sodium balance or drug interactions. The features of this syndrome are primarily exhibited in the nervous system, and include coarse tremor, increased reflexes, ataxia, increased muscle tone, seizures and coma.Treatment depends above all on the patient's clinical state, but also on the duration of previous lithium exposure, serum lithium concentration, renal lithium clearance, and the extent of dehydration.Gastric lavage may be necessary if there are obtunded laryngeal reflexes, but is usually of no value if used more than 4 hours after lithium ingestion. Saline diuresis may be needed to increase renal lithium excretion, but dialysis may be necessary if lithium is not being excreted adequately. Peritoneal dialysis and continuous arteriovenous haemodiafiltration reduce serum lithium concentrations more slowly than haemodialysis, which is still the most frequent measure employed in severe cases, despite some doubts about its value. Haemodialysis is normally used if patients have clear neurological symptoms and signs, particularly if these are deteriorating, if lithium clearance is less than 7 ml/min, and serum lithium concentrations are above 3 mmol/L.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

Opioid dependence is a chronic, relapsing condition that is associated with significant morbidity and mortality. Methadone maintenance therapy involves the provision of a controlled supply of an orally administered opioid, thereby stabilising the opioid-dependent patient. Research studies have shown that methadone maintenance reduces illicit opioid use, opioid-related crime, premature mortality and the risk of HIV infection. It is most effective when prescribed at an adequate dosage (usually 60 to 100 mg/day) and when long term maintenance on methadone is the goal of treatment rather than detoxification from all drugs including methadone. Successful long term methadone maintenance is more likely when it takes place within the context of a well established therapeutic relationship and when the medical, social and psychological needs of patients are met either through direct assistance or referral.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

There has been a large increase in the cost of medical care of patients with epilepsy and this is particularly evident in the cost of drug treatment. This increase is due to the availability of a number of new anticonvulsants such as vigabatrin, lamotrigine, gabapentin and, more recently, topiramate. All these new drugs have significantly higher acquisition costs than the more established anticonvulsants. The increase in the cost of epilepsy care caused by the use of these new drugs has been estimated to be in the region of $US500 million a year in the US.However, estimates of the cost of any treatment may be misleading if formal economic evaluation is not applied. It is important to assess all potential costs, not just acquisition costs, so that cost-effective drug treatment can be rationally planned. For example, it has been shown that anticonvulsants may consume up to 61% of the total cost of medical care for patients with epilepsy, and that if the newer drugs are used this is likely to be significantly higher, even allowing for the increasing costs of other aspects of epilepsy care, such as neuroimaging and epilepsy surgery. However, it is possible that these increases in costs may be offset by savings in other aspects of the costs that patients incur, such as unemployment.Nevertheless, to date, few studies have examined these areas, and claims for the cost-benefit advantages of the new drugs have not been substantiated. Healthcare systems around the world are already assessing policies to curb the rising costs of medical care and this may prevent future new anticonvulsants from being freely available. New drugs with lower risk-benefit ratios are still required by patients with epilepsy and it is hoped that inevitable changes in healthcare funding will not lead to a reduction in new drug development programmes.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

No single sensitive clinical outcome measure is capable of reliably reflecting the broad spectrum of clinical manifestations seen in multiple sclerosis (MS). Disease activity in groups of patients with MS is more readily detected by magnetic resonance imaging (MRI) of the brain and spinal cord than by neurological examination. However, the appearance of new lesions and progression of total lesion area as detected by MRI fails to predict reliably sustained progression of neurological impairment in individual patients. For this reason MRI is accepted as a primary outcome measure in exploratory clinical trials, while sustained progression of neurological impairment is the preferred primary outcome measure for pivotal phase II/III trials that lead to the approval of new treatments for MS.A comparison of proportions of patients meeting treatment failure as defined by discrete data at a specified time has previously been used in clinical trials of treatments for MS. Fewer patients may be needed to detect treatment effects when treatment failure is defined by continuous data that are analysed in a time-to-failure framework. Also, it may be possible to have nurses or trained technicians, rather than clinicians, administer tests that are continuous measures of neurological function.It is anticipated that recommendations provided by the Task Force on Clinical Outcomes for MS sponsored by the National Multiple Sclerosis Society of the US will include new multidimensional disease-specific composite outcome measures that better reflect the broad range of clinical expression and activity of MS. However, it is unclear whether investigators are prepared to abandon neurologist-based ratings as the principal method for determining disease severity and response to treatment. More sensitive clinical outcomes may improve the predictive validity of certain MRI techniques and facilitate expeditious testing of promising therapies in trials involving fewer patients.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS

摘要:

SynopsisClonidine is an established &agr;2adrenoceptor agonist with antihypertensive properties which, when administered epidurally, has an analgesic action that is largely mediated by &agr;2adrenoceptors in the dorsal horn of the spinal cord. After epidural administration, the drug undergoes rapid systemic absorption and is able to pass through the placenta.Data from clinical studies evaluating the efficacy of epidural clonidine indicate that it is a useful adjunct to opioid and/or local anaesthetic agents for postoperative analgesia after major abdominal or orthopaedic surgery or after caesarean section. Epidural clonidine has also proved to be an effective analgesic that enhances the duration of action of local anaesthetic agents during labour without neonatal adverse effects. Continuous infusions of epidural clonidine are effective in patients with cancer pain of neuropathic origin. Similarly, the utility of this agent appears to extend to patients with chronic non-cancer pain.At doses producing the desired analgesic effects, sedation, bradycardia and hypotension are the most common adverse events associated with epidural clonidine. There has been a single report of rebound hypertension after abrupt cessation of epidural clonidine.In conclusion, the available data suggest a role for epidural clonidine as an adjunctive agent for the control of pain (of postoperative, malignant or non-malignant origin and during labour). In particular, it may be useful in patients unsatisfied with opioid or local anaesthetic agents or in those tolerant to opioids. However, the place of epidural clonidine as an alternative or adjunctive analgesic agent in any given patient group is likely to depend on the acceptability of the epidural route of administration and haemodynamic and sedative effects of the drug.Pharmacodynamic PropertiesThe analgesic effects of spinally administered &agr;2adrenoceptor agonists are believed to be mediated by &agr;2adrenoceptors in the dorsal horn of the spinal cord. Amelioration of foot, but not hand, pain caused by immersion in iced water in healthy volunteers after epidural administration of clonidine indicated a spinal mechanism of action for the analgesic effect of the drug.Decreases in mean arterial pressure and heart rate (HR) and ventilatory changes have been reported in healthy volunteers and surgical patients after epidural administration of clonidine. Such cardiovascular effects are generally evident within 15 to 30 minutes of epidural injection of clonidine and last for up to 3 hours. Changes in blood pressure (BP) appear to be dose-dependent.Pharmacokinetic PropertiesClonidine is moderately lipid soluble, with a large apparent steady-state volume of distribution (approximately 2 L/kg) after intravenous administration. The drug is 20 to 40% bound to plasma proteins and is excreted predominantly via renal mechanisms.Clonidine appears to be absorbed rapidly into the systemic circulation after epidural administration, with peak plasma drug concentrations being reached 8 to 15 minutes after administration. Peak concentrations in CSF were attained more slowly (after approximately 30 to 45 minutes) but were up to 362 times greater than those in plasma.The pharmacokinetics of single dose epidural clonidine have been described by a first-order 2-compartment model, with short absorption half-lives in CSF and plasma followed by longer elimination phases in both fluids.Placental transfer of clonidine has been demonstrated after epidural administration. At delivery, the mean maternal plasma concentration of clonidine was 0.62 ng/L, compared with 0.56 ng/L in umbilical cord plasma, after a cumulative dose of 150μg.Therapeutic EfficacyIn patients with postoperative pain after major abdominal or orthopaedic surgery or caesarean section, epidural clonidine adjunctive to opioids or local anaesthetic agents provided effective and prolonged analgesia with a consequent decreased requirement for supplemental analgesia. The overall postoperative analgesic effect obtained with combinations involving clonidine was at least as good as that seen with opioids or local anaesthetic agents used alone or in combination.Epidural clonidine administered as an adjunct to local anaesthetics during labour provided effective analgesia that was superior to and of longer duration than that seen with the latter agents alone. Limited data indicate that combinations of epidural clonidine and opioids have similar efficacy to combinations of local anaesthetics and opioids when a single dose is given. However, efficacy appears to be partially lost when subsequent doses of epidurally administered mixtures of clonidine and opioids are used. The use of epidural clonidine during labour did not worsen neonatal Apgar or adaptive capacity scores.A continuous infusion of epidural clonidine provided effective analgesia in clinical studies in patients with intractable cancer pain, with a consequent decrease in supplemental opioid requirements. Efficacy was notably better in patients with neuropathic pain than in those with non-neuropathic pain. Likewise, limited data indicate that, in patients with chronic non-cancer pain, epidural clonidine provides analgesia at least as good as that seen with epidural morphine.TolerabilityAt clinically effective doses, sedation, hypotension and bradycardia are the main adverse effects of epidural clonidine. In general, clonidine did not intensify decreases in either BP or HR when combined with opioids and/or local anaesthetics. Rebound hypertension has been reported in a single patient after abrupt cessation of epidural clonidine.Epidural clonidine, unlike local anaesthetic agents, did not interfere with proprioception or produce motor blockade. Unlike epidural opioid agents, clonidine did not produce respiratory depression or worsen the risk of urinary retention, nausea, vomiting or pruritus when administered concomitantly with these agents.Dosage and AdministrationIn general, bolus doses of epidural clonidine 75 to 150μg administered concurrently with opioid or local anaesthetic agents have been shown to provide analgesia at least as good as that achieved with the opioids or local anaesthetic agents alone. Dosage regimens comprising a bolus dose followed by continuous infusion appear to be particularly well suited for analgesia during labour and postoperative analgesia.

ISSN:1172-7047    

出版商:ADIS    

年代:1996

数据来源: ADIS