Ibuprofen and Acetaminophen Essay

Organic chemical substance compounds retrovert a vast number of isomers, molecules with the same molecular formula that different atomic arrangement, of which there be three types structural, geometric and optical. The intimately closely-linked of isomers are optical isomers, which differ only by the three-dimensional localisation of the molecules attachments, which renders its mirror images to be non-superimposable. The presence of optical isomerism in spite of appearance a molecule is determined by the existence of a chiral affectiona carbon atom with four different groups (see addition, embark 1). staring(a) optical isomers apply identical physical properties such as thaw point, stewing point and density, as well as identical chemical properties thus there are only two ways that they poop be distinguished their inter achievement with other chiral substances and their interaction with matt polarized rest. An enantiomorph (one out of a pair of optical isomers) rotat es plane polarized lighter in the oppo turn up direction of which the other enantiomer rotates the plane polarized light, of equal fiat (see vermiform touch on A, get a line 2). An enantiomer that shifts plane polarized light to the left is abandoned the prefix L (levorotatory) or S, while an enantiomer that shifts plane polarized light to the right is given the prefix D (dextrorotatory) or R.Despite their physical and chemical similarities, optical isomers are known to have substanti whollyy different behaviours deep down the human body. This is due to the fact that enzymes and receptors in the body are stereospecific, meaning that they derriere interact with one enantiomer of certain molecules and not the other. For instance, the human body can only dissect down D-glucose (dextrose) for energy but not L-glucose, and can only put on L-amino group unpleasants rather than D-amino acids. While one form of a stereoisomer whitethorn be beneficial, the other may be ineffectiv e or even harmful, in some cases.Thus, it is crucial that optical isomerism is translaten into account during medicinal medicate development and usage. For example, the sedative thalidomide was available in Europe in the mid-sixties for purposes of alleviating morning sickness in pregnant women. However, the medicine was interchange as a racemic mixture, which contains equal portions of both enantiomers (this would not shift plane polarized light as the two enantiomers shift in different directions),and while R-thalidomide (see adjunct A, figure 3) works effectively as a sedative S-thalidomide can cause genetic damage leading to mutation of the fetus. Consequently, 12 000 infants were natural worldwide with malformation of the limbs.To further illustrate the importance of optical isomers in drug action, the drug isobutylphenyl propionic acid can be explored. isobutylphenyl propionic acid is a drug used for anti-inflammatory drug purposes such as torture relief, fever and s welling reduction, and is classified as a nonsteroidal anti-inflammatory drug (NSAID). Derived from propanoic acid in the 1960s by a pharmacy grasp called Boots UK Limited, ibuprofen was initially launched as a interposition for rheumatoid arthritis, and was awarded the Queens Award for Technical Achievement in 1987. It is currently available under(a) a variety of trademarks such as Advil, Motrin, Nurofen, and Brufen, among others.Ibuprofen works by inhibiting the enzymatic action of cyclooxygenase (COX1 and COX2) within the body, which catalyzes the conversion of a compound called arachidonic acid into prostaglandins. Prostaglandins are locally-acting hormones that cause swelling, heat, departure of function, fever and pain, collectively known as inflammation, at a site of injury with the accumulation of white blood cells. Through inhibiting this reaction, harrowing symptoms can be reduced or eliminated.The IUPAC name for ibuprofen is 2-(4-(2-methylpropyl) phenyl) propanoic a cid. It is a carboxylic acid which in addition contains a phenyl group (see Appendix A, figure 5). Due to its chirality, ibuprofen has two enantiomers (see Appendix A, figure 6) S-ibuprofen, which rotates plane polarized light to the left and is pharmacologically active, and R-ibuprofen, which rotates plane polarized light to the right and has no anti-inflammatory effect (and is thus inactive as a drug, since . However, ibuprofen is sold on the market as a racemic mixture. Thus, a dose of ibuprofen contains only 50% of the active enantiomer, S-ibuprofen. Nevertheless, R-ibuprofen undergoes species-specific chiral inversion within the body, in which near 60% of R-ibuprofen is converted into S-ibuprofen. The tool of the inversion is through an enzyme, alpha-methylacyl-CoA racemase (AMACR) that is present in the liver, the kidney and gastrointestinal tract. Asubstitution nucleophilic bimolecular (SN2) reaction must take place (see Appendix B, figure 1), which results in the complet e conversion of either molecule of one enantiomer to the other. In this case, only R-ibuprofen is converted into S-ibuprofen (see Appendix B, figure 2).The benefits associated with ibuprofen use accept its efficiency as a NSAID in decreasing inflammation, in addition to be non-addictive and affordable. However, ibuprofen often causes stomach irritation, and can impede concentration and cause drowsiness. It may as well as result in a variety of adverse military position do (see Appendix C, figure 1). An alternative to ibuprofen is the drug acetaminophen, also known as paracetamol. Acetaminophen, (see Appendix A, figure 7), is commercially available under brand names such as Tylenol and Anacin (see Appendix A, figure 8). It works by inhibiting the synthesis of prostaglandins. It does not, however, have any anti-inflammatory action and thus only targets tissue of the nervous systemeasing pain without being directed towards the root of the problem. Acetaminophen is known to cause few aspect cause than ibuprofen however for a list of side effects, see Appendix C, figure 2.Acetaminophen does not have a chiral centre, and therefore does not have any optical isomers. Both drugs are used to relieve headache pains and fever however their change properties impact their function and effectiveness in treating specific symptoms.The solubility of ibuprofen in water is 0.0002M. Although its carboxyl functional group is highly polar, the sizable non-polar component greatly decreases its overall polarity. As like dissolves like, ibuprofen does not dissolve well in water, which is polar. To solve this problem, ibuprofen is reacted with the amino acid lysine (see Appendix A, figure 9), which together forms the salt ibuprofen lysinate. Ibuprofen is then released into the bloodstream in which the reaction can reverse. On the other hand, acetaminophen is highly soluble in water with a solubility of 0.091M. Because it contains an amide and an alcohol, there is a substantia l degree of hydrogen bonding resulting in high polarity (see Appendix A, figure 10). This allows the drug to be oblivious into the bloodstream effectively.Ibuprofen has a pKa (acid dissociation constant) of approximately 4.43, while the pKa of acetaminophen is 9.51 and 25C, making ibuprofen more acidic. Because neutral substances pass through bodily membranes more easily, acetaminophen is more easily absorbed. Acetaminophen also has more acid stability. Administered orally, an ibuprofen capsule has an enteric coating, which prevents stomach acid from breaking down the drug before it reaches the small intestine, where it is absorbed. A conduct coating is used on a tablet of acetaminophen, which protects the tongue from the contents, as well as protecting the contents from moisture and light. Within the body, the rent can be broken down by saliva or stomach acid, and the way in which the drug is absorbed is not affected.Appendix A Images embark 1 Molecule with a chiral centre work 2 unconditional polarized light beamed through a filter. The two enantiomers shift light in opposite directions.Figure 1 Type of isomer vs. molecule melting and boiling point Type of IsomersMoleculesMelting Point and Boiling Pointgeomorphologic Isomersbutane2-methylpropaneMP -140C BP -1 CMP -159.6C BP -11.7 Cgeometrical Isomerscis-butenetrans-buteneMP -138.9 C BP 3.7 CMP -105.5 C BP 0.9 C optic IsomersL-2-butanolD-2-butanolMP -115 C BP 98-100 CMP -115 C BP 98-100 CFigure 3 The two optical isomers of thalidomide. R-thalidomide works effectively as a sedative, while S-thalidomide can damage the fetus.Figure 5 Skeletal draw of ibuprofen, with the functional group labeledAppendix A (contd) ImagesFigure 6 Optical isomers of ibuprofen S-ibuprofen is on the left and R-ibuprofen is on the rightFigure 7 Skeletal diagram of acetaminophen,with the functional groups labeledFigure 9 Skeletal diagram of the amino acid lysine, which is reacted with ibuprofen in order to allow it to ultimately di ssolve into the bloodstreamFigure 10 house of ibuprofen vs. acetaminophenAppendix B ReactionsFigure 1 The process of a substitution nucleophilic bimolecular (SN2) reactionFigure 2 The mechanism of the enzymatic chiral inversion of R-ibuprofen (42) into S-ibuprofen. At first, the carboxylic acid is converted into an mediocre thioester (43a) by acyl-CoA ligase This is then converted to the opposite configuration by an epimerase, and the sequent thioester (43b) is hydrolyzed by a hydrolase, releasing S-ibuprofen.Appendix C TablesFigure 1 Side effects of ibuprofenMild side effects includeupset stomach, mild heartburn, diarrhea, constipationbloating, gasdizziness, headache, nervousnessskin rub or snowstormblurred vision effective side effects includechest pain, weakness, shortness of breath, slurred speech, problems with vision or end black, bloody, or tarry stools, coughing up blood or spew that looks like coffee grounds swelling or rapid angle gainurinating less than usual or n ot at allnausea, upper stomach pain, itching, dismission of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes) fever, sore throat, and headache with a severe blistering, peeling, and red skin rash bruising, severe tingling, numbness, pain, muscle weakness or severe headache, neck stiffness, chills, change magnitude sensitivity to light, and/or seizure (convulsions).Figure 2 Side effects of acetaminophenMild side effects includedrowsinessSerious side effects includelow fever with nausea, stomach pain, and loss of appetitedark urine, clay-colored stools orjaundice (yellowing of the skin or eyes)liver failure (with overdose)BibliographyCHAPTER 5 RULES FOR SPECIFICATION OF CHIRALITY. 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Retrieved October 8, 2013, from http//lxsrv7.oru.edu/alang/onsc/solubility/allsolvents.php?solute=ibuprofenThis is credible because it is an educational institution.1C http//www.fda.gov/ohrms/dockets/ac/02/briefing/3882b2_06_international%20ibuprofen%20foundation.htm 2C http//www.lef.org/magazine/mag2007/dec2007_report_acetaminophen_02.htmhttp//books.google.ca/books?id=9xYuQKZSDkIC&pg=PA205&lpg=PA205&dq=how+is+r-ibuprofen+converted+into+s-ibuprofen&source=bl&ots=D4iuQfKoyT&sig=WS9y5uMJa0Hr68Og5FhkJr73OfQ&hl=en&sa=X&ei=WcZVUoqJDpCi4APKyoDoBg&ved=0CFcQ6AEwBQv=onepage&q=how%20is%20r-ibuprofen%20converted%20into%20s-ibuprofen&f=false2B http//books.google.ca/books?id=Zgx13oMZaYUC&pg=PA363&lpg=PA363&dq=how+is+r-ibuprofen+converted+into+s-ibuprofen&source=bl&ots=sWD8D0j8HI&sig=L_5r42H68KotX