The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.
IntroductionThe present study was designed to evaluate the efficacy of clonidine, butorphanol, and tramadol in control of shivering under spinal anesthesia, and to compare their side effects.MethodsThis randomized, prospective study was conducted in 90 patients who developed shivering under spinal anesthesia during various abdominal or orthopedic surgery procedures. On shivering, patients were randomly allocated to receive an intravenous, 1 mL bolus dose of 50 mg tramadol, or 1 mg butorphanol, or 150 μg clonidine, in a double blinded manner. Control of shivering, time taken for cessation, recurrence, hemodynamic changes, axillary temperatures, and side effects were noted and compared for all 3 groups. Collected data were analyzed using appropriate statistical tests.ResultsButorphanol and tramadol were more effective than clonidine in suppressing shivering. Butorphanol, tramadol, and clonidine completely controlled rigors in 83%, 73%, and 53% of cases, respectively, and incompletely suppressed rigors in 16%, 26%, and 46% of cases, respectively. Time taken to terminate rigors was significantly higher for clonidine (3.3 ± 0.9 minutes) than for butorphanol and tramadol (2.1 ± 1.0 minutes and 1.8 ± 0.5 minutes; P < 0.001).ConclusionButorphanol had an edge over tramadol in controlling shivering with lower chances of recurrence, though both were superior to clonidine for this purpose with an early onset of action. We conclude that both these opioids control rigors better than α-2 agonists.
Background COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. Scope and approach This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions : Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.
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