Current Drug Therapy - Volume 6, Issue 3, 2011

Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events associated with anesthesia and surgery, with a high incidence after major gynecological surgery (e.g., abdominal hysterectomy). Numerous antiemetics have been studied for the prevention and treatment of PONV after this surgical procedure. Most of the published trials indicate the improved prevention of PONV by avoiding risk factors and/or by using antiemetic therapy in women undergoing major gynecological surgery. Pharmacological approaches include phenothiazines (e.g., perphenazine), butyrophenones (e.g., droperidol), benzamides (e.g., metoclopramide), antihistamines (e.g., cyclizine), proppofol, dexamethasone, ephedrine, serotonin receptor antagonists (e.g., ondansetron, granisetron) and neurokinin-1 receptor antagonists (e.g., aprepitant). None of the currently available antiemetics is entirely effective, perhaps because most of them act through the blockade of one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone preventing PONV. Combination antiemetic regimens (e.g., ondansetron plus droperidol) are highly effective in the prevention of PONV. As non-pharmacological therapy, acupressure and acupuncture at the P6 (Nei-Kuwan) point are effective for preventing PONV. For the treatment of established PONV, granisetron is more effective than droperidol or metoclopramide. In the management of PONV after major gynecological surgery, the benefits and risks of these clinical strategies should be considered.

The underlying pathogenesis of Alzheimer's disease (AD) is complex and is still under exploration. This has hampered the attempts to design highly selective and potent agents to treat AD. This review summarizes the present status of AD, present strategies and hypotheses (with underlying upstream and downstream events) for designing new drugs for AD. It also appraises the drugs based on present strategies that are in various stages of clinical trials, failures and the reasons for their failure. Further, it describes the future strategies being adopted for the anti-alzheimer's drug design. The recent approaches like immunotherapy, multi-targeted drug ligand design, usage of electromagnetic radiation and nanoparticle-mediated drug delivery are upcoming tools to overcome the impediment and have been discussed in this review.

Alzheimer's disease (AD) is the fourth major cause of death in the developed countries and it is the most common neurodegenerative disorder and the most prevalent cause of dementia with ageing. AD is characterized by the development of senile plaques and neurofibrillary tangles, which are associated with neuronal destruction; particularly in cholinergic neurons. The identification of disease causing autosomal dominant mutations as well as gene polymorphisms that alter the risk for pathology indicates that, it is a genetically complex disorder. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in diagnosis and treatment. Novel drugs that are currently in use or undergoing trial are briefly reviewed. To date, only a few acetylcholine esterase inhibitors have been licensed for AD, but more beneficial drugs are being actively sought by many different approaches. The development of additional drugs requires greater basic research on the pathogenesis of AD. Future therapeutic strategies for AD on the basis of recent findings concerning the pathogenesis of AD are also reviewed. Here, we review clinical features of the available cholinesterase inhibitors including their pharmacological properties and the emerging evidence for the use of memantine in AD. New therapeutic approaches including those more closely targeted to the pathogenesis of the disease will also be reviewed. Current treatments are briefly reviewed, followed by an introduction to emerging disease-modifying therapies.

This review summarizes recent findings on the therapeutic potential of hepatocyte growth factor (HGF) for a variety of neurological diseases. HGF, originally identified and molecularly cloned as a potent mitogen for hepatocytes, exhibits multiple biological effects, including mitogenic, motogenic, morphogenic, and anti-apoptotic activities in a wide variety of cells by binding to the c-Met/HGF receptor tyrosine kinase (c-Met). HGF is thus potentially a powerful tool as an organotropic factor for protection and regeneration of a variety of organs, and has an ability to exert the multipotent activities under pathophysiological conditions. In the nervous system, HGF and c-Met are expressed in not only developing brain but also adult mature brain, indicating that HGF-c-Met system plays a functional role in the central nervous system. Indeed, many studies have demonstrated that HGF shows neurotrophic activities in the hippocampal, cerebral cortical, midbrain dopaminergic, motor, sensory, sympathetic, parasympathetic, and cerebellar granule neurons in vitro. In in vivo studies, HGF exerted neuroprotective effects by preventing neuronal cell death in animal models of cerebrovascular diseases including ischemic brain injuries and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). These reports suggested that HGF is an effective therapeutic agent for the treatment of various neurological diseases.

Saponins comprise a class of plant natural products that incorporate a lipophilic terpenoid core, to which is appended one or more carbohydrate residues. They are amphiphilic molecules and often exhibit toxic biological profiles, likely as a result of their roles as vital components in protective coatings to defend against phytopathogen infection and insect predation. The most notable of adjuvant-active saponins investigated for vaccine development come from the Chilean Soapbark Tree, Quillaja saponaria (i.e., QS). More than 30 years ago, semi-purified extracts (i.e., Quil A) from the cortex of Quillaja saponaria were found to be highly effective as adjuvants in veterinary vaccines. However, due to significant and variable toxicity effects, Quil A was not deemed appropriate for human vaccines. More refined purification methods have led to multiple fractions which are derived from the original plant extract. As such, QS-21 to date appears to be one of the more scientifically interesting and robust adjuvants in use in vaccinology. The role of QS-21 as an adjuvant for use in a variety of cancer vaccine trials and its comparison to other adjuvants is discussed in this review.

In the past few years, an increasing number of in situ gel forming systems have been reported in the literature for various biomedical applications, including drug delivery, cell encapsulation, and tissue repair. The possible mechanisms that lead to in situ gel formation are solvent removal, ionic cross-linkage, light-sensitive, pH change and temperature modulation. The ability to inject a drug incorporated into a polymer to a localized site and have the drug from a semi-solid depot has a number of advantages. The advantages include ease of application, localized and prolonged drug delivery. For these reasons a large number of in situ setting polymeric delivery systems have been developed and investigated. This article reviews the stimuli-sensitive polymers and the use of these polymers in parenterals, ocular, peroral, rectal, vagina, nasal, dermal and transdermal drug delivery.

The transdermal drug delivery system (TDDS) acts as a substitute for oral route as well as parentral route as it avoids the limitation of conventional dosage forms like avoidance of hepatic first pass metabolism, reduced side effects and can deliver the drug at a predetermined rate over a prolonged period of time. It also avoids the discomfort associated with the parenteral therapy and improves patient compliance. This review covers types of transdermal drug delivery system, factors affecting TDDS, mechanism of action of TDDS, evaluation parameters for TDDS and various recent marketed products.