Global management, people, and the digital divide Essay - 4

Global management, people, and the digital divide - Essay Example In poverty stricken areas, many people do not enjoy the benefits afforded by ICT, such as internet accessibility and networking. This is why such regions extensively rely on markets and donor driven aid to build their ICT infrastructure (Jonathan, 2005, pp. 22-25). However, failure to access such funds continues to widen the gap between the poor and the rich, especially in regard to internet accessibility. This inequality is rampant not only in developing countries, but in developed ones as well. In recognition of the identified digital divide, donors are increasingly considering the need to bridge this gap, through creation of low cost technologies, which can aid in enhancing internet accessibility in these regions. An excellent example is the recently adopted laptop per child policy, which seeks to ensure that children in underprivileged societies attain some level of technological advancement (Strover, 2003, pp. 275-277). The program further seeks to ensure that students experience a media rich environment both at home and school, which will make them more creative and critical with information technology. The program is also instrumental in increasing opportunities for students to overcome educational inequality. The One Laptop per Child (OLPC) program is a high profile initiative designed to bridge the digital divide, by providing poor kids with low cost computers that support network capability. These laptops are specifically designed to handle low-power supply, as well as, the ruggedness of poor rural and urban regions (vanDuersen and vanDijk, 2011, pp. 895-905). Additionally, the laptops’ software features graphical programs and user interface that are designed to enhance learning. For instance, in the largely rural state of Maine, students from poor backgrounds have benefited from the OPLC program by acquiring means to access

The Most Effective Ways of Writing an Essay in English

The Most Effective Ways of Writing an in English - Essay Example The essay introduction of any paper has to get control of the reader's thoughts. For one to achieve these, stylistic conventions such as proverbs, real or fake interesting incident, surprising information, and curiosity questions are used (page 202). Cottrell (2008) explains that the introduction has three main purposes. A statement describing the idea of the essay is made to establish the scope of the essay from a general to a more specific subtopic. Questions such as why, when, where, why and how to focus on the overall question that is the thesis statement (page 204). Addressing these major question calls for a clear and specific statement made near the end of the introductory paragraph (Greetham, 2008). With this, the introduction will give a picture of the major points yet to be discussed that will possess the reader’s attention. In addition to a good introduction, the body forms the content address to the title (Cottrell, 2008). The discussion is organized and presented in at least three body paragraphs according to the number of topics chosen. â€Å"Each body paragraph forms its main idea† (page192). The body paragraphs have three main sections; the main point, the supporting statements, and the last statement relating to the next paragraph. The main point connects with the central purpose of the essay. For an effective essay, the body paragraph will often start with a topic sentence. The topic sentence forms the summary of the paragraph which reflects on the main statement summarizing the whole essay. Though the topic sentence comes after the body paragraph introduction, the topic sentence may come first (Greetham, 2008). Providing supporting explanations, evidence, and examples make the most interesting part of the body paragraph (page 142).  

Surface analysis Assignment Example | Topics and Well Written Essays - 1750 words

Surface analysis - Assignment Example These ions on collision dislodge atoms from the surface creating secondary ions. Using a combination of electrostatic and magnetic fields which distinguishes the ions on the mass to charge ratio, these secondary ions are drawn into a mass spectrometer. By varying the strength of the magnetic field one can assess ions of different mass to charge ratios. (Surface Analysis, 2000) Some of the applications of SIMS include (i) Identifying the isotopes in a material that might have same atomic masses as it is capable of producing mass resolutions to tune of 7000. (ii) It is capable of finding out the extent of impurity concentration present in a specimen and represents the same as a function of depth. The sensitivity of this instrument is in the range of 1 ppb (-10^13 at/cm^3) (iii) It can accurately map the interface layers and the impurities that may be located at these grain boundaries. (iv) It uses the raster scanning technique to produce three dimensional images of the grain distributi on. (v) Using the secondary ions it can directly produce an image showing the arrangement of trace elements. Source: Surface Analysis, 2000 2. ... Some of the applications of AES include (i) This is used to identify compositions of elements in solid materials with high output sensitivities in the range of 0.5 atomic percent for lithium to uranium. (ii) This is useful in carrying out the volumetric analysis of a specimen. (iii) This is capable of producing magnified images to the tune of 20000x and is used extensively in microelectronics. 3. X-Ray Photoelectron Spectroscopy (XPS) (Surface Analysis, 2000) This advanced technique uses x rays in dislodging electrons from specimens and these have distinct kinetic energies depending on the nature of emitted electrons. It is particularly useful in providing information regarding the type of bonds that exist between electrons. This is because any change in binding energy is reflected in the XPS spectrum chart which shows crests and troughs. The crests obviously reflect the high chemical boding energy that existed and the troughs vice versa. Its applications include (i) Determining mole cular composition of surfaces along with information regarding the atomic bonding. (ii) It can identify very accurately to the tune of 0.5 atomic % the presence of lithium and uranium. (iii) This can create depth profiles for materials in the range of 1Â µm thickness. (iv) This method of analysis is particularly useful to study functional groups in polymers. 4. Scanning Probe Microscopy (SPM) This is also referred to as Atomic Force Microscopy (AFM). This is capable of generating a profile that shows the topographical nature of the specimen surface. Schematic of atomic force microscope operation Source: Surface Analysis, 2000 This essentially consists of a tip mounted on a cantilever. The specimen is placed below this cantilever and

Marketing communications tools Essay Example | Topics and Well Written Essays - 2500 words

Marketing communications tools - Essay Example Notably, it can be ascertained that in the past few years’ digital technology and the expansion of targeting capabilities has shifted from the traditional marketing tools to digital marketing tools. Due to the continuous revolution in the field of marketing communication tools particularly the internet, it has be found that both small organizations as well as big organizations are widely inclined towards using modern digital marketing tools over the conventional tools. Traditional marketing tools involving print media (such as magazines, newspapers and newsletters) electronic media (such as broadcasting through television and radios) and direct marketing among others can be ascertained to be barely used by the contemporary business organizations. Nonetheless, both the traditional and digital marketing tools have some advantages and disadvantages. Hence, it would be wise to use the combine form of traditional and digital marketing tools in order to achieve the best outcome. ... Significance of Traditional Forms of Marketing Communications in the Contemporary Organizations It can be affirmed that digital marketing tools particularly internet has attracted the contemporary marketers to a great extent. However, heavy reliability on modern marketing tools does not mean that traditional marketing is disappearing. In this regard, it has been ascertained from a survey report that approximately USD $ 295billion was spent on television advertisement in the US during 2007. A huge investment on traditional marketing tool in this cotemporary world signifies vast majority of traditional media. At the same time, newspaper and magazines can also be ascertained to be effective marketing communication tools despite of its reducing importance amid the contemporary marketers. It is important to note that despite of inclination towards the new media few renowned companies like Procter and Gamble spent USD $3.5 billion on advertising purpose in 2006 with the use of TV, print an d other old media (Winer, 2008). Every business has different marketing requirements. It is not possible to state which marketing tool is best for the particular business. In the contemporary business environment an organization should not rely on one type of marketing, rather integrating both the traditional and digital marketing tools would be more feasible for the organization to attain the desire marketing communication goals. It can be firmly stated that integrating the two approaches will support the organization to achieve its broad marketing communication objectives. It can be stated that integration of traditional and digital marketing tools facilitate the organizations to develop the most appropriate

Example Creative Project Analysis as Film Studies Essay Example for Free

Example Creative Project Analysis as Film Studies Essay In my storyboard I started with normal diegetic sound to create the normal, realistic atmosphere of sounds such as gates creaking and the wind blowing. This is so the audience is aware of the surroundings, considering no establishing shot was used prior to this to show the setting also generates a dark and mysterious atmosphere to begin with, leaving it to the audience’s imagination to guess what is going to happen as no hints to the genre have even been made yet. Then we have non-diegetic sound as music influenced by the beat from Jaws starts to play. This makes the audience feel uneasy and unusual as they realise something bad may happen because of the sinister music. I was conscious of the significant use of music to create atmosphere within the horror genre and therefore wanted the soundtrack to emphasise the tension on screen. The music gets louder and louder as the attacker gets closer to the victim to emphasise the fact that there is danger ahead and something bad is clearly about to happen. The music stops just before the murder as the girl screams as it is inevitable now that the girl is going to die, it builds up tension more and pulls you into a false sense of security. At the end the only sound we hear is the diegetic sound of the attacker laughing, this is so all the focus is on her and shows she has no guilt over what she has done, leaving the audience wondering about the character so it keeps it interesting and intriguing for them to watch. Costume is used in this storyboard to show normalcy. The attacker is dressed like a normal teenage girl so the audience can somehow relate to her as well as the other character and to suggest she is just another typical modern girl, which is why it is a shock to the audience when she kills the other girl and impacts so greatly. The killer in this film is also a female because they are usually seen to be damsels in distress that need saving so you’d never expect her to kill someone, which is another way I have attempted to make the film be original and shock the audience. Women serial killers may not be as strong as a male would be but they have a bigger impact on the victims and on the audience watching, the influence for this idea comes from films such as Friday The 13th, Audition and Phenomena. The props in this storyboard are also significant, especially the use of the knife in the picture when the attacker is at the door. The use of the knife is taken from the 1996 slasher/horror film scream which greatly influenced the film and how the killing took place, this is to help when marketing to a specific target audience and so the audience can have something to compare the film too without it being too over-predictable. In picture 10, the girl is being killed and has a teddy bear in her hand; this is to imply she is young, innocent and vulnerable and also shows that she is just a normal child in the comfort of her own home and was not expecting anything like that to happen, which is an effective contrast to when she is being stabbed. The lighting used was very dim and minimal throughout as it was shot at night so the killer could hide in the shadows effectively to make her seem mysterious at first and to make the audience wonder about her. This is to play on the audience’s natural fear of the dark and shadows, which is a usual characteristic of the genre and is seen in many other horror films. The main camera shots used where over the shoulder shots and point of view shots from the killer itself, this is so the audience can actually identify with the killer and the audience will drive pleasure from the actions of the killer because if the audience is there to see a horror film they expect there to be deaths and blood as it is typical of the genre itself to play on natural human fears. During the attack there is rapid use of camera movement such as a zoom used to intensify the stabbing action and to put it in clear perspective for the audience. The extreme close up at the end is also used to emphasise on the psychotic glare of the killer as she laughs and is meant to unnerve the audience. In my creative sequence I wanted to use micro features in keeping with the horror genre in order to create audience response. My choice of sound, mise en scene and cinematography was done so to maximise the effect of my chosen scene and to effectively make a different type of horror film with an addition of originality and an addition of normal generic conventions, overall I think it was successful.

The Mental Health Nurses Role Social Work Essay

The Mental Health Nurses Role Social Work Essay Care planning, provision and management are essential parts of the mental health nurses role. Ongoing interaction and assessment of clients needs creates a basis for providing and organising care that is inclusive, effective and adaptive through evaluation and review. The creation of a framework of care established on the premise of recovery, as it is viewed in mental health terms, can not only provide for a clients basic needs but can also allow them to continue to grow as an individual and lead a fulfilling life even in the presence of a mental health problem or illness (Hall, Wren Kirby, 2008). This case study will explain and discuss the nursing care of an individual that has a mental health problem. A plan of care will be outlined including the reasoning and evidence base that prompted such direction. Parahoo (2006) reminds us that all nursing practice should be based on sound principles and processes that stem from reliable sources. Firstly we will look at the specifics of the scenario and set up some working premises which will then allow us to further speculate on the development and implementation of a structured care plan. The case study is based around a 69 year old female named Simone. After recent lapses in memory, orientation and changes in mood were disclosed to her GP she was further assessed and consequently diagnosed with early onset dementia. Simone lives with her 40 year old daughter in a semi detached bungalow in a quiet suburban area. Simones daughter has paraplegia after an accident ten years ago. She is able to care for herself to a certain extent but does require occasional assistance from Simone. Simones daughter also recently experienced bouts of depression which lasted several months. Recently Simone had an incident when she became disorientated on a trip to the local shops and had to be escorted home by a neighbour. The role of the nurse in this case study is that of a community psychiatric nurse working with older adults. After meeting Simone and carrying out an initial assessment there are several pertinent pieces of information to continue with: Simone appears to be physically well and her home is clean and well equipped for both her and her daughter; She seems to understand where she is but at times can become flustered when unable to answer certain questions; Her daughter reports that, on a few recent occasions, Simone has burned food while cooking; She has no other family living locally and has lost touch with many of her friends since looking after her daughter; Simone states that she does not require any assistance at this time as she feels that she will be able to cope, however, she seems to be very anxious about her diagnosis and the consequences for her and her daughter and whether they will be able to continue managing to live at home. To be able to begin to make any kind of conjecture on what plans of care may be suitable for Simone we have to make several key assumptions about the skill of the nurse. For this we will use some of the attributes identified by Gerard Egan (2010) in his skilled helper model. Firstly we must assume that through accomplished communication skills and core empathic values a working therapeutic relationship is possible to establish. Also that the care plan proposals which are being put forward are ones that have been discussed and accepted by all involved parties as suitable to Simones preferences after reviewing alternatives. Finally, we must presume that through encouragement, motivation and reasoning, Simone will consent to nursing, psychiatric and other agency involvement. From the initial assessment it would seem that Simone has an apparent need for information pertaining to her condition as well as emotional support and counselling. She may require psychiatric input in terms of ongoing assessment, medication prescribing and monitoring. It also seems as though Simone may need some sort of support or assistance in certain daily activities, this could be direct support or the creation of systems and routines which enable her to perform tasks independently. A growing level of social isolation looks to be occurring and Simone may benefit by having assistance to address this. Simone may need access to support groups relating to her diagnosis of dementia, her role as a carer but also to her social and personal interest or activities. These could promote social inclusion as well as cognitive enhancement. Simone has also stated that she has concerns over the wellbeing of her daughter if she should be unable to perform the duties for her that she has up until this point. This may require a level of involvement within Simones care for her daughter, to learn about Simones condition and also to look at possible ways in which she can assist, perhaps by considering some form of support for herself or by means of being actively involved in the care plans. Therefore, with these needs in mind, we can begin to create an all encompassing, holistic care plan which is not purely based on the historical medical model that you are ill and we can cure you, or even the more modern social model that purports that you have needs and we can meet them but is instead more firmly based on the progressive view of recovery which states that you may have a problem but with help you can grow beyond it (Hall, Wren Kirby, 2008). This positivity in the face of such adversity may go against the grain of traditional treatment of dementia sufferers but the goal of restoring and maintaining mental health to its achievable optimum capacity, even when it may be in inexorable decline, should remain exactly the same as in all other areas of mental health treatment (Hughes, 2006). For care plans to be efficient they also have to be specific, measurable, achievable, realistic and timed (SMART), as this allows a flexibility to the planning process because effectivene ss can be evaluated and appropriate changes can be made as required (Brooker Waugh, 2007). So for this particular case study, the initial care plan would comprise of tasks for the nurse to complete, either as a direct care provider or as a care manager. These tasks would hopefully address the current needs of Simone over an interim period, whilst improving relations, knowledge, involvement and empowerment which could help to provide her with a greater amount of control over her current situation. The tasks will firstly be detailed in a basic format and then what each task entails will be comprehensively discussed thereafter. As care provider: Weekly home visits Liaise with psychiatrist, monthly psychiatric appointments Family work Risk assessment Creation of advanced statements As care manager: Link in with multidisciplinary team Signpost, assist to access support/interest groups Being able to have face to face communication with an individual on a regular basis is the cornerstone of effective nursing practice (Ewels Simnett, 2003). As Simone had stated that she did not feel that she required any external involvement at this time, even when we are working on the assumption that she will accept it, it would be important not to initially overwhelm her. She may be feeling very frightened and vulnerable. A study of older independent living people in 1998 identified dementia as a primary fear, rating higher than cancer (Mackinlay, 2006). General awareness of dementia issues is relatively low even though it is a common enough condition to affect more than 1 in 100 people aged over 65 (Alzheimers Scotland, 2010). A bombardment of too much input or information may cause her to be defensive and withdraw her engagement with CPN services. Starting off with a planned weekly visit of around one hour in length which follows up on the preliminary visit and assessment would perhaps not seem overly intrusive. During this time the nurse can provide much needed emotional support and counselling, building up a more robust working relationship. Information about Simones diagnosis, such as how her dementia developed to this point, how it may progress in the future, what to expect, how to prepare, what options are available and any other pertinent questions can be answered as and when Simone feels ready to discuss such things. Overtime Simone can start to identify weaknesses to focus on and strengths which can be utilised and begin to compile her own plans and goals which she can work on in a more independent fashion. These can be more specific goals such as taking up a new hobby or interest or could even be to plan how to visit the local shops and return home safely or cook a meal without the worry of burning it. These goals can then be broken down into achievable tasks for Simone which she can carry out with minimal support. Increased independence can ofte n involve an element of therapeutic risk and it is important not to confuse care with control (Watkins, 2009). Weekly visits give the opportunity to provide tangible support and to continually assess the progress of Simones dementia, mental health, general health, the continuing suitability and condition of her residence, activity levels, relationships and inclusiveness in the wider community. Informal and also formal rating scales, such as the MMSE (Mini Mental State Examination), MADRS (Montgomery Asberg Depression Rating Scale) as well as clinical observations can be regularly recorded to monitor any developments, patterns or trends. Frequent visits allow more effective methods of communication techniques to be developed which suit Simones personality and current capabilities. Care becomes not only person centred but also relationship centred and this bond can foster trust and relieve anxiety, stress and agitation (Innes, 2009) The community psychiatric nurse would work in tandem with a designated psychiatrist, reporting to them weekly. The psychiatrist that originally assessed Simone and made the diagnosis of dementia would be most preferable to aid continuity of care. For this commencement period of Simones involvement with psychiatric services to have a monthly appointment with a psychiatrist would be both realistic and achievable. This would be an opportunity to receive further support and review ongoing mental health and mental state assessments such as the MMSE or the more comprehensive ACE-R (Addenbrookes Cognitive Examination Revised). A psychiatrist would be able to provide any ongoing prescription support if required or provide access to relevant psychosocial therapies. The NICE-SCIE Guidelines for Dementia Care (2006) states that this would depend on the results of cognitive tests and perceived cognitive functioning. Using the MMSE as an example, it is recommended that only people with a score b etween 10-20, denoting moderate Alzheimers type dementia should begin courses of acetylcholinesterase inhibitors such as donepezil, galantamine and rivastigmine. The effectiveness of these drugs for individuals scoring lower than 10 points drops dramatically. For people with mild to moderate Alzheimers type dementia, scores over 20, should be given the opportunity to participate in structured group cognitive stimulation programmes and alternative therapies. In the journal article, Dementia: Symptoms, Diagnosis and Management, Salama (2008) recognises the effectiveness of these programmes and therapies for the management of cognitive symptoms such as agitation, anxiety, depression and aggression. It would seem from the needs outlined from the scenario this type of intervention would be beneficial to Simone. It is always important to remember that often people with dementia do not exist solely in isolation and inevitably family members and friends will become involved in their journey. Innes (2009) talks about the importance of a partnership between the nurse and individual diagnosed with dementia and states that these partnerships can extend to close family members or carers creating a triad of care. With Simones consent, sessions could include her daughter, helping to educate and inform her therefore better preparing her to cope with the possible demands of continued cohabitation with her mother. The NICE- SCIE Guidelines for Dementia Care (2006) state that people living in the community diagnosed with dementia should be supported to remain living in their own homes for as long as possible rather than being uprooted to an unfamiliar environment. Also if Simones dementia is seen to have a possible genetic link her daughter should be briefed on the risk of developing the condition hersel f. Simones daughter may be able to inform of ways in which she may be able to assist, however, the information provided in the case study suggests that due to Simones daughters disability her ability to support her mother in some aspects of care may be limited. Studies have consistently shown that stressors faced by family members of people with dementia are amongst the most difficult to cope with of all chronic illnesses and this can lead to an increased risk of depression, loneliness and self injury (Keady cited in Norman and Ryrie, 2009). As Simones daughter is already prone to depression a recommendation of how to assist her mother could be to receive more direct support herself subsequently alleviating some of the caring duties for Simone. The importance of relationships and friendships should not be underestimated. The emotional support from an extended social network can be invaluable and Simone should be encouraged to renew links with family and friends to strengthen existin g relations and reduce isolation. Leff and Warner (2006) identify social inclusion as one of the key factors to maximising mental health in dementia. One of the most important duties of the community mental health nurse is to ensure the health and wellbeing of the client, their family and wider community. In order to do this they have to assess the risks involved within the situation. For Simone, her recent dementia symptoms pose new risks, to herself and others, which consequently have to be identified and managed. The most appropriate way to assess risk is in conjunction with the individual you are working with, even though their view of the risks involved may vary from yours. This collaboration means that any decisions feel agreed rather than imposed and are therefore more likely to be conformed to whilst also enhancing the therapeutic relationship between the individual and nurse (Ramsay et al, 2001). From the case study we can see that there are possibilities for Simone to inadvertently bring harm to either herself, her daughter, her neighbours or even the wider community through a number of negative eventualities such as wan dering, causing fire hazards or lapses while driving if she does indeed drive. However, although assessing risk can highlight the dangers a situation or condition can cause it can also help to recognise positive skills and strengths which may be utilised. As part of a recovery focused care plan therapeutic risk must be considered and encouraged in order for Simone to maintain the sense that she is still author to her own story. Barker (2009) promotes the idea that personal growth and development through new or continued experiences does not stop with a diagnosis of mental illness or dementia but should be encouraged to continue unabated. Another consideration which could be brought to Simones attention is advanced statements. These are personal statements of preference in terms of the types of treatments a person with a mental illness may or may not wish to have in the future in the event of a decline in their mental health. These wishes and preference must then be upheld under Part 18 of the Mental Health (Care and Treatment) (Scotland) Act 2003. Simone may not feel ready to start compiling these statements straight away but if she is aware of them, over time, her preferences can be documented. Under Part 17 Chapter 2 of the same mental health act Simone also has the right to independent advocacy which she may wish to utilise to create any advance statements or to reinforce them if required. If Simones dementia does decline to the stage where she is no longer deemed to have adequate capacity for appropriate decision making she would come under the legal realm of the Adults with Incapacity (Scotland) Act 2000. In tim es of better mental health Simone may wish to select a named person to act on her behalf should this be required in the future. All decisions made on Simones behalf must be to her benefit and be the least restrictive option. With these factors in mind, part of the community psychiatric nurses role would be to promote the use of advance statements in order that Simone may continue to be cared for in a manner of her choosing, even after the possible loss of capacity, thus maintaining a sense of self and control over her own treatment. Both of these elements are identified by Pilgrim (2009) as being key points in aiding recovery in mental health treatment. Multidisciplinary team and multiagency working is an essential part of modern health care provision (Brooker and Waugh, 2007). Community nurses can appear to be working autonomously but are often supported by and linked in with a number of other health professionals and social care workers such as physiotherapists, dieticians, occupational therapists, social workers, general practitioners, psychiatrists and care assistants to name but a few. Norman and Ryrie (2009) claim that the effectiveness of this way of working lies in the diversity of skills and experience which is able to be drawn upon to facilitate more effective care for specialist needs or requirements. In the case of Simone any identified needs that would be unable to be met by the community nurse or that would be more effectively met by other workers could be referred on. In this way Simones care becomes collaborative, with her at the centre and people with the specific knowledge and skills being utilised around her. As well as engagement with health and social care professionals there are numerous charities, agencies, groups and organisations that offer external support. For Simone this could be in the form of local support groups for issues that affect her, such as dementia, stress or being a carer, or could perhaps be more focused on activities that suit her general interests. The community psychiatric nurse could possibly assist Simone to source, access or even in the short term, attend these kinds of pursuits. Interacting with others in groups or focusing on enjoyable tasks has the therapeutic benefit of enhancing both social and cognitive proficiency for a person diagnosed with dementia (Gilhooly et al 2003). Leff and Warner (2006) also stress the importance of social inclusion by naming it amongst their four key areas for improved quality of life alongside independence, health and choice. So in summary, we have outlined the case study scenario of Simone, identified her needs and created a plan that is intended to meet these needs. In addition to meeting the identified needs, a deeper analysis of the plan depicts how it will benefit Simone in a more holistic sense. By keeping the notion of recovery firmly in mind, the overall aim is to build up Simone, the person, as a whole and not purely to assist with the symptoms of dementia. For Simone to recover she must be supported to live a full life in the existence if her dementia, be able to remain independent for as long as possible, be included in the community, plan for the future and enjoy a quality of life that she finds gratifying. As this care plan created for Simone progresses, being updated and augmented as required, it should mean that her dementia should become to be viewed as illness which is being managed and not as a defining characteristic of her personality. Paraphrasing from a letter written to the notable neurologist Oliver Sacks: A person does not consist of memory alone. They have feeling, will, sensibilities and moral being, matters of which neurology cannot speak. It is here, beyond the realm of an impersonal psychology, that you may find ways to touch them, and to change them (Luria cited in Sacks 1985).

Drug Discovery And Development

Drug Discovery And Development A drug is created through lots of stages. This essay provides the description of the basic concepts of drug discovery and development, and identifies the role of some medicinal chemistry, such as pharmacology and pharmacokinetics. There are lots of processes of creating new drugs, where we may mainly distinguish between drug discovery and drug development. Drug discovery comes about in several different ways. The method is to subject new chemical entities to a set of screening tests designed to detect different types of biological activity. These include in Vitro screens as well as in Vivo screens. The history of drug discovery has changed gradually. Before 1990, medicines were produced by chemical synthesis or were isolated from existing compounds exhibiting poly-pharmacology or side effects, such as plants and herbs. Also, screenings were carried out through low throughput screening. More recently, the understanding of human receptors and substances which cause specific activity has proceeded, so this led to new drugs, such Cimetizine and Ranitizine. The studies of DMPK and ADME have progressed as well, so the studies were applied to drug discovery. In addition to that, the change from low throughput screeni ng to high throughput screening allowed mass screening. Since 2000, the incredible advance of understanding of the human genome has led to novel medicines, such as Aranesp, Epogen, and Enbral, which are more biological than before. Toxicology developed and has been adapted to drug discovery as well. At the same time, attempts with using computers are increasing. As I mentioned above, the method of finding lead compounds has changed. Nowadays, main six methods to find lead compounds are becoming popular. Firstly, it is to improve existing drugs. Secondly, it is to create new drugs on the basis of natural products. Also, rational drug design using protein crystallography is becoming popular. The rest is high throughput screening, fragment screening, and virtual screening. In addition, there are the main two methods of designing structures, which are structure based design and ligand based design respectively. Targets of finding new lead compounds are mainly eight targets, which are re ceptors, enzymes, ion-channels, nuclear receptors, kinases, bacterial/viral targets, human genome, and others. The process of drug discovery is complex, so it takes 4 to 8 years to finish it. In the process of drug discovery, the small structural changes of chemicals sometimes cause large changes and effects. For instance, propranol shows both ÃŽ ²1 andÃŽ ²2 adrenoceptor selectivity. On the other hand, atenolol shows only ÃŽ ²1 adrenoceptor selectivity. The structural differences between propranolol and atenolol are small, but their showing effects are different respectively. Once a new chemical compound has been discovered, drug development has to be carried out, culminating in its being licensed for use and marked. Preclinical tests on isolated tissues and in animals should ensure that the drug has the required mechanism of action and at least in animals will produce appropriate system responses. At this stage, the new drug will be tested against standard drugs in comparative assays. Toxicity tests in animals should in most cases allow some prediction of toxic effects in humans. In comparisons of drugs used clinically, potency does not necessarily relate directly to therapeutic usefulness. It is important to consider also the maximum achievable response and the incidence of unwanted effects. Clinical testing in humans involves four phases. Phase 1 is the measurement of pharmacological activity, pharmacokinetics and side effects in healthy volunteers. Phase 2 is pilot studies in small groups of patients to confirm that the drug works on the target condit ion and to establish the dosage regimen to be used in phase 3. Phase 3 is formal clinical trials in a large number of patients to determine the incidence of unwanted effects. Phase 4 is post marketing surveillance to establish efficacy and toxicity in general use. The detection of rare, adverse effects is most likely to occur in this phase. It takes 5 to 8 years to finish this stage, and costs much money than drug discovery stage. It takes about 10 to 12 years from an idea to marketable drugs totally. Also, it takes approximately 800 million dollars to develop one new drug. The duration of a drugs patent from the time of its registration with the UK Patent Office is 20 years. Therefore, pharmaceutical industries have to recoup their investment and make a profit, some of which will spend researching and developing other drugs. After a drugs patent expired, other pharmaceutical companies can make and sell the quite similar drug which is called a generic drug. As a result, the price often drops significantly. As a generic drug has become popular among people due to the price and the efficacy, generic drugs market is growing rapidly. The definition of medicinal chemistry Medicinal chemistry is a chemistry based on discipline which is involved in aspects of biological, medical and pharmaceutical science. Also, it is concerned with the invention, discovery, design, identification and preparation of biologically active compounds. The chemistry is a study of their metabolism, mode of action at a molecular level, and relationships between chemical structure and activity. The role of pharmacokinetics in drug discovery and drug development Pharmacokinetics is the science of exploring the changes in drug concentrations throughout the body with time. It is important to understand the time course of drug effects. The time course of drug action usually follows that of the concentration at the target site. There are 4 main phases in the pharmacokinetic process, which are absorption, distribution, metabolism, and excretion. Drugs can be administered through the gut or by other route, which is called absorption. Most drugs dont spread rapidly throughout the whole of body water. A drugs penetration into these compartments is indicated by its volume of distribution that would be required to hold the amount of drug in the body at the measured plasma concentration. The plasma membrane of the cells constitutes a hydrophobic lipid barrier and drug permeation can occur by direct distribution through the lipid and carrier mediated transport. Diffusion of a drug depends on its concentration gradient and its diffusion coefficient. The concentration gradient established within the cell membrane depends on the drugs lipid/water partition coefficient. This is estimated by the drugs distribution between water and a simple organic solvent. Most drugs are ionised in aqueous solution. The ionised form is hydrophilic, so the ionisation impedes passive membrane permeation. When a drug enters the body, it is subjected to the processes that have been developed for dealing with toxic foreign molecules, which are called metabolism and excretion. The liver is the main site of drug metabolism, and the kidney is the main site of excretion. There are some important terms in pharmacokinetics, which are half-life, AUC, and drug clearance. Half-life is the time taken for any given plasma concentration to decrease by 50%. AUC is a measure of the extent of absorption. Drug clearance is defined as the volume of plasma cleared of drug per unit time. Drug metabolism in drug discovery The main purpose of drug metabolism is to cause detoxification. Metabolism involves two main processes. Firstly, the molecule is made more hydrophilic to reduce the possibility of reabsorption in the renal tubules. Secondly, it is conjugated to reduce its effects and aid excretion. As I mentioned above, there are two phases of metabolism. Phase à ¢Ã¢â‚¬ ¦Ã‚   is mainly oxidative reactions, such as oxidation, reduction, and hydrolysis. The oxidation of a drug requires the cytochrome P450 which is the major enzyme. Phase à ¢Ã¢â‚¬ ¦Ã‚ ¡ is conjugation reactions with sugar residue, such as glucuronidation, glycosidation, and sulfation. UDPGT is the main enzyme at this stage. Interestingly, there are species differences in metabolism. For example, lidocaine is metabolised to 4-hydroxylidocaine by hydroxylation in rats. On the other hand, lidocaine is metabolised to monoethylglycinexylidide by deethylation in dogs or men. The main reason why these differences occurred is the difference o f enzymes between species. There are some particular enzymes in men and dogs, but there may be not the enzymes in rats. When the situation happens, species differences occur in metabolism. to The role of pharmacology in drug discovery Pharmacology concerns the study of how drugs affect the function of host tissues or combat infectious organisms. In most cases, drugs bind selectively to target molecules within the body, usually proteins but other macromolecules as well. The main drug targets are receptors, enzymes, ion channels, and transporters. It is generally desirable that a drug should have a higher affinity for its target than for other binding sites. One of the main roles of pharmacology in identifying new drugs is drug target identification with using compounds known pharmacological properties to identify new target mechanisms, and identifying new receptors, ion channels, transporters, and enzymes. Receptors are protein molecules in or on cells that act as recognition sites for endogenous ligands such as neurotransmitters, hormones, inflammatory mediators. Many drugs used in medicine make use of these receptors. The effect of a drug may produce the same responses to an endogenous ligand or prevent the actio n of an endogenous ligand. A drug that binds to a receptor and activates the cells response is termed an agonist. A drug that reduces or inhibits the action of an agonist is termed an antagonist. Some drugs produce the maximum response that the tissue can give. These are termed full agonists. Other drugs may not give the maximum tissue response in any concentration, which is called partial agonists. A drug shifts the equilibrium in favour of the non active form, so reducing background activity. Such drugs are referred to as inverse agonists. An antagonist is defined as a drug that reduces the action of an agonist. There are three main antagonism mechanisms, which are competitive antagonism, irreversible antagonism, and non-competitive antagonism. A competitive antagonist binds to the receptor and prevents the binding of an agonist. If the antagonist binds reversibly, then the effect of the antagonist can be overcome by raising the concentration of the agonist so that it competes mor e effectively for the binding sites. In irreversible antagonism, the antagonist binds irreversibly, reducing the number of receptors available for binding. In non-competitive antagonism, the antagonist does not block the receptor itself but blocks the signal transduction process initiated by receptor activation. Enzymes catalyse a chemical reaction, so convert substrates to products. In most cases, enzymes are proteins, and their targets are intracellular. Ion channels are fundamental membrane proteins, and convey ions across cell membranes. There are three main types of ion channel, which are voltage-gated channels, ligand-gated channels, and G-protein regulated channels. Voltage-gated channels are closely involved in ion gradients, and make the tissues excitable. Ligand-gated channels consist of a number of transmembrane subunits. The channel governs fast cell to cell communication. G-protein regulated channels modulate the excitability of excitable tissue. Transporters are protei ns which can penetrate a cell membrane without modifying it, and transport substances. Drugs can modify this action by blocking a binding site, or acting as a false substance, and being transported into a cell. The importance of oral administration and oral bioavailability Oral administration is the most convenient and acceptable route, because of the importance from the point of view of patients. It is much easier for patients to take medicine orally than taking by other routes. The important factors of oral drugs are potency, selectivity, rapid dissolution, and rapid transfer across the membranes of the gastrointestinal tract, low clearance, absence of dose independent and time independent in pharmacokinetics, and no interaction with other drugs. Oral bioavailability is the proportion of the orally administered dose that reaches the systemic circulation. Incomplete release from the dosage form, destruction within the gut, poor absorption and first-pass elimination are important causes of low bioavailability. There are two main factors controlling oral absorption, which are physical barriers and biological barrier. Physical barrier comprises solubility, ionisation, lipophilicity, drug formulation, and interaction with other substances. As I discussed above, solubility, lipophilicity, and ionisation are closely related to absorption. Drugs must dissolve to establish a concentration gradient for absorption, the rate and extent of absorption depending on the pharmaceutical formulation. Rapid absorption of a drug requires its disintegration into small particles. In general, food will slow absorption by reducing the drugs concentration. On the other hand, biological barriers comprise efflux, transporters, and metabolism. Efflux is a biological reaction which forces out unnecessary substances. The reaction prevents drugs from entering inside of a cell. Metabolism is one of the biological barriers, because of different enzymes which are mainly CYP 450. Transporters are one of biological barriers, but the role of transporters preventing drugs from entering an interior cell is not clear now. The example of drugs Histamine is a mediator in both acute inflammation and the immediate hypersensitivity response. There are two main types of histamine receptor which are H1 and H2 receptors. Antihistamine drugs can target each receptor type. The main physiological aspects of the gastrointestinal tract are gastric acid secretion. The excess of gastric acid secretion cause peptic ulcers. In peptic ulcer, the balance between gastric acid secretion and mucosal-protective mechanisms is altered. The main approach to peptic ulcer is drugs used to reduce acid secretion. The H2 receptor antagonists, Cimetizine, Ranitizine, reduce gastric acid secretion in response to histamine, gastrin, and food. The proton pump is responsible for the secretion of gastric acid into the stomach. Therefore, the proton pump inhibitors show the effect of reduction in the secretion of gastric acid. Antibacterial drugs are compounds used to treat bacterial infections. There are some targets for antibacterial drugs, such as cell wall, nucleotide mechanism, and protein synthesis. One of the important targets is cell wall which provides support for the membrane. Its main constituent is peptidoglycan which is an excellent target for drugs. Drugs affecting peptidoglycan synthesis include penicillins and penicillin G. Conclusion I learned the basis of drug discovery and development through these lectures, and I found the importance of medicinal chemistry, such as pharmacology and pharmacokinetics. It is essential to understand medicinal chemistry for discovering and developing novel and ideal drugs. At the same time, I feel we should consider discovering and developing drugs from the point of view of patients as well.