Pharmacology Pharmacokinetics Pharmacodynamics History And Development Biology Essay

Pharmacology Pharmacokinetics Pharmacodynamics History And Development Biology Essay The hemp plant cannabis sativa, versatile plant named by Swedish botanist Linaeus in 1735 originated in Central Asia has been widely distributed around the world. The earliest use of the drug has been known to be in existence since 700 BC in Assyrian tablets drug finding its place even in the British Pharmaceutical Codex, as late as 1949(G. Geoffrey, W. Brain and R. Philip;2004). Cannabis is an annual dioecious developing from seed, fast growing plant which reaches the maturity in 60 days. It has a lance shaped leaflets with saw tooth edge with woody angular hairy stem with a height of 50 ft or more. Cannabis indica is smaller subspecies it a height of 4 feet other varieties are obtained by crossing cannabis sativa and cannabis indica. Cannabis is used as psychoactive drug. Around 20 million people in USA and Europe and many other part of world use cannabis on a regular basis although consumption is illegal in most of the countries. The psychoactive ingredient of cannabis is delta-9-tetra hydrocannabinol (THC). Cannabis is also known by the names like marijuana, hashish, charas, bhang, ganga and sinsemilla among this hashish and charas are most potent with THC content 10 20%. High concentration of THC can be found in the fine droplets of sticky resin produced by glands at the base of the fine hairs that coats leaves and flower heads (J. Robert,A primer of Drug Action; 1998). Fig 1 Cannabis sativa (http://ja.treknature.com) Fig 2 Cannabis tincture (http://www.medicalmarijuanacure.com) History and Development of Cannabis Fig 3 (M.D. Vincenzo; 2006) Chemistry of THC: Chemical structure of THC was elucidated in 1964; thereafter many chemical analogues have been synthesized and tested. Phenolic hydroxyl group(C-1) is for cannabiniol activity, side chain(C-9) is important as potency can be increased by increase in chain length, also methyl group substitution at side chain carbon adjacent to aromatic ring and northern aliphatic hydroxyl group enhances the activity of THC.THC was isolated during the world war II from red oil fraction of cannabis and other optically active component isolated was cannabidiol. ( G. Geoffrey, W. Brain and R. Philip;2004) Fig 4 Structures of delta-9-tetra hydrocannabinol(THC) IUPAC Name: (à ¢Ãƒâ€¹Ã¢â‚¬  )-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H- benzo[c]chromen-1-ol Molecular weight: 314.45 daltons. Formula: C21H30O2 Pharmacology (Cannabiniod receptor): First cannabinoid receptor was identified in 1990 which lead to further studies. In central nervous system cannabinoid receptor are found in G-proteins with seven transmembrane spanning segments which are strongly expressed in basal ganglia, cerebellum and hippocampus, at higher concentration expressed on afferent spinal cord regions and at lower concentrations at brain stem it has a chain of 473 amino acids with a hydrophobic domain (B. David, P. Gareth, G. Gavin, and T. Alan; 2003).Second receptor (CB2) is expressed by leucocytes and in haemopoeitic development. Endocannabiniods have cannabinoid receptor binding activity and function of the endocannabinoid system is to regulate synaptic neurotransmission. First endocannabiniod was observed in 1992 by Devan and co-workers from porcine brain which was anandamide it showed behavioural, hypothermic, and analgesic effects similar to that of cannabinoids many other are found in central nervous system (CNS) but exact physiological roles a re not yet know ( L.A.Matsuda, S.J. Brownstein, et al;1990). Fig 5 CB expression on brain. (B. David, P. Gareth, G. Gavin, and T. Alan; 2003) Pharmacodynamics: Effects of THC on CNS studies shows impairment in learning, psychomotor performance and associative processes. Heavy users showed impairment in attention and à ¢Ãƒ ¢Ã¢â‚¬Å¡Ã‚ ¬Ãƒâ€¦Ã¢â‚¬Å"amotivationalà ¢Ãƒ ¢Ã¢â‚¬Å¡Ã‚ ¬Ã‚  syndrome with chronic use of marijuana(R.I. Block, R. Fairnpour, and K.Braverman;1998). Commonly seen physiological effects on cardiovascular system are increased blood pressure, heart rate with dry mouth, dizziness and slight nausea(H.G.Pope and D.Yurgelun-Todd;1996). Long-term use leads to immunosuppression of immune system, also Cannabiniod receptors inhibit intracellular adenylate cyclase second-messenger system resulting into decrease spleen cell liberation on immune response and increase the susceptibility of infections or disease. Chronic use results into reduction in fertility and sexual potency in the individual.( P.A. Fried;1995). THC readily passes through placenta and affects the new born with visual perception, language comprehension and frequent me mory loss. ( M.A. Huestis, A.H. Sampson, B.J. Holicky, et al;1992) Pharmacokinetics: Most commonly cannabis is taken by smoking which is through inhalation followed by rapid absorption from lungs into the bloodstream though bioavailability is less (10-27%).Oral administration has plasma levels much lower compared to Intra-venous infusions and inhalation this is due to first pass metabolism in the liver resulting in to poor bioavailability. Bioavailability is higher by sublingual and rectal administration. Cannabinoids are lipophilic in nature (log Kow=7.4) and gets widely distributed in brain, kidney, liver and fat with steady release in the blood,90% of cannabinoids are bound to plasma proteins and 10% to red blood cells( M. Wahlqvist, M.I. Nilsson, F. Sandberg, S;1970). Phase I metabolism of cannabinoids is catalysed by cytochrome P450 in liver with oxidase system. Majority of THC metabolites are excreted in faeces (65%) and rest in urine through glucuronide conjugates (M. Bornheim and A. Correia;1989). Tolerance and dependence: The long known use of the drug has not really given a clear scientifically proven picture that the drug or the derivatives of the plant are beneficial for therapeutic purposes (A. Duffy and R. Milin; 1996). Although there are no severe dependency problems, on the hind side, the toxic nature of Cannabinoids, has also seen increased heart rate, lowering of blood pressure, euphoric intoxication and toxic psychosis resulting from a loss of cognitive performance. Extensive clinical trials over the years have seen the drug being classified into lesser harmful categories, classified into Schedules from 1 to 3, with 3 being of least harm (C. P. OBrein; 1995). Funded by Medical Research Council, the research includes testing on 660 patients over a time period of 3 years. Another research involves 400 patients who would be treated with different forms of cannabis plant and compared with conventional analgestics. The trails are supported by nations like UK, USA, Switzerland, Germany with each country supplying the distinct Cannabis extracts. Another trial in UK is for treatment of multiple sclerosis and other neurological disorders and use a sub-lingual spray as the method of drug delivery. Each of the manufactured extract needs to comply with the Good Manufacturing Practice(s) that oversees selection of plant material, solvent used, and the entire processing itself. (C. P. OBrein; 1995). Analytical Methods: Initial screening of drug of abuse is generally carried out by immunoassay and confirmation of the results is done using chromatographic methods. Radioimmunoassay is generally used for detection cannabinoids in the biological samples. Gas chromatography (GC) is most frequently used analytical method to analyse product but due to decarboxylation during the analysis in neutral forms determination of acidic cannabinoids is not possible. High speed liquid chromatography (HPLC) method used for determination of composition of cannabinoids is one of the efficient and the simplest way to elucidate major cannabinoids but overlapping of peaks is a concern (Y. Ruiqin, X. Wenlin;2006). Though combination of mass spectroscopy and HPLC rectifies errors due to overlapping of peaks and combination of HPLC/GC can produce effective analysis. (B. Benjamin, D. Benjamin, L.Pierre, T.Laetitia, D.Nathalie, D.Lies, V. Alain, H. Philippe, C.Corinne,Innovative; 2009). Fig 6 GC chromatogram of a standard solution of D9-THCA-A analysed (F.E. Dussy et al; 1996) Fig 7 HPLC chromatogram of THC recorded at 220nm (F.E. Dussy et al; 1996) Small amount of sample can be reused with simple operation using solid-phase micro-extraction (SPME) to study cannabinoids followed by GC/MS for target molecule confirmation and determination presence of THC in saliva and hair using SPME-GC/MS can be determined (F.E. Dussy et al;1996).LC-IT/MS is used for quantification and conformation of various cannabinoids in a single method though this method is cost effective so use is limited.(A.A.M. Stolker, J. van Schoonhoven, A.J. de Vries, I. Bobeldijk-Pastorova, W.H.J. Vaes, R. van den Berg;2004) Legalization: The legal position held on this drug is still in a state of confusion with no conclusive evidence on the actual therapeutic effects it has. Many countries have softened their stand on the punishment for possession of cannabis, with Netherlands going to the extent of decriminalizing soft drugs in 1976. Belgium followed suit, with the clause that it should not lead to social nuisance, risks and problematic consumption. The USA took a U turn to prohibit the drug due to not enough evidence after certain states allowed the use of the drug for medicinal purposes. Canadian law allows the usage of drug for exceptional cases of patients with prior support from the medical practitioner. Due to its activity on the nervous system, the drug has primarily been used in medicinal treatment of muscle spasms, menstrual cramps, rheumatism, tetanus convulsions, rabies and epilepsy with the current day applications being witnessed in treatment of anorexia, bronchial asthma, epilepsy, glaucoma, hypertension, muscle spasticity, nausea, vomiting and pain. But these applications have just fetched two licensed cannabinoids for medicinal purpose THC (Marinol) and Nabilone, both of which are synthetic (A.C.Moffat; 2006). Conclusion: The Cannabis plant (Cannabis sativa.) is used as recreational drug with a long history and is a part of traditional medicine from the past. The relatively recent discovery of cannabinoid receptors and the human endocannabinoid system has opened up a new and exciting field of research. Bioavailability is obtained by rectal and sublingual administration and rapid absorption takes place with intra-venous and inhalation. But despite the potential, cannabis is categorized as a narcotic drug it is prevented to develop into modern medicine. Dependence and addiction to this drug is quite rare. Psychoactive cannabinoid tetrahydrocannabinol (THC) has received great attention, and much is known about its biological effects and mechanisms of action, analytical methods, pharmacokinetics, and structure-activity relationships, it will be a challenge to see cannabis as a routine medicine for various disorders.

Gatsbys Dream and Daisys Conflicts in The Great Gatsby by F. Scott Fi

Gatsby's Dream and Daisy's Conflicts in The Great Gatsby by F. Scott Fitzgerald Jay Gatsby, the central character of F. Scott Fitzgerald?s The Great Gatsby symbolizes the American dream. The American dream offers faith in the possibility of a better life. Its attendant illusion is the belief that material wealth alone can bring that dream to fruition. Through Gatsby, Fitzgerald brings together both these ideas. Jay Gatsby thinks money is the answer to anything he encounters. He has the best of everything. The fanciest car, the largest house, and the finest clothes. Jay has everything except the object he most desires, Daisy. Gatsby believes he can win Daisy over with wealth, that he could achieve the ideal she stood for through his material possessions. One look at Gatsby?s past and it could be seen that he was destined to get ahead in life. Mr. Gatz told Nick, ?Jimmy was bound to get ahead. He always had some resolves like this or something. Do you notice what he?s got about improving his mind? He was always great for that. He told me I et like a hog once and I beat him for it? (182). Gatsby?s determination to gain a large bankroll is a huge part of the American dream. He believes that once he achieved his financial goal it would lead to a better life. In America, the car is one of the greatest status symbols. Gatsby?s gorgeous machine is one of the most majestic cars created. Nick?s comments on the vehicle describe its luster, ?...and there in its monstrous length with triumphant hatboxes and supper-boxes and tool-boxes...Sitting down behind many layers of glass in a sort of leather conservatory we started towards town? (68). The use of the symbolic automobile can be seen as a demonstration of how a... ...ul. When he met Daisy, his dream was to be on a level with Daisy, and to show her what he had and to buy her love with materialistic things. This did not go off without a hitch, for Daisy had married Tom, and with that came love for him. Although Daisy told Gatsby she loved him, there was still her affection for Tom. The way the conflicts created by Daisy help the theme are numerous. The most significant way is that she is the central corruption of Gatsby?s dream. The dream began as a simple bid for happiness, yet Gatsby was corrupted by money. He wanted money, and he believed that money would make him happy. When he became rich, his dream then became focused upon Daisy. Daisy was the only thing (or at least he thought) between him and happiness. Bibliography: Fitzgerald, Scott F. The Great Gatsby. Simon and Schuster, New York. 1925.

Do the Right Thing (Spike Lee) Film Analysis

Color Evokes Emotion Spike Lee, the director of Do the Right Thing (1989), makes sure the audience understands how the heat is affecting the characters on the day the film takes place, and to do this he uses color. To subtly express how heated, physically and metaphorically, the characters in the film are, Lee uses warm colors such as red and orange. Likewise, he rids the presence of warm colors and uses cool colors such as blue and white in order to signal to the audience that things have cooled down and the atmosphere has a more loving vibe . From beginning to end Lee makes sure that the audience is aware of the temperature outside.The film uses the words hot and heat a countless number of times throughout the movie, but Lee also uses visuals to engage a sense that is not generally used to identify with temperature . The color red is present in the clothes that the characters wear, the buildings the characters live in and are in front of, and it is the color of numerous props in th e film. For instance, the hottest location in the film, the Pizzeria, had tabletop items, small decorations on the seats and walls, and even the color of the brick oven were a very vivid red that really stood out.The same subtle usage goes for the color orange, but in addition street lights are an orange color, and there is a eye-straining orange tint to the entire film. Lee uses these warm colors to allow the audience connect with the characters, and helps them feel the frustration the heat adds to the already riled up characters. The presence of these heated colors also help enhance the notion of heat, for this film, representing the tension amongst the different races, and the minorities towards the whites. During the climax of the film the Pizzeria is set into flames, and its heavy orange glow is reflected on the faces of Sal and his sons.In the couple of scenes where tension is not so high, and people are not completely suffering from the heat, Lee removes the orange tint and w arm colors and instead replaces them with cool tone colors such as blue and white. Specifically, in the scene where the two boys unscrew the fire hydrant and use its water to entertain and cool off the people of the neighborhood the audience will notice an absence of the orange tint and the presence of people wearing blue and white. This cooled down scene is then interrupted and upset by a white man driving a car that happens to be red.Lee also uses the cool toned colors to show love. When the main character, Mookie, and his baby’s mother, Tina, are having an intimate moment he has her remove the clothes she has on which happen to be warm colors. Similarly, when he goes to the freezer to retrieve an ice cube his son and Tina’s mom are in there, both dressed in blue shirts. Taking away the warm colors and orange tint allows the audience to feel the same kind of sense of relief as the characters feel in theses scenes. Lee’s usage of color is to help the audience f eel, on a deeper level, what the characters in the film are feeling.Whether it be from the actual heat of the sun or the heat produced by the tension in the neighborhood and with â€Å"the man†. The most tension and hate filled moment in the film is topped off with a fire burning bright oranges and reds. Lee also made sure to allow the audience to experience more than just hate (or heat) by including scenes that did not have an orange tint or warm colors, but instead cool colors. Lee successfully appealed to the audience’s feelings through the use of colors and made sure they could connect with the characters more personably.

Charles Beard’s Article, Framing the Constitution

Charles Beard’s article, Framing the Constitution, alleges the members of the Constitutional Convention in Philadelphia were â€Å"disinterested† in providing basic rights for citizens. He stated that the framers of the Constitution of the United States were only concerned in improving their own economic well–being and personal agendas. Therefore, providing information of the events that led up to the Philadelphia Convention and an overview of the Constitution will dismiss his statements, and state his article was a self-serving, conspiracy theory. The Articles of Confederation of 1781 produced the first endeavor of government structure. This attempt of forming a national and state government failed. Some of the issues that transpired†¦show more content†¦While examining the Constitution, it was concluded a new document was imperative for the welfare of the nation. There were seven Articles established in the Constitution of the United States. The fi rst three Articles dealt with the separation of powers. A three branch, federal government was formed along with checks and balances. This format promoted the equalization of power among each entity. The Fourth Article outlined the relationship between the states and the federal government. The Fifth Article pertains to the amending of the Constitution. The Sixth Article states that the laws of states and the nation should not conflict. And the Seventh Article declared that this was the Constitution of the United States. The Constitution provided a system of government that acknowledged the needs of each state, person, and the nation as a whole. Beard claimed that the minorities were not represented in the new Constitution but amendment fifteen provided protection against the majority. Along with the formation of the Electoral College which allowed the minority to be heard his claim can be dismissed. His claim that the delegates were only interested in their economic growth can be rejected. While each of the framers was successful in their own rights, they each had the foresight and knowledge to create a successful document that represented the welfare and rights