鼻腔给药的中药制剂最新研究进展

鼻腔给药、口服药物、静脉注射,三种治疗方法中口服药物一直是人们治疗疾病的主要给药方法。鼻腔给药具有药物利用率高、药物吸收速度快、作用力强、使用方便、患者易接受等优点,使用鼻腔给药治疗鼻炎、头面部疾病、全身性疾病、婴幼儿疾病及特殊病症等方面都可以取得很好的疗效。通过介绍鼻腔给药中药制剂的优点和制剂的类型及实际应用情况了解该种制剂的研究进展。     

癫痫的药物治疗原则

癫痫是神经内科常见的反复发作性慢性脑病 ,药物是目前治疗癫痫最常用和最重要的手段。正规有序的药物治疗 ,可使大部分病人的发作得到有效控制 ,但由于多种原因 ,许多病人未能得到正确的治疗 ,癫痫频繁发作导致继发性脑损害 ,严重影响病人生存质量 ,甚至致死。本文就癫痫发作的分类与选药 ,以及癫痫发作间隙期、癫痫持续状态、难治性癫痫和癫痫妇女妊娠期间的治疗等问题 ,介绍癫痫的临床药物治疗原则。     

Acorda安定鼻腔给药制剂Plumiaz遭FDA拒绝

Acorda医疗公司称,美国FDA拒绝该公司一种安定鼻腔给药制剂Plumiaz,安定是目前用于反复发作癫痫患者的标准治疗药物。表示这款治疗药物预期今年不会获得FDA批准,其股票应声下跌11%。     

207例抗癫痫药物血药质量浓度测定结果分析

目的探讨抗癫痫药物血药质量浓度监测对抗癫痫药物合理应用的意义。方法建立我院抗癫痫药Access数据库,回顾性分析我院所监测的207例样品。结果 207例样品的患者控制有效率为76.32%。结论监测癫痫患者服药后的血药质量浓度,对临床及时调整给药方案、降低癫痫的发作率、减少癫痫药物的不良反应具有重要的意义。     

癫癎治疗中值得关注的问题

探讨癫痫治疗过程中可能遇到的、值得注意的问题。如癫痫的预防性治疗、第一次发作是否治疗、药物之间的选择及相互作用、药物治疗原则等，并对药物抵抗性癫痫、药物性癫痫、药物和妊娠、药物的监测等进行了讨论。明确发作类型，选择合适的药物，首选单药治疗，应用最小的剂量，达到最大程度的控制及最小的不良反应，是治疗成功的关键。     

鼻腔给药治疗上呼吸道感染的进展

目的：介绍鼻腔给药治疗上呼吸道感染的临床应用情况。方法：通过查阅近年国内医药学刊物，总结鼻腔给药用于呼吸道感染治疗的献。结果：多种化学药物、中药以及生物缺点品都被用于鼻腔给药治疗上呼吸道感染，分别从缓解症状、抗感染等途径发挥局部或全身疗效。结论：鼻腔给药是治疗上呼吸道感染的一种新给药途径，具有作用迅速、应用方便及用药量小等特点，但尚需进一步深入研究。     

鼻腔给药的研究进展

<正> 鼻腔给药已有悠久的历史,但以往多用于治疗鼻炎等局部性疾患。近年,随着药物新剂型的开发和对鼻腔吸收药物的深入研究,发现鼻腔给药可达到全身性用药的目的,从而引起了人们对鼻腔给药系统的重视。目前,经鼻腔途径给的药物已有心血管药物、抗生素、脑垂体激素、多肽类等。鼻腔之所以成为引人瞩目的给药新途径,关键在于鼻腔的生理状态。 1.药物鼻腔吸收的特点 鼻腔独特的药物吸收特点是由其粘膜的生理状况所决定的。鼻腔粘膜表面积较大,     

鼻腔给药的研究进展

鼻腔给药具有生物利用度高、起效快、无损伤性、使用方便等特点，成为制剂领域的研究热点；鼻腔与脑部的生理联系，使鼻腔给药成为有效治疗脑部疾病的一种新途径。鼻腔给药存在的最大问题是大分子药物的促吸收和鼻粘膜纤毛毒性问题。本文结合鼻腔的生理特点，综述了近年来鼻腔给药的研究进展。     

PartⅡ治疗癫痫在社区:如何选择抗癫痫药物?

<正>目前有多种抗癫痫药可使用,但不同类型的癫痫发作选择的治疗药物不尽相同。长期坚持规范、合理的药物治疗可有效控制癫痫发作。全科医生应对长期服用抗癫痫药的患者进行定期随访,以了解其是否坚持遵医嘱按时服药、疗效如何、是否有药物不良反应等问题。此外,全科医生还须了解常用抗癫痫药的相关知识,及抗癫痫药与其他药物的相互作用及其不良反应等知识,以便在药物治疗方面给予患者及时的指导。     

小儿癫痫患者丙戊酸钠血药浓度监测及影响分析

丙戊酸钠是临床上用于治疗各种癫痫的药物，由于其治疗指数低、个体差异大^[1]、毒副作用大，血药浓度易受机体各种因素及合并用药的影响，因此，为控制癫痫发作，减少不良反应的发生，必须进行血药浓度监测，以便调整给药剂量做到个体化给药。     

The promise of new antiepileptic drugs

Epilepsy is the most common serious disorder of the brain and comprises a wide range of different conditions with varying aetiologies. The long-established antiepileptic drugs (AEDs) control seizures in 50% of patients developing partial seizures, and 60-70% of those developing generalized seizures. Several AEDs were made available in the 1990s. These drugs have efficacy, but have had only a modest impact on those with refractory epilepsies. A 50% seizure reduction, which is commonly used as an endpoint in clinical trials, confers little benefit to a patient. Of the newer AEDs, lamotrigine and oxcarbazepine are now licensed for use as monotherapy and vigabatrin has a monotherapy licence for infantile spasms. Careful and prolonged postmarketing surveillance is essential to detect adverse effects, which may not be evident in premarketing clinical trials. At this time, there are 10 AEDs currently in varying stages of clinical development. Current strategies for selecting an AED for a particular patient are crude. Magnetic resonance spectroscopic measures of cerebral neuro-transmitters and genetic analysis may allow better prediction of which drug is most likely to be efficacious and to have low risk of adverse effects. Present AEDs suppress the occurrence of seizures. Agents that prevent the development of epilepsy and which protect the brain from the consequences of seizures would be of great value, but it will be difficult to prove their effectiveness. At present AEDs are given continually and systemically. Local drug delivery is feasible and could avoid the adverse effects of AEDs. The combination of local drug delivery with prediction of seizure occurrence could revolutionize the treatment of currently refractory epilepsies.     

Adenosine kinase, epilepsy and stroke: mechanisms and therapies

Adenosine is an inhibitory modulator of brain activity with neuroprotective and anticonvulsant properties. Adenosine levels are regulated mainly by adenosine kinase (ADK), an enzyme that is responsible for the removal of adenosine via phosphorylation to AMP. Recent evidence indicates that expression of ADK undergoes rapid coordinated changes during brain development and following brain injury, such as after epileptic seizures and stroke. Thus, transient downregulation of ADK after acute brain injury protects the brain from seizures and cell death. Conversely, chronic overexpression of ADK causes seizures in epilepsy and promotes cell death in epilepsy and stroke. These findings have direct implications for the rational definition of ADK as a therapeutic target. In recent years, novel treatment strategies have been developed that make use of the intracerebral transplantation of cells that are ADK deficient and, thus, release adenosine. A new era of cell-based delivery of adenosine has begun, which holds great promise for novel therapies for epilepsy and stroke.     

Ultra-fast absorption of amorphous pure drug aerosols via deep lung inhalation

A deficiency of most current drug products for treatment of acute conditions is slow onset of action. A promising means of accelerating drug action is through rapid systemic drug administration via deep lung inhalation. The speed of pulmonary drug absorption depends on the site of aerosol deposition within the lung and the dissolution rate and drug content of the deposited particles. Alveolar delivery of fast-dissolving, pure drug particles should in theory enable very rapid absorption. We have previously shown that heating of thin drug films generates vapor-phase drug that subsequently cools and condenses into pure drug particles of optimal size for alveolar delivery. Here we present a hand held, disposable, breath-actuated device incorporating this thermal aerosol technology, and its application to the delivery of alprazolam, an anti-panic agent, and prochlorperazine, an anti-emetic with recently discovered anti-migraine properties. Thermal aerosol particles of these drugs exist in an amorphous state, which results in remarkably rapid drug absorption from the lung into the systemic circulation, with peak left ventricular concentrations achieved within 20 s, even quicker than following rapid (5 s) intravenous infusion. Absorption of the thermal aerosol is nearly complete, with >80% absolute bioavailability found in both dogs and human normal volunteers.     

Inhalation drug delivery devices and emerging technologies

Driven by the pharmaceutical industry to realise the full potential of the lungs for local and systemic treatment of diseases, pulmonary drug delivery by inhalation aerosols has been undergoing rapid development in the past decade. This has led to novel invention of aerosol delivery devices including the propellant-driven metered-dose inhalers, dry powder inhalers and atomisers. Closely coupled to these inhaler devices are the formulations and new technologies that are required to produce particles of defined characteristics for improved delivery. This review highlights some of the recent advances in this expanding field.     

Levetiracetam: a novel antiepileptic drug.

Levetiracetam is a new antiepileptic drug, structurally and mechanistically dissimilar to other marketed antiepileptic drugs. It is effective in reducing partial seizures in patients with epilepsy, both as adjunctive treatment and as monotherapy. Levetiracetam has many therapeutic advantages for patients with epilepsy. It has favorable pharmacokinetic characteristics (good bioavailability, linear pharmacokinetics, insignificant protein binding, lack of hepatic metabolism, and rapid achievement of steady-state concentrations) and a low potential for drug interactions. Recommended starting dosages are considered to be clinically effective; therefore, patients can have some protection from seizures soon after they begin levetiracetam. The most common adverse effects observed with levetiracetam are mild and include somnolence, asthenia, and dizziness. Clinical experience and data from meta-analyses indicate that levetiracetam is well tolerated, with efficacy comparable or slightly better than that observed with other new antiepileptic drugs. Levetiracetam may be particularly useful in patients who are unresponsive to other antiepileptic drugs, patients receiving drugs with increased potential for drug interactions, or those with hepatic impairment.     

Effect of formulation on methylphenidate release patterns

Attention-deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children. Currently, the most widely prescribed therapy for ADHD is methylphenidate. Several formulations of methylphenidate have been developed that modify the delivery of the drug into the body. These include immediate-release (IR) tablets and modified-release preparations including sustained-release tablets, controlled-delivery capsules and tablets, and transdermal delivery systems. The IR tablet is taken two or three times daily and has been demonstrated to show efficacy through its rapid onset of action. The modified-release formulations deliver methylphenidate at a controlled rate and are administered once daily; they were developed to mimic the efficacy of the IR tablet by controlling drug release. The latest formulation development efforts have been directed towards combining the rapid release and onset of action of an IR component with an extended-release component that would maintain drug levels and allow for once-daily administration. The rationale for the development of various delivery systems of methylphenidate stems from the need for drug coverage for at least 8 hours for ADHD patients. This would maintain efficacy over the entire school day and would eliminate the need for repeated administrations while the patient was at school. Early formulation development targeted a constant-release profile or an apparent zero-order input with the intention of maintaining plasma drug levels at a constant level for the required time period. However, it was demonstrated that the constant delivery of methylphenidate did not provide equivalent efficacy to the repeated administration of the IR product over the school day and resulted in tolerance to the effects of the drug. This suggested that sustained-release formulations that maintained constant drug levels over the treatment period would not result in the optimal therapeutic condition. In contrast, a drug delivery profile that maintained a drug release pattern with increase-release kinetics would be able to overcome the tolerance that was observed with the constant delivery formulations. Therefore, the formulation development for modified-release once-daily administration products of methylphenidate has been targeted to mimic the repeated administrations of IR methylphenidate.     

Oromucosal midazolam: a review of its use in pediatric patients with prolonged acute convulsive seizures

Oromucosal midazolam (Buccolam?) is a benzodiazepine approved for the treatment of pediatric patients with acute, prolonged, convulsive seizures. This article reviews the pharmacologic properties of oromucosal midazolam and its clinical efficacy and tolerability for the treatment of prolonged acute convulsive seizures in pediatric patients aged 3 months to <18 years. Midazolam exerts its action by enhancing the effects of γ-aminobutyric acid (GABA) on GABA(A) receptors, resulting in neural inhibition. Oromucosal midazolam has a rapid onset (<10 minutes; due to rapid absorption across the buccal membrane and high lipophilicity) and short duration of effect (categorized by the short elimination half-life of midazolam and its active metabolite). The oromucosal administration of the drug avoids first-pass hepatic metabolism; as a result, it has a higher bioavailability than oral midazolam. Oromucosal midazolam is at least as effective at seizure cessation as rectal or intravenous diazepam and appears as well tolerated as these diazepam formulations in pediatric patients with acute convulsive seizures (additionally, midazolam has been available for use for decades in various formulations, and is historically well tolerated). Moreover, oromucosal midazolam was associated with a similar or shorter time to response than rectal diazepam. While the time to response was longer with oromucosal midazolam than with intravenous diazepam, the latter took significantly longer to apply than the former, leading to a significantly shorter overall controlling time with oromucosal midazolam. Respiratory depression occurred at a similar rate in recipients of oromucosal midazolam to that observed in recipients of rectal diazepam. Overall, oromucosal midazolam is at least as effective as rectal diazepam and as effective as intravenous diazepam in the treatment of children with prolonged acute convulsive seizures, and is generally well tolerated in this population. It has several advantages over rectal diazepam, the previous gold standard of treatment, such as having a more socially acceptable administration route and having a likely more predictable absorption profile. Oromucosal midazolam is a promising first-line treatment option for children with prolonged acute convulsive seizures, in particular where intravenous access is precluded.     

Target pharmacology of topiramate, a new antiepileptic drug

Topiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (gamma-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.     

Intranasal Treatment of Central Nervous System Dysfunction in Humans

One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit without cost. However, intranasal delivery is emerging as a noninvasive option for delivering drugs to the CNS with minimal peripheral exposure. Additionally, this method facilitates the delivery of large and/or charged therapeutics, which fail to effectively cross the blood-brain barrier (BBB). Thus, for a variety of growth factors, hormones, neuropeptides and therapeutics including insulin, oxytocin, orexin, and even stem cells, intranasal delivery is emerging as an efficient method of administration, and represents a promising therapeutic strategy for the treatment of diseases with CNS involvement, such as obesity, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, depression, anxiety, autism spectrum disorders, seizures, drug addiction, eating disorders, and stroke.     

Oxcarbazepine in the treatment of epilepsy.

Oxcarbazepine is a new antiepileptic drug (AED) that has been registered in more than 50 countries worldwide since 1990 and recently received approval in the United States and the European Union. Oxcarbazepine is a keto analog of carbamazepine and has a more favorable pharmacokinetic profile. It is rapidly absorbed after oral administration and undergoes rapid and almost complete reductive metabolism to form the pharmacologically active 10-monohydroxy derivative. Oxcarbazepine exhibits linear pharmacokinetics, no autoinduction, and minimal interaction with other AEDs. Ten controlled trials demonstrated that oxcarbazepine is safe and efficacious in the treatment of partial seizures across a wide range of ages (children to adults), situations (recent onset to treatment-resistant epilepsy), and uses (monotherapy and adjunctive therapy). The most common treatment-emergent adverse events are related to the central nervous system. Treatment-emergent hyponatremia (defined as serum sodium level < 125 mEq/L) occurred in 3% of patients treated with oxcarbazepine in clinical trials. According to the efficacy and safety profile established in the controlled trials, oxcarbazepine represents an important new treatment option indicated for monotherapy and adjunctive therapy in adults with partial seizures and as adjunctive therapy in children aged 4 years or older with partial seizures. Although structurally similar to carbamazepine, significant differences exist in the pharmacokinetics, drug interaction potential, adverse-effect profile, and dosage and titration between these two agents, and they should be considered distinct therapeutic agents.