Methadone Pharmacology and Its Mechanism of Action

Methadone Pharmacology and Its Mechanism of Action Table of Contents (Jump to) 1. Goal 2. Aims and Objectives 3. Background 4. Methadone Pharmacology and Its Mechanism of Action 4.1 Methadone History Background 4.2 Benefits of Methadone 4.3 Deaths Involving Methadone 4.4 Pharmacokinetics and Metabolism of Methadone 4.4 Cytochrome P450 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions 1. Goal Methadone is the most common and widely used drug for the opioid dependence in Ireland as in most of the countries in the E.U. Methadone treatment is undoubtedly effective however; the reports on methadone related mortalities have definitely stirred the public concern. The challenge for biotechnologists is to determine whether the application of pharmacogenomics can solve this dispute. The fact regarding any drug or opioid is that they affect different individuals in a different way. To solve this â€Å"Biological Puzzle† this case study links the role of methadone and CYP2D6 gene variations with the metaboliser status of individuals, which may serve as an adjunct in methadone related fatalities. CYP2D6 is a member of cytochrome P450 mixed oxidase system, which is involved in the metabolism of many toxicologically important drugs that commonly implicates in fatal poisoning. CYP2D6 gene is located on chromosome 22 and is highly polymorphic in nature. Single Nucleotide Polymorph ism (SNP) variation at the exon 4 position of the gene results in a single nucleotide change of G to A, which ensue in poor metabolism of the drug. This variation is amongst 5 to 10% of the Caucasian population. 2. Aims and Objectives The specific aims of this report are as follows: Describe the methadone pharmacology and its mechanism of action, which will include the pharmacokinetics and the pharmacodynamics of the drug. The role of cytochrome P450 in the metabolism of methadone. The focus will be on the genetic polymorphism and the adverse drug reaction. This research will further investigate on methadone’s safety profile and mortalities associated with the drug. 3. Background Methadone is a synthetic opioid, invented during the Second World War (White Torres, 2010). The first chemical synthesis of the drug was in 1939 at the pharmaceutical laboratories of I.G. Farbenkonzern, Germany. Methadone was introduced to the market during 1960’s and since then it is one of the most valued drug which has proved its effectiveness from the prevention of abstinence syndrome that occurs after rapid interruption of continuous opioid administration (Zweben Payte, 1990; Dole Nyswander, 1965). Methadone is also one of the most common medications administered for the treatment of heroin addiction, however; there are many fatal poisonings reported over the years (Bunten et al 2010). Methadone is a liposoluble basic drug, often administered orally as a racemic mixture of two enantiomers i.e. R-Met and S-Met (Garrido Troconiz, 2000). It has a long plasma elimination half-life that lies between 13 and 55 hours and a high bioavailability of 70% 90% when administered orally (Moffet et al, 2004). It is extensively metabolised in liver and is converted into its primary metabolite which is 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (Crettol, Monnat Eap, 2007) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) (Lugo et al, 2005). Blood methadone concentration in drug tolerant individuals reaches >0.84 mg/l, whereas in cases of fatality or poisoning concentrations typically range from 0.4 mg/l to 1.8 mg/l. Fatalities have also been reported with concentrations as low as 0.05 mg/l which is significantly lower than the average concentration in blood (Caplehorn, Drummer Fatal, 2002). Studies suggests that the largest patient associated deaths are during t he drug induction phase, when either individual drug tolerance is overestimated or the presence of other drugs are also found in the system (Bunten et al 2010; CSAT, 2004). The revolutions in the molecular techniques in postgenomic era provide us a significant platform for the diagnostics and clinical purposes. Pharmacogenomics is the study of the impact of heritable traits on pharmacology and toxicology that acts as bridge to certify opioid fatalities (Wong et al 2002). The significant inter-individual variation in blood methadone concentrations and individual susceptibility to methadone toxicity might be explained through genetic variations of the genes encoding the drug metabolism enzymes. Pharmacogenomics acts as the linkage between an individual’s genotype and individual’s ability to metabolise a foreign compound (Linder, Prough Valdes 1997). Most xenobiotics, including therapeutic drugs, are metabolised by cytochromes P450 to some extent (Guengerich, 2006). The metabolism of these drugs results in detoxification and elimination of drug or activation of the prodrug to its biologically active form. Cytochrome P450 (CYP450) shows a wide interindividual variation in their protein expression and/or catalytic activity, which results in unique drug metabolism (Jannetto et al 2002). Among the P450 subfamilies, CYP2D6 plays a critical role in determining the response to several drug groups/families (Sadee 1999). CYP2D6 gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are mono-oxygenases, consisting of more than 30 enzymes (Schur et al 2001) which catalyze many reactions involved in drug metabolism. This protein localizes to the endoplasmic reticulum and is known to metabolise as many as 20% of commonly prescribed drugs. CYP2D6 gene substrates include debrisoquine (Wennerholm et al, 1999) an adrenergic-blocking drug; sparteine and propafenone, both anti-arrythmic drugs; and amitryptiline, an anti-depressant. CYP2D6 gene is highly polymorphic in population (Neafsey et al, 2009); certain alleles result in the poor metaboliser phenotype, characterized by a decreased ability to metabolise the enzymes substrates. The polymorphism is due to multiple mutations of the gene, which result in absent, functionally deficient, under-expressed or over-expressed protein (Shiran et al, 2003). The gene is located near two cytochrome P450 pseudogenes on chromosome 22q13.1 (Gouch et al, 1993). Alternatively spliced transcript variants encoding different isoforms have been found for this gene (Toscano et al, 2006). CYP2D6 is a polypeptide of 497 amino acids that accounts for only small a percentage of all hepatic P450s but its role in drug metabolism is extensively higher than its relative content (Zanger et al, 2010). 4. Methadone Pharmacology and Its Mechanism of Action 4.1Methadone History Background Methadone was introduced to the market in 1960’s (Serban, 2011; Liebrenz et al, 2010). The drug was approved by the Food and Drug Administration (FDA) in 1947 as an analgesic; by 1950 it was used for the treatment of painful symptoms from heroin withdrawal and other opioids (SAMSHA, 2004). In 1964, researchers discovered that continuous, daily maintenance doses of oral methadone allowed opioid-addicted patients to function more normally in the process of their recovery (Payte, 1991; Zweben and Payte, 1990; Dole, 1988; Gearing and Schweitzer, 1974). Fig: 2 Methadone Chemical Structure Methadone in the modern medicine is used both as an analgesic for severe pain relief as well as in the treatment of opioid dependence (Rowley, 2011; Potter, 2010). Many scientific articles reviewed methadone to be the currently preferred drug of choice for the treatment of opioid dependence in many countries, including the U.K. (Nosyk et al, 2010; Verster and Buning, 2000). Fredheim et al, (2008) in their review reported that currently, methadone has had a renaissance in the treatment of pain because it has proven its usefulness as a second line drug in opioid switching when other opioids fail to show their effectiveness. Methadone has also been found to be the valued medication for its effectiveness in reducing the number of deaths associated with opioid addiction as well as various medical and behavioural prevalence of diseases associated with addictive disorders (Maxwell, Pullum Tannert 2005; Sheilds et al. 2007). However, the news headlines of many prominent newspapers including the New York Times and the Washington Times, in 2002 and 2003 hyped its publicity by reporting the opioid medications were the major cause of deaths in drug abuse treatment (Belluck, 2003a, 2003b, 2003c; Associated Press, 2002; Washington Times, 2003). New York Times even mentioned methadone as a â€Å"Killer Drug† which is widely abused and dangerous (Washington Times, 2003). After these issues it was decided by the U.N. to put methadone in the class of controlled drug. Methadone was declared in a controlled drug category by the United Nations convention and placed under the controlled substances (â€Å"narcotics†) by the Single Convention on Narcotic Drugs, 1961 (Single Convention) (Bosnjak et al,2011). However, it can only be prescribed in the UK, as in most countries, by prescription till present (Verster Buning, 2000; CSAT 200b). 4.2 Benefits of Methadone Methadone is one of the most preferred drugs not only in Ireland but also across several continents around the globe. In the report published by European Monitoring Centre for Drugs and Drug Addition (EMCDDA), there is a seven fold increase in the opioid treatment between 19993 -2000. The drug is widely recognised amongst doctors and patients due to its several socio-economic reasons. It is observed that there is a significant decrease in the crime graph and a noticeable increase in the employment services amongst the patients undergoing methadone maintenance treatment. No doubt, there is a reduction in illicit drug use by the opiate users and increase in social integration is one of the benefits of methadone. In addition, methadone also helps in reducing morbidity and mortality among opiate users. 4.3 Deaths Involving Methadone Methadone is a highly potent drug for the treatment of opioid dependence and acts as an analgesic for second line management of chronic pain. However, increase in mortality due to methadone administration has instigated controversies regarding the drug use (Lowe, Brooks Petry, 2010; Bunten et al 2010). Law enforcement agencies in the United States (U.S.) and the Drug abuse Warning Network (DAWN) ranked methadone as the third most apprehended analgesic used in the treatment of pain management, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (Fig:2.1.1) (SAMSHA, 2007). Various researches conducted amongst patients undergoing addiction treatment shows that the majority of methadone related deaths occur during the drug induction phase. Post-mortem sample predicts either an overestimation of the drug or combined usage of various other central nervous system (CNS) depressant in addition to the prescribed methadone (Bunten et al, 2010; Lowe, Johnson Petry, 2007). Fig: Methadone as the third most apprehended analgesic, fourth among all controlled pharmaceuticals, and eighth among all controlled substances (SAMASHA, 2007) The side effects associated with methadone overdose includes nausea, vomiting, dizziness, clouding of consciousness and pruritus (itching) (Davis Walsh, 2001). However, the primary toxic effect of excessive methadone is respiratory depression and hypoxia, sometimes accompanied by pulmonary edema and/or aspiration pneumonia (White and Irvine, 1999; Harding-Pink, 1993). Methadone related deaths during later phases of the additiction treatment mainly signify the presence of other illicit drugs. Researchers generally use the term â€Å"poison cocktail† describing the fatality due to intake of multiple psychotropic drugs (Borron, et al., 2001) such as alcohol, benzodiazepines, and other opioids. Several opioids when used or prescribed alone are relatively moderate respiratory depressants; however, when combined with methadone, their additive or synergistic effects can be lethal (Kramer, 2003; Payte and Zweben, 1998). Safety Information and Adverse Event Reporting Program a subsidiary of Food and Drug Administration (FDA) confirms 1,114 cases of methadone-associated fatalities in adults from 1970 through 2002. Critically, a greater number of deaths were reported in 2001 alone than during the entire period from1990 through 1999; the number doubled itself in 2002. In the U.K. 225 individuals died whilst undergoing methadone treatment in 1993. In 1997, data confirms 449 deaths due to the same cause. However, the mortality graph went down in 2001 by reporting 279 deaths caused by methadone but in 2002, it again rose to 316. Therefore, we can conclude that there is no regular trend in methadone related deaths. However, Corkery et al (2004), mentions that it is always not necessary for methadone to be the cause of death even according to the death certificate of the individuals. In an individual study, methadone was detected in the post-mortem blood of 352 unexplained sudden deaths in Scotland between 1 991 and 2001. 23 % of these deaths were not directly linked with methadone. However, there were other drugs and/or alcohol found in the blood sample of the individuals. The Substance Abuse and Mental Health Services (CSAT) in 2004 states that all methadone related poisoning eventually leads to cardio-toxicity and respiratory depression. Methadone deaths expressed as Percent of all poisoning deaths (CSAT, 2007). United States Poison Control Centres states that the overall number of opioid-related deaths has been on the rise, with many cases involving other opioids that include oxycodone and hydrocodone (Litovitz, et al., 2002; Florida Department of Law Enforcement, 2002) 4.4 Pharmacokinetics and Metabolism of Methadone Methadone is a liposoluble basic drug with a pKa of 9.2 and is usually administered orally as a recemic mixture of two enantiomers: R-methadone (R-Met) and S-methadone (S-Met) (Fig.2.2) (Trescot, 2010). The plasma half-life of the drug is highly variable and is between 13 and 55 hours but it is usually assumed to be an average of 25 hours (Letsky et al, 2011; Albion et al, 2010; Wolff et al, 2002). The bioavailability is 70% to 90% when administered orally (Bunten et al, 2010; Lowe, Brooks Petry, 2010). Studies indicate that in drug naive individuals, a single dose of methadone can show its clinical effects up to 72 hours in duration (Olsen et al, 1997). However, the peak plasma concentration reaches in 2 to 4 hours. The analgesic effect of the drug sets in about 15 minute after the subcutaneous injection (Eap et al, 2002). The chemical structure of r-(-)-methadone and s-(+)-methadone (asterisk (*) denotes chiral centre). There is a wide distribution of methadone amongst tissues, which generally range from 60 to 90%. As a result, the drug shows slow elimination and cumulative effect. Methadone is mostly metabolised in liver. The primary metabolite of the drug is 2-ethylidene-1, 5- dimethyl-3, 3-diphenylpyrrolidine (EDDP) (Fig) (Bunten et al, 2010) and to some extent 3, 3-diphenyl-1-pyrroline (EMDP) (Corkery et al, 2004). However, both of these metabolites are inactive and elimination of these inactive metabolies is through urine and faeces. Anggard and Inturrisi et al. (1975) (1990) mentioned that as a result of the basic (pKa =9.2) and lipophylic properties, methadone undergoes a hepatic metabolism and renal excretion. Fig: 4 Metabolic Conversion of Methadone to EDDP 4.4 Cytochrome P450 Cytochrome P450 (P450) is a large superfamily of enzymes. The origin of P450’s superfamily is since prokaryotes much before the existence of eukaryotes (Omura, 2010). The gene P450, commonly known as â€Å"CYP† is present in the genomes of virtually all organisms. Moreover, studies suggest that heme proteins are the building blocks of CYP450 enzymes. These enzymes play a crucial role in the metabolism of the various xenobiotics, steroids and other chemicals. Most of the drugs and chemicals are lipophilic to become more water soluble before excretion. Therefore, P450 superfamily of hemoproteins serves as terminal oxidases of the mixed function oxidase system (Wrighton and Stevens, 1992). The heme prosthetic group binds oxygen after electron transfer reactions from the reduced form of 24 nicotinamide adenine dinucleotide phosphate (NADPH). This reaction incorporates a single atom of molecular oxygen into a substrate with the concomitant reduction of the other atom to wate r (Synder, 2000; Omura, 1999). In cytochrome P450, ‘P’ denotes the pigment and the number ‘450’ is the spectral properties for the absorption band at 450 nm of the reduced CO-bound complex (Benhardt, 2006; Reichhart Feyereisen, 2000). However, according to the nomenclature society, the term â€Å"CYP† is followed by number of families which are generally group of proteins with more than 40% amino-acid sequence identity, a letter for subfamilies and a number for the gene e.g. – CYP2D6. Studies indicate that P450 superfamily is highly diverse (Mathew, 2010). Diversity of P450’s is mainly due to the extensive process of gene duplications. However, gene amplifications, conversions, genome duplications, gene loss, and lateral transfers are certain scenarios that are less documented. 4.5 Cytochrome P450 Polymorphism and Adverse Drug Reactions Drugs affect different individuals in a different way. Genetic variations, which affect the response of the drug metabolism, can be of the most probable reasons (Mayer Zanger, 1997). Johansson Sunderberg (2010) also reported that the difference in drug metabolism among individuals might be due to several factors e.g. epigenetic, pathophysiological, or it might be due to some environmental factors. In a population, genetic polymorphism is divided according to individual ability to perform drug transformation reaction (Srivastava, 2003). Moreover, polymorphic trait is also noticed due to certain mutation in the genes and/or a single nucleotide polymorphism (SNP) which results in the enzyme variation and leads towards higher or lower activity. As a result, there is a partial or complete absence of an enzyme protein in the system. (FIG:) Fig: Polymorphism of Drug Metabolism Enzymes (Evans Relling, 1999). As we can see from the above figure that the genetic polymorphism applies for a wide range of drugs and xenobiotic metabolizing enzymes. Identification of these variations were by the occurrence of adverse reactions after normal doses of drugs in patients or volunteers. In adverse drug reactions, drug-drug interactions have its key role. In fact, adverse drug reactions (ADRs) are one of the major causes of death which is reported in many scientific articles, reviews and even government scripts. According to Substance Abuse and Mental Health Administration (SAMSHA) (2007), there is a record of approximately 100,000 deaths in the United States due to drug toxicity. In addition, Eichelbaum et al., (2006) stated that ADRs is also responsible for up to 7% of hospitalizations and the number has increased to > 30% in the elderly population (> 70 years of age) (Paul et al., 2008). ADRs mainly affect cardiac function or cause liver toxicity (Need et al., 2005). The CYP families metabolises approximately, 75% of all clinically used drugs (Bertz and Granneman, 1997; Evans and Relling, 1999).The human genome contains 115 CYP genes, out of which 57 are found to be functional and the rest are reported as pseudogenes (Johansson Sundberg, 2010; Wang et al,2003). Among CYP families, there are 22 different P450 isoforms, which shows a high degree of polymorphism. Therefore, we can divide the polymorphic xenobiotic metabolizing CYP enzymes into two classes according to their interindividual susceptibility for xenobiotics: Class I: Composed of CYP1A1, CYP1A2, CYP2E1, and CYP3A4 without important functional polymorphism and active in metabolism of drugs. Class II: Composed of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP2D6, which are highly polymorphic and are important for the metabolism of drugs.

Understanding The Yellow Wallpaper -- Yellow Wallpaper essays

Understanding The Yellow Wallpaper      Ã‚   There are more reported cases of clinical depression in women than their are in men. There is also, generalized in western cultures, a stereotype that women are fragile and should be more dedicated to maintaining the home, doing feminine things, that they shouldn't work, and be discouraged from intellectual thinking. In the Victorian period (1837-1901) aside from women's suffragette movements the Victorian woman usually upheld this stereotype of a well behaved wife, more or less a possession then an individual. However, there were a few who defied the odds and took it to heart to let the world know about the indifference's that they went through. Charlotte Perkins Gilman, feminist, was one of these women who used her writing to express the differences and hardships women went through. One of her more famous works, the Yellow Wallpaper, is known as both a feminist piece and a depiction of Victorian life and indifferences for women. It is a piece that can have controversial me anings that can be taken to heart to why Gilman ever wrote it.    "The Yellow Wallpaper" has a simple enough story, the woman is taken to a rented house to recover from a nervous depression that she was experiencing. The depression was something common in women of the time, especially in more upper class women with little to do. The antidote " the cure" was developed by a Weir Mitchell, for psychoneurosies, in theory a women should inhibit herself from any kind of work or thinking and to get as much fresh air as possible. The heroine is subjected to this cure. Having been confined to a room in the house she starts imagining things in the wallpaper that she hates so much. However, as the story progresses it i... ...it to show that kind of diversity. She probably wanted a release, to share her life, to get back at the Wier Cure, to show the injustice brought to women of the period and to probably just be creative. In finding reviews and biographies on Gilman one does not find too many bad words written on her. She is held as a very prestigious writer. As for the yellow wallpaper it really expands the minds and makes one have to sit back and analyze what was really going on.    Works Cited    Gilman, Charlotte Perkins. Why I Wrote "The Yellow Wallpaper"? http://www.cwrl.utexas.edu/ daniel/amlit/wallpaper/Whywrote.html    Korb, Rena. An Overview of "The Yellow Wallpgper," in Exploring Short Stories Literature Resource Center. Gale Research, 1998.    Stone, Les. Charlotte (Anna) Perkins (Stetson) Gilman. Contemporary A uthors Online. The Gale Group, 2000.

A business plan in transportation industry Essay

This demonstrates of a business plan in cargo and parcel transportation. This type of the business requires a lot of capital to venture into it. Firstly, transportation machinery such as motor vehicles, motorcycles, trains, aeroplanes and other equipment for transport are expensive to acquire. The business is client based. By client based, it means that, the business depends entirely on clients as customers for its survival. It is a great challenge to get clients for a new business. People would prefer to transport through people whom they have worked before with, and created a confidence on them that they are trusted people. The goal of the business is to ensure efficient, effective and customer satisfaction in transportation of client’s goods. Beginning a new business is faced by several challenges. It would require a rather market research before kicking off the business. Marketing research would mean employing professional in marketing to help the business venture strategi cally in the market. Employing professional in marketing to conduct a research is expensive for a business especially in its onset, hence, a great challenge to the start of the business (Barnhart, 119). Transportation of parcels and cargos is a business that cannot fail to take place at whatever cost it might mean. People will always keep on exchanging parcels, individuals and firms will always transact in cargos. The business of goods transportation will always be there as long as the world and people exist. The biggest challenge to this new business is how to get clients and source of the capital to start the business. In obtaining customers for this business, a rather marketing will be entailed. Such marketing may be contacted through advertising in television channels, personal approaches to different firms and holding business talks, billboard advertisement in city centres and all other related such marketing techniques. Not every other business would survive without suppliers. A business needs suppliers for its stock, equipment or machinery. Most, a company based on transportation and logistics would need a group of suppliers for it to survive. For an easy venture in the marke t, a business may opt to collaborate with another established business, to win a large market within a short time. In addition, collaborating with another business that latter business act, as complement to what it offers would mean strategic kick off a business. The business under discussion focuses on merging with one of the airlines company in the city to market itself. In the market there are several business offering the same services. These are actually the real to competitors to the business (Abrams, 18). There will always be competitors to a business; competitors may either be direct or indirect competitors. Direct competitors are those that offer same services and goods to those that another business is offering. On the other hand, indirect competitors are the ones that offer substitute products to those that another business is offering. The company will be well structure to counter with the competitors offering the same services in the market. Amongst the measures at hand to deal with competition are, relatively lower charges. This would help to attract more clients to the company. Increased clients means increased customers hence, increased output of this business. Relatively lower charges, is another strategy that will help to reduce the payback period or time of our business project. It is very essential for a business to have an environment that is conducive for its success. By engagement into corporate social responsibilities, the business will not ensure a health social environment for itself, but also act as way of promoting itself. Through involvement in corporate social responsibilities, the business creates a good shape to the people. It is also a way of publicizing a business. Both political and social environment ought to be maintained by the company. Our company will have at hand all proper and valid documentation for its legality. By having a business vision and mission, it will create a source of inspiration and centre of focus both to the employees and the shareholders to the company. The strategy to ensuring the business is a success is clear enough. Due to wise selection of the business to collaborate with, it will be easy for the business to start at high gear. Firstly, there is a ready market for to transport, this is because we are collaborating with an airline firm. Our company will execute all the transactions involving transport by the particular airline. We also need to have strategic location of our offices. All offices to the company are found within the city centre. This means that they are highly accessible to the customers. Simple and clear terms of the contract with the client will also quicken the conduct of the transactions of the company. These just but some of the strategies put in place to ensure that the company will be successful in its endeavours. Good and clear communication is another major element for a success of every business. Communication within the company shall be made as simple and clear as much as possible. Delegation of duties f rom directors to the casual worker will create a good leadership within the organization. Through delegation, a strong teamwork and network of employees will be maintained in the organization. This will ensure that the organization maintains good and clear communication skills. Good communication improves employees productivity, hence an increase in the general output of the company. It would be a great challenge of to get capital to start the business. The company has therefore to portray a good strategy for it to attract people to be shareholders or financiers. A good business plan can also be used to attract a capital borrowing in some government agencies that lend out finances to motivate entrepreneurship. The business strategy is clear and comprehensive enough to stand a chance to win capital borrowing from any investment bank or government policy. This is a strategy of selling the company’s idea to the potential investors (Karin, 313). In conclusion, people share so much in common, yet are so magnificently different. They think differently; they have different and sometimes competing values, motivations and objectives. It’s therefore very important to study the nature of the individuals so as to live peacefully with them to avoid confrontations with them. This same case applies to all business ventures. A business ought to conduct a viable market research before kicking off. Good market research would help a business recognise its strength and weaknesses. It will increase on strengths and try to minimise on the weakness, through this, a strong business idea would be realize that could see any business venture a success. References Abrams, Rhonda M. The Successful Business Plan: Secrets & Strategies. Palto Alto, Calif: Planning Shop,  2003. Print. Barnhart, Cynthia, and Gilbert Laporte. Transportation. Amsterdam: North Holland,  2007. Print. Jo?eveer, Karin. Sources of Capital Structure: Evidence from Transition Countries. Tallinn: Eesti Pank,  2006. Print. Source document

The Lit Of Western World - 1588 Words

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Graduation Speech My Ideal Class - 954 Words

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Euthanasia - Physician Assisted Suicide - 1641 Words

Physician Assisted Suicide John Key once said â€Å"If I had terminal cancer, I had a few weeks to live, I was in tremendous amount of pain - if they just effectively wanted to turn off the switch and legalize that by legalizing euthanasia, I d want that† (Brainyquote, web). John Key, the Prime Minister of New Zealand, supports euthanasia. Since Key has been in office, the public support for euthanasia went up 70%. If people are changing around the world, then why are Americans not changing to accept that assisted suicide is morally correct and provides the terminally ill with the right to die with dignity? Five states legalized physician assisted suicide. These states are Oregon, Vermont, Washington, New Mexico, and Montana. The laws state that physician assisted suicide allows terminally ill patients to end their lives easily and painlessly. The process is simple. People have a right to die. There are two key points supporting why this law should morally has to be passed all throughout the country. If someone is suffering, the choice to end their lives should be an option. However, from a legal standpoint, it can run the risks of being considered murder. Therefore, this all depends on the legal and ethical forms of assisted dying. Starting in 1994, as mentioned above, five states in the U.S. gave the option of physician assisted suicide. Oregon, the first state to approve physician assisted suicide, let the people vote if they want the Death with Dignity Act, the name wasShow MoreRelated Physician-Assisted Suicide Essay - Euthanasia Should Not be Legalized793 Words   |  4 PagesEuthanasia Should Not be Legalized      Ã‚   It is conceivable, that life can deteriorate to the point where persons lose their dignity and self-respect and are unable to communicate; life in such a form no longer meets meets the basic criteria of human- ness.   (OKeefe, A1)   Under these circumstances only should Euthanasia be practiced and then only passively (pulling the plug).   Dutch Death, Euthanasia, doctor assisted suicide, whatever you want to call it, it Read MoreEuthanasia And Physician Assisted Suicide865 Words   |  4 Pagessubject for people; add in the idea of assisted suicides and there’s an uproar in society. Euthanasia or physician assisted suicide is a very controversial topic in our society today. Physician assisted suicide by definition is â€Å"suicide by a patient facilitated by means (as a drug prescription) or information (as an indication of a lethal dosage) provided by a physician aware of the patient’s intent (Merriam-Webster). There are two modes of looking at assisted suicides; either it’s seen as an absurd immoralRead MoreEuthanasia And Physician Assisted Suicide918 Words   |  4 Pagesallows terminally ill patients to end their lives with the assistance of a physician. According to the legislature, patients who seek assisted-death must only have six months to live and are required to submit a written request as well as two oral requests at least 15 days apart. (Reilly). While Gov. Jerr y Brown still has yet to approve this new law, the act has shed light on the topic of euthanasia/physician-assisted suicide. With the pending status of the law, the question remains on whether or notRead MoreEuthanasia Or Physician Assisted Suicide961 Words   |  4 PagesEuthanasia or physician assisted suicide, is the painless killing of a patient, suffering from a painful or incurable disease, like cancer, or alzheimer s, the practice is illegal in most countries, including the United States, although in the United States, it is a state decision, the only state in the United States that it is legal in is Oregon. Oregon passed the Death with Dignity Act in 1994, making euthanasia legal for chronically ill patients, the only caveat is that the doctor is allowedRead MoreEuthanasia, And Physician Assisted Suicide863 Words   |  4 Pagesare: euthanasia, and physician assisted suicide. Internationally, assisted suicide is a doctor prescribing drugs that end life. The patient is res ponsible for taking them. Euthanasia is the medication administered by doctors. Today, four countries have laws that allow euthanasia. (Ellis and Bronwyn) A few have laws for physician assisted suicide, and several countries have no laws against suicide. (Humphry) The United States of America have recently added a 5th state to offer assisted suicideRead MorePhysician Assisted Suicide And Euthanasia Essay1039 Words   |  5 PagesPhysician Assisted Suicide Is physician assisted suicide ethical? Physician assisted suicide is an up and coming ethical question that examines a person’s right to their own death. Many people support physician assisted suicide, citing that it can save a lot of pain and suffering. Others claim that the concept of physician assisted suicide is a slippery slope. A slippery slope in the sense that if society accepts euthanasia as a rightful death for the terminally ill, they will potentially acceptRead MoreEuthanasia And Physician Assisted Suicide1629 Words   |  7 Pagesproblems, assisted suicide creates options to reduce the amount of suffering the patient must enduring. 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Many patients claim that they reserve the right to physician assisted suicide—killing oneself with meansRead MoreEuthanasia And Physician Assisted Suicide997 Words   |  4 PagesEuthanasia and Physician Assisted Suicide: The Right to Die with Dignity (The Legalization, At Risk Groups, and Rebuttal) The possible legalization of voluntary euthanasia and physician assisted suicide brings concerns in regards to how well it will be accepted. There are contradictions that exists between government and church when it comes to the morals and values placed on human life. Although, society has concerns in regards to at risk community groups and the type of treatment availableRead MoreEuthanasia And Physician Assisted Suicide1504 Words   |  7 Pageslegalizing euthanasia and physician-assisted suicide, we would provide â€Å"vulnerable† patients with better overall protection and health care, give patients (who are excruciatingly suffering and have no chance of recovery) the option to end their lives before they ever needed to go through such an ordeal and giving them peace of mind, and spare the families of the patients the emotional pain of watching their loved one slowly and painfully passing away. For these reasons, I believe that euthanasia and Physician-Assisted

Economics Indicators free essay sample

Macroeconomics is â€Å"the study of how households and firms make decisions and how they interact in markets†(Mankiw, 2012, p. 29). While microeconomics is â€Å"the study of economywide phenomena, including inflation, unemployment, and economic growth†(Mankiw, 2012, p. 29). Understanding economic indicators is an integral part of assessing the economy as a whole. Economic indicators allow the government, businesses, and consumers, alike, to analyze and predict the future status of the economy. It is important to recognize the source of changes and how they ultimately, affect the economy. This paper will explain six economic indicators: Gross domestic product (GDP), unemployment, productivity, consumer price index (CPI), money supply, and consumer credit report. It will also explain the business cycle, why they it is utilized and show the importance through charts and graphs, Economic Indicators â€Å"Economic indicators are key statistics showing the state of the economy. These include the average workweek, weekly claims for unemployment insurance, new orders, vendor performance, stock prices, and changes in the money supply†(Friedman, 2012, p. 225). Leading Economic Indicators â€Å"Leading indicators are economic statistics that often change direction before the general economy changes. Stock market indexes are considered leading indicators, as stock indexes often decline before the economy declines and improve before the general economy recovers from a recession. Leading economic indicators therefore help predict the future economy†(Friedman, 2012, p. 396). Lagging Economic Indicators â€Å"Lagging Indicators are economic indicators that change after a change in the economy has occurred. Lagging indicators are observed as a means of confirming trends†(Friedman, 2012, p. 391). Definition – Gross Domestic Product is (GDP) â€Å"a figure that represents the total value of all goods and services produced in a country in a given time period. More simply, it is a measure of the total size of an economy â€Å"(Riggs, 2008, p. 96). How is the economic indicator determined? â€Å"It is calculated using the selling prices in the period in question of the â€Å"final† goods†(Kolb2008, p. 1044). â€Å"Government economists calculate GDP every quarter (in the financial world, each year is commonly broken down, for purposes of analysis, into four three-month periods called quarters), as well as yearly. It is used by government officials as an aid in creating policies, by business leaders in making business decisions, and by economists to improve their understanding of the economy†(Riggs, 2008, p. 96). What it measures? â€Å"In order to avoid counting certain goods (those that are part of other goods) multiple times, GDP measures only what are known as final products, or products that are sold to consumers on the open market† (Riggs, 2008, p. 96). Strengths, weakness, problems, or criticisms Strengths (Barnes, 2013): †¢GDP is considered the broadest indicator of economic output and growth. Real GDP takes inflation into account, allowing for comparisons against other historical time periods. †¢The Bureau of Economic Analysis issues its own analysis document with each GDP release, which is a great investor tool for analyzing figures and trends, and reading highlights of the very lengthy full release Weakness (Barnes, 2013): †¢Data is not very timely it is only released quarterly. †¢Revisions can change historical figures measurably (the difference between 3% and 3. 5% GDP growth is a big one in terms of monetary policy) Historical Data – GDP reflects how much we would actually pay for something and is therefore, the market value. The chart below reflects GDP from 2007 through 2012. it is a reflection of the market value of all final goods and services, produced within the country between this period. GROSS DOMESTIC PRODUCT (BEA, 2013) ? Definition – Unemployment is â€Å"the state of being unemployed; can also mean the rate of unemployment (the percentage of a nation’s workforce that cannot find jobs)†(Riggs, 2008). The national unemployment rate is defined as the percentage of unemployed workers in the total labor force. It is widely recognized as a key indicator of labor market performance†(Investopedia, 2013). How is the economic indicator determined? â€Å"In any given month, the flow between these three pools of employed, unemployed, and out of the labor force creates the â€Å"measured unemployment rate. † By the BLS definition, the unemployment rate I percentage terms is the ratio of the number of unemployed divided by the labor force times 100†(Kolb, 2008, p. 2134). Unemployment is determined by the total number of workers (employed plus unemployed). â€Å"Persons are classified as unemployed if they do not have a job, have actively looked for work in the prior 4 weeks, and are currently available for work. Persons who were not working and were waiting to be recalled to a job from which they had been temporarily laid off are also included as unemployed†(Investopedia, 2013). What it measures? â€Å"Unemployment measures the total number of employed, unemployed, or not in the labor force. It measures job losers, job leavers, and new entrants/reentrants into the labor force†(Kolb, 2008, 2133) Strengths, weakness, problems, or criticisms Strengths (Mankiw, 2012): †¢Unemployment insurance †¢Government programs †¢Usually short term 6-9 months Weakness (Mankiw, 2012): Some workers give up the job search because they cannot find worker and essentially become discouraged. †¢Structural unemployment for company-wide lay-offs Historical Data There are four main causes of unemployment: cyclical, frictional, seasonal, and structural unemployment. These are associated with different economic situations and different economic concepts. The chart below list the percentage rate unemployment for 16 years and older from 2007 to 2012. Labor Force Statistics from the Current Population Survey Original Data Value Series Id:LNS14000000 Jumps in productivity tend to make their way to corporate bottom lines quickly via margin expansion. †¢Release shows results with and without the effects of inflation †¢Detailed productivity measures at the industry and sector level allow investors to analyze the relative productivity performance of many of their holdings. †¢One of very few indicators that shows results compared to other advanced economies; shows how the U. S. stacks up against the world in terms of productivity gains. †¢Productivity results represent the lions share of total GDP (about 75%); only government results and nonprofit groups are removed from calculations. Weakness (Barnes, 2013): †¢Not a timely indicator; first report comes five weeks after the quarter, and the revised report nearly two months †¢No new series of data is released, only derivations of previous data sets †¢Can be very volatile quarter to quarter; long-term measurements are the most effective use of this indicator when analyzing sustainable, long-term rates of productivity growth Historical Data- Maximizing output became even more important after the Industrial Revolution because of the high costs associated with mass producing goods. Thus, not long after the rise of factories came an outpouring of productivity and efficiency studies as well as numerous methods for getting the most possible output from a factory†(Riggs, 2008, p. 194). Major Sector Productivity and Costs Original Data Value Series Id:PRS85006092 Sector:Nonfarm Business Measure:Labor productivity (output per hour) Duration:Percent change from previous quarter at annual rate Base Year:- Years:2007 to 2012 YearQtr1Qtr2Qtr3Qtr4Annual 2007-0. 23. 34. A large increase in the CPI over a short period of time represents growing inflation, and a drop in the CPI signifies deflation, both of which can be harmful to an individual’s finances and a nation’s economy†(Riggs, 2008, p. 108). What it measures? â€Å"CPI measures the change in prices that consumers pay for goods and services from year to year†(Riggs, 2008, p. 108). Strengths, weakness, problems, or criticisms Strengths (Barnes, 2013): †¢Gives most insight into future Fed rate moves †¢Highly watched and analyzed in the media †¢Good regional and industry breakdowns for investor research Weakness (Barnes, 2013): †¢Volatile month to month What it measures? â€Å"Consumer credit is considered a good indicator of the potential future spending levels seen in the Personal Consumption and Retail Sales reports, and shows the extent to which benchmark interest rates such as the fed funds rate and prime rate have manifested themselves at the consumer level (it can take six months to a year for macro interest rates to work their way down to consumers)†(Barnes, 2013). Strengths, weakness, problems, or criticisms Strengths (Barnes, 2013): †¢Contains detailed breakdown of auto loan figures, such as average maturity and prevailing interest rates †¢Data is provided with and without seasonal adjustments. †¢Release shows comparisons against previous month, previous year, and also against results from the last five years Weakness (Barnes, 2013): †¢Only total growth in outstanding loans is shown; there is no way of knowing if consumer payments have fallen off or if new loan growth has slowed based on a falling consumer credit number (and vice versa). †¢Absence of home-equity debt provides for an incomplete picture. †¢Because it comes out after the consumer confidence report and retail sales reports for the month, some analysts will not look as intently at the consumer credit figures month to month, instead reviewing multi-period trends once or twice a year Historical Data- â€Å"It covers revolving and non-revolving credit. Revolving credit can be increased by the consumer up to a limit without contacting the creditor (as in credit cards), while non-revolving terms are fixed at the time the loan (as with an auto loan)†( (Barnes, 2013). The consumer credit report shows outstanding balances for commercial banks, finance companies, credit unions, Federal government and Sallie Mae, savings institutions, non-financial businesses, and securitized asset pools†(Barnes, 2013). Definition- Retail Sales â€Å"tracks the dollar value of merchandise sold within the retail trade by taking a sampling of companies engaged in the business of selling end products to consumers†(Barnes, 2008). How is the economic indicator determined? The data released will cover the prior months sales, making it a timely indicator of not only the performance of this important industry (consumer expenditures generally make up about two-thirds of total gross domestic product), but of price level activity as a whole. Retail Sales is considered a coincident indicator, in that activity reflects the current state of the economy. It is also considered a vital pre-inflationary indicator, which creates the biggest interest from Wall Street watchers and the Conference Review Board, which tracks data for the Federal Reserve Boards directors. What it measures? â€Å"Retail sales measures â€Å"the release will contain two components: a total sales figure (and related percentage change from the previous month), and one ex-autos, as the large ticket price and historical seasonality of auto sales can throw off the total figure disproportionately. Companies of all sizes are used in the survey, from Wal-Mart to independent, small-town businesses†(Barnes, 2013). Strengths, weakness, problems, or criticisms Strengths (Barnes, 2013): †¢The retail sales data is extremely timely, and is released only two weeks after the month it covers. †¢The data release is robust; investors can download a full breakout of component sectors, as well as spreadsheet historical data to examine trends. †¢Retail sales reports get a lot of press. Its an indicator that is easy to understand and relates closely to the average consumer. †¢A revised report comes out later (two to three months on average), amending any errors. †¢Analysts and economists will take out volatile components to show the more underlying demand patterns. The most volatile components are autos, gas prices and food prices. †¢Data is adjusted seasonally, monthly and for holiday differences month to month. Weakness (Barnes, 2013): †¢Revisions to the report (released about two months after the advance report) can be quite large, and the sample size is relatively small compared to the number of retailers opening their doors to consumers. †¢Retail sales data is often volatile from month to month, which makes trend-spotting difficult. †¢The indicator is based on dollars spent and does not account for inflation. This makes it difficult for individual investors to make decisions based on the raw data. †¢Does not account for retail services, only physical merchandise. The U. S. is an increasingly service-based economy, so not all retail activity is captured. Historical Data- Retail Sales is one of the big ones a report that can shed a lot of light on the economy. It provides detailed industry information and can really move the market. Investors will best be served by waiting for the analysts to sort through the report, removing any overly volatile components, and drawing conclusions from there. Conclusion Economic indicators are fundamental in the health and wealth of the nation’s economy. Gross domestic product is a part of every economic indicator because it measures the size of the total economy. Six important indicators has been defined and discussed within this paper. As the economy evolves, it is important to save at the appropriate times and spend when appropriate. Keeping a watchful eye on the economic indicators, being knowledgeable about the economy, preparing for inflation as well as deflation, is necessary in order to stay ahead of an ever-changing economy.