DOCSLIB.ORG

A Review on Enzymes As Diagnostic Reagents and Therapeutic Agents

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Review on Enzymes As Diagnostic Reagents and Therapeutic Agents Volume 5, Issue 12, December – 2020 International Journal of Innovative Science and Research Technology ISSN No:-2456-2165 A Review on Enzymes as Diagnostic Reagents and Therapeutic Agents Afreen H1, Kiran Manoj2, Rajeev Nateshkumar3 Anna University Chennai1, Central University of Rajasthan2, University of Mumbai3 Abstracts:- The present review is based on papers There originates a confusion in interpreting the results as published between 1972 and 2020 and gives Comparative there are several modes/units to express cholinesterase activity information about the most common enzymes as and thus a careful standardization of the different units needs Diagnostic reagents and their clinical applications in to be done. disorders. Activities of following enzymes: Acid Phosphatase, Alanine Aminotransferase, Alkaline The main applications of these methods could be helpful Phosphatase, Cholinesterase, Creatinine Kinase, Gamma in identifying the serum cholinesterase levels which may be an Glutamyl Transferase, Lactate Dehydrogenase, Renin, indication of some disease or disorder, especially of the Urokinase. nervous system as acetylcholine is present in the synaptic junctions of the neurons and functions as a chemical Keywords:- Enzymes, Renin, Therapeutic applications of messenger. This could further help to develop commercial enzymes, Diagnostic Reagents, Phosphatase. reagent kits or point of care devices for the accurate and early diagnosis of the said disorders. I. INTRODUCTION AND DISCUSSION Activity of phenyl carbamate analogues of Rivastigmine as Cholinesterase a novel therapeutic agent for the treatment of Alzheimer’s disease. Quantitative analysis and estimation of cholinesterase for There have been several strategies that have been diagnostic purposes for laboratory and commercial use. followed for the treatment of Alzheimer’s of which the use of The different quantification methods being employed for cholinesterase inhibitors is the most studied and most used the estimation of cholinesterase have been discussed briefly. form of palliative treatment. Due to many advantageous There is an increasing need for reliable tests for assessing the features, donepezil has been the most used drug. cholinesterase status of patients. This will be useful in identifying the poisonings caused by cholinesterase inhibitors In this paper, the studies have been centred around such as the organophosphate or carbamate insecticides. rivastigmine which is the next best treatment and the pros and cons have been elaborated. Rivastigmine shows an interesting The basic hydrolysis of acetylcholine, a selectivity in the brain regions that are most affected by neurotransmitter, yields choline and acetic acid, of which the neuronal degradation. Some limitations in the usage of this acetic acid produced needs to be quantified to measure the drug is the short half-life period, difficulty in intake and the cholinesterase activity in a specimen. The different methods high cost associated with the synthesis of its intermediate – N- that have been studied and utilised for clinical and commercial ethyl-N-methyl carbamoyl chloride. purposes are briefly stated as follows: electrometric, titrimetric, manometric and colorimetric methods. The main Some recent studies have been conducted on dimethyl, criteria for the assays were sensitivity and reproducibility. diethyl and n-hexyl carbamates related to rivastigmine to try and overcome these limitations. The synthesised compounds The titrimetric method utilised the pH-stat where have been evaluated for the acetylcholinesterase and electronic means are used to maintain a constant pH. This butyrylcholinesterase in different cerebral regions such as the method is very sensitive and the most reproducible but the cortex, striatum and hippocampus. The LD50, IC50 and ED50 only limitation was that the cost of the equipment is high. The values have been estimated for the several compounds. manometric method is also sensitive but it is more time consuming in comparison with the other methods. Graded Thus, the therapeutic effects of the carbamate derivatives colour changes are observed under controlled reaction of Rivastigmine have been analysed for their efficacy and conditions in the colorimetric method and this method could toxicity. Conformational analysis has also been performed to be employed in places with no access to laboratories as well. determine the minimal energy conformations that is best suited for our needs. The different compounds have been compared and analysed to suggest which of them would be IJISRT20DEC024 www.ijisrt.com 27 Volume 5, Issue 12, December – 2020 International Journal of Innovative Science and Research Technology ISSN No:-2456-2165 useful as a potential drug candidate. The further clinical trials Donepezil, is a non-competitive, reversible have not been done on this drug and there is still much more cholinesterase inhibitor with high selectivity used to reduce information to be understood before it could be decisively neuronal degradation. The limitation is that it is not able to considered as a potential candidate. penetrate the blood brain barrier (BBB), thereby exhibiting a limited potential in treatment of AD. Clinical evidence-based studies recommendations for the use of cholinesterase inhibitors – A Literature Review The different hypotheses regarding the pathogenesis of Cholinesterase inhibitors have been a standard therapy Alzheimer’s are discussed here including the cholinergic for patients with Alzheimer’s disease. Tacrine was the first hypothesis, amyloid hypothesis, oxidative stress hypothesis used compound for the treatment of AD, but it was later and bio metal hypothesis. It has been discussed how different replaced by donepezil due to the substantial hepatotoxicity it structural/biochemical modifications have been done on the caused. Donepezil (Aricept), rivastigmine (Exelon) and donepezil and its analogues and how effective they are in the galantamine (Reminyl) have been considered for this study. treatment of Alzheimer’s. The papers that have been collected for this review were With the help of molecular docking, several different grouped into 3 classes; Class I that included randomised, compounds have been produced by making structural controlled, clinical trials and overviews (meta-analysis); Class modifications to the enzyme, and this could serve as potential II that included well designed observational studies with drug targets. This is the main idea behind the development of concurrent controls and Class III that included expert multi-target directed ligands (MTDLs). The main properties opinions, case series, case reports and historical controls. that are being focussed are the BBB permeation, additional antioxidant property, additional inhibition, ROS scavenge The 3 cholinesterase inhibitors that have been considered ability, improving memory performance, etc. in this study have different half-life and metabolisms. Donepezil has a longer half-life in comparison with the other Of the available drugs, almost all of them are only used two drugs. Donepezil and galantamine are metabolised with to relieve the symptoms or slow down the progression of the the help of cytochrome p450 enzymes while rivastigmine is disease. Hence, it is the need of the hour to develop hybrids of hydrolysed to a phenolic by product and excreted through the available drugs with a MTDL property wherein two or urine. Donepezil has the highest protein binding. Galantamine more distinct pharmacophores that recognise diverse targets and rivastigmine have delayed absorption caused by intake of that may be closely related to AD are combined to yield a drug food. with multiple benefits and minimal side effects. If more detailed analysis is done, some of these compounds could be MEDLINE and PUBMED are scientific journals that shortlisted to be potential drug targets for the treatment of have been used as a source for the papers that have been Alzheimer’s. published and a comparison in action between the different drugs employed and a spectrum of varying responses have Creatine Kinase been identified from patients and the outcomes have been distinguished as primary and secondary outcomes. Serum creatine kinase as a biomarker in systemic lupus erythematosus. The overall efficacy of these cholinesterase inhibitors This paper summarises a case report of a patient has been thoroughly summarised based on a comparative prognosis and treatment administered for systemic lupus study of all the literature that has been published. This helps erythematosus (SLE). The different therapies that have been us understand the precise action of the drug, the possible side administered and the side effects caused have been studied. A effects and also if it gives rise to any comorbidities depending better understanding of the primary SLE-induced infection of on the patient’s medical history. However, the clinical issues the musculoskeletal system and the drug-induced side effects of when to stop the treatment have not been studied or is important for appropriate treatment of SLE patients. reported. There is an absence of direct comparative trials. The patient had initially presented with arthralgia, Multi-target directed ligands against cholinesterase for arthritis, myalgia, pleuritis, and Raynaud’s phenomenon and Alzheimer’s treatment based on modifications on was diagnosed as having a mixed connective tissue disease. Donepezil Glucocorticosteriods and chloroquine were provided as a Despite the detailed studies on Alzheimer’s,
Load more

Recommended publications
  • Failed Reversal of Neuromuscular Blockade Despite Sugammadex: a Case of Undiagnosed Pseudocholinesterase Deficiency
    CASE REPORT Failed reversal of neuromuscular blockade despite sugammadex: A case of undiagnosed pseudocholinesterase deficiency Gozde Inan, MD*, Elif Yayla, MD** and Berrin Gunaydin, MD*** *Consultant; **Resident; ***Professor Department of Anesthesiology and Reanimation, Gazi University, School of Medicine, Besevler, Ankara (Turkey) Correspondence: Gozde Inan, MD, Gazi University School of Medicine, Department of Anaesthesiology and Reanimation, Besevler, Ankara (Turkey); Tel: +90 312 202 4166; Fax: +90 312 202 4166; E-mail address: [email protected] ABSTRACT The management of an undetected pseudocholinesterase deficiency in a parturient who underwent urgent cesarean section has been presented. After rapid sequence induction with succinylcholine, rocuronium was used for maintenance of neuromuscular block. At the end of the operation neostigmine was given to antagonize the residual block. Upon persistent prolonged neuromuscular blockade sugammadex was administered. Probable reasons, drug interactions, the importance of suspecting pseudocholinesterase deficiency and the need of neuromuscular monitoring have been argued in this case report. Key words: Pseudocholinesterase deficiency; Cesarean section; Sugammadex Citation: Inan G, Yayla E, Gunaydin B. Failed reversal of neuromuscular blockade despite sugammadex: A case of undiagnosed pseudocholinesterase deficiency. Anaesth Pain & Intensive Care 2015;19(2):184- 186 INTRODUCTION induction of neuromuscular block was provided by succinylcholine and maintained with rocuronium, Prolonged neuromuscular blockade is a common neostigmine and sugammadex were administered complication that every anesthesiologist has to antagonize the blockade. We aimed to discuss the experienced sometime in his clinical practice. management of prolonged neuromuscular block Pseudocholinesterase (PChE) deficiency should probably due to an undetected PChE deficiency in be suspected in case of prolonged neuromuscular a parturient who underwent emergency cesarean blockade.1 PChE is an enzyme synthesized in the liver, section (C/S).
    [Show full text]
  • Cholinesterase Activity As Biomarker of Neurotoxicity: Utility in The
    Revista da Gestão Costeira Integrada 13(4):525-537 (2013) Journal of Integrated Coastal Zone Management 13(4):525-537 (2013) http://www.aprh.pt/rgci/pdf/rgci-430_Jebali.pdf | DOI:10.5894/rgci430 Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination * Actividade da colinesterase como biomarcador de neurotoxicidade: avaliação da contaminação em ambientes aquáticos ** Jamel Jebali @, 1, Sana Ben Khedher 1, Marwa Sabbagh 1, Naouel Kamel 1, Mohamed Banni 1, Hamadi Boussetta 1 ABSTRACT Cholinesterase can take place in aquatic organisms under a series of environmental adverse conditions. The study of cholinesterases in these organisms can give important information about their physiological status and about environmental health. However, it is very important to know how the environmental factors such as fluctuation of physicochemical parameters associated to the presence of pollutants might affect these cholinesterase activities. We studied the response of cholinesterase activity in the caged cockleCerastoderma glaucum. In addition, we evaluated the potential uses of cholinesterase activity in the common sole, which inhabit the Tunisian coast, subjected to different stress conditions, such as the exposure to different contaminants. This review summarizes the data obtained in some studies carried out in organisms from the Tunisian aquatic environment. Keywords: Cholinesterases, Environmental stress, Biomonitoring, Aquatic Environments. RESUMO A colinesterase está presente nos organismos aquáticos em condições de stress ambiental. O estudo da colinesterase fornece informações acerca da condição fisiológica e saúde ambiental. Contudo é importante averiguar de que modo os factores ambientais, tais como a flutuação dos parâmetros físico-químicos, associados à presença de poluentes afectam a actividade das colinesterases.
    [Show full text]
  • Neuronal Nicotinic Receptors
    NEURONAL NICOTINIC RECEPTORS Dr Christopher G V Sharples and preparations lend themselves to physiological and pharmacological investigations, and there followed a Professor Susan Wonnacott period of intense study of the properties of nAChR- mediating transmission at these sites. nAChRs at the Department of Biology and Biochemistry, muscle endplate and in sympathetic ganglia could be University of Bath, Bath BA2 7AY, UK distinguished by their respective preferences for C10 and C6 polymethylene bistrimethylammonium Susan Wonnacott is Professor of compounds, notably decamethonium and Neuroscience and Christopher Sharples is a hexamethonium,5 providing the first hint of diversity post-doctoral research officer within the among nAChRs. Department of Biology and Biochemistry at Biochemical approaches to elucidate the structure the University of Bath. Their research and function of the nAChR protein in the 1970’s were focuses on understanding the molecular and facilitated by the abundance of nicotinic synapses cellular events underlying the effects of akin to the muscle endplate, in electric organs of the acute and chronic nicotinic receptor electric ray,Torpedo , and eel, Electrophorus . High stimulation. This is with the goal of affinity snakea -toxins, principallyaa -bungarotoxin ( - Bgt), enabled the nAChR protein to be purified, and elucidating the structure, function and subsequently resolved into 4 different subunits regulation of neuronal nicotinic receptors. designateda ,bg , and d .6 An additional subunit, e , was subsequently identified in adult muscle. In the early 1980’s, these subunits were cloned and sequenced, The nicotinic acetylcholine receptor (nAChR) arguably and the era of the molecular analysis of the nAChR has the longest history of experimental study of any commenced.
    [Show full text]
  • [3H]Acetylcholine to Muscarinic Cholinergic Receptors’
    0270.6474/85/0506-1577$02.00/O The Journal of Neuroscience CopyrIght 0 Smety for Neurosmnce Vol. 5, No. 6, pp. 1577-1582 Prrnted rn U S.A. June 1985 High-affinity Binding of [3H]Acetylcholine to Muscarinic Cholinergic Receptors’ KENNETH J. KELLAR,2 ANDREA M. MARTINO, DONALD P. HALL, Jr., ROCHELLE D. SCHWARTZ,3 AND RICHARD L. TAYLOR Department of Pharmacology, Georgetown University, Schools of Medicine and Dentistry, Washington, DC 20007 Abstract affinities (Birdsall et al., 1978). Evidence for this was obtained using the agonist ligand [3H]oxotremorine-M (Birdsall et al., 1978). High-affinity binding of [3H]acetylcholine to muscarinic Studies of the actions of muscarinic agonists and detailed analy- cholinergic sites in rat CNS and peripheral tissues was meas- ses of binding competition curves between muscarinic agonists and ured in the presence of cytisin, which occupies nicotinic [3H]antagonists have led to the concept of muscarinic receptor cholinergic receptors. The muscarinic sites were character- subtypes (Rattan and Goyal, 1974; Goyal and Rattan, 1978; Birdsall ized with regard to binding kinetics, pharmacology, anatom- et al., 1978). This concept was reinforced by the discovery of the ical distribution, and regulation by guanyl nucleotides. These selective actions and binding properties of the antagonist pirenze- binding sites have characteristics of high-affinity muscarinic pine (Hammer et al., 1980; Hammer and Giachetti, 1982; Watson et cholinergic receptors with a Kd of approximately 30 nM. Most al., 1983; Luthin and Wolfe, 1984). An evolving classification scheme of the muscarinic agonist and antagonist drugs tested have for these muscarinic receptors divides them into M-l and M-2 high affinity for the [3H]acetylcholine binding site, but piren- subtypes (Goyal and Rattan, 1978; for reviews, see Hirschowitz et zepine, an antagonist which is selective for M-l receptors, al., 1984).
    [Show full text]
  • Butyrylcholinesterase Inhibitors
    DOI: 10.1002/cbic.200900309 hChAT: A Tool for the Chemoenzymatic Generation of Potential Acetyl/ Butyrylcholinesterase Inhibitors Keith D. Green,[a] Micha Fridman,[b] and Sylvie Garneau-Tsodikova*[a] Nervous system disorders, such as Alzheimer’s disease (AD)[1] and schizophrenia,[2] are believed to be caused in part by the loss of choline acetyltransferase (ChAT) expression and activity, which is responsible for the for- mation of the neurotransmitter acetylcholine (ACh). ACh is bio- synthesized by ChAT by acetyla- tion of choline, which is in turn biosynthesized from l-serine.[3] ACh is involved in many neuro- logical signaling pathways in the Figure 1. Bioactive acetylcholine analogues. parasympathetic, sympathetic, and voluntary nervous system.[4] Because of its involvement in many aspects of the central nerv- Other reversible AChE inhibitors, such as edrophonium, neo- ous system (CNS), acetylcholine production and degradation stigmine, pyridostigmine, and ecothiopate, have chemical has become the target of research for many neurological disor- structures that rely on the features and motifs that compose ders including AD.[5] In more recent studies, a decrease in ace- acetylcholine (Figure 1). They all possess an alkylated ammoni- tylcholine levels, due to decreases in ChAT activity,[6] has been um unit similar to that of acetylcholine. Furthermore, all of the observed in the early stages of AD.[7–9] An increase in butyryl- compounds have an oxygen atom that is separated by either cholinesterase (BChE) has also been observed in AD.[6] Depend- two carbons from the ammonium group, as is the case in ace- ing on the location in the brain, an increase and decrease of tylcholine, or three carbons.
    [Show full text]
  • Sugammadex Reversal of Rocuronium-Induced Neuromuscular Blockade: a Comparison with Neostigmine–Glycopyrrolate and Edrophonium–Atropine
    Sugammadex Reversal of Rocuronium-Induced Neuromuscular Blockade: A Comparison with Neostigmine–Glycopyrrolate and Edrophonium–Atropine Ozlem Sacan, MD BACKGROUND: Sugammadex is a modified ␥ cyclodextrin compound, which encap- sulates rocuronium to provide for a rapid reversal of residual neuromuscular Paul F. White, MD, PhD blockade. We tested the hypothesis that sugammadex would provide for a more rapid reversal of a moderately profound residual rocuronium-induced blockade Burcu Tufanogullari, MD than the commonly used cholinesterase inhibitors, edrophonium and neostigmine. METHODS: Sixty patients undergoing elective surgery procedures with a standard- ized desflurane–remifentanil–rocuronium anesthetic technique received either Kevin Klein, MD sugammadex, 4 mg/kg IV (n ϭ 20), edrophonium, 1 mg/kg IV and atropine, 10 ␮g/kg IV (n ϭ 20), or neostigmine, 70 ␮g/kg IV and glycopyrrolate, 14 ␮g/kg IV (n ϭ 20) for reversal of neuromuscular blockade at 15 min or longer after the last dose of rocuronium using acceleromyography to record the train-of-four (TOF) responses. Mean arterial blood pressure and heart rate values were recorded immediately before and for 30 min after reversal drug administration. Side effects were noted at discharge from the postanesthesia care unit. RESULTS: The three groups were similar with respect to their demographic character- istics and total dosages of rocuronium prior to administering the study medication. Although the initial twitch heights (T1) at the time of reversal were similar in all three groups, the time to achieve TOF ratios of 0.7 and 0.9 were significantly shorter with sugammadex (71 Ϯ 25 and 107 Ϯ 61 s) than edrophonium (202 Ϯ 171 and 331 Ϯ 27 s) or neostigmine (625 Ϯ 341 and 1044 Ϯ 590 s).
    [Show full text]
  • Human Erythrocyte Acetylcholinesterase
    Pediat. Res. 7: 204-214 (1973) A Review: Human Erythrocyte Acetylcholinesterase FRITZ HERZ[I241 AND EUGENE KAPLAN Departments of Pediatrics, Sinai Hospital, and the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Introduction that this enzyme was an esterase, hence the term "choline esterase" was coined [100]. Further studies In recent years the erythrocyte membrane has received established that more than one type of cholinesterase considerable attention by many investigators. Numer- occurs in the animal body, differing in substrate ous reviews on the composition [21, 111], immunologic specificity and in other properties. Alles and Hawes [85, 116] and rheologic [65] properties, permeability [1] compared the cholinesterase of human erythro- [73], active transport [99], and molecular organiza- cytes with that of human serum and found that, tion [109, 113, 117], attest to this interest. Although although both enzymes hydrolyzed acetyl-a-methyl- many studies relating to membrane enzymes have ap- choline, only the erythrocyte cholinesterase could peared, systematic reviews of this area are limited. hydrolyze acetyl-yg-methylcholine and the two dia- More than a dozen enzymes have been recognized in stereomeric acetyl-«: /3-dimethylcholines. These dif- the membrane of the human erythrocyte, although ferences have been used to delineate the two main changes in activity associated with pathologic condi- types of cholinesterase: (1) acetylcholinesterase, or true, tions are found regularly only with acetylcholinesterase specific, E-type cholinesterase (acetylcholine acetyl- (EC. 3.1.1.7). Although the physiologic functions of hydrolase, EC. 3.1.1.7) and (2) cholinesterase or erythrocyte acetylcholinesterase remain obscure, the pseudo, nonspecific, s-type cholinesterase (acylcholine location of this enzyme at or near the cell surface gives acylhydrolase, EC.
    [Show full text]
  • Cholinesterase Levels in Blood Plasma and Erythrocytes from Calves, Normal Delivering Cows and Cows Suffering from Parturient Paresis
    Acta vet. scand. 1983, 24, 185-199. From the Department of Cattle and Sheep Diseases, College of Veteri­ nary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden. CHOLINESTERASE LEVELS IN BLOOD PLASMA AND ERYTHROCYTES FROM CALVES, NORMAL DELIVERING COWS AND COWS SUFFERING FROM PARTURIENT PARESIS By Kristina Forslund, Camilla Bjorkman and Mainor Abrahamsson FORSLUND, K., C. BmRKMAN and M. ABRAHAMSSON : Cholin esterase levels in blood plasma and erythrocytes from calves, normal delivering cows and cows suffering from parturient paresis. Acta vet. scand. 1983,24, 185-199.- Plasma cholinesterase (pChE) levels and erythrocyte acetylcholinesterase (eAChE) levels were studied in 6 cows before, during and after parturition (Groul? l), their calves (Group II), 38 cows suffering from parturient paresis (Group III) and 14 newly delivered non-paretic cows (Group IV) . The mean of the pChE level in Group I was 1.5 p.kat/l ± 0.20 before parturition and decreased significantly (P 0.05) to 1.2 ukat/! ± 0.16 after parturition. The eAChE level was before parturition'" 140 lLkat/1 and decreased to 130 ukat/I 4--5 weeks after parturition. At birth the pChE level was 12.8 p.kat/l ± 5.9 in Group II. After 4 weeks the level had decreased to 2.3 p.kat/l ± 0.3. In the bull calves the pChE level started to increase when they were 6 weeks old and reached a level of 5.7 p.kat/l ± 0.6 before slaughter at 6 months of age. The heifers did not show this increase. They had a level of around 2 ILkat/l throughout the investigation.
    [Show full text]
  • Cholinergic Treatments with Emphasis on M1 Muscarinic Agonists As Potential Disease-Modifying Agents for Alzheimer’S Disease
    Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics Cholinergic Treatments with Emphasis on M1 Muscarinic Agonists as Potential Disease-Modifying Agents for Alzheimer’s Disease Abraham Fisher Israel Institute for Biological Research, P. O. Box 19, Ness-Ziona 74100, Israel Summary: The only prescribed drugs for treatment of Alzhei- formation of ␤-amyloid plaques, and tangles containing hyper- mer’s disease (AD) are acetylcholinesterase inhibitors (e.g., phosphorylated tau proteins) are apparently linked. Such link- donepezil, rivastigmine, galantamine, and tacrine) and meman- ages may have therapeutic implications, and this review is an tine, an NMDA antagonist. These drugs ameliorate mainly the attempt to analyze these versus the advantages and drawbacks symptoms of AD, such as cognitive impairments, rather than of some cholinergic compounds, such as acetylcholinesterase halting or preventing the causal neuropathology. There is cur- inhibitors, M1 muscarinic agonists, M2 antagonists, and nico- rently no cure for AD and there is no way to stop its progres- tinic agonists. Among the reviewed treatments, M1 selective sion, yet there are numerous therapeutic approaches directed agonists emerge, in particular, as potential disease modifiers. against various pathological hallmarks of AD that are exten- Key Words: Alzheimer’s, cholinergic, ␤-amyloid, tau, acetyl- sively being pursued. In this context, the three major hallmark cholinesterase inhibitors, M1 muscarinic, nicotinic, agonists, characteristics of AD (i.e., the CNS cholinergic hypofunction, M2 muscarinic antagonists. INTRODUCTION (␣-APPs) that is neurotrophic and neuroprotective. In an alternate pathway, ␤-secretase (BACE1) cleaves APP Alzheimer’s disease (AD) is a progressive, neurode- releasing a large secreted derivative sAPP␤ andaC- generative disease that is a major health problem in terminal fragment C99 that can be further cleaved by modern societies.
    [Show full text]
  • Treating Dementia with Cholinesterase Inhibitors Patient Information - Older Persons Mental Health
    Treating Dementia with Cholinesterase Inhibitors Patient information - Older Persons Mental Health www.cdhb.health.nz/patientinfo Dementia is a progressive disease of the brain in which brain cells die and are not replaced. It results in impaired memory, thinking and behaviour. In recent years a number of medications for dementia have become available in New Zealand, includ- ing cholinesterase inhibitors, which are discussed below. For more information, please contact your GP or specialist. Other useful sources of information are Alzhei- mer’s Canterbury (314 Worcester St, Christchurch, phone (03) 379 2590) and the website www.alzheimers.org.nz click on “your Alzheimer’s organisation” to take you to Canterbury. Cholinesterase Cholinesterase Treating Dementia with with Dementia Treating Inhibitors Older Older Persons Mental Health How do cholinesterase inhibitors work? Cholinesterase inhibitors are designed to enhance memory and other brain functions by influencing chemical activity in the brain. Acetylcholine is a chemical messenger in the brain that is thought to be important for the function of brain cells involved in memory, thought and judgement. Acetylcholine is released by one brain cell to transmit a message to another. Once a message is received, various enzymes, including some called cholinesterases, break down the chemical messenger for reuse. In the brain affected by dementia, the cells that produce acetylcholine are damaged or destroyed, resulting in lower levels of the chemical messenger. A cholinesterase inhibitor is designed to reduce the activity of the cholinesterases, thereby slowing down the breakdown of acetylcholine. By maintaining levels of acetylcholine, the drug may help compensate for the loss of functioning brain cells.
    [Show full text]
  • Drug Treatments for Alzheimer's Disease
    Factsheet 407LP Drug treatments December 2014 for Alzheimer’s disease There are no drug treatments that can cure Alzheimer’s disease or any other common type of dementia. However, medicines have been developed for Alzheimer’s disease that can temporarily alleviate symptoms, or slow down their progression, in some people. This factsheet explains how the main drug treatments for Alzheimer’s disease work, how to access them, and when they can be prescribed and used effectively. For more information about Alzheimer’s disease see factsheet 401, What is Alzheimer’s disease? Contents n What are the main drugs used? n How do they work? n Are these drugs effective for everyone with Alzheimer’s disease? n Are there any side effects? n How are these drugs prescribed? n Are these drugs effective for other types of dementia? n Taking the drugs n Questions to ask the doctor when starting the drugs n Stopping treatment n NICE guidance: a summary n Research into new treatments n Other useful organisations. 2 Drug treatments for Alzheimer’s disease Drug treatments for Alzheimer’s disease Drug treatment for Alzheimer’s disease is important, but the benefits are small, and drugs should only be one part of a person’s overall care. Non- drug treatments, activities and support are just as important in helping someone to live well with Alzheimer’s disease. Many drugs have at least two names. The generic name identifies the substance. The brand name varies depending on the company that manufactures it. For example, a familiar painkiller has the generic name paracetamol and is manufactured under brand names such as Panadol and Calpol, among others.
    [Show full text]
  • Sugammadex: a Neuromuscular Blockade Agent Encapsulator
    ICU ROUNDS Sugammadex: A neuromuscular blockade agent encapsulator Victoria Yepes Hurtado BSN, RN ABSTRACT Sugammadex sodium, a modifiedγ -cyclodextrin, represents a new class of drugs effective at reversing non-depolarizing muscle relaxants rocuronium and vecuronium. The cylindrical, basket-like structure encapsulates neuromuscular blocking agents which results in rapid reversal of paralysis within three minutes. The current literature was reviewed to analyze the clinical implications and considerations with its administration. Keywords: cyclodextrin, encapsulation, selective relaxant binding agent, sugammadex, supramolecular Sugammadex sodium, a modified γ- cyclodextrin receptors to prevent recurarization. In addition, gly- and a pioneer of its kind, represents a new class of copyrrolate or atropine is usually administered con- drugs effective at reversing the non-depolarizing currently with neostigmine to counteract the adverse muscle relaxants rocuronium and vecuronium.1 In effects associated with neostigmine use alone. The order to induce paralysis, non-depolarizing neuro- adverse effects of atropine and glycopyrrolate are muscular blocking agents (NMBAs) compete with related to muscarinic antagonism and cause dry acetylcholine (ACh) for the cholinergic receptors at mouth, urinary retention, and tachycardia, the latter the motor end-plate of the neuromuscular junction. of which can negatively affect the hemodynamic sta- Traditional reversal of non-depolarizing NMBAs con- tus in patients with cardiac disease. Conversely, sug- sists
    [Show full text]