Community behavior Essay

African American spirituality has woven collectively the best of African Anglo cultures to creatively shape their own African American identity. While black peoples have not been socially, politically or economically free in the history, the practice of spirituality has facilitated the development of different forms of cultural and spiritual freedom by interpreting, transcending and embracing, the constraints of an oppressive culture. Furthermore, the development of their own beliefs, norms, forms, practices, and structures has given rise to a culture and life that is a distinctive form of human survival, existence, and, freedom most importantly. The black churches as the centers of freedom influenced the praxis of African-American spirituality. They have become safe places where blacks gathered to embrace their combined concerns as a community of faith. They have been the only institutions in the African American experience that has continued relative independence from the domesticating influence of white pressure and overlords. Some black churches consider may be the last place to see integration due to the need to maintain a power base not available to black people elsewhere. After reviewing some aspects of worship as the context for cultural and spiritual freedom, black preaching in and out sides of the black churches are one of the most powerful expressions of freedom for black people in America. The ability to produce a soul language that defines truth into systems of meaning gives power and purpose to black people. Subsequently, Black community successfully adopts and adapts the structures of the much larger culture for their own purpose this practice comes from a double consciousness or translating. African Americans translated the experience of one kind to that of another which leading them to freedom. Therefore, black people spirituality gave freedom to the spirit and mind that the external condition could not take away. The religious approach is due to a deep faith in the sacredness of life that reaffirmed a personal dignity in blacks which resulted in the practice of nonviolence and mercy. Black community determines themselves how they responded to oppression. Various forms expressing improvisation and innovation from black soul forces constituted black culture. These forms under the subtitles black music, literature, humor, folk tales, sports, art and dance; and their worship forms under the headings of prayer, shouting, healing, dancing, singing praising and instrumental music transformation, teaching and preaching. These forms express that what is true and valuable will be determined by black community itself and will subvert and defy attempts of the larger culture to discern. Churches can prove to be of great importance as it helps in providing a psychological and physical assistance to their congregants by providing treatment and prevention oriented programs in the society. A great example from the history is the Black Church that has served through decades as an informal social guider. And its effectiveness posed people to research on the formal means. Substance abuse, support, health screening and education were some of the fields where the Black Church provided its services. Individuals and churches that are associated with it hold significant importance in the history as it created a chain between informal and formal system of care that benefited the society specially those who are marginalized or underserved. These programs were encouraged by many others like lay persons, natural helpers, and religious leaders. As far as these religious leaders are concerned, they made their finding in the treatment of mental illness and they made everyone realize that paraprofessional counselors are in no way less then the professional counselors. They made their achievement in four areas of community medicine: primary care delivery, health promotion and disease prevention, community mental health and health policy. The church had great potentials. It provided and outstanding performance in collaborating with formal care systems to maximize its programs. Eng et al. helped a great deal in promoting the church’s health care programs. Such â€Å"natural helpers† have gone through a training program where they learnt how to interact with the health professionals, resource mobilization, primary self-care skills and prevention, organization of educational and services-oriented activities. Whilst the lay advisors were supposed to foster social support, they were expected to promote a healthy general well-being of people and were asked to keep a close link with the formal care system. As far as the roles of religious leaders are concerned, they are not fully described in the health care literature. In the early 1970’s, a need for psychiatrics developed in rural areas, as these individuals were recognized the more underserved population. These investigations evolved and helped in the contribution of understanding the mental health status between the urban and the rural individuals. Social, economic and geographical factors are the attributes of such rural problems. The main difficulty in the rural life of South was to separate the effects of poverty from the effects of race, color, cast etc. but after some time the solution was discovered. But later it was discovered that only 3% of the licensed psychiatrics were practicing the rural areas and the rest were gone to nowhere. Rural populations were again left to the same position as it was before. â€Å"The Black Church has no challenger as the cultural womb of the black community. Not only did it give birth to new institutions such as schools, banks, insurance companies, and low income housing, it also provided an academy and an arena for political activities, and it nurtured young talent for musical, dramatic, and artistic development† (1990, 8) The factor of race still existed between these populations no-matter if it’s urban or rural; it also greatly affected the mental healths of each individual. Many theorists believe that White American have been always against the black consumers, because they have no understanding of black’s culture, traditions, beliefs etc. But on the other hand blacks are not either interested in consuming goods or services from the Whites. They are less likely to trust White therapists and try not to interact with them in any case. Studies proved that Blacks are interested in consuming goods and seeking services from the blacks due to the understanding of same culture and traditions, it is also based on the preference of similar attitudes and racial compatibility. The research grew further and further. The research helped in understanding the need to change and acceptance of cultural and attitudinal differences and system-levels barriers. Studies proved that racial identity can be a part of success. Here racial identity means that identification of diverse racial backgrounds; it includes the basic knowledge of one’s culture and traditions. Accepting the non normative behavior of minorities can also help in dealing with societies; therapists play a big role in understanding the culture background. Lack of understanding of cultural responsiveness may result in disturbance between racial differences and help seeking environment. As compare to white blacks are more tolerant of psychological distress. They are very quick in diagnoses of schizophrenia and psychosis and control such diseases in their premature stages. Individuals, interpersonal and system-level factors promote understanding of service utilization and psychiatric morbidity. They focus on individuals because individuals predict reasonable outcomes related to services and treatment. Researchers always pick out individuals to get correct outcomes; the individual factors include race, religiosity, beliefs about mental health and copying styles. Social support, stigma and social distance are included in interpersonal level. â€Å"The Black church tradition provided an environment for reapplying already learned processes for interdependence. Embedded within the individual were past experiences, traditions, values, and norms for emotions, cognitions, and behaviors conducive to relatedness and â€Å"interpersonal ness† that reflected a collective sense of belonging with, rather than to, caring, similar others† (2001, 40) Management of mental illness is essential to the social support in rural areas. An alternative to expensive or inaccessible impatient or out patient services are neighbors or extended families. Researchers have also identified the contributions made by natural helpers in promoting positive changes to the environment. Mental illness and health care systems motivated natural helpers to provide social support to the rural black communities. A powerful indicator of poor utilization of care is Stigma that is influenced by individuals and interpersonal levels. It discourages the search for formal services but encourages the social support and informal care systems. The study says that Blacks have higher levels of tolerating psychological distress; the main reason behind this is stigma and fear of hospitalization. This sometimes results in help-seeking from specialty providers but this happens only in extreme cases. This hypothesis shows the higher emergency level among Blacks compared to Whites, Asians and Hispanics. Informal systems are fostered by fear and stigma amongst the rural Blacks. It was noticed that poorer Blacks were more likely to experience distress, physical, mental and interpersonal problems as compared to wealthier Blacks. But as compared to Whites, 15% Blacks are less likely to seek help for emotional problems than their physical or interpersonal problems. Furthermore, Blacks seek help for their financial problems but this is limited to their geographical boundaries and economic barriers. The above study has made it clear that, urban counterparts provide more social and mental services as compared to the rural churches and it also have less links with the formal system and promote the informal systems of care. We also analyzed that White churches have more links with the formal system of care than Black Churches but Black Churches provide more social and mental health service.

Happy the Man

â€Å"Happy The Man† by John Dryden John Dryden was born on 9 August in 1631 in a small town in Northamptonshire, England, the eldest of 14 children, was an influential English poet, literary critic, translator, and playwright who dominated the literary life of Restoration England to such a point that the period came to be known in literary circles as the Age of Dryden. Walter Scott called him â€Å"Glorious John. â€Å"[1] He was made Poet Laureate in 1668. As a humanist public school, Westminster maintained a curriculum which trained pupils in the art of rhetoric and the presentation of arguments for both sides of a given issue.This is a skill which would remain with Dryden and influence his later writing and thinking, as much of it displays these dialectical patterns. The Westminster curriculum also included weekly translation assignments which developed Dryden’s capacity for assimilation. This was also to be exhibited in his later works. In 1650 Dryden went up to Trinity College, Cambridge.. Dryden died on April 30, 1700. Happy the Man is sublime in its brevity in defining happiness. It’s a short poem as compared to many of the larger writings of Glorious John, as Walter Scott called him.Yet, it encompasses some eternal truths for personal happiness. What a fantastic line:   Ã¢â‚¬Å"Not Heaven itself upon the past has power†Ã¢â‚¬â€how   many people spend valuable time worrying, regretting, fretting and wishing they could change the past? The things you’ve done or failed to do already can’t be changed, but the future is yours to shape. John Dryden is trying to explain that his life has been lived and he is happy with what he has done all his life and evn if there are something’s in his past he cannot change and even if the future isn’t so good he is still happy ,he did everything .Everything he has done he had enjoyed and he is still enjoying to this day . He is happy . I have had my hour ,means he has lived his life . Work toward living each day to the fullest and owning your disappointments and failures as much as your successes – â€Å"†¦fill the unforgiving minute with sixty seconds’ worth of distance run,† for a life that won’t leave you thinking only about the past, but rather always pushing on toward a brighter future. Notice how all of the end-of-couplet rhymes are end-stopped. Notice, besides that, how all of the lines are end-stopped.Compare this to Thomas Middleton’s Verse of just a generation or so before. They make Middleton look like an Allen Ginsberg. Notice also, especially with Dryden, how you can extract any one of his couplets and they will more or less make a complete syntactical unit. One tender Sigh of hers to see me languish, Will more than pay the price of my past anguish: The verse is regular Iambic Pentameter with some variant, trochaic first feet. Don’t be fooled by the following line, which some might read as follows: I can die |with her,|| but not live | without her:Here’s how Dryden means us to read it: I can | die with | her, but | not live | without her: When reading poetry, especially, from this period, always try to read with the meter. The last thing to notice about Dryden’s poem is that, despite the tightly laced poetry, this poem is about sex, sex, sex. The meter itself! Every single line ending is a feminine ending – a sort of metrical double entendre. Every rhyme of the poem is a feminine rhyme (otherwise known as a multiple rhyme) – en-deavor/leave her; please us/seize us. It is chalk full of pornographic double-entendres.Don’t be fooled by the straight-laced formality of the poetry from this period. Some of the most depraved, erotic and sexual poetry ever written comes from this period. Dryden use of tone in the first stanza tricks the reader into believing that the essence of the poem is about his love for his girlfriend or maybe h is wife; but it is much deeper than that. The last line of that stanza goes into what is to come of the nature of the poem. Furthermore the second stanza when considering the word usage further conveys the real theme.So whats the theme or the subject. line 7 â€Å"Beware, O cruel fair how you smile on me†. The occasion in stanza one begins with the attraction he has with this woman then in stanza two it develops into the moment he has with this woman. This is noted by the use of line1,2,3 â€Å" Love has in store for me one happy minute†, â€Å"Then no day void of bliss, or pleasure leaving†, â€Å"Ages shall slide away without perceiving. â€Å"One Happy Moment† by John Dryden because it exemplify the emotions felt by the speaker, yet at the same time it views and feelings on the . Their situations and settings were that he was losing their lovers and feeling the agony of the moment. In both poems the speaker is anguished at the prospect: â€Å"I can d ie with her, but not live without her. † (Dryden, Line 4)The speaker then comes to the conclusion that the only way to avoid the issue is a solution unfavored by all: â€Å"I cannot live with you-it would be life. . . †, â€Å"I could not die-with you. . . † (Dickinson, Lines 1-2, 13) In Dickinson’s case it is necessary, in Dryden’s case it is the only choice left.

Miracles provide great hope for a hurting world Essay

Miracles can provide great hope for a hurting world because they can be a last resort when all else fails. If someone has been diagnosed with terminal cancer and doctors have given up on them, the hope for a miracle can be the only thing that keeps them from total despair. When nature seems insufferably cruel, believing that God can overcome nature is infinitely reassuring. Miracles also reaffirm the believer’s faith, thus providing hope. Miracles by their very nature are sign that reveal God’s great nature. For example, the Bible records that when Jesus was crucified a great darkness covered the land. This miracle has been historically verified by contemporary middle-Eastern historians Thallus and Africanus. Miracles such as this can be used to convert people to God and give them a sense that he cares for them, thus providing hope. Theologians such as Dr Michael Brown assert that miracles are proof of God’s continued presence in this world through the Holy Spirit, and if we pray earnestly we may be able to experience a miracle. Jesus himself said, â€Å"ask and it shall be given unto you. † Finally, miracles point to an eternal hope beyond this world. They suggest that this world is not all there is; there is another much greater world that we catch glimpses of through miracles. The miracle central to Christianity – Christ’s resurrection – can give a hurting person hope. Christ said that, â€Å"In my father’s house there are many rooms, I will go to prepare a place for you. † Even if they are not healed in this world, the miracle of the crucifixion gives them the hope that they can experience heaven. On the other hand, miracles may not provide hope and happiness because they are so sporadic and seemingly random. Wiles said that miracles were the work of, â€Å"a capricious and arbitrary God. † By this he was referring to the fact that God heals some and not others. Why doesn’t God heal all sick children, instead of a select few? This calls God’s traits into question. If he was omnibenevolent he would want to heal everyone, and if he was omnipotent he would have the power to do so. But he doesn’t, so this calls his very existence into question. Therefore miracles do not provide hope. Dawkins also disagrees with the premise that miracles could provide hope. He claimed that miracles were simply events that fell towards the end of the probability spectrum, and if they do occur they are immense luck. He believes that there is no point in raising people’s hopes for an event that statistically will never occur to them. Many believers, particularly more conservative ones, would believe that miracles and wonders have mostly ceased in our time and what the hurting world really needs for hope is faith. Scholars such as Dr James White believe that modern churches that place far too much emphasis on needing miracles for hope are pushing people away from true, saving faith in Christ. Jesus himself chastised the people for only wanting to see signs and wonders rather than having true faith. Furthermore, miracles are not what is needed to provide hope for a hurting world. Science is. Instead of wasting time praying for individual healings, we should pour out time and energy into discovering cures and vaccines instead. Atheists such as Hawking use smallpox as an example. The human race was able to eradicate this disease through effort, intelligence and science. There was no need for divine intervention to cause hope. Overall, even if miracles are not real, what is wrong with giving desperate people a bit of hope? Nearly all nations have their own accounts of miracles which bring their people hope, it is unlikely they are all wrong.

Company assignment Essay Example | Topics and Well Written Essays - 2750 words

Company assignment - Essay Example These statutory provisions applied in conjunction with established principles of common law and equity in relation to directors duties2. However, in the consultation phase leading to the implementation of the CA 2006, the Government expressed dissatisfaction at the inherent uncertainty of these provisions and have attempted to codify both the common law and statutory provisions pertaining to directors duties under the CA 20063. In turn this has lead to some commentators arguing that the CA 2006 codification of directors’ duties has resulted in tighter controls on the exercise of director’s duties. This paper critically evaluates this argument with a comparative analysis of the previous legal position and how far this has been changed by the CA 2006 provisions. If we firstly consider the previous position under common law and equity, the issue of fiduciary duty has commonly arisen in constructive trust and tracing cases. Additionally, issues have arisen regarding the int errelationship between director’s duties and the abuse of the corporate structure as exemplified by phoenix company syndrome4. The term â€Å"phoenix† company is utilised to define a corporate structure where assets of one limited company are moved to another legal entity5. Commonly, some or all of the directors and management will remain directors in the successor company and in some instances the successor company will have the same or similar name to the failed business6. In simple terms, a phoenix company is a limited liability company: â€Å"housing individuals, or the directors by name or otherwise, who abuse the corporate form by dissolving one company and creating another to avoid payment of debt†7. Furthermore, it has been commented that the Register of Companies is â€Å"littered with cases involving phoenix companies†¦Ã¢â‚¬ ¦ ones which fail and then seemingly reappear overnight in substantially the same form and with substantially the same mana gement8†. Typically, a phoenix company will use all or some of the assets of the insolvent company and will trade in the same industry and similar manner to the failed predecessor9. Whilst it is perfectly legal to form a new company from the debris of a failed company, â€Å"phoenix syndrome† has repeatedly been criticised as a means of abusing the statutory provisions implemented to protect against wrongful trading and abuse of position10. For example, a director of a failed company can become a director of a new company unless they are bankrupt or subject to a disqualification11. One the hand, it is clear that not all legitimate businesses will succeed on first attempt and the Small Business Service12 estimates that one in three businesses shuts down within three years13. Nevertheless, it is submitted that reasons for failure are multifarious and it would be undesirable for the law to penalise honest individuals from acting as directors simply due to difficulties in r unning a business. Accordingly, it is propounded that in such circumstances, the phoenix company arrangement is beneficial in allowing a business to start again14. Moreover, the phoenix arrangement enables profitable aspects of the failed business to survive into the successor company, thereby preserving an element of continuity for both suppliers and employees15. Conversely however, in the

American Identity Paper Essay Example | Topics and Well Written Essays - 500 words

American Identity Paper - Essay Example e people live in a well established society and it carries all the negative aspects whereas in America the society is not well established and whatever it has, it displays more of positive aspects. In the very outset of the letter the author makes it clear that there is not much of disparity between the rich and the poor in America as the poor and the rich are far removed from each other in Europe; for him, one can find in America â€Å"no aristocratical families, no courts, no kings, no bishops, no ecclesiastical dominion, no invisible power giving to a few a very visible one; no great manufacturers employing thousands, no great refinements of luxury in Europe† (Crevecoeur, p.49). In America people are after the primary needs of the society whereas in Europe people have already achieved the primary needs and they are after the secondary or tertiary needs of the society. In America all are equipped with ‘the spirit of an industry which is unfettered and unrestrained’ (Crevecoeur, p.50). As the Americans have no superiors to work for, they work for themselves and everyone adheres to the common goodness. No castles and no proud mansions can be seen here: on t he other way the perfect living of both cattle and men are here. J. Hector St. John de Crevecoeur considers an American as â€Å"a new man, who acts upon new principles; he must therefore entertain new ideas, and form new opinions. From involuntary idleness, servile dependence, penury, and useless labour, he has passed toils of a very different nature, rewarded by ample subsistence† (Crevecoeur, p.56). The life in the British colonies of the North America had contributed a lot to the unique identity of the American people. In the British North American colonies people migrated from various places like England, Scotland, Ireland, France, Denmark, Germany, and Sweden. In each and every place of the colonies people had different attitudes, aspects, and notions too. When these mixtures of people joined together

Critically analyse the significance, both strategically and Essay

Critically analyse the significance, both strategically and operationally, of the use of databases in an area of administrative, or economic, or social activity 01292 - Essay Example A brief summary regarding the evolution of database in the commercial world has been included. Additionally, the use of databases and their contributions towards managing information has been analyzed. Modern day organizations irrespective of their type, size and nature of activities, depend heavily upon databases for managing the day to day information transmission needs. Accurate data recording and updating is crucial in achieving organizational success. Databases are largely maintained in organizations for tracking sales, movement of materials, maintaining invoices and accounting reports. Computerized networks and systems are essential for preparation and maintenance of databases (Watson and Hewett, 2006). Databases not only facilitate information storage but also assist in promoting the relationships that exists between employees, mangers and other external factors. Organizational databases are developed and maintained in a manner such that all related parties of the business can access it at any given time. Databases form an important source of information for taking managerial decision making. The manner in which an organization stores information determines how quickly they are able to perform tasks, provide information to clients and consumers and provide directions to employees. The most common types of databases which organizations use are Oracle, Microsoft Access, SQL, Paradox and DB2. The type of database an organization selects to maintain depends upon its requirements and nature of data (Hoffer, 2004). Broadly, databases can be of two types: desktop and server based database. Desktop databases are mainly related to single user applications. Server databases are based on multi user applications and are based on mechanisms which promote reliability and data consistency. Such databases require high performance servers and speedy network access. Hence

Challenges IT Managers face when moving to cloud computing Research Paper

Challenges IT Managers face when moving to cloud computing - Research Paper Example As a result, many IT managers are cautious in adopting and moving to the cloud because of the challenges thereon including potential vendor lock-in and security concerns. These challenges are mostly non-technical since they are concerned with how existing management, policies, processes and employees are affected by a move to the cloud (Beheshti, 2011). For IT managers, a move to the cloud is potentially a disruptive process to the current workplace. For instance, an IT manager for an organization who in the past decade has been patching OSs, locking down data center hardware, securing applications and developing disaster recovery plans would be in rush of moving on to the cloud (Holtsnider & Jaffe, 2012). They will be faced with the question of SLAs-Service Level Agreements; this is because, if proper care is not taken, some SLAs may lock them into remaining with a cloud provider that does not meet expectations. IT managers need to understand what level of services they can rely on when moving to the cloud. Secondly, there is the question of application security; protection of clients and organizations data is on top of any IT manager’s priority list. IT managers, therefore, have the responsibility of checking the security standard of any cloud service they intend to employ. Cloud computing offers very many choices with reg ards to applications or software the company needs to use, as a result, a choice dilemma arises. IT managers, when moving to the cloud are faced with the issue of loss of control and reliability issues. Other challenges include the need of creating cost-reflective charging and metering of service consumption; managing service brownouts and blackouts; architecting frictionless, pure virtualized services and applications that are easily scalable (Molen, 2010). Despite these challenges, there are several benefits that IT managers derive from

The Constructive Role of Ambiguity in the Policy Process Essay

The Constructive Role of Ambiguity in the Policy Process - Essay Example Furthermore, contradictions between long-term and short-term goals are likely to bring in ambiguities in policy formation and implementation, as well as compromises between irreconcilable intentions, like protected natural reservoir and dam projects. This essay discusses the positive contributions of ambiguities to policy formation and implementation, particularly in the sectors of health and environment. More importantly, the discussion tries to demonstrate how these ambiguities provide an opportunity to successfully and productively integrate diverse perspectives, worldviews, and values of different stakeholders, as well as how such ambiguities create and strengthen a system of participation. Strain brought about by ambiguities in policy formation and implementation may have serious ramifications on the opportunity to develop a rational policy-making process and employ practical systematic instruments for priority setting (Birkland 2010). There is a need for ambiguities to be recognised and organised, normally in a course of increased stakeholder involvement with an emphasis on social concerns instead of procedural concerns only. An Overview of the Pros and Cons of Ambiguity in the Policy Process Ambiguity may be not as much of a tactical tool used by policy-makers as they wish than an unavoidable outcome of the political mechanism. It is thought that implementation becomes unsuccessful because system of government is either not adequately capable or unduly independent (Hill & Hupe 2002). Nevertheless, the complexity innate in realising effective implementation, that is, the alleged ‘implementation deficit’ (Lane 2000, 106), may reveal a much more severe risk to the notion of policy implementation. According to Birkland (2010), the policy system could function to make ambiguity general in each and every policy. Hence, policy implementation becomes unsuccessful not due to a discrepancy between sound policy formation and inadequate policy implementation but because of the policy’s inaccuracy. More importantly, it is claimed that policy is inseparable from implementation, that, in contrast, policy is only recognisable in the implementation process. Thus, the entire notion of a policy framework could be relegated to the mere study of public governance or organisational research (Lipsky 1971). However, if ambiguity in the policy-making process were as common as argued, if policy were the consequence of implementation, then is it possible that policy ambiguity assists policy formation and implementation? Ambiguity, far from being an impediment or an abnormality, is a necessary component of policy process. It has disadvantages because it causes disorder, chaos, and uncertainty in policymaking. Ambiguity obliges experts to have plenty of information (Sabatier 2007). However, a great deal of information will not automatically eliminate ambiguity; it will only increase the clarity of the process. According to Colebatch (2009), perspective rather than intention becomes crucial. Resolutions seldom mitigate difficulties; they only apply or work them out. Nevertheless, ambiguity also confers advantages. Improvement thrives because it grants new i nsights an opportunity to be implemented to work out old issues. It allows disagreement or inconsistency to be scattered

Community Policing Essay Example | Topics and Well Written Essays - 500 words

Community Policing - Essay Example approach it recognizes that crime is a community and not exclusively police problem, so that the effective solutions may be found only in case of the community involvement into the problem solving. It is a long-term process of identifying, analyzing and developing solutions to community problems. Community policing is rather directed at community issues and fear of crime problem than at the actual crime. Besides, crime prevention, the three core components of community policing are community partnership, problem solving and organizational change. They are represented in three major principles: shared responsibility, prevention, increased officer discretion. Shared responsibility means that there is frequent and on-going interaction between the community members and police, built on mutual trust and cooperation. It is recognized that ‘police work is not an isolated activity performed in a social vacuum and even traditional police work, including preventative patrol, rapid respon se, and apprehending offenders, cannot be performed without the regular cooperation of the citizens’ (Bad-Boys Net. 2007). The community members are to be actively involved in crime prevention through timely reporting crimes and organizing volunteer patrol groups. Though traditional arrests are necessary, there are alternative, less traditional ways of effective dealing with crime problem. Currently, these methods are used after the arrest has taken place. Police is to react to all the problems distinguished by the community, demonstrating respect for all residents. An officer is given enough time to get acquainted with the community and participate in community activities. Prevention is directed at diagnosing the problem before the crime has been committed, or analyzing the criminal conditions with the aim of altering them. This presupposes the involvement of police and community, public and non-profit organizations. Increased officer discretion suggests that community polic ing is based

Direct, Interactive & Digital Marketing Essay Example | Topics and Well Written Essays - 2000 words

Direct, Interactive & Digital Marketing - Essay Example Direct marketing is highly contributing to the growth of digital marketing and social media in the following ways. First, direct marketing is leading many firms to move from the monopolistic nature of marketing to the competitive type of market. Most firms are doing so in order to reach many clients across the world. In addition, they agree into the competitive market to be flexible in terms of their production to meet the customers demand. For instance, Tesco offers its clients with variety of products in its various branches across the world. It enables its clients to buy products online thus making it more competitive market. Moreover, direct marketing leads to the development of information environment within the society. That is; it opened transmission between individuals. Moreover, direct marketing made socialization and the society possible. The transformation of information networks is another significant role of direct marketing in the development of digital marketing and social media. Direct marketing is highly transforming information into the market place therefore giving clear understanding between the individuals. For example, Tesco club card is offering more discounting to the employees depending on how the client will agree with company management. In addition, one will also receive a voucher depending on the frequency of using the Tesco Club card. Moreover, the information, will aid to remove old barriers in the marketing industry and thus reducing inconvenience in the marketing industry. The message sent will not be distorted. That is the message you sent will ever be saved because of the backup from the sent items from the sending company. In addition, direct marketing is a faster way that can enable an individual to reach the audience quickly and without many difficulties. In addition, the technique allows the firm to have personal communication with the clients hence getting better understanding of the customers’

Journal Research Paper Example | Topics and Well Written Essays - 500 words - 3

Journal - Research Paper Example The first one, â€Å"Boys and Girls†, lets the reader know that Nenny is still too young to be a friend to her sister and yet, the unnamed older sister is already looking forward to the time when Nenny will be old enough to be her friend and enjoy each others company. The sense of sibling love is quite strong in this story because she feels protective of her younger sister and looks out for her because not all the kids in their neighborhood are nice children and she does not want her sister exposed to any bad influences. The end of the story makes one wonder what might have become of the sisters after some years had passed. That is why it was nice to see the relationship progression in the second story â€Å"Our Good Day†. In â€Å"Our Good Day†, the readers learn that Nenny is no longer a little child. She is already old enough to be the friend of her sister and that the relationship between them is one filled with trust and care. It also shows that the older sister keeps her younger sibling in mind and is very happy to be able to share any good fortune that she might come into in life with her. However, the story that shows us the greatest development in the relationship of the sisters can be seen in the story â€Å"Laughter†. Look at that house, I said, it looks like Mexico. Rachel and Lucy look at me like I am crazy, but before they can let out a laugh, Nenny says yes: Yes, thats Mexico all right. Thats what I was thinking exactly. This shows that the sisters have reached a point in their sibling-ship where they know each other so well that they trust that the other will know what the one is trying to say. Even more impressive, is that the sisters already think alike. Which is a sign that the siblings are quite in-tune with one another and share more than just a superficial relationship. I guess that is why I enjoyed reading about these stories so much. The short stories give a sense of character development and

Jacob Isaacksz van Ruisdaels Wheatfields Essay Example for Free

Jacob Isaacksz van Ruisdaels Wheatfields Essay Ruisdaels painting, Wheatfields, depicts a Dutch rural panoramic landscape. The medium used is oil on canvas and the actual size of the composition is very large, which adds to the grandeur created through his techniques of depiction. Ruisdael painted Wheatfields in c. 1670 in the later years of his life. The organisation of Ruisdaels pictorial space encourages the spectator to feel small. The mass of the rustic, realistic natural environment is encumbering, with the small figures of people and animals. The angle of the spectators vision is directly central to the picture plane, which allows us an expansive view to both the left and right. To the far left we can see the sea, on which boats are sailing. From the middle to the right we see intricately painted trees and an old brick building through the trees. Our line of vision follows an old dirt track which hedges, logs and blades of grass line before meeting the expansive wheat fields. The line of perspective is approximately two thirds from the top of the picture in which Ruisdael devotes the upper end of his picture to his depiction of the sky. Ruisdaels use of tone and colour is wide-ranging and natural, the bright blues and whites of the sky contrast and complement the yellow and orange hues of the fields below them. The merging colours are only interrupted by the browns and greens of the trees. The light source is sunlight broken only by the mass of clouds, which serve to provide shade to the landscape below. The overall effect served by this landscape is one of overwhelming natural bounty. The diminutive human and animal figures emphasise the symbolic them of vanitas. The landscape with its brown hues suggests an autumn setting, perhaps implying that even nature is not exempt from the passing of time and futility of life. Through his fine intricate, sharp detail Ruisdael provides an epic of a painting, overwhelming, yet contrastingly peaceful.

Drugs in the Treatment of Gastrointestinal Disease

Drugs in the Treatment of Gastrointestinal Disease Introduction Many of the drug groups discussed elsewhere in this book have important applications in the treatment of diseases of the gastrointestinal tract and other organs. Other groups are used almost exclusively for their effects on the gut; these are discussed in the following text according to their therapeutic uses. Drugs Used in Acid-Peptic Diseases Acid-peptic diseases include gastroesophageal reflux, peptic ulcer (gastric and duodenal), and stress-related mucosal injury. In all these conditions, mucosal erosions or ulceration arise when the caustic effects of aggressive factors (acid, pepsin, bile) overwhelm the defensive factors of the gastrointestinal mucosa (mucus and bicarbonate secretion, prostaglandins, blood flow, and the processes of restitution and regeneration after cellular injury). Over 90% of peptic ulcers are caused by infection with the bacterium Helicobacter pylori or by use of nonsteroidal anti-inflammatory drugs (NSAIDs). Drugs used in the treatment of acid-peptic disorders may be divided into two classes: agents that reduce intragastric acidity and agents that promote mucosal defense. Agents that Reduce Intragastric Acidity Physiology of Acid Secretion The parietal cell contains receptors for gastrin (CCK-B), histamine (H2), and acetylcholine (muscarinic, M3) (Figure 62-1). When acetylcholine (from vagal postganglionic nerves) or gastrin (released from antral G cells into the blood) bind to the parietal cell receptors, they cause an increase in cytosolic calcium, which in turn stimulates protein kinases that stimulate acid secretion from a H+,K+ ATPase (the proton pump) on the canalicular surface. In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells also have receptors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP) and activates protein kinases that stimulate acid secretion by the H+,K+ ATPase. In humans, it is believed that the major effect of gastrin upon acid secretion is mediated indirectly through the release of histamine from ECL cells rather than through direct parietal cell stimulation. In contrast, acetylcholine provides potent direct parietal cell stimulation. Antacids Antacids have been used for centuries in the treatment of patients with dyspepsia and acid-peptic disorders. They were the mainstay of treatment for acid-peptic disorders until the advent of H2-receptor antagonists and proton pump inhibitors. They continue to be used commonly by patients as nonprescription remedies for the treatment of intermittent heartburn and dyspepsia. Antacids are weak bases that react with gastric hydrochloric acid to form a salt and water. Their principal mechanism of action is reduction of intragastric acidity. After a meal, approximately 45 mEq/h of hydrochloric acid is secreted. A single dose of 156 mEq of antacid given 1 hour after a meal effectively neutralizes gastric acid for up to 2 hours. However, the acid-neutralization capacity among different proprietary formulations of antacids is highly variable, depending on their rate of dissolution (tablet versus liquid), water solubility, rate of reaction with acid, and rate of gastric emptying. Sodium bicarbonate (eg, baking soda, Alka Seltzer) reacts rapidly with hydrochloric acid (HCL) to produce carbon dioxide and sodium chloride. Formation of carbon dioxide results in gastric distention and belching. Unreacted alkali is readily absorbed, potentially causing metabolic alkalosis when given in high doses or to patients with renal insufficiency. Sodium chloride absorption may exacerbate fluid retention in patients with heart failure, hypertension, and renal insufficiency. Calcium carbonate (eg, Tums, Os-Cal) is less soluble and reacts more slowly than sodium bicarbonate with HCl to form carbon dioxide and calcium chloride (CaCl2). Like sodium bicarbonate, calcium carbonate may cause belching or metabolic alkalosis. Calcium carbonate is used for a number of other indications apart from its antacid properties (see Chapter 42). Excessive doses of either sodium bicarbonate or calcium carbonate with calcium-containing dairy products can lead to hypercalcemia, renal insufficiency , and metabolic alkalosis (milk-alkali syndrome). Formulations containing magnesium hydroxide or aluminum hydroxide react slowly with HCl to form magnesium chloride or aluminum chloride and water. Because no gas is generated, belching does not occur. Metabolic alkalosis is also uncommon because of the efficiency of the neutralization reaction. Because unabsorbed magnesium salts may cause an osmotic diarrhea and aluminum salts may cause constipation, these agents are commonly administered together in proprietary formulations (eg, Gelusil, Maalox, Mylanta) to minimize the impact on bowel function. Both magnesium and aluminum are absorbed and excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents long-term. All antacids may affect the absorption of other medications by binding the drug (reducing its absorption) or by increasing intragastric pH so that the drugs dissolution or solubility (especially weakly basic or acidic drugs) is altered. Therefore, antacids should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and iron. H2-Receptor Antagonists From their introduction in the 1970s until the early 1990s, H2-receptor antagonists (commonly referred to as H2 blockers) were the most commonly prescribed drugs in the world (see Clinical Uses). With the recognition of the role of H pylori in ulcer disease (which may be treated with appropriate antibacterial therapy) and the advent of proton pump inhibitors, the use of prescription H2 blockers has declined markedly. Chemistry Pharmacokinetics Four H2 antagonists are in clinical use: cimetidine, ranitidine, famotidine, and nizatidine. All four agents are rapidly absorbed from the intestine. Cimetidine, ranitidine, and famotidine undergo first-pass hepatic metabolism resulting in a bioavailability of approximately 50%. Nizatidine has little first-pass metabolism. The serum half-lives of the four agents range from 1.1 to 4 hours; however, duration of action depends on the dose given (Table 62-1). H2 antagonists are cleared by a combination of hepatic metabolism, glomerular filtration, and renal tubular secretion. Dose reduction is required in patients with moderate to severe renal (and possibly severe hepatic) insufficiency. In the elderly, there is a decline of up to 50% in drug clearance as well as a significant reduction in volume of distribution. BID, twice daily; HS, bedtime. Clinical Uses H2-receptor antagonists continue to be prescribed but proton pump inhibitors (see below) are steadily replacing H2 antagonists for most clinical indications. However, the over-the-counter preparations are heavily used by the public. Gastroesophageal Reflux Disease (GERD) Patients with infrequent heartburn or dyspepsia (fewer than 3 times per week) may take either antacids or intermittent H2 antagonists. Because antacids provide rapid acid neutralization, they afford faster symptom relief than H2 antagonists. However, the effect of antacids is short-lived (1-2 hours) compared with H2 antagonists (6-10 hours). H2 antagonists may be taken prophylactically before meals in an effort to reduce the likelihood of heartburn. Frequent heartburn is better treated with twice-daily H2 antagonists (Table 62-1) or proton pump inhibitors. In patients with erosive esophagitis (approximately 50% of patients with GERD), H2 antagonists afford healing in less than 50% of patients; hence proton pump inhibitors are preferred because of their superior acid inhibition. Peptic Ulcer Disease Proton pump inhibitors have largely replaced H2 antagonists in the treatment of acute peptic ulcer disease. Nevertheless, H2 antagonists are still sometimes used. Nocturnal acid suppression by H2 antagonists affords effective ulcer healing in most patients with uncomplicated gastric and duodenal ulcers. Hence, all the agents may be administered once daily at bedtime, resulting in ulcer healing rates of more than 80-90% after 6-8 weeks of therapy. For patients with ulcers caused by aspirin or other NSAIDs, the NSAID should be discontinued. If the NSAID must be continued for clinical reasons despite active ulceration, a proton pump inhibitor should be given instead of an H2 antagonist to more reliably promote ulcer healing. For patients with acute peptic ulcers caused by H pylori, H2 antagonists no longer play a significant therapeutic role. H pylori should be treated with a 10- to 14-day course of therapy including a proton pump inhibitor and two antibiotics (see below). This regimen achieves ulcer healing and eradication of the infection in more than 90% of patients. For the minority of patients in whom H pylori cannot be successfully eradicated, H2 antagonists may be given daily at bedtime in half of the usual ulcer therapeutic dose to prevent ulcer recurrence (eg, ranitidine, 150 mg; famotidine, 20 mg). Nonulcer Dyspepsia H2 antagonists are commonly used as over-the-counter agents and prescription agents for treatment of intermittent dyspepsia not caused by peptic ulcer. However, benefit compared with placebo has never been convincingly demonstrated. Prevention of Bleeding from Stress-Related Gastritis Clinically important bleeding from upper gastrointestinal erosions or ulcers occurs in 1-5% of critically ill patients as a result of impaired mucosal defense mechanisms caused by poor perfusion. Although most critically ill patients have normal or decreased acid secretion, numerous studies have shown that agents that increase intragastric pH (H2 antagonists or proton pump inhibitors) reduce the incidence of clinically significant bleeding. However, the optimal agent is uncertain at this time. For patients without a nasoenteric tube or with significant ileus, intravenous H2 antagonists are preferable over intravenous proton pump inhibitors because of their proven efficacy and lower cost. Continuous infusions of H2 antagonists are generally preferred to bolus infusions because they achieve more consistent, sustained elevation of intragastric pH. Adverse Effects H2 antagonists are extremely safe drugs. Adverse effects occur in less than 3% of patients and include diarrhea, headache, fatigue, myalgias, and constipation. Some studies suggest that intravenous H2 antagonists (or proton pump inhibitors) may increase the risk of nosocomial pneumonia in critically ill patients. Mental status changes (confusion, hallucinations, agitation) may occur with administration of intravenous H2 antagonists, especially in patients in the intensive care unit who are elderly or who have renal or hepatic dysfunction. These events may be more common with cimetidine. Mental status changes rarely occur in ambulatory patients. Cimetidine inhibits binding of dihydrotestosterone to androgen receptors, inhibits metabolism of estradiol, and increases serum prolactin levels. When used long-term or in high doses, it may cause gynecomastia or impotence in men and galactorrhea in women. These effects are specific to cimetidine and do not occur with the other H2 antagonists. Although there are no known harmful effects on the fetus, H2 antagonists cross the placenta. Therefore, they should not be administered to pregnant women unless absolutely necessary. The H2 antagonists are secreted into breast milk and may therefore affect nursing infants. H2 antagonists may rarely cause blood dyscrasias. Blockade of cardiac H2 receptors may cause bradycardia, but this is rarely of clinical significance. Rapid intravenous infusion may cause bradycardia and hypotension through blockade of cardiac H2 receptors; therefore, intravenous injections should be given over 30 minutes. H2 antagonists rarely cause reversible abnormalities in liver chemistry. Drug Interactions Cimetidine interferes with several important hepatic cytochrome P450 drug metabolism pathways, including those catalyzed by CYP1A2, CYP2C9, CYP2D6, and CYP3A4 (see Chapter 4). Hence, the half-lives of drugs metabolized by these pathways may be prolonged. Ranitidine binds 4-10 times less avidly than cimetidine to cytochrome P450. Negligible interaction occurs with nizatidine and famotidine. H2 antagonists compete with creatinine and certain drugs (eg, procainamide) for renal tubular secretion. All of these agents except famotidine inhibit gastric first-pass metabolism of ethanol, especially in women. Although the importance of this is debated, increased bioavailability of ethanol could lead to increased blood ethanol levels. Proton Pump Inhibitors Since their introduction in the late 1980s, these efficacious acid inhibitory agents have assumed the major role for the treatment of acid-peptic disorders. Proton pump inhibitors (PPIs) are now among the most widely prescribed drugs worldwide due to their outstanding efficacy and safety. Chemistry Pharmacokinetics Five proton pump inhibitors are available for clinical use: omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. All are substituted benzimidazoles that resemble H2 antagonists in structure (Figure 62-3) but have a completely different mechanism of action. Omeprazole is a racemic mixture of R- and S-isomers. Esomeprazole is the S-isomer of omeprazole. All are available in oral formulations. Esomeprazole and pantoprazole are also available in intravenous formulations . Proton pump inhibitors are administered as inactive prodrugs. To protect the acid-labile prodrug from rapid destruction within the gastric lumen, oral products are formulated for delayed release as acid-resistant, enteric-coated capsules or tablets. After passing through the stomach into the alkaline intestinal lumen, the enteric coatings dissolve and the prodrug is absorbed. For children or patients with dysphagia or enteral feeding tubes, capsules may be opened and the microgranules mixed with apple or orange juice or mixed with soft foods (eg, applesauce). Lansoprazole is also available as a tablet formulation that disintegrates in the mouth, or it may be mixed with water and administered via oral syringe or enteral tube. Omeprazole is also available as a powder formulation (capsule or packet) that contains sodium bicarbonate (1100-1680 mg NaHCO3 ; 304-460 mg of sodium) to protect the naked (non-enteric-coated) drug from acid degradation. When administered on an empty stomach by m outh or enteral tube, this immediate-release suspension results in rapid omeprazole absorption (Tmax The proton pump inhibitors are lipophilic weak bases (pKa 4-5) and after intestinal absorption diffuse readily across lipid membranes into acidified compartments (eg, the parietal cell canaliculus). The prodrug rapidly becomes protonated within the canaliculus and is concentrated more than 1000-fold by Henderson-Hasselbalch trapping (see Chapter 1). There, it rapidly undergoes a molecular conversion to the active form, a reactive thiophilic sulfenamide cation, which forms a covalent disulfide bond with the H+,K+ ATPase, irreversibly inactivating the enzyme. From a pharmacokinetic perspective, proton pump inhibitors are ideal drugs: they have a short serum half-life, they are concentrated and activated near their site of action, and they have a long duration of action. Pharmacodynamics In contrast to H2 antagonists, proton pump inhibitors inhibit both fasting and meal-stimulated secretion because they block the final common pathway of acid secretion, the proton pump. In standard doses, proton pump inhibitors inhibit 90-98% of 24-hour acid secretion (Figure 62-2). When administered at equivalent doses, the different agents show little difference in clinical efficacy. In a crossover study of patients receiving long-term therapy with all five proton pump inhibitors, the mean 24-hour intragastric pH varied from 3.3 (pantoprazole, 40 mg) to 4.0 (esomeprazole, 40 mg) and the mean number of hours the pH was higher than 4 varied from 10.1 (pantoprazole, 40 mg) to 14.0 (esomeprazole, 40 mg). Clinical Uses Gastroesophageal Reflux Disease (GERD) Proton pump inhibitors are the most effective agents for the treatment of nonerosive and erosive reflux disease, esophageal complications of reflux disease (peptic stricture or Barretts esophagus), and extraesophageal manifestations of reflux disease. Once-daily dosing provides effective symptom relief and tissue healing in 85-90% of patients; up to 15% of patients require twice-daily dosing. GERD symptoms recur in over 80% of patients within 6 months after discontinuation of a proton pump inhibitor. For patients with erosive esophagitis or esophageal complications, long-term daily maintenance therapy with a full-dose or half-dose proton pump inhibitor is usually needed. Many patients with nonerosive GERD may be treated successfully with intermittent courses of proton pump inhibitors or H2 antagonists taken as needed (on demand) for recurrent symptoms. In current clinical practice, many patients with symptomatic GERD are treated empirically with medications without prior endoscopy, ie, without knowledge of whether the patient has erosive or nonerosive reflux disease. Empiric treatment with proton pump inhibitors provides sustained symptomatic relief in 70-80% of patients, compared with 50-60% with H2 antagonists. Because of recent cost reductions, proton pump inhibitors are being used increasingly as first-line therapy for patients with symptomatic GERD. Sustained acid suppression with twice-daily proton pump inhibitors for at least 3 months is used to treat extraesophageal complications of reflux disease (asthma, chronic cough, laryngitis, and noncardiac chest pain). Peptic Ulcer Disease Compared with H2 antagonists, proton pump inhibitors afford more rapid symptom relief and faster ulcer healing for duodenal ulcers and, to a lesser extent, gastric ulcers. All the pump inhibitors heal more than 90% of duodenal ulcers within 4 weeks and a similar percentage of gastric ulcers within 6-8 weeks. H pylori-Associated Ulcers For H pylori-associated ulcers, there are two therapeutic goals: to heal the ulcer and to eradicate the organism. The most effective regimens for H pylori eradication are combinations of two antibiotics and a proton pump inhibitor. Proton pump inhibitors promote eradication of H pylori through several mechanisms: direct antimicrobial properties (minor) and—by raising intragastric pH—lowering the minimal inhibitory concentrations of antibiotics against H pylori. The best treatment regimen consists of a 14-day regimen of triple therapy: a proton pump inhibitor twice daily; clarithromycin, 500 mg twice daily; and either amoxicillin, 1 g twice daily, or metronidazole, 500 mg twice daily. After completion of triple therapy, the proton pump inhibitor should be continued once daily for a total of 4-6 weeks to ensure complete ulcer healing. Recently, 10 days of sequential treatment consisting on days 1-5 of a proton pump inhibitor twice daily plus amoxicillin, 1 g twice daily, and followed on days 6-10 by five additional days of a proton pump inhibitor twice daily, plus clarithromycin, 500 mg twice daily, and tinidazole, 500 mg twice daily, has been shown to be a highly effective treatment regimen. NSAID-Associated Ulcers For patients with ulcers caused by aspirin or other NSAIDs, either H2 antagonists or proton pump inhibitors provide rapid ulcer healing so long as the NSAID is discontinued; however continued use of the NSAID impairs ulcer healing. In patients with NSAID-induced ulcers who require continued NSAID therapy, treatment with a once- or twice-daily proton pump inhibitor more reliably promotes ulcer healing. Asymptomatic peptic ulceration develops in 10-20% of people taking frequent NSAIDs, and ulcer-related complications (bleeding, perforation) develop in 1-2% of persons per year. Proton pump inhibitors taken once daily are effective in reducing the incidence of ulcers and ulcer complications in patients taking aspirin or other NSAIDs. Prevention of Rebleeding from Peptic Ulcers In patients with acute gastrointestinal bleeding due to peptic ulcers, the risk of rebleeding from ulcers that have a visible vessel or adherent clot is increased. Rebleeding of this subset of high-risk ulcers is reduced significantly with proton pump inhibitors administered for 3-5 days either as high-dose oral therapy (eg, omeprazole, 40 mg orally twice daily) or as a continuous intravenous infusion. It is believed that an intragastric pH higher than 6 may enhance coagulation and platelet aggregation. The optimal dose of intravenous proton pump inhibitor needed to achieve and maintain this level of near-complete acid inhibition is unknown; however, initial bolus administration (80 mg) followed by constant infusion (8 mg/h) is commonly recommended. Nonulcer Dyspepsia Proton pump inhibitors have modest efficacy for treatment of nonulcer dyspepsia, benefiting 10-20% more patients than placebo. Despite their use for this indication, superiority to H2 antagonists (or even placebo) has not been conclusively demonstrated. Prevention of Stress-Related Mucosal Bleeding As discussed previously (see H2-Receptor Antagonists) proton pump inhibitors (given orally, by nasogastric tube, or by intravenous infusions) may be administered to reduce the risk of clinically significant stress-related mucosal bleeding in critically ill patients. The only proton pump inhibitor approved by the Food and Drug Administration (FDA) for this indication is an oral immediate-release omeprazole formulation, which is administered by nasogastric tube twice daily on the first day, then once daily. For patients with nasoenteric tubes, immediate-release omeprazole may be preferred to intravenous H2 antagonists or proton pump inhibitors because of comparable efficacy, lower cost, and ease of administration. For patients without a nasoenteric tube or with significant ileus, intravenous H2 antagonists are preferred to intravenous proton pump inhibitors because of their proven efficacy and lower cost. Although proton pump inhibitors are increasingly used, there are no controlled trials demonstrating efficacy or optimal dosing. Gastrinoma and Other Hypersecretory Conditions Patients with isolated gastrinomas are best treated with surgical resection. In patients with metastatic or unresectable gastrinomas, massive acid hypersecretion results in peptic ulceration, erosive esophagitis, and malabsorption. Previously, these patients required vagotomy and extraordinarily high doses of H2 antagonists, which still resulted in suboptimal acid suppression. With proton pump inhibitors, excellent acid suppression can be achieved in all patients. Dosage is titrated to reduce basal acid output to less than 5-10 mEq/h. Typical doses of omeprazole are 60-120 mg/d. Adverse Effects General Proton pump inhibitors are extremely safe. Diarrhea, headache, and abdominal pain are reported in 1-5% of patients, although the frequency of these events is only slightly increased compared with placebo. Proton pump inhibitors do not have teratogenicity in animal models; however, safety during pregnancy has not been established. Nutrition Acid is important in releasing vitamin B12 from food. A minor reduction in oral cyanocobalamin absorption occurs during proton pump inhibition, potentially leading to subnormal B12 levels with prolonged therapy. Acid also promotes absorption of food-bound minerals (iron, calcium, zinc); however, no mineral deficiencies have been reported with proton pump inhibitor therapy. Recent case-control studies have suggested a modest increase in the risk of hip fracture in patients taking proton pump inhibitors over a long term compared with matched controls. Although a causal relationship is unproven, proton pump inhibitors may reduce calcium absorption or inhibit osteoclast function. Pending further studies, patients who require long-term proton pump inhibitors—especially those with risk factors for osteoporosis—should have monitoring of bone density and should be provided calcium supplements. Respiratory and Enteric Infections Gastric acid is an important barrier to colonization and infection of the stomach and intestine from ingested bacteria. Increases in gastric bacterial concentrations are detected in patients taking proton pump inhibitors, which is of unknown clinical significance. Some studies have reported an increased risk of both community-acquired respiratory infections and nosocomial pneumonia among patients taking proton pump inhibitors. A small increased risk of enteric infections may exist in patients taking proton pump inhibitors, especially when traveling in underdeveloped countries. Hospitalized patients may have an increased risk for Clostridium difficile infection. Potential Problems Due to Increased Serum Gastrin Gastrin levels are regulated by intragastric acidity. Acid suppression alters normal feedback inhibition so that median serum gastrin levels rise 1.5- to 2-fold in patients taking proton pump inhibitors. Although gastrin levels remain within normal limits in most patients, they exceed 500 pg/mL (normal, The rise in serum gastrin levels in patients receiving long-term therapy with proton pump inhibitors raises a theoretical concern because gastrin may stimulate hyperplasia of ECL cells. In female rats given proton pump inhibitors for prolonged periods, gastric carcinoid tumors developed in areas of ECL hyperplasia. Although humans who take proton pump inhibitors for a long time may exhibit ECL hyperplasia in response to hypergastrinemia, carcinoid tumor formation has not been documented. At present, routine monitoring of serum gastrin levels is not recommended in patients receiving prolonged proton pump inhibitor therapy. Other Potential Problems Due to Decreased Gastric Acidity Among patients infected with H pylori, long-term acid suppression leads to increased chronic inflammation in the gastric body and decreased inflammation in the antrum. Concerns have been raised that increased gastric inflammation may accelerate gastric gland atrophy (atrophic gastritis) and intestinal metaplasia—known risk factors for gastric adenocarcinoma. A special FDA Gastrointestinal Advisory Committee concluded that there is no evidence that prolonged proton pump inhibitor therapy produces the kind of atrophic gastritis (multifocal atrophic gastritis) or intestinal metaplasia that is associated with increased risk of adenocarcinoma. Routine testing for H pylori is not recommended in patients who require long-term proton pump inhibitor therapy. Long-term proton pump inhibitor therapy is associated with the development of small benign gastric fundic-gland polyps in a small number of patients, which may disappear after stopping the drug and are of uncertain clinical signifi cance. Drug Interactions Decreased gastric acidity may alter absorption of drugs for which intragastric acidity affects drug bioavailability, eg, ketoconazole, itraconazole, digoxin, and atazanavir. All proton pump inhibitors are metabolized by hepatic P450 cytochromes, including CYP2C19 and CYP3A4. Because of the short half-lives of proton pump inhibitors, clinically significant drug interactions are rare. Omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin. Esomeprazole also may decrease metabolism of diazepam. Lansoprazole may enhance clearance of theophylline. Rabeprazole and pantoprazole have no significant drug interactions. Mucosal Protective Agents The gastroduodenal mucosa has evolved a number of defense mechanisms to protect itself against the noxious effects of acid and pepsin. Both mucus and epithelial cell-cell tight junctions restrict back diffusion of acid and pepsin. Epithelial bicarbonate secretion establishes a pH gradient within the mucous layer in which the pH ranges from 7 at the mucosal surface to 1-2 in the gastric lumen. Blood flow carries bicarbonate and vital nutrients to surface cells. Areas of injured epithelium are quickly repaired by restitution, a process in which migration of cells from gland neck cells seals small erosions to rees Drugs in the Treatment of Gastrointestinal Disease Drugs in the Treatment of Gastrointestinal Disease Introduction Many of the drug groups discussed elsewhere in this book have important applications in the treatment of diseases of the gastrointestinal tract and other organs. Other groups are used almost exclusively for their effects on the gut; these are discussed in the following text according to their therapeutic uses. Drugs Used in Acid-Peptic Diseases Acid-peptic diseases include gastroesophageal reflux, peptic ulcer (gastric and duodenal), and stress-related mucosal injury. In all these conditions, mucosal erosions or ulceration arise when the caustic effects of aggressive factors (acid, pepsin, bile) overwhelm the defensive factors of the gastrointestinal mucosa (mucus and bicarbonate secretion, prostaglandins, blood flow, and the processes of restitution and regeneration after cellular injury). Over 90% of peptic ulcers are caused by infection with the bacterium Helicobacter pylori or by use of nonsteroidal anti-inflammatory drugs (NSAIDs). Drugs used in the treatment of acid-peptic disorders may be divided into two classes: agents that reduce intragastric acidity and agents that promote mucosal defense. Agents that Reduce Intragastric Acidity Physiology of Acid Secretion The parietal cell contains receptors for gastrin (CCK-B), histamine (H2), and acetylcholine (muscarinic, M3) (Figure 62-1). When acetylcholine (from vagal postganglionic nerves) or gastrin (released from antral G cells into the blood) bind to the parietal cell receptors, they cause an increase in cytosolic calcium, which in turn stimulates protein kinases that stimulate acid secretion from a H+,K+ ATPase (the proton pump) on the canalicular surface. In close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like (ECL) cells. ECL cells also have receptors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in activation of adenylyl cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP) and activates protein kinases that stimulate acid secretion by the H+,K+ ATPase. In humans, it is believed that the major effect of gastrin upon acid secretion is mediated indirectly through the release of histamine from ECL cells rather than through direct parietal cell stimulation. In contrast, acetylcholine provides potent direct parietal cell stimulation. Antacids Antacids have been used for centuries in the treatment of patients with dyspepsia and acid-peptic disorders. They were the mainstay of treatment for acid-peptic disorders until the advent of H2-receptor antagonists and proton pump inhibitors. They continue to be used commonly by patients as nonprescription remedies for the treatment of intermittent heartburn and dyspepsia. Antacids are weak bases that react with gastric hydrochloric acid to form a salt and water. Their principal mechanism of action is reduction of intragastric acidity. After a meal, approximately 45 mEq/h of hydrochloric acid is secreted. A single dose of 156 mEq of antacid given 1 hour after a meal effectively neutralizes gastric acid for up to 2 hours. However, the acid-neutralization capacity among different proprietary formulations of antacids is highly variable, depending on their rate of dissolution (tablet versus liquid), water solubility, rate of reaction with acid, and rate of gastric emptying. Sodium bicarbonate (eg, baking soda, Alka Seltzer) reacts rapidly with hydrochloric acid (HCL) to produce carbon dioxide and sodium chloride. Formation of carbon dioxide results in gastric distention and belching. Unreacted alkali is readily absorbed, potentially causing metabolic alkalosis when given in high doses or to patients with renal insufficiency. Sodium chloride absorption may exacerbate fluid retention in patients with heart failure, hypertension, and renal insufficiency. Calcium carbonate (eg, Tums, Os-Cal) is less soluble and reacts more slowly than sodium bicarbonate with HCl to form carbon dioxide and calcium chloride (CaCl2). Like sodium bicarbonate, calcium carbonate may cause belching or metabolic alkalosis. Calcium carbonate is used for a number of other indications apart from its antacid properties (see Chapter 42). Excessive doses of either sodium bicarbonate or calcium carbonate with calcium-containing dairy products can lead to hypercalcemia, renal insufficiency , and metabolic alkalosis (milk-alkali syndrome). Formulations containing magnesium hydroxide or aluminum hydroxide react slowly with HCl to form magnesium chloride or aluminum chloride and water. Because no gas is generated, belching does not occur. Metabolic alkalosis is also uncommon because of the efficiency of the neutralization reaction. Because unabsorbed magnesium salts may cause an osmotic diarrhea and aluminum salts may cause constipation, these agents are commonly administered together in proprietary formulations (eg, Gelusil, Maalox, Mylanta) to minimize the impact on bowel function. Both magnesium and aluminum are absorbed and excreted by the kidneys. Hence, patients with renal insufficiency should not take these agents long-term. All antacids may affect the absorption of other medications by binding the drug (reducing its absorption) or by increasing intragastric pH so that the drugs dissolution or solubility (especially weakly basic or acidic drugs) is altered. Therefore, antacids should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and iron. H2-Receptor Antagonists From their introduction in the 1970s until the early 1990s, H2-receptor antagonists (commonly referred to as H2 blockers) were the most commonly prescribed drugs in the world (see Clinical Uses). With the recognition of the role of H pylori in ulcer disease (which may be treated with appropriate antibacterial therapy) and the advent of proton pump inhibitors, the use of prescription H2 blockers has declined markedly. Chemistry Pharmacokinetics Four H2 antagonists are in clinical use: cimetidine, ranitidine, famotidine, and nizatidine. All four agents are rapidly absorbed from the intestine. Cimetidine, ranitidine, and famotidine undergo first-pass hepatic metabolism resulting in a bioavailability of approximately 50%. Nizatidine has little first-pass metabolism. The serum half-lives of the four agents range from 1.1 to 4 hours; however, duration of action depends on the dose given (Table 62-1). H2 antagonists are cleared by a combination of hepatic metabolism, glomerular filtration, and renal tubular secretion. Dose reduction is required in patients with moderate to severe renal (and possibly severe hepatic) insufficiency. In the elderly, there is a decline of up to 50% in drug clearance as well as a significant reduction in volume of distribution. BID, twice daily; HS, bedtime. Clinical Uses H2-receptor antagonists continue to be prescribed but proton pump inhibitors (see below) are steadily replacing H2 antagonists for most clinical indications. However, the over-the-counter preparations are heavily used by the public. Gastroesophageal Reflux Disease (GERD) Patients with infrequent heartburn or dyspepsia (fewer than 3 times per week) may take either antacids or intermittent H2 antagonists. Because antacids provide rapid acid neutralization, they afford faster symptom relief than H2 antagonists. However, the effect of antacids is short-lived (1-2 hours) compared with H2 antagonists (6-10 hours). H2 antagonists may be taken prophylactically before meals in an effort to reduce the likelihood of heartburn. Frequent heartburn is better treated with twice-daily H2 antagonists (Table 62-1) or proton pump inhibitors. In patients with erosive esophagitis (approximately 50% of patients with GERD), H2 antagonists afford healing in less than 50% of patients; hence proton pump inhibitors are preferred because of their superior acid inhibition. Peptic Ulcer Disease Proton pump inhibitors have largely replaced H2 antagonists in the treatment of acute peptic ulcer disease. Nevertheless, H2 antagonists are still sometimes used. Nocturnal acid suppression by H2 antagonists affords effective ulcer healing in most patients with uncomplicated gastric and duodenal ulcers. Hence, all the agents may be administered once daily at bedtime, resulting in ulcer healing rates of more than 80-90% after 6-8 weeks of therapy. For patients with ulcers caused by aspirin or other NSAIDs, the NSAID should be discontinued. If the NSAID must be continued for clinical reasons despite active ulceration, a proton pump inhibitor should be given instead of an H2 antagonist to more reliably promote ulcer healing. For patients with acute peptic ulcers caused by H pylori, H2 antagonists no longer play a significant therapeutic role. H pylori should be treated with a 10- to 14-day course of therapy including a proton pump inhibitor and two antibiotics (see below). This regimen achieves ulcer healing and eradication of the infection in more than 90% of patients. For the minority of patients in whom H pylori cannot be successfully eradicated, H2 antagonists may be given daily at bedtime in half of the usual ulcer therapeutic dose to prevent ulcer recurrence (eg, ranitidine, 150 mg; famotidine, 20 mg). Nonulcer Dyspepsia H2 antagonists are commonly used as over-the-counter agents and prescription agents for treatment of intermittent dyspepsia not caused by peptic ulcer. However, benefit compared with placebo has never been convincingly demonstrated. Prevention of Bleeding from Stress-Related Gastritis Clinically important bleeding from upper gastrointestinal erosions or ulcers occurs in 1-5% of critically ill patients as a result of impaired mucosal defense mechanisms caused by poor perfusion. Although most critically ill patients have normal or decreased acid secretion, numerous studies have shown that agents that increase intragastric pH (H2 antagonists or proton pump inhibitors) reduce the incidence of clinically significant bleeding. However, the optimal agent is uncertain at this time. For patients without a nasoenteric tube or with significant ileus, intravenous H2 antagonists are preferable over intravenous proton pump inhibitors because of their proven efficacy and lower cost. Continuous infusions of H2 antagonists are generally preferred to bolus infusions because they achieve more consistent, sustained elevation of intragastric pH. Adverse Effects H2 antagonists are extremely safe drugs. Adverse effects occur in less than 3% of patients and include diarrhea, headache, fatigue, myalgias, and constipation. Some studies suggest that intravenous H2 antagonists (or proton pump inhibitors) may increase the risk of nosocomial pneumonia in critically ill patients. Mental status changes (confusion, hallucinations, agitation) may occur with administration of intravenous H2 antagonists, especially in patients in the intensive care unit who are elderly or who have renal or hepatic dysfunction. These events may be more common with cimetidine. Mental status changes rarely occur in ambulatory patients. Cimetidine inhibits binding of dihydrotestosterone to androgen receptors, inhibits metabolism of estradiol, and increases serum prolactin levels. When used long-term or in high doses, it may cause gynecomastia or impotence in men and galactorrhea in women. These effects are specific to cimetidine and do not occur with the other H2 antagonists. Although there are no known harmful effects on the fetus, H2 antagonists cross the placenta. Therefore, they should not be administered to pregnant women unless absolutely necessary. The H2 antagonists are secreted into breast milk and may therefore affect nursing infants. H2 antagonists may rarely cause blood dyscrasias. Blockade of cardiac H2 receptors may cause bradycardia, but this is rarely of clinical significance. Rapid intravenous infusion may cause bradycardia and hypotension through blockade of cardiac H2 receptors; therefore, intravenous injections should be given over 30 minutes. H2 antagonists rarely cause reversible abnormalities in liver chemistry. Drug Interactions Cimetidine interferes with several important hepatic cytochrome P450 drug metabolism pathways, including those catalyzed by CYP1A2, CYP2C9, CYP2D6, and CYP3A4 (see Chapter 4). Hence, the half-lives of drugs metabolized by these pathways may be prolonged. Ranitidine binds 4-10 times less avidly than cimetidine to cytochrome P450. Negligible interaction occurs with nizatidine and famotidine. H2 antagonists compete with creatinine and certain drugs (eg, procainamide) for renal tubular secretion. All of these agents except famotidine inhibit gastric first-pass metabolism of ethanol, especially in women. Although the importance of this is debated, increased bioavailability of ethanol could lead to increased blood ethanol levels. Proton Pump Inhibitors Since their introduction in the late 1980s, these efficacious acid inhibitory agents have assumed the major role for the treatment of acid-peptic disorders. Proton pump inhibitors (PPIs) are now among the most widely prescribed drugs worldwide due to their outstanding efficacy and safety. Chemistry Pharmacokinetics Five proton pump inhibitors are available for clinical use: omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. All are substituted benzimidazoles that resemble H2 antagonists in structure (Figure 62-3) but have a completely different mechanism of action. Omeprazole is a racemic mixture of R- and S-isomers. Esomeprazole is the S-isomer of omeprazole. All are available in oral formulations. Esomeprazole and pantoprazole are also available in intravenous formulations . Proton pump inhibitors are administered as inactive prodrugs. To protect the acid-labile prodrug from rapid destruction within the gastric lumen, oral products are formulated for delayed release as acid-resistant, enteric-coated capsules or tablets. After passing through the stomach into the alkaline intestinal lumen, the enteric coatings dissolve and the prodrug is absorbed. For children or patients with dysphagia or enteral feeding tubes, capsules may be opened and the microgranules mixed with apple or orange juice or mixed with soft foods (eg, applesauce). Lansoprazole is also available as a tablet formulation that disintegrates in the mouth, or it may be mixed with water and administered via oral syringe or enteral tube. Omeprazole is also available as a powder formulation (capsule or packet) that contains sodium bicarbonate (1100-1680 mg NaHCO3 ; 304-460 mg of sodium) to protect the naked (non-enteric-coated) drug from acid degradation. When administered on an empty stomach by m outh or enteral tube, this immediate-release suspension results in rapid omeprazole absorption (Tmax The proton pump inhibitors are lipophilic weak bases (pKa 4-5) and after intestinal absorption diffuse readily across lipid membranes into acidified compartments (eg, the parietal cell canaliculus). The prodrug rapidly becomes protonated within the canaliculus and is concentrated more than 1000-fold by Henderson-Hasselbalch trapping (see Chapter 1). There, it rapidly undergoes a molecular conversion to the active form, a reactive thiophilic sulfenamide cation, which forms a covalent disulfide bond with the H+,K+ ATPase, irreversibly inactivating the enzyme. From a pharmacokinetic perspective, proton pump inhibitors are ideal drugs: they have a short serum half-life, they are concentrated and activated near their site of action, and they have a long duration of action. Pharmacodynamics In contrast to H2 antagonists, proton pump inhibitors inhibit both fasting and meal-stimulated secretion because they block the final common pathway of acid secretion, the proton pump. In standard doses, proton pump inhibitors inhibit 90-98% of 24-hour acid secretion (Figure 62-2). When administered at equivalent doses, the different agents show little difference in clinical efficacy. In a crossover study of patients receiving long-term therapy with all five proton pump inhibitors, the mean 24-hour intragastric pH varied from 3.3 (pantoprazole, 40 mg) to 4.0 (esomeprazole, 40 mg) and the mean number of hours the pH was higher than 4 varied from 10.1 (pantoprazole, 40 mg) to 14.0 (esomeprazole, 40 mg). Clinical Uses Gastroesophageal Reflux Disease (GERD) Proton pump inhibitors are the most effective agents for the treatment of nonerosive and erosive reflux disease, esophageal complications of reflux disease (peptic stricture or Barretts esophagus), and extraesophageal manifestations of reflux disease. Once-daily dosing provides effective symptom relief and tissue healing in 85-90% of patients; up to 15% of patients require twice-daily dosing. GERD symptoms recur in over 80% of patients within 6 months after discontinuation of a proton pump inhibitor. For patients with erosive esophagitis or esophageal complications, long-term daily maintenance therapy with a full-dose or half-dose proton pump inhibitor is usually needed. Many patients with nonerosive GERD may be treated successfully with intermittent courses of proton pump inhibitors or H2 antagonists taken as needed (on demand) for recurrent symptoms. In current clinical practice, many patients with symptomatic GERD are treated empirically with medications without prior endoscopy, ie, without knowledge of whether the patient has erosive or nonerosive reflux disease. Empiric treatment with proton pump inhibitors provides sustained symptomatic relief in 70-80% of patients, compared with 50-60% with H2 antagonists. Because of recent cost reductions, proton pump inhibitors are being used increasingly as first-line therapy for patients with symptomatic GERD. Sustained acid suppression with twice-daily proton pump inhibitors for at least 3 months is used to treat extraesophageal complications of reflux disease (asthma, chronic cough, laryngitis, and noncardiac chest pain). Peptic Ulcer Disease Compared with H2 antagonists, proton pump inhibitors afford more rapid symptom relief and faster ulcer healing for duodenal ulcers and, to a lesser extent, gastric ulcers. All the pump inhibitors heal more than 90% of duodenal ulcers within 4 weeks and a similar percentage of gastric ulcers within 6-8 weeks. H pylori-Associated Ulcers For H pylori-associated ulcers, there are two therapeutic goals: to heal the ulcer and to eradicate the organism. The most effective regimens for H pylori eradication are combinations of two antibiotics and a proton pump inhibitor. Proton pump inhibitors promote eradication of H pylori through several mechanisms: direct antimicrobial properties (minor) and—by raising intragastric pH—lowering the minimal inhibitory concentrations of antibiotics against H pylori. The best treatment regimen consists of a 14-day regimen of triple therapy: a proton pump inhibitor twice daily; clarithromycin, 500 mg twice daily; and either amoxicillin, 1 g twice daily, or metronidazole, 500 mg twice daily. After completion of triple therapy, the proton pump inhibitor should be continued once daily for a total of 4-6 weeks to ensure complete ulcer healing. Recently, 10 days of sequential treatment consisting on days 1-5 of a proton pump inhibitor twice daily plus amoxicillin, 1 g twice daily, and followed on days 6-10 by five additional days of a proton pump inhibitor twice daily, plus clarithromycin, 500 mg twice daily, and tinidazole, 500 mg twice daily, has been shown to be a highly effective treatment regimen. NSAID-Associated Ulcers For patients with ulcers caused by aspirin or other NSAIDs, either H2 antagonists or proton pump inhibitors provide rapid ulcer healing so long as the NSAID is discontinued; however continued use of the NSAID impairs ulcer healing. In patients with NSAID-induced ulcers who require continued NSAID therapy, treatment with a once- or twice-daily proton pump inhibitor more reliably promotes ulcer healing. Asymptomatic peptic ulceration develops in 10-20% of people taking frequent NSAIDs, and ulcer-related complications (bleeding, perforation) develop in 1-2% of persons per year. Proton pump inhibitors taken once daily are effective in reducing the incidence of ulcers and ulcer complications in patients taking aspirin or other NSAIDs. Prevention of Rebleeding from Peptic Ulcers In patients with acute gastrointestinal bleeding due to peptic ulcers, the risk of rebleeding from ulcers that have a visible vessel or adherent clot is increased. Rebleeding of this subset of high-risk ulcers is reduced significantly with proton pump inhibitors administered for 3-5 days either as high-dose oral therapy (eg, omeprazole, 40 mg orally twice daily) or as a continuous intravenous infusion. It is believed that an intragastric pH higher than 6 may enhance coagulation and platelet aggregation. The optimal dose of intravenous proton pump inhibitor needed to achieve and maintain this level of near-complete acid inhibition is unknown; however, initial bolus administration (80 mg) followed by constant infusion (8 mg/h) is commonly recommended. Nonulcer Dyspepsia Proton pump inhibitors have modest efficacy for treatment of nonulcer dyspepsia, benefiting 10-20% more patients than placebo. Despite their use for this indication, superiority to H2 antagonists (or even placebo) has not been conclusively demonstrated. Prevention of Stress-Related Mucosal Bleeding As discussed previously (see H2-Receptor Antagonists) proton pump inhibitors (given orally, by nasogastric tube, or by intravenous infusions) may be administered to reduce the risk of clinically significant stress-related mucosal bleeding in critically ill patients. The only proton pump inhibitor approved by the Food and Drug Administration (FDA) for this indication is an oral immediate-release omeprazole formulation, which is administered by nasogastric tube twice daily on the first day, then once daily. For patients with nasoenteric tubes, immediate-release omeprazole may be preferred to intravenous H2 antagonists or proton pump inhibitors because of comparable efficacy, lower cost, and ease of administration. For patients without a nasoenteric tube or with significant ileus, intravenous H2 antagonists are preferred to intravenous proton pump inhibitors because of their proven efficacy and lower cost. Although proton pump inhibitors are increasingly used, there are no controlled trials demonstrating efficacy or optimal dosing. Gastrinoma and Other Hypersecretory Conditions Patients with isolated gastrinomas are best treated with surgical resection. In patients with metastatic or unresectable gastrinomas, massive acid hypersecretion results in peptic ulceration, erosive esophagitis, and malabsorption. Previously, these patients required vagotomy and extraordinarily high doses of H2 antagonists, which still resulted in suboptimal acid suppression. With proton pump inhibitors, excellent acid suppression can be achieved in all patients. Dosage is titrated to reduce basal acid output to less than 5-10 mEq/h. Typical doses of omeprazole are 60-120 mg/d. Adverse Effects General Proton pump inhibitors are extremely safe. Diarrhea, headache, and abdominal pain are reported in 1-5% of patients, although the frequency of these events is only slightly increased compared with placebo. Proton pump inhibitors do not have teratogenicity in animal models; however, safety during pregnancy has not been established. Nutrition Acid is important in releasing vitamin B12 from food. A minor reduction in oral cyanocobalamin absorption occurs during proton pump inhibition, potentially leading to subnormal B12 levels with prolonged therapy. Acid also promotes absorption of food-bound minerals (iron, calcium, zinc); however, no mineral deficiencies have been reported with proton pump inhibitor therapy. Recent case-control studies have suggested a modest increase in the risk of hip fracture in patients taking proton pump inhibitors over a long term compared with matched controls. Although a causal relationship is unproven, proton pump inhibitors may reduce calcium absorption or inhibit osteoclast function. Pending further studies, patients who require long-term proton pump inhibitors—especially those with risk factors for osteoporosis—should have monitoring of bone density and should be provided calcium supplements. Respiratory and Enteric Infections Gastric acid is an important barrier to colonization and infection of the stomach and intestine from ingested bacteria. Increases in gastric bacterial concentrations are detected in patients taking proton pump inhibitors, which is of unknown clinical significance. Some studies have reported an increased risk of both community-acquired respiratory infections and nosocomial pneumonia among patients taking proton pump inhibitors. A small increased risk of enteric infections may exist in patients taking proton pump inhibitors, especially when traveling in underdeveloped countries. Hospitalized patients may have an increased risk for Clostridium difficile infection. Potential Problems Due to Increased Serum Gastrin Gastrin levels are regulated by intragastric acidity. Acid suppression alters normal feedback inhibition so that median serum gastrin levels rise 1.5- to 2-fold in patients taking proton pump inhibitors. Although gastrin levels remain within normal limits in most patients, they exceed 500 pg/mL (normal, The rise in serum gastrin levels in patients receiving long-term therapy with proton pump inhibitors raises a theoretical concern because gastrin may stimulate hyperplasia of ECL cells. In female rats given proton pump inhibitors for prolonged periods, gastric carcinoid tumors developed in areas of ECL hyperplasia. Although humans who take proton pump inhibitors for a long time may exhibit ECL hyperplasia in response to hypergastrinemia, carcinoid tumor formation has not been documented. At present, routine monitoring of serum gastrin levels is not recommended in patients receiving prolonged proton pump inhibitor therapy. Other Potential Problems Due to Decreased Gastric Acidity Among patients infected with H pylori, long-term acid suppression leads to increased chronic inflammation in the gastric body and decreased inflammation in the antrum. Concerns have been raised that increased gastric inflammation may accelerate gastric gland atrophy (atrophic gastritis) and intestinal metaplasia—known risk factors for gastric adenocarcinoma. A special FDA Gastrointestinal Advisory Committee concluded that there is no evidence that prolonged proton pump inhibitor therapy produces the kind of atrophic gastritis (multifocal atrophic gastritis) or intestinal metaplasia that is associated with increased risk of adenocarcinoma. Routine testing for H pylori is not recommended in patients who require long-term proton pump inhibitor therapy. Long-term proton pump inhibitor therapy is associated with the development of small benign gastric fundic-gland polyps in a small number of patients, which may disappear after stopping the drug and are of uncertain clinical signifi cance. Drug Interactions Decreased gastric acidity may alter absorption of drugs for which intragastric acidity affects drug bioavailability, eg, ketoconazole, itraconazole, digoxin, and atazanavir. All proton pump inhibitors are metabolized by hepatic P450 cytochromes, including CYP2C19 and CYP3A4. Because of the short half-lives of proton pump inhibitors, clinically significant drug interactions are rare. Omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin. Esomeprazole also may decrease metabolism of diazepam. Lansoprazole may enhance clearance of theophylline. Rabeprazole and pantoprazole have no significant drug interactions. Mucosal Protective Agents The gastroduodenal mucosa has evolved a number of defense mechanisms to protect itself against the noxious effects of acid and pepsin. Both mucus and epithelial cell-cell tight junctions restrict back diffusion of acid and pepsin. Epithelial bicarbonate secretion establishes a pH gradient within the mucous layer in which the pH ranges from 7 at the mucosal surface to 1-2 in the gastric lumen. Blood flow carries bicarbonate and vital nutrients to surface cells. Areas of injured epithelium are quickly repaired by restitution, a process in which migration of cells from gland neck cells seals small erosions to rees

The Wizard of Oz-Beyond the Yellow Brick Road

The Wizard of Oz-Beyond the Yellow Brick Road â€Å"Toto, I have a feeling were not in Kansas anymore,† claims Dorothy Gale as she explores her new world of lively color in the Land of Oz. The film The Wizard of Oz, adapted from L. Frank Baums childrens book The Wonderful Wizard of Oz, released in movie theaters in 1939 and nominated for an Oscar Award for Best Cinematography and Color (The Internet Movie Database).The famous musical tells a story of a young girl Dorothy who gets lost in the Land of Oz and travels long and far to the Emerald City. At the Emerald City, she finds the Wizard of Oz, who she hopes will help her get back home to Kansas. On her journey she befriends the Scarecrow, the Tinman, and the Cowardly Lion; at the same time, she must also avoid the Wicked Witch of the West who tries to take Dorothys enchanted ruby slippers. The Wizard of Oz has a unique characteristic in that it was one of the first films to include Technicolor (The Internet Movie Database). Transitioning into colored films became an imp ortant event in film history. The movie industry now had the technology capable of filming in sound and color, which dynamically influences a movie. The Wizard of Oz contains many colorful items that play key roles in the film: the yellow brick road, Dorothys ruby slippers, and the Emerald City. One might find it intriguing to learn that since the idea of Technicolor has been applied, certain colors symbolize important ideas. Although many viewers enjoy watching The Wizard of Oz and may think nothing more of it but as a mere fairy tale classic, the use of Technicolor conveyed many aspects about American history in the early 1900s including racial issues, economic issues, and political issues. Colors were used as a technique to represent social classes or certain races. Once Dorothy steps out of her house after the twister, she stares in awe at the vibrant colors of Munchkinland. These colors help the audience to determine the protagonist and antagonists. For instance, the Wicked Witch of the West and her Winkies, the guardians of the castle, have green skin, unlike those who appear to be human like Dorothy. The differences in color tie to the â€Å"public discourse on race in 1900† (Ritter 173). These references to racial disputes reflected the times in the early 1900s, or post Civil War. While recovering from the Civil War, many former African American slaves struggled to continue living their lives now that Abraham Lincolns Emancipation Proclamation has been established. They had the opportunity to find jobs, but still had difficulty merging with the white community. Baum published The Wonderful Wizard of Oz in 1900 and incorporated racial (social) issues at that certain point in time in order to point out that there existed a segregated culture. Historians refer to the late nineteenth century and early twentieth century as the Gilded Age, an era which featured concerns about social change (190).The movie depicts the differences among the groups of characters and displays how they do not cooperate well together. Another example of utilizing color to express a change in social class is coloring the Emerald City. As Dorothy and her friends trot along the yellow brick road, the film captures the Emerald Citys elegant, resplendent towers from afar; the city itself has magnificent structures radiant in green splendor. Baum associates the people of the Emerald City as well as the Wizard of Oz with the color â€Å"wealthy green . . . [as] . . . selfish, st ingy, and false,† (184) which in the end, the Wizard proves to be when he does not keep his promise to help Dorothy and her newfound friends. The reference to green does not indicate that a certain race is selfish; rather, it exemplifies the idea that at this time in history, serious turmoil existed between different cultures and races. Overall, color orientation enables the audience to understand relationships among the characters. The film also uses Technicolor to recognize the economic crisis occurring during the late nineteenth century, referred to as the Gilded Age and during Americas Great Depression. In the beginning and end of the motion picture, Dorothy is back home in Kansas, where the setting is set in a bronze, sepia color, unlike the Land of Oz, containing all the colors of the rainbow. The overall look of Kansas is â€Å"bleak. . . [including] . . . the house, people, and prairie . . .[which] . . . are all ‘dull and gray† (177). The dramatic contrast in colors between Kansas and the Land of Oz shows how dismal and depressed the residents of Kansas felt while suffering from the poor economy; this represents the dismay many farmers experienced in the United States during the early 1900s. In the film, Dorothy comes from Kansas, where there reside clusters of independent farmers. Baum published The Wonderful Wizard of Oz in 1900, the â€Å"cusp between the decline of Populism and producer ism and the rise of consumerism and corporate liberalism† (198). At this time, many farmers created labor movements due to devastating droughts (198). In 1939, â€Å"Metro-Goldwyn-Mayer brought the Oz tale to screen in vivid color . . . [while] . . . the nation was recuperating from the depression and preparing itself for the challenge of World War II† (199). Color made an impact on the audience in that it inspired them to regain hope that â€Å"[America] would emerge, as Dorothy did, stronger for the difficulties they faced and overcame† (199). In the movie, transitioning from black and white to bright colors allows the audience to relate to Dorothy. The black and white setting represents America during the Great Depression. When Dorothy, representing the common people, is in the Land of Oz, she overcomes her obstacles, which represents America overcoming World War II. The use of color gives off a sense of optimism for the audience about the troubles that lay ahead. Many noticeable items in the movie play a key role in Dorothys journey, but also correspond to important political ideas. In fact, â€Å"The economic and political tumult of the 1880s and 1890s was reflected in competing cultural understandings of American society† (198). Glinda, the Witch of the North, explains to Dorothy that the Wizard of Oz can help her find her way home to Kansas. In order to reach the Wizard of Oz, she must follow the yellow brick road that leads her to the Emerald City, found in the center of the Land of Oz. The yellow brick road symbolizes the gold standard, the current form of currency (Rockoff 746). Many financial reformers â€Å"criticized the gold standard and the National Banking System [. . .] for favoring industrial over agricultural development† (191). Many have analyzed both the movie and book and have interpreted it as a monetary allegory about Populists (Hansen 254). Dorothy represents the Populist Party, while the yellow brick road that leads to the Emerald City signifies Washington, D.C., â€Å"controlled by the ‘Money Power and gold traders† (Ritter 194). Even though the yellow brick road shows Dorothy the way to the Wizard, she still does not find her solution of returning home when she arrives. Very much like a moment in history, this event correlates to the decline of the Populists who cried out to government in dire need for help with crops and farmland. For example, a group of â€Å"unemployed men, suffering under the economic depression of the 1890s, [. . .] marched from Ohio to Washington to demand work and relief, but [. . .] were dispersed rather than rewarded† (183). Dorothys journey and this small group of men are alike in that both parties sought for help, but never initially received any. In t he Emerald City, the significance of the color green relates to greenbacks, or paper money, which many people of the United States referred to as â€Å"a form of false value† (184). This color coding can also relate back to the Wizard. The Wizard of Oz provides important historical references that took place in the United States of America. The movie allows us to escape from reality and discover somewhere over the rainbow a fantasy dreamland where adventure and excitement await us. The magic of The Wizard of Oz has an indelible memory to all ages, throughout the ages. As one of the most notable films in pop culture, the motion picture has obtained many outstanding awards thanks to an unforgettable cast and crew. Not only does the film remain a Hollywood classic, but it serves as historical documentation. As technology has progressed throughout time, the film has used the latest advances of Technicolor to produce a meaningful piece of artwork embedded with racial, economic, and political references. No matter what type of audience views the movie, each individual can relate to the idea that despite ongoing conflicts, â€Å"theres no place like home.†