摘要:

Esterase hydrolysis is a metabolic pathway that can be exploited to increase the rate of metabolism and elimination and so reduce the duration of the pharmacodynamic effects of drugs. Previously applied to &bgr;-adrenergic blocking agents and muscle relaxants, this concept was recently used to develop an esterase-metabolised opioid, remifentanil.Remifentanil has a predictable rapid onset, short duration and rapid offset of analgesic effect. This is likely to allow easy titration of analgesia to changing anaesthesia requirements during surgery. The metabolism of remifentanil by non-specific esterases in the blood and tissues prevents accumulation, even when given at high dosages over prolonged periods. Clinical recovery from anaesthesia is very rapid, irrespective of the age or physical status of the patient or the type or duration of surgery. In addition, the non-organ dependent elimination of remifentanil obviates the usual requirement for opioid dose adjustments in patients with hepatic impairment.Adverse events of remifentanil are those typical of μ-opioid receptor agonists, including respiratory depression, muscle rigidity, hypotension and bradycardia.Thus, the major benefits of remifentanil, the prototype esterase-metabolised opioid, are the achievement of intense, titratable intraoperative analgesia allowing for rapid clinical recovery without the risk of inducing recurrent postoperative respiratory depression. In addition, residual opioid activity disappears rapidly following discontinuation of the drug.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Antidepressant medications are taken daily or more frequently based on both tradition and pharmacokinetics of the drugs. However, weekly administration may be a feasible option for drugs with a long elimination half-life and flat dose-response curve. In addition to providing effective control of symptoms, it is possible that weekly administration could also benefit patients by reducing costs and minimising drug interactions and adverse effects. The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine appears to be a candidate for once weekly administration.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

The patient who feels pain can best assess the degree of its relief, and therefore the effective pharmacological treatment of pain requires the active participation of the patient. Patient-controlled analgesia (PCA) involves the patient in a direct manner; the patient is given control over at least some aspects (usually the timing of doses) of analgesic drug administration. A wide range of therapeutic strategies fall under the umbrella of PCA. In one major area of application, the control of severe acute pain such as postoperative pain, the term PCA is used to describe a specific type of treatment. This involves a device consisting of a pump, containing a reservoir of drug, and a handset that administers a dose of drug when activated by the patient. Such a system was first used by Sechzer over 20 years ago. Today, the device may be a microprocessor-controlled system, able to implement complex instructions programmed by the prescriber and keep a record of the patientdevice interactions, or it may be a simple disposable pump powered by mechanical means such as a spring or an elastomeric drug reservoir.The usual route of PCA drug administration after surgery is intravenous, but others, particularly the epidural route, are also used. The most commonly used drugs are opioid μ-receptor agonists such as morphine and fentanyl. While many such agents have been used, the differences between them in terms of efficacy and adverse effects are modest. When administering analgesics by PCA the prescriber can choose the drug to be used and the size of each dose to be administered, and can impose certain constraints on drug administration. The most common constraint is a lockout interval, a period following the administration of a dose during which the device will not administer a second dose, even though the patient activates the handset. Within the constraints, the patient controls when doses of the drug are administered. Variants of PCA include the addition of a background infusion of the drug, which may vary or be constant, providing the patient with control over the size and timing of doses, and the addition of other drugs, such as antiemetics, to the drug reservoir. In practice, a standard PCA prescription will be used at a particular hospital (e.g. drug: morphine sulphate, demand dose: 1mg, lockout interval: 5 minutes, background infusion: none).Although PCA is well accepted by most patients, simply initiating PCA does not guarantee good pain control. Patients must be selected appropriately, and educated preoperatively in the effective use of PCA. This information should be reinforced by nursing staff during the postoperative period. Pain control and adverse effects need to be monitored regularly, and the prescriber must be prepared to change the prescription (e.g. dose size or lockout interval) to meet the individual needs of the patient.Extensive experience with intravenous PCA has shown the risk of serious adverse events to be low. The risk is increased measurably when the patient's degree of control over drug administration is reduced, such as when a background infusion is added, and additional monitoring may then be required to maintain the level of safety. Experience with epidural PCA is more limited but, whilst there are additional risks, it is still relatively well tolerated. Although modern PCA devices are very reliable, there are a number of reports every year of patients put at risk by mistakes made by staff when initiating PCA.The direct cost of providing postoperative analgesia by PCA is greater than that of traditional approaches such as nurse-administered intramuscular injection of analgesics. However, given the good efficacy and excellent patient satisfaction, the benefits of PCA outweigh the small additional costs.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

There are a number of therapeutic options for the prevention of stroke (primary or recurrent) or other thrombotic events in antiphospholipid antibody-positive individuals, although none is of proven benefit. Control of modifiable vascular risk factors and avoidance of thrombogenic drugs should be recommended for all persons with antiphospholipid antibodies, whether symptomatic or not. Therapies to prevent thrombosis include antiplatelet agents and anticoagulants, with warfarin the preferred choice in high risk patients who have recurrent events. Immunebased therapies, including plasma exchange, immunoglobulins, corticosteroids and immunosuppressants, are alternative treatment modalities for patients who have recurrent events despite receiving high-dosage anticoagulants.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

Autism is a neurodevelopmental disorder that affects 10 to 20 children per 10 000. A comprehensive clinical assessment and medical examination are important features that enable an accurate diagnosis to be made. The treatment of autism should be multimodal, involving a combination of structured and special educational techniques, individual behavioural modification, hometraining, family counselling and placement in special schools or daycare centres. Drug treatment can play an important role in the treatment of maladaptive and distressing target symptoms, such as hyperactivity, aggression, excitement, negativism, and ritualised, stereotyped or self-injurious behaviours.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

The mechanism of action of antidepressants is still unknown. The delayed onset of their therapeutic effect suggests that they act through an adaptive process. Recent research has demonstrated that neural plasticity and learning, which may underlie the induction of depression by repetitive psychosocial stress, involve gene transcription through the cyclic adenosine monophosphate (cAMP)— and calcium-responsive element (CRE) and its cognate transcription factor CREB. By downregulating &bgr;-adrenergic receptors linked to cAMP-formation and serotonin 5-HT2receptors linked to intracellular calcium mobilisation and blocking voltage-dependent calcium channels, antidepressants can inhibit gene transcription through the CRE. Thus, modification of CRE-directed transcription may contribute to the therapeutic efficacy of antidepressants.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

The receptor to which benzodiazepine hypnosedatives and anticonvulsants bind was discovered and characterised in the late 1970s. Agonists and inverse agonists that act at various sites within the receptor complex have been identified. In addition, antagonists of the benzodiazepine receptor have been synthesised. At present, flumazenil is the only agent of this class that is available clinically.Flumazenil has well documented benefits in the treatment of hepatic encephalopathy and benzodiazepine overdose. The drug has also been studied as a potential treatment for neuropsychiatric illnesses in which dysfunction of the &ggr;-aminobutyric acid (GABA)ergic system is implicated as a causal factor. Potential therapeutic benefits are suggested in benzodiazepine tolerance and withdrawal, benzodiazepine-related amnesia, epilepsy, sleep disorders, cognitive disorders and idiopathic recurrent stupor. In contrast, no clear benefits have been found in alcoholism, anxiety and movement disorders. Flumazenil induces few adverse effects, and so represents a promising tool for pharmacological investigations of the GABAergic system and for imaging of the benzodiazepine receptor. As an imaging agent it has been used for quantification of the receptor, and as a neuronal marker in epilepsy and cerebral ischaemia.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

摘要:

▴ Propentofylline (HWA 285) is a novel xanthine derivative which is being developed for the treatment of primary degenerative (Alzheimer's) and vascular dementia.▴ Propentofylline enhances extracellular adenosine levels via inhibition of adenosine uptake, and prevents the enzymic degradation of cyclic adenosine monophosphate and cyclic guanosine monophosphate through inhibition of cyclic nucleotide phosphodiesterases.▴ It modulates the activation of microglial cells, reduces or prevents various aspects of neuronal damage, and has beneficial effects on cognitive behaviour and performance in animal models of ischaemia.▴ In placebo-controlled studies lasting up to 12 months in patients with mild or moderate Alzheimer's or vascular dementia, propentofylline prevented clinical deterioration and produced significant clinical improvement according to most, but not all, efficacy evaluations.▴ Propentofylline appears to be generally well tolerated; gastrointestinal disturbances, dizziness, headache and heartburn were the most common adverse events during clinical trials.

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:1997

数据来源: ADIS