Rizal Analysis free essay sample

?Por Telepono or By Phone is a play written by Philippine national hero, Jose Rizal. It discusses social issues and plans for the Philippines by two Friars. It was published in 1889 as a reply to a friar named Fr. Salvador Font in connection to his discrimination about Noli Me Tangere and for initiating the banning of Noli in the fall of 1889. The first pamphlet was printed in Barcelona under the authorship of Dimas Alang. Por Telefono is a satirical comedy about Father Font, who was at Madrid speaking with a provincial priest in San Agustin Monastery using a telephone line that is spear-headed by The Trans-Oceanic Telephone Co. Por Telepono is full of symbolism. It unveils how friars lived their lives and how they give thanks for the donations given by ilustrados. Every line that has been uttered in Madrid is like an echo that fills the corners of the Philippines. We will write a custom essay sample on Rizal Analysis or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page By Telephone by Dimas Alang (Jose Rizal) In this article Rizal writes as if from the future and, with satire and irony, condemns the rule of the friars in his day. Rizal sent his manuscript to Mariano Ponce and, under his direction, it was published in Barcelona in 1889. F. Salvador Font, who censored Rizals Noli Me Tangere, occasioned this ridicule In the year 1900 the Philippines was for the first time connected with the Motherland by means of a Telephone Line by an English-Catalonian firm called The Trans-Oceanic Telephone Company, well known in its time for its truly enterprising spirit. Thanks to the perfection of the instruments, there could be heard in Madrid the mystical sighs of the friars here as they prayed with great piety before the sacred images, likewise their humble talk, their words of conformity and resignation, and even their thanksgiving for the alms of rice and fish which the people gave out of compassion for their fasting and abstinence. Such was the perfection of the telephone that even the silence which prevailed in the refectories could be transmitted, and from the noise of mastication, it could be definitely known that the most gluttonous of the friars did not eat over five mouthfuls a day. How poor and virtuous these priests are! exclaimed he affected democrats in Madrid. How poor and virtuous these priests are! repeated the telephone in the Philippines, and this was circulated everywhere, in the convents, churches, and so forth. Upon learning this, the friars reduced further the quantity of their morels fearing that there might be a hungry native. They taught the youth how to read and write and forcibly also instructed them in the Spanish language, not seldom suffering insults and fist-blows from the parents of the youths for daring to open their eyes. God be praised! the friars would answer, turning the other cheek saying: All for the sake of God and Mother Spain! Thus they continued to teach just as soon as the despotic native had gone away, if the Government, impelled by the parents, would not institute action against them for teaching an offense constituting a great crime by endangering the integrity of the country. By request of the natives, the Overseas Minister, the Procurator of the Augustinian friars one day telephoned from Madrid to Manila, is offering our Order an hacienda in order that the friars might not die of hunger but live with a certain comfort. What shall I answer him? The telephone transmitted the offer to the Augustinian convent. O Jesus, my Jesus! Holy God, might Saint, immortal Saint! May God protect us from all temptation exclaimed all the friars, and on hearing this news, they dropped on their knees and covered their ears. Lord, Lord! cried the Provincial beating his breast soundly, and not as one who would only deceive the faithful to get money from them. I have ruined the little soul of Salvadorcito by sending him to Madrid as the Procurator! He was so good, so humble, so simple, so ingenuous, so silent, so chaste, and so frank when he was here! Now he is ruined! Imagine giving such proposals, such sinful ones! Alas! Alas! Domine quare deleriquiste eum? Oh, Lord, why didst thou forsake him? All the inmates of St. Augustine groaned, and all the friars were beating their breasts and scourging one another to do penance and to bring the soul of little Salvadorcito Tont to the right path. All this consternation in the convent of St. Augustine was heard in Madrid by telephone, and Salvadorcito Tont exclaimed with the simple air of a good boy: I wonder if they have imprisoned all my brothers for failing to read all the pamphlets which the natives published against them, insulting them with ecclesiastical approval! After all, this has been rightly done. Who commands to answer and counter? If they insult us in the booklets we, as imitators and ministers of Christ, should be compelled to read them all, especially if there are indulgences, and they should prohibit us from answering them and defending ourselves. That is why we have vows of haughtiness. . . . I am going immediately to see the Minister and ask him to flog any priest of my religion who through pride, will not say ‘Amen’ to everything and regard the truth; he will thus see that, although a simpleton, I do not lack love of Justice. . . Then he looked for his shoes with holes in the soles because what he had on had no soles. The good Augustinian had to go on foot to the Ministry, as he does not even have carfare, notwithstanding his vow of wealth! Salvadorcito, Salvadorcito! called the telephone. Salvadorcito recognized the voice of the Provincial and began to tremble, as he was very obedient. At your orders, Father! he answered and he knelt down by the telephone in order to be in a more respectful position, although this was forbidden by his vow of haughtiness. How did you permit yourself to be tempted by the enemy of evil into accepting for a moment the offer to give us a hacienda? My son, did you not perceive that this was only a trap laid by the enemy, inspired, no doubt, by that damned soul, Rizal, so that we may thus become rich, haughty, powerful, and licentious because that wretch from Calamba desires nothing better than that we practice our vows of wealth, haughtiness, and licentiousness which the sacrilegious founders have imposed upon us all? Don’t you dare again listen to such offers. Here we not only work and construct our churches with our hands, we not only sow and help the poor, but what little they give us, we, in turn, hand over to the rich and proud in order that they may tyrannize us more so that their greed may be increased and they may exploit and ruin us the more, put us in prison, exile us, and so forth. . . Thus we spread the law of Christ everywhere in the islands were we are exiled; then there will be more imitators. . . There is not one faithless Igorot left, not even a single non-Christian in the mountains; all have been baptized and they all exploit us as good Christians. What you should propose to the Minister in order that our doctrine may triumph, is that he emulate the Roman praetors [= a Roman magistrate [rly] and send us cruel and bloodthirsty governors to violate the laws and persecute us. Thus will the dormant one awaken, the lukewarm be strengthened, and the attention of the indifferent who are now so many be aroused. . . Remember that in order to make a cause triumph, it is necessary that it be persecuted. Let them go ahead and persecute us! Thus will the dormant one awaken, the lukewarm be strengthened and the attention of the indifferent who are now so many be aroused. . . Remember that in order to make a cause triumph, it is necessary that it be persecuted. Let them go ahead and persecute us! In the meantime, I impose as a penance upon you, who are neither vain nor insincere, to have your picture taken in several positions, but always in the attitude of meditating, or as if writing a sermon, with pen in hand, and beside a lamp, wearing eyeglasses, even though you don’t need them; do you understand? You will exhibit these photographs in public so that everyone will say, even if it is not believed, ‘What a thinker he is; what a great orator Salvadorcito Tont must be! He is always writing sermons and has to time even to have his picture taken! ’ This will make you miserable, because even if you have the vows of wealth, haughtiness and licentiousness, you pay no attention to them. . Don’t forget to have your picture taken in a pensive mood and as a comedian! God be with you! Thy will be done! sighed Salvadorcito resignedly, and his whole house resounded with laments. Salvadorcito was so humble that he was tortured by the idea of appearing in public, even if only in a photograph, and that is why, whenever he had to preach, he assumed a hollow and cavernous voice to make his hearers afraid and see if they would leave him alone. Salvadorcito, Salvadorcito! again shouted the telephone. At your orders, the good procurator answered, and this time he fell on his hands and knees so that he could listen more reverently to his Provincial. Request the Minister not to make Fr. Rodriguez a bishop. Tell him that he is very busy researching and looking for words deriving from Calamba, such as Calamban, Calambanian, Calamian, Calam, etc. Imagine what a task this is fro him! He is sweating to beat the band! He has no time to be a bishop, although he would make a good one, because he is condemned by our Father, St. Augustine, to be stupid all his life. For God’s sake, don’t let them make him a bishop! It is not the Minister who wants to make him a Bishop, but the Dominicans who wish to avoid the office, owing to the spirit of haughtiness! answered Salvadorcito. Then tell the Minister that there is nobody like the Dominicans for bishops. I know one here who is so friendly to the natives and an enemy of our faith that he does not let the Chinese take part in ceremonies, although he knows very well that as soon as they leave the country they give up Christianity. They take to Christianity for convenience. Among Chinese, the worst Christians they are the better persons they become. The Dominicans know this and even if the Chinese offer to give them money, they would not accept it. No, sir! They manage to prevent the natives from quarreling with the mestizos and the latter from quarreling with the Chinese, all against the express mandate of Jesus Christ to ‘divide in order to rule. ’ For this disobedience, they ought to be made bishops. They should be made to carry miters on their heads as symbol of pride, like the Assyrian and Persian priests who wore such ornaments. These people follow Machiavelli, that accursed Machiavelli, who said that peace and harmony should be preached. Talking about harmony, do you know, Salvadorcito, that Father Baldomero and another one went to visit the college bearing the same name, which is a school for girls, if you don’t remember well. . . Of course, they did not visit the dormitories while the girls were dressing and changing their clothes, neither did they talk with the prettiest girls, and the few words they exchanged with them were not said in the dark nor behind doors far from other people. . . Oh, but what misery they suffered! They who were so chaste, so virtuous and so pure-minded! The Sisters were so aloof, so unaccommodating and so intolerant! All the time they were there they talked only of God always assuming a penitent and solemn mood! Alas, alas! Why, what’s the matter, Salvadorcito? Please take me away from the Office of Procurator, because here I am suffering what Baldomero and the other fellow must have suffered in the girls’ College. What a lot of beautiful girls and women. . . Oh, my! I wish to go back to Manila! Madrid is doomed! Here the natives will imprison and exile you without trial! For simply writing a secret report they will. . . Never mind! You will die of hunger and will not ride a coach! I travel on foot here. I warn you that you will have to salute the natives, otherwise they will file an administrative case against you, and exile you. I don’t care! I prefer all that to living among beautiful. . . women. Remember that if you do not accommodate the gobernadorcillo, he will accuse you of being anti-Spanish. . .. I will protest and say that I love Spain. They won’t believe you, because the natives are very rich and they publish pamphlets against the friars with permission of the authorities. Then what shall I do? Oh, what shall I do? Remain there as Procurator. Oh, my! Present Chinese and Japanese gifts to the Ministers, the Delegates, and the Senators in order to promote our ends. Yes, that’s it, the Chinese! And what else? Wait until they make you a Bishop. Oh, my! And later, a Cardinal! Alas But in the meanwhile, you must have the government award crosses, estates, and offices to our enemies. And suppose they will engineer a revolt and claim that it is we who are behind it because we are ‘bistirufels’? Silence. What shall I say about ‘bistriufelism’? Silence. ‘Bistirufelism’ did you say? ’ answered a voice at last. You tell the Minister that it does not exist, but if he wants it to exist, just let him think about it and it will. Tell him that we have already suffered too much, that we suffer now and will suffer more. However, as nothing is eternal in this life, our sufferings will some day come to an end, that day when we are convinced that the Government is with our enemies. Prometheus Bound: Jose Rizal once sculpted a small sculpture â€Å"Prometheus Bound†, that depicted Prometheus who brought fire to man according to the Greek myth. By Prometheus’ very act of empowering mankind, Zeus punished him by chaining him on the Caucasus mountains. Everyday an eagle comes and eats his liver, only to be grown back again at night, so that on the next day the eagle will come again to eat it. I’d like to think that Rizal thought of the great potential of Filipinos, chained by 300 years of superstition, ignorance, and feudalism as he sculpted a similar scene depicted on this painting. If you know how the story goes, Hercules eventually kills the eagle and frees Prometheus. As to who will be Hercules of the Philippines, one who will empower every Filipino, I look forward to the future with hope. Triumph of science over death Triumph of Death Over Life by Dr. Jose Rizal â€Å"In the penetrating psycho- logical analysis of the man by Mr. Blumentritt there is mention of Rizal’s sensitivity as an artist, Mr. Blumentritt being the possessor of three terracotta statues: ‘Prometheus Bound’, ‘The Victory of Death Over Life’, and ‘The Triumph of the Intellect Over Death’†. â€Å"We are losing in Rizal not only a faithful friend of Germany and German scholarship but also the only man with sufficient knowledge and resolution to open a way for modern thought into that far-off island world. †

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Biography of Ernest Hemingway, Journalist and Writer Ernest Hemingway (July 21, 1899–July 2, 1961) is considered one of the most influential writers of the 20th century. Best known for his novels and short stories, he was also an accomplished journalist and war correspondent.  Hemingways trademark prose style- simple and spare- influenced a generation of writers. Fast Facts: Ernest Hemingway Known For: Journalist and member of the Lost Generation group of writers who won the Pulitzer Prize and Nobel Prize in LiteratureBorn: July 21, 1899 in Oak Park, IllinoisParents: Grace Hall Hemingway and Clarence (Ed) Edmonds HemingwayDied: July 2, 1961 in Ketchum, IdahoEducation: Oak Park High SchoolPublished Works: The Sun Also Rises, A Farewell to Arms, Death in the Afternoon, For Whom the Bell Tolls, the Old Man and the Sea, A Moveable FeastSpouse(s):  Hadley Richardson (m. 1921–1927), Pauline Pfeiffer (1927–1939), Martha Gellhorn (1940–1945), Mary Welsh (1946–1961)Children: With Hadley Richardson: John Hadley Nicanor Hemingway (Jack 1923–2000); with Pauline Pfeiffer: Patrick (b. 1928), Gregory (Gig 1931–2001) Early Life Ernest Miller Hemingway was born on July 21, 1899 in Oak Park, Illinois, the second child born to Grace Hall Hemingway and Clarence (Ed) Edmonds Hemingway. Ed was a general medical practitioner and Grace a would-be opera singer turned music teacher. Hemingways parents reportedly had an unconventional arrangement, in which Grace, an ardent feminist, would agree to marry Ed only if he could assure her she would not be responsible for the housework or cooking. Ed acquiesced; in addition to his busy medical practice, he ran the household, managed the servants, and even cooked meals when the need arose. Ernest Hemingway grew up with four sisters; his much-longed-for brother did not arrive until Ernest was 15 years old. Young Ernest enjoyed family vacations at a cottage in northern Michigan where he developed a love of the outdoors and learned hunting and fishing from his father. His mother, who insisted that all of her children learn to play an instrument, instilled in him an appreciation of the arts. In high school, Hemingway co-edited the school newspaper and competed on the football and swim teams. Fond of impromptu boxing matches with his friends, Hemingway also played cello in the school orchestra. He graduated from Oak Park High School in 1917. World War I Hired by the Kansas City Star in 1917 as a reporter covering the police beat, Hemingway- obligated to adhere to the newspapers style guidelines- began to develop the succinct, simple style of writing that would become his trademark. That style was a dramatic departure from the ornate prose that dominated literature of the late 19th and early 20th centuries. After six months in Kansas City, Hemingway longed for adventure. Ineligible for military service due to poor eyesight, he volunteered in 1918 as an ambulance driver for the Red Cross in Europe. In July of that year, while on duty in Italy, Hemingway was severely injured by an exploding mortar shell. His legs were peppered by more than 200 shell fragments, a painful and debilitating injury that required several surgeries. As the first American to have survived being wounded in Italy in World War I, Hemingway was awarded a medal from the Italian government. While recovering from his wounds at a hospital in Milan, Hemingway met and fell in love with Agnes von Kurowsky, a nurse with the American Red Cross. He and Agnes made plans to marry once he had earned enough money. After the war ended in November 1918, Hemingway returned to the United States to look for a job, but the wedding was not to be. Hemingway received a letter from Agnes in March 1919, breaking off the relationship. Devastated, he became depressed and rarely left the house. Becoming a Writer Hemingway spent a year at his parents home, recovering from wounds both physical and emotional. In early 1920, mostly recovered and eager to be employed, Hemingway got a job in Toronto helping a woman care for her disabled son. There he met the features editor of the Toronto Star Weekly, which hired him as a feature writer. In fall of that year, he moved to Chicago and became a writer for  The Cooperative Commonwealth, a monthly magazine, while still working for the Star. Hemingway, however, longed to write fiction. He began submitting short stories to magazines, but they were repeatedly rejected. Soon, however, Hemingway had reason for hope. Through mutual friends, Hemingway met novelist Sherwood Anderson, who was impressed by Hemingways short stories and encouraged him to pursue a career in writing. Hemingway also met the woman who would become his first wife: Hadley Richardson. A native of St. Louis, Richardson had come to Chicago to visit friends after the death of her mother. She managed to support herself with a small trust fund left to her by her mother. The pair married in September 1921. Sherwood Anderson, just back from a trip to Europe, urged the newly married couple to move to Paris, where he believed a writers talent could flourish. He furnished the Hemingways with letters of introduction to American expatriate poet Ezra Pound and modernist writer Gertrude Stein. They set sail from New York in December 1921. Life in Paris The Hemingways found an inexpensive apartment in a working-class district in Paris. They lived on Hadleys inheritance and Hemingways income from the Toronto Star Weekly, which employed him as a foreign correspondent. Hemingway also rented out a small hotel room to use as his workplace. There, in a burst of productivity, Hemingway filled one notebook after another with stories, poems, and accounts of his childhood trips to Michigan. Hemingway finally garnered an invitation to the salon of Gertrude Stein, with whom he later developed a deep friendship. Steins home in Paris had become a meeting place for various artists and writers of the era, with Stein acting as a mentor to several prominent writers. Stein promoted the simplification of both prose and poetry as a backlash to the elaborate style of writing seen in past decades. Hemingway took her suggestions to heart and later credited Stein for having taught him valuable lessons that influenced his writing style. Hemingway and Stein belonged to the group of American expatriate writers in 1920s Paris who came to be known as the Lost Generation. These writers had become disillusioned with traditional American values following World War I; their work often reflected their sense of futility and despair. Other writers in this group included F. Scott Fitzgerald, Ezra Pound, T.S. Eliot, and John Dos Passos. In December 1922, Hemingway endured what might be considered a writers worst nightmare. His wife, traveling by train to meet him for a holiday, lost a valise filled with a large portion of his recent work, including carbon copies. The papers were never found. Getting Published In 1923, several of Hemingways poems and stories were accepted for publication in two American literary magazines, Poetry and The Little Review. In the summer of that year, Hemingways first book, Three Stories and Ten Poems, was published by an American-owned Paris publishing house. On a trip to Spain in the summer of 1923, Hemingway witnessed his first bullfight. He wrote of bullfighting in the Star, seeming to condemn the sport and romanticize it at the same time. On another excursion to Spain, Hemingway covered the traditional running of the bulls at Pamplona, during which young men- courting death or, at the very least, injury- ran through town pursued by a throng of angry bulls. The Hemingways returned to Toronto for the birth of their son. John Hadley Hemingway (nicknamed Bumby) was born October 10, 1923. They returned to Paris in January 1924, where Hemingway continued to work on a new collection of short stories, later published in the book In Our Time. Hemingway returned to Spain to work on his upcoming novel set in Spain: The Sun Also Rises. The book was published in 1926, to mostly good reviews. Yet Hemingways marriage was in turmoil. He had begun an affair in 1925 with American journalist Pauline Pfeiffer, who worked for the Paris Vogue. The Hemingways divorced in January 1927; Pfeiffer and Hemingway married in May of that year. Hadley later remarried and returned to Chicago with Bumby in 1934. Back to the U.S. In 1928, Hemingway and his second wife returned to the United States to live. In June 1928, Pauline gave birth to son Patrick in Kansas City. A second son, Gregory, would be born in 1931. The Hemingways rented a house in Key West, Florida, where Hemingway worked on his latest book, A Farewell to Arms, based upon his World War I experiences. In December 1928, Hemingway received shocking news- his father, despondent over mounting health and financial problems, had shot himself to death. Hemingway, whod had a strained relationship with his parents, reconciled with his mother after his fathers suicide and helped support her financially. In May 1928, Scribners Magazine published its first installment of A Farewell to Arms. It was well-received; however, the second and third installments, deemed profane and sexually explicit, were banned from newsstands in Boston. Such criticism only served to boost sales when the entire book was published in September 1929. The Spanish Civil War The early 1930s proved to be a productive (if not always successful) time for Hemingway. Fascinated by bullfighting, he traveled to Spain to do research for the non-fiction book, Death in the Afternoon. It was published in 1932 to generally poor reviews and was followed by several less-than-successful short story collections. Ever the adventurer, Hemingway traveled to Africa on a shooting safari in November 1933. Although the trip was somewhat disastrous- Hemingway clashed with his companions and later became ill with dysentery- it provided him with ample material for a short story, The Snows of Kilimanjaro, as well as a non-fiction book, Green Hills of Africa. While Hemingway was on a hunting and fishing trip in the United States in the summer of 1936, the Spanish Civil War began. A supporter of the loyalist (anti-Fascist) forces, Hemingway donated money for ambulances. He also signed on as a journalist to cover the conflict for a group of American newspapers and became involved in making a documentary. While in Spain, Hemingway began an affair with Martha Gellhorn, an American journalist and documentarian. Weary of her husbands adulterous ways, Pauline took her sons and left Key West in December 1939. Only months after she divorced Hemingway, he married Martha Gellhorn in November 1940. World War II Hemingway and Gellhorn rented a farmhouse in Cuba just outside of Havana, where both could work on their writing. Traveling between Cuba and Key West, Hemingway wrote one of his most popular novels: For Whom the Bell Tolls. A fictionalized account of the Spanish Civil War, the book was published in October 1940 and became a bestseller. Despite being named the winner of the Pulitzer Prize in 1941, the book did not win because the president of Columbia University (which bestowed the award) vetoed the decision. As Marthas reputation as a journalist grew, she earned assignments around the globe, leaving Hemingway resentful of her long absences. But soon, they would both be globetrotting. After the Japanese bombed Pearl Harbor in December 1941, both Hemingway and Gellhorn signed on as war correspondents. Hemingway was allowed on board a troop transport ship, from which he was able to watch the D-day invasion of Normandy in June 1944. The Pulitzer and Nobel Prizes While in London during the war, Hemingway began an affair with the woman who would become his fourth wife- journalist Mary Welsh. Gellhorn learned of the affair and divorced Hemingway in 1945. He and Welsh married in 1946. They alternated between homes in Cuba and Idaho. In January 1951, Hemingway began writing a book that would become one of his most celebrated works: The Old Man and the Sea. A bestseller, the novella also won Hemingway his long-awaited Pulitzer Prize in 1953. The Hemingways traveled extensively  but were often the victims of bad luck. They were involved in two plane crashes in Africa during one trip in 1953. Hemingway was severely injured, sustaining internal and head injuries as well as burns. Some newspapers erroneously reported that he had died in the second crash. In 1954, Hemingway was awarded the career-topping Nobel Prize for literature. Decline and Death In January 1959, the Hemingways moved from Cuba to Ketchum, Idaho. Hemingway, now nearly 60 years old, had suffered for several years with high blood pressure and the effects of years of heavy drinking. He had also become moody and depressed and appeared to be deteriorating mentally. In November 1960, Hemingway was admitted to the Mayo Clinic for treatment of his physical and mental symptoms. He received electroshock therapy for his depression and was sent home after a two-month stay. Hemingway became further depressed when he realized he was unable to write after the treatments. After three suicide attempts, Hemingway was readmitted to the Mayo Clinic and given more shock treatments. Although his wife protested, he convinced his doctors he was well enough to go home. Only days after being discharged from the hospital, Hemingway shot himself in the head in his Ketchum home early on the morning of July 2, 1961. He died instantly. Legacy A larger-than-life figure, Hemingway thrived on high adventure, from safaris and bullfights to wartime journalism and adulterous affairs, communicating that to his readers in an immediately recognizable spare, staccato format. Hemingway is among the most prominent and influential of the Lost Generation of expatriate writers who lived in Paris in the 1920s. Known affectionately as Papa Hemingway, he was awarded both the Pulitzer Prize and the Nobel Prize in literature, and several of his books were made into movies.   Sources Dearborn, Mary V. Ernest Hemingway: A Biography. New York, Alfred A. Knopf, 2017.Hemingway, Ernest. Moveable Feast: The Restored Edition. New York: Simon and Schuster, 2014.Henderson, Paul. Hemingways Boat: Everything He Loved in Life, and Lost, 1934–1961. New York, Alfred A. Knopf, 2011.Hutchisson, James M. Ernest Hemingway: A New Life. University Park: The Pennsylvania State University Press, 2016.

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Drug Mechanisms and Reactions

Drug Mechanisms and Reactions Phase 1: Drug Metabolism The whole range of biochemical processes that occur within an organism, Metabolism consists both of anabolism and catabolism (the buildup and breakdown of substances, respectively). The biochemical reactions are known as metabolic pathways and involve enzymes that transform one substance into another substance, either breaking down a substance or building a new chemical substance. The term is commonly used to refer specifically to the breakdown of food and its transformation into energy. The liver is the principal site of drug metabolism. Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active sometimes even more than the parent compound. An inactive or weakly active substance that has an active metabolite is called a pro-drug, especially if designed to deliver the active moiety more effectively. Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization, whatever the process, the goal is to make the drug easier to excrete. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver. Drug metabolism rates vary among patients. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached, in others, metabolism may be so slow that usual doses have toxic effects. Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism). For many drugs, metabolism occurs in two phases: Phase I reactions: Which involve formation of a new or modified functional group or cleavage, these reactions are nonsynthetic. Phase II reactions Which involve conjugation with an endogenous substance, these reactions are synthetic. Metabolites formed in synthetic reactions are more polar and more readily excreted by the kidneys (in urine) and the liver (in bile) than those formed in nonsynthetic reactions. Some drugs undergo only phase I or phase II reactions, thus, phase numbers reflect functional rather than sequential classification. Phase I Drug Metabolism Phase I metabolism includes oxidation, reduction, hydrolysis and hydration reactions, as well as other rarer miscellaneous reactions. Oxidations performed by the microsomal, mixed-function oxidase system (cytochrome P450-dependent) is considered separately because of its importance and the diversity of reactions performed by this enzyme system. Classification of Phase I Reactions: Oxidation Reduction Hydrolysis Hydration Dethioacetylation Isomerization Oxidations involving cytochrome P450 (the microsomal mixed-function oxidase) The mixed-function oxidase system found in microsomes (endoplasmic reticulum) of many cells (notably those of liver, kidney, lung and intestine) performs many different functionalisation reactions. CYP 450: The cytochrome P450(CYP) enzyme system consists of a superfamily of hemoproteins that catalyse the oxidative metabolism of a wide variety of exogenous chemicals including drugs, carcinogens, toxins and endogenous compounds such as steroids, fatty acids and prostaglandins. The CYP enzyme family plays an important role in phase-I metabolism of many drugs. The broad range of drugs that undergo CYP mediated oxidative biotransformation is responsible for the large number of clinically significant drug interactions during multiple drug therapy. All of these reactions require the presence of molecular oxygen and NADPH as well as the complete mixed-function oxidase system (cytochrome P450, NADPH-cytochrome P450 reductase and lipid). All reactions involve the initial insertion of a single oxygen atom into the drug molecule. A subsequent rearrangement and/or decomposition of this product may occur, leading to the final products formation. (i) Aromatic hydroxylation: This is a very common reaction for drugs and xenobiotics containing an aromatic ring. In this example the local anaesthetic and antidysrhythmic drug, lignocaine, is converted to its 3-hydroxy derivative. (ii) Aliphatic hydroxylation: Another very common reaction, e.g. pentobarbitone hydroxylated in the pentyl side chain. (iii) Epoxidation: Epoxides are normally unstable intermediates but may be stable enough to be isolated from polycyclic compounds (e.g. the precarcinogenic polycyclic hydrocarbons). Epoxides are substrates of epoxide hydrolase (discussed later), forming dihydrodiols, but they may also spontaneously decompose to form hydroxylated products or quinones. It has been suggested that epoxide formation is the first step in aromatic hydroxylation. (iv) Dealkylation: This reaction occurs very readily with drugs containing a secondary or tertiary amine, an alkoxy group or an alkyl substituted thiol. The alkyl group is lost as the corresponding aldehyde. The reactions are often referred to as N-, O- or S-dealkylations, depending on the type of atom the alkyl group is attached to. (v) Oxidative deamination: Amines containing the structure -CH(CH3)-NH2 are metabolised by the microsomal mixed-function oxidase system to release ammonium ions and leave the corresponding ketone. As with dealkylation, oxidative deamination involves an intermediate hydroxylation step with subsequent decomposition to yield the final products. The product of the oxidative deamination of EPI or NE is 3,4-didydroxyphenylclycoaldehyde (DOPGAL). DOPGAL is subject to reduction to the corresponding alcohol (3,4-dihydroxyphenylethylene glycol, DOPEG) or oxidation to the corresponding carboxylic acid (3,4-dihydroxymandelic acid, DOMA), the latter being the major pathway. (vi) N-oxidation: Hepatic microsomes in the presence of oxygen and NADPH can form N-oxides. These oxidation products may be formed by the mixedfunction oxidase system or by separate flavoprotein N-oxidases. The enzyme involved in N-oxidation depends on the substrate under study. Many different chemical groups can be N-oxidised including amines, amides, imines, hydrazines and heterocyclic compounds. (vii) S-oxidation: Phenothiazines can be converted to their S-oxides (sulfoxides (SÂ ¼O) and sulfones (Â ¼SÂ ¼O)) by the microsomal mixed-function oxidase system. (viii) Phosphothionate oxidation: The replacement of a phosphothionate sulfur atom with oxygen is a reaction common to the phosphothionate insecticides, e.g. parathion. The product paraoxon is a potent anticholinesterase and gives the potent insecticide action as well as the toxicity in humans. Oxidations not catalysed by cytochrome P450 (Non-Microsomal) A number of enzymes in the body not related to cytochrome P450 can oxidize drugs. (i) Alcohol Oxidation by Alcohol dehydrogenase: This enzyme catalyses the oxidation of many alcohols to the corresponding aldehyde and is localised in the soluble fraction of liver, kidney and lung cells. This enzyme uses NAD+ as co-factor and is a true dehydrogenase. (ii) Aldehyde oxidation: Aldehydes can be oxidised by a variety of enzymes involved in intermediary metabolism, e.g. aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase (the latter two being soluble metalloflavoproteins). (iii) Oxidation by Xanthine oxidase: This enzyme will metabolise xanthine-containing drugs, e.g. caffeine, theophylline and theobromine, and the purine analogues to the corresponding uric acid derivative. Metabolic Reduction (i) Azo- and nitro-reduction can be catalysed by cytochrome P450 (but can also be catalysed by NADPH-cytochrome P450 reductase). (ii) Ring cleavage: Epoxides can be converted back to the parent hydrocarbon, e.g. benzo(a)anthracene- 8,9-epoxide whereas some heterocyclic compounds can be ring cleaved by reduction. (iii) Reductive defluorination: Fluorocarbons of the halothane type can be defluorinated by liver microsomes in anaerobic conditions. Metabolic Hydrolysis Esters, amides, hydrazides and carbamates can readily be hydrolysed by various enzymes. (i) Ester hydrolysis: The hydrolysis of esters can take place in the plasma (nonspecific acetylcholinesterases, pseudocholinesterases and other esterases) or in the liver (specific esterases for particular groups of compounds). Procaine is metabolised by the plasma esterase, whereas pethidine (meperidine) is only metabolised by the liver esterase. (ii) Amide hydrolysis: Amides may be hydrolysed by the plasma esterases (which are so non-specific that they will also hydrolyse amides, although more slowly than the corresponding esters) but are more likely to be hydrolysed by the liver amidases. Ethylglycylxylidide, the N-deethylated phase 1 product of lignocaine, is hydrolysed by the liver microsomal fraction to yield xylidine and ethylglycine. (iii) Hydrazide and carbamate hydrolysis: Less common functional groups in drugs can also be hydrolysed, such as the hydrazide group in isoniazid or the carbamate group in the previously used hypnotic, hedonal. Factors Affecting Metabolism Many factors can affect liver metabolism, such as: In aging, the numbers of hepatocytes and enzyme activity declines. Diseases that reduce hepatic blood flow like heart failure or shock can also reduce the metabolic potential of the liver. Also the use of other drugs as well as dietary and environmental factors can influence liver metabolic function. Metabolism can also be altered due to a genetic deficiency of a particular enzyme. Differences in metabolism that result from functional genetic polymorphisms can be accommodated by knowing the frequency of different genotypes, and by modifying either the enzyme abundance (null alleles, for example, in the case of CYP2D6 poor metabolizers) or the intrinsic enzyme activity (for example, CYP2C9 variants). Data on developmental changes in the abundance and activity of different CYPs can also be incorporated into the models to predict hepatic clearance in neonates, infants and children. Conclusion Metabolism is the breakdown of Drugs inside the body, to disable their activity, forming inactive metabolites, however some drugs are either not affected by metabolism or activated by it, some even form toxic metabolites Examples: Imipiramine not affected by metabolism: Paracetamol produce Toxic Metabolite Metabolism occurs in two phases, Phase I Metabolism, and Phase II Metabolism. Phase I Metabolism converts the drug into metabolite by formation of a new functional group or modifying it, while phase II Metabolism or reactions involve conjugation with indigenous substance. Phase I Reactions Include: Oxidation, reduction, hydrolysis and hydration reactions, and other rare miscellaneous reactions. Oxidation can be divided into Microsomal or non Microsomal according to whether it involves mitochondrial CYP 450 enzymes. Oxidation involves: Microsomal Aromatic Hydroxylation, Aliphatic Hydroxylation, Epoxidation, Dealkylation, oxidative deamination, N- oxidation, S-oxidation and Phosphothionate oxidation. Non-Microsomal Alcohol Oxidation by Alcohol dehydrogenase, Aldehyde Oxidation and Oxidation by Xanthine oxidase. Reduction involves: Azo- and nitro-reduction, Ring cleavage, Reductive defluorination Hydrolysis involves: Ester hydrolysis, Amide hydrolysis, Hydrazide and carbamate hydrolysis

Analysis of Marrysong Dennis Scott Essay

Then Scott having to ‘chart’ – suggesting the creation of a map in order to discover his wife, this emphasises the exploration of this ‘new-found-land’. The poem suggests an unsure attitude, as we see in the first line, ‘year after year’ we don’t know whether this suggest a long, drawn out relationship that could become dull, or whether this means he is happy, and the year after year suggests commitment. Time takes a prominent role in the poem, with what is described as ‘year after year’ is then shortened to passing ‘seasons’ then shrunk still to an ‘hour’ until the shifting of moods becomes sudden, ‘suddenly she would change’. This suggests confusion within the relationship for Scott, as the changing of her attitudes becomes unexplainable and undetectable. This unpredictability leads us to the point of the heavy use of ‘enjambment’ in the first five lines, painting a vivid picture of uncertainty for Scott; conversely, as the poem progresses, we see a much more structured approach. On the contrary, the poem as a whole is generally lacking in structure. The constant use of caesurae, which breaks lines using pauses, denoted by commas and full stops. Also, the stutter of ‘[a]ll, all’’ disrupts the flow of the poem much like the punctuation mentioned. This disruptiveness also contributes to the uncertainty of Scott within the marriage. However, as we approach the concluding lines of the poem Scott evokes a discovery of certainty. He says ‘accepting her geography’ and stating that he ‘wondered’ which maybe suggests that he has no need to wander anymore. This final couplet also features a rhyming final two lines, which suggests stability and an atmosphere of certainty. The oxymoronic use of ‘jaunty helpless journey’ suggest that Scott is at his lover’s mercy; this is significant, as the whole poem conveys the idea that the woman dominates the relationship, and that Scott is exploring her and trying to figure her out. At the beginning of the poem we see that Scott says that she is under control by saying ‘under his eye’, this oxymoron features near to the end of the poem and, with numerous time frames being described in the lines between these two phrases, seems to suggest that after all this time he still has not been able to work her out or even gain control of their relationship. Conversely, this contrasts with the following two lines in which Scott is stated to have figured her out ‘find his way among the landscapes of her mind’. The fourth line, ‘in the walled anger of her quarried hurt’ takes a prominent role within the poem. The use of ‘walled’ and ‘quarried’ suggests an inescapable ‘territory’ into which Scott seems to be stuck. ‘Quarried’ also suggests that Scott is trying to unearth her personality, with ‘walled’ being the defensive behavior with which he does this. Love is a dangerous unreliable territory seems to be one of the main themes evoked by the poem. We see that Scott is continuously trying to gain power in the relationship. This seems to be unobtainable throughout the poem, however the title in itself reveals a childlike innocence about Scott; ‘Marrysong’ isn’t really a word, and sounds like a word a child would make up. It also evokes the bewildering nature of love and the complexity of marriage. Ovid: Ars Amatoria 1. 469-78 states that ‘dura tamen saxa’ (nonetheless, hard rocks) ‘molii cavantur aqua’ (are hollowed out by soft water). At one stage of the poem Scott states that one can see ‘cool water laughing where the day before there were stones in her voice’ – Scott maybe saying that the water hollowed out the rocks and overcame the rocks to make way for love. Furthermore, in relation to territory, Ovid states that ‘capta vides Pergama sero capita tamen’ (You can see that Troy was captured after a long delay, but she was captured in the end) relating to Scott claiming that his lover’s logic is like a territory needing to be explored, and the references of time relate to Ovid stating that Troy was captured ‘after a while’.