Hydromorphone

Hydromorphone The name of the drug is called Hydromorphone. The systematic name (IUPAC) is 4,5-epoxy-3-hydroxy-17-methylmor-phinan-6-one. Hydromorphone has a chemical formula of C17H19NO3 . There are four functional groups in Hydromorphone: An Ether group A Ketone group An Amine group (tertiary) A Phenol group Stereochemistry and conformation: Hydromorphone has 4 chiral centres (Four different groups attached to a sp3 hybridised carbon one chiral centre). Therefore it has 24 = 16 stereoisomers. Carbon number 1 has R-configuration Carbon number 2 has R-configuration Carbon number 3 has S-configuration Carbon number 4 has R-configuration Hydromorphone is a semi-rigid molecule because it is composed of a five-member ring system: the phenolic ring (A), the cyclohexane ring (B), the cyclohexanone ring (C), the N-methyl piperidine ring (D), and the tetrahydrofuran ring (E). The molecule has a T shape. Rings A, B and E form a vertical plane where the C and D form the horizontal plane. Ring C exists in a chair conformation due to saturation of C-C double between C7 and 8. Ring D also exists in chair conformation. Synthesis: Commercially, Hydromorphone is made from morphine via either direct rearrangement (reflux alcoholic or acidic aqueous solution of morphine with platinum or palladium catalyst) or reduction of morphine via catalytic hydrogenation, this two reactions both produce Dihydromorphine. The Dihydromorphine then undergo Oppenauer oxidation, where it is oxidised with benzophenone in the presence of potassium tert butoxide or aluminium tert butoxide to form Hydromorphone. Drug stability: The half-life of Hydromorphone is 2.6hours through oral route, where it takes 18.6 hours for sustained release Palladone. Hydromorphone hydrochloride is affected by light, although hydromorphone hydrochloride injection may develop a slight yellowish discoloration, this change does not indicate loss of potency. Hydromorphone hydrochloride injection should be protected from light and stored at a controlled room temperature of 25 degrees C, but can be exposed to temperatures ranging from 15 to30 degrees C; freezing of the injection should be avoided. Hydromorphone hydrochloride tablets should be stored in tight, light-resistant containers, usually at 15 to30 degrees C; however, the manufacturer recommends that the 8-mg tablets be stored at 15 to 25 degrees C. Hydromorphone hydrochloride oral solution should be stored in light-resistant containers at 15 to 25 degrees C, and suppositories of the drug should be stored at 2 to 8 degrees C. Hydromorphone hydrochloride injection reportedly is physically and chemically stable for at least 24 hours in most common IV infusion solutions when protected from light at 25 degrees C. Hydromorphone is slightly soluble in water, freely soluble in alcohol and very soluble in chloroform. Formulation and packaging: In the U.K. Hydromorphone is only available in form of oral capsules and modified release capsules, which means it is released slowly to extend the length of the drugs effect. Available strengths for hydromorphone hydrochloride (Palladone ®): 1.3mg (orange/clear), net price 56-capsules pack =  £8.82; 2.6mg (red/clear), 56- capsules pack =  £17.64. Where for the modified (release Palladone ® SR): m/r, hydromorphone hydrochloride 2mg (yellow/clear), net price 56- capsules pack =  £20.98; 4mg (pale blue/clear), 56- capsules pack =  £28.75; 8mg (pink/clear), 56- capsules pack =  £56.08; 16mg (brown/clear), 56- capsules pack =  £106.53; 24mg (dark blue/clear), 56-cap pack =  £159.82. [BNF 56 page 235-236]. Lipinskis Rules: The molecular weight of Hydromorphone is 285 g/mol. (below 500) The Log P of Hydromorphone is +1.69. (lower than +5) There is only one hydrogen bond donating group, which is the hydroxyl group in Phenol. (less than 5 groups) here are only three hydrogen bond accepting groups. (less than 10 groups) The functional groups are generally stable to metabolism, i.e. hydrolysis and oxidations. According to the Lipinskis rules of five, Hydromorphone is an orally active drug. LogP and discussion of hydrophobic/hydrophilic properties: It is possible to predict the Log P of a molecule by using the Hydrophilic-Lipophilic Values (p Values) for organic fragments. This gives (+0.5 x 11) + (+2 x 1) + (-1 X 3) + (-1 X1) = +3.5. Therefore, the Predicted LogP = +3.5. Since 3.5 is greater than 0.5, hydromorphone is insoluble in water. (Soluble in water if smaller than 0.5) According to the predicted LogP, Hydromorphone is a very hydrophobic (lipophilic) drug and it can pass through the membrane layers in cell and enter the bloodstream (high absorption). Hydromorphone is insoluble in water because of its non-polar groups. They are: The long aliphatic and aromatic hydrocarbons, i.e. cyclohexanes and the phenyl group. These non-polar groups will not interact with polar water molecules as they cannot form hydrogen bonds together and therefore insoluble. pKa and ionisation state: Hydromorphone has a pKa of 8.2 at 20 degrees C [Medicine Complete], it is weakly acidic. To calculate the percentage of ionization of Hydromorphone (weak acid) at different pH, Equation 1 can be used: Equation 1 % ionisation= 1001+antilog(pKa-pH) At pH 2: % ionization = 1001+antilog(8.2-2) = 6.31 x 10-5 % At pH 7.4: % ionization = 1001+antilog(8.2-7.4) = 13.7% At pH 10: % ionization = 1001+antilog(8.2-10) = 98.4% From the calculations on the previous page, I can conclude that only 6.31 x 10-5 % of hydromorphone is ionized at pH 2, i.e. in the stomach. Therefore, there are 100% 6.31 x 10-5 % = 99.9999% of unionised Hydromorphone which can pass through the membrane barrier and enter the bloodstream. Hydromorphone is highly absorbed by the body in stomach. Mode of action: Hydromorphone is an opioid analgesic; it reacts with the opioid mu-receptors. The mu-receptors are discretely distributed in the human brain with high density in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. These receptors are also found in the spinal cord and gastrointestinal tract. It binds onto the mu-receptors and exerts its principle pharmacological effect on the Central Nervous System and gastrointestinal tract to produce analgesia and sedation. Hydromorphone is highly absorbed by the human body and it shows the analgesia effect very quickly once enter the body. It is 8 to 10 times stronger than morphine due to its hydrophobicity (very lipophilic). Bibliography: Samuel, B., Stanley,G., Robert, R. (2004), Process for the Synthesis of Hydromorphone, http://www.wipo.int/pctdb/en/wo.jsp?WO=2006005112IA=AU2005001002DISPLAY=DESC, Date accessed 23/04/10. Author unknown. (Date unknown), One-pot Isomerization of Morphine to Dihydromorphinone (Hydromorphone), http://www.erowid.org/archive/rhodium/chemistry/dihydromorphinones.html, Date accessed 23/04/10. Author unknown.(2006), Hydromorphone, http://www.patient.co.uk/medicine/Hydromorphone.htm, Date accessed 23/04/10. Hildebrand, K., Elsberry, D., Anderson, V. (2001), Stability and Compatibility of Hydromorphone Hydrochloride in an Implantable Infusion System, Journal of Pain and Symptom Management, 22 (6), Page 1042-1047. Author unknown. (2010), Hydromorphone Suppository, http://www.drugs.com/cdi/hydromorphone-suppository.html, Date accessed 24/04/10 Lipinski, C. (2004), Lipinskis rule-of-five, http://www.bioscreening.com/reference/lipinski_rule.htm, Date accessed 24/04/10. Author unknown. (2009), Showing drug card for Hydromorphone (DB00327), http://www.drugbank.ca/drugs/DB00327, Date accessed 24/04/10. Clarkes. (2006), Clarkes Analysis of Drugs and Poisons Hydromorphone, http://www.medicinescomplete.com/mc/clarke/2009/CLK0851.htm, Date accessed 24/04/10. Author unknown. (2008), Monograph Hydromorphone Hydrochloride, http://www.medscape.com/druginfo/monograph?cid=meddrugid=11338drugname=Hydromorphone+Rectmonotype=monographprint=1, Date accessed 24/04/10. BMJ Group,. (2008). British National Formulary 56, London, RPS Publishing. Bruice, P,. (2004). Organic Chemistry, Fourth Edition,Prentice Hall ,Pearson. Lo,K,. (1998) Synthesis of N- Phenethylnorhydromorphone, https://circle.ubc.ca/bitstream/handle/2429/11862/ubc_2001-0456.pdf;jsessionid=8D12F28D380E801AE9A422C0F9CD3435?sequence=1, Date accessed 26/04/10

Essay --

To Russians the word food means very much, their whole world revolves around food. Russians always eat three times a day and each one of those meals is huge. They start off their day with breakfast, which mostly consists of kasha – (a type of porridge made from different grains) sometimes they could make a buterbrod which is a type of sandwich that consists of one slice of bread and one topping they could also make some eggs or just have a cup of coffee with cheese. To Russians the more important meals are lunch and dinner. For lunch Russians eat a lot which mean that they will usually have hot soup as the first course and then potatoes or pasta with salad as the second, which then leads to third course, which is usually something sweet. Dinner is another important meal of the day because that is when the whole family sits together to eat discuss their day and watch some TV at the same time. A typical Russian dinner consists of a table full of food. For dinner everything usu ally is taken out of the fridge what Russians snack on before the main dish is ready. There will always be a salad and snacks like salami slices, cabbage, vegetables, bread etc. Main dish is usually meat with potatoes or fish. In Russia, there is never any meal without bread on the table. There are special feelings that Russians have towards rye bread Russians call it "black" bread because of its dark color. "Black" bread is considered a traditional food in Russian homes. When it comes to drinks even though Russia is mostly known for vodka, Russian traditional drink is Kvass - a fermented beverage made from rye bread. Kvass has very low alcohol content in it which hardly reaches to 1% and therefore it is enjoyed by everybody even kids. This bubbly dink is ... ...ue by the ingredients that are used to make food. But also because of the way the make their food the old famous Russian stove. The stove was used to make food in and heat up houses. Russians used to sleep on the stoves as well because it was always so warm and that was the only heat that was provided to them. The food prepared in stoves was so delicious because of the way it was made, heated from all sides inside the stove. Even though there are still house with stoves unfortunately Russian stoves are not being used anymore even in the villages. Electric stoves and microwave ovens have replaced them today but the food still remains delicious. Russians have always been very passionate about food, at the family gatherings especially, the amount of plates of food could reach up to 150 different appetizers. Nobody ever leaves a Russian house hungry or unsatisfied.

When Did The Nazis Decide On Genocide? Critically Discuss With A Focus On The Jewish Population Of Europe

Introduction The current essay examined the question of when the Nazis decided on genocide with a specific focus on the extermination of European Jewry. While it is difficult to pinpoint a precise date for the commencement of the Final Solution, this essay suggests the policy was decided upon by high ranking Nazis in 1941 and, finally, legally codified in 1942 in the Wannsee Conference. The Confluence of Several Dangerous Ideas No political idea simply becomes government policy overnight; rather, the process from one to the other occurs in complex ways. Indeed, the critic Christopher Browning, who penned an entire book titled The Origins of the Final Solution (2005), broadly concludes that there is no specific origin or beginning point, as such. As Browning puts it, â€Å"there is no clear and unambiguous dividing line between origins and implementation that would be valid for all regions of Europe under German occupation†. For this reason, trying to pinpoint the precise moment that the Nazis, so to speak, decided on genocide is problematic. For instance, if we wish to identify the senior level administrative policy decision on the Final Solution, we may reasonably cite the 20th of January 1942 as a key date: this was the date of the Wannsee Conference, whereat the â€Å"policy agreement† for the â€Å"Final Solution of the European Jewish question† was formulated, thereby outlining â⠂¬Å"the procedural guidelines for the future exterminations for physically healthy Jews were laid down once and for all†. (The procedure in question was liquidation via hard labour.) Yet manifold instances and legal rulings prior to this admittedly significant moment testify to a good deal of genocidal forethought long in advance of the Wannsee Conference. One of the primary critical difficulties in unlocking the truth behind the Nazis’ policy of genocide is the cloak of euphemism the Reich upheld to conceal the reality of their dreadful actions. â€Å"Final Solution† is itself a euphemism, as is (or, perhaps better to say, was) the term â€Å"concentration camp† (standing in for â€Å"extermination camp†). Because the Nazis employed a discourse of obscurity in their legislative pronouncements, it can be difficult to get to the truth of the matter. As it happens, the difference between what official Nazi language would suggests and what historical f acts prove to be the case represents a vast semantic gulf. Although it is hard as a contemporary reader to distance oneself from the connotations of the term â€Å"concentration camp†, one should bear in mind the extremely different implications this term evokes as compared to â€Å"extermination camp†. Such semantic dissonance is rife in Nazi legislature and official Reich discourse. As a result, scholars note the â€Å"appearance of contradictions between policy and practice†: an issue which can be explained with reference to â€Å"the euphemisms used† to â€Å"cloak† major implementations of liquidation programmes. While 1942 may be described as the year in which the formal decision was taken and, in effect, made policy, there are good grounds to mark 1941 as the year in which an integral Party decision was taken: that set the course for the systematic extermination of European Jewry. As a consequence, the scholar Richard Breitman argues that th is was the year in which the â€Å"fundamental decision to exterminate the Jews† was made; and that, in direct consequence of this decision, â€Å"the Final Solution was just a matter of time – and timing†. The Final Solution was at this inception stage targeted very specifically at European Jews. This is to do firstly with geographical reasons. Germany as a European country bordering on a number of other European countries was more directly in contact with European Jews than those from other continents. While the Nazis’ official hatred for the Jews was not in theory localised (indeed, Hitler despised the Jews as a race, as opposed to a religion on nationally heterogeneous people), in practice the European Jews felt the brunt of its brutality. This very likely had a lot to do with Hitler’s bearing a specific resentment for German Jews (a distinction which the Fuhrer tried to negate), whom, for various and highly dubious reasons, he blamed for causi ng Germany to lose the First World War. Interestingly, there is some debate as to how much Hitler actually knew about the Final Solution and all its grisly details. In this regard, an entry from Goebbels’s diary recounts an episode from December of that year. Hitler had gathered all the highest ranking Nazi officials to his Berlin apartment for a special meeting, the Reichsleiter and Gauleiter. The journal runs: â€Å"Concerning the Jewish question, the Fuhrer is determined to make a clean sweep. He prophesied to the Jews that if they were once again to cause a world war, the result would be their own destruction†; Goebbels goes on to affirm that the latter ominous assertion was â€Å"no figure of speech†. Indeed it was not; the policy was already underway. This commenced with the 1941 invasion of the USSR, whereupon was witnessed the â€Å"crystallisation of a general policy of killing†. At the same time, large numbers of Jews from Easter and central Eur ope were being shipped out to camps, with fatal intent. Conclusion The aforementioned obliqueness of Reich discourse makes it impossible to say for sure how informed and involved Hitler was in the Holocaust; how and when the decision for genocide was made. But we may nonetheless posit an informed surmise. By the end of 1942, the evidence clearly indicates, Hitler knew exactly what was going on and was fixed on a course of action: genocide. References Bloxham D, Kushner T, Kushner A R J, The Holocaust: Critical Historical Approaches (Manchester University Press, 2005). Breitman R, â€Å"Plans for the Final Solution in Early 1941† (1994) German Studies Review, 17, 483-489. Browning C, The Origins of the Final Solution (Arrow Books, 2005). Cesarani D, The Final Solution: Origins and Implementation (Taylor and Francis, 2002). Falk A, Anti-Semitism: A History and Psychoanalysis of Contemporary Hatred (Praeger, 2008). Fleming, G. Hitler and the Final Solution (University of California Press, 1991). Kerr J, Germany, 1919-1939 (Heinemann, 2003).

Insomnia Literature Review Essay - 1006 Words

Insomnia Insomnia affects almost half of adults living in America. (# 8, 2012) This is a shared sleeping disorder that many people across the universe are diagnosed with. Several causes of insomnia include exercising too much, stress, withdrawal from alcohol or a certain drug, physical circumstances, and diseases. People with insomnia usually have trouble going to sleep or staying asleep, which causes people to have poor-quality sleep, which will affect their mood, energy, and productiveness for the next day. (MediLexicon, Intl., 2012) More symptoms of insomnia include waking up earlier than needed, having trouble falling back asleep, and being in a bad mood the following day. Insomnia can cause many more problems such as weight†¦show more content†¦A few of the articles that were used in studying this disorder agreed that sleeping more at night could help those people lose weight. One article that was used said that sleeping pills and tranquilizers could increase a person’s risk of death, (#4, 2010) while another article used in this research said that prescription pills could be used to prevent insomnia. (MediLexicon, Intl., 2012) With the research that is currently being put towards this disorder, researchers should start to agree more on insomnia and ways to prevent or cure it. An article that was used made the statement that pills prescribed or bought OTC to cure or prevent insomnia can actually increase a person’s risk of death. (#4, 2010) Heath Ledger’s death in 2008 caused a lot of confusion and curiosity as what sleeping pills are really doing for people. When an autopsy returned after Ledger’s death, the results showed that he had Xanax, Valium, Restoril, and several other drugs to aid his insomnia, anxiety, and depression. With this outcome, it is safe to say that mixing prescription medicine and multiple amounts of those medicines could be fatal. 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