Clonidine/Quinapril - Essay Example

? Clonidine/Quinapril Chemistry Table of Contents Table of Contents Clonidine 2 (a) A discussion of the potential degradation reactions of the molecule. 2 (b) The pH rate profile of the molecule and an explanation of the basis for the profile. 2 (c) A statement of the probable shelf life of the molecule. 4 Quinapril 4 (a) A discussion of the potential degradation reactions of the molecule. 5 (b) The pH rate profile of the molecule and an explanation of the basis for the profile. 5 (c) A statement of the probable shelf life of the molecule. 7 Sources Cited 7 Clonidine (a) A discussion of the potential degradation reactions of the molecule. Clonidine is metabolized by the liver and degrades into four main metabolites when exiting the body in the urine. Currently, only p-hydroxyclonidine is identified by clinical research as present in the urine as a byproduct of the degradation reaction of Clonidine in patients. (DrugBank, 2011) Research identifies a number of cyto-chromes of the heme-thiolate mono-oxygenases as byproducts of the degradation reaction of Clonidine, which may negatively affect patients who are undergoing simultaneous treatment for other conditions of the heart, liver, and kidneys. (DrugBank, 2011) The substrate ‘Cytochrome P450 3A4’, another form of p-hydroxyclonidine, may additionally influence the effect of the heart rate on the patient. (DrugBank, 2011) With the use of Clonidine, patients with existing heart or liver conditions should be monitored closely for any additional strain the use of this pharmaceutical could add to cardio-vascular, hepatic, or renal functions. (b) The pH rate profile of the molecule and an explanation of the basis for the profile. pH calculation is a measurement of the molarity of a solution, or the measurement of “the concentration of the hydronium ion in moles per liter” through the use of a negative algorithm. (Chem Purdue, 2011) In calculating the pH rate of the molecule Clonidine (C9H9Cl2N3), the formula to use is: pH = - log [H3O+] Clonidine is found in a number of commercially available medications, therefore in order to calculate the pH rate profile the “CLONIDINE HYDROCHLORIDE injection, solution” by PharmaForce, Inc. was chosen, in which “each mL of the 100 mcg/mL (0.1 mg/mL) concentration contains 100 mcg of clonidine hydrochloride and 9 mg sodium chloride in water for injection.” (NIH, 2011) This solution uses HCL for balancing the pH rate for clinical use. In calculating the pH rate of Clonidine, the pKa value is taken to be 8.3. (Foye, 2007, p. 403) Molecule: C9H9Cl2N3 Initial concentration = 0.1 Ka1 = 5.0118723362727E-09 ( pKa1 = 8.3 ) pKw: 14 From this the pH rate for Clonidine (C9H9Cl2N3) is = 4.6500443179791 This calculation is based upon the formula pKw = -log Kw, where the negative log of the water ion product (Kw) is used to calculate the pH rate of Clonidine in water. (Volland, 2005) Similarly, Dollery (1991) and Buchanan et al (2009) have established a pKa value for Clonidine (C9H9Cl2N3) at 8.05. (Buchanan et al., 2009) In comparing the previous calculation of Clonidine with a pKa value at 8.3 vs. a pKa value of 8.05 at the same values, a solution in sterile water, the result is: Molecule: C9H9Cl2N3 Initial concentration = 0.1 Ka1 = 8.9125093813374E-09 ( pKa1 = 8.05 ) pKw: 14 From this the pH rate for Clonidine (C9H9Cl2N3) is = 4.5250622422896 In these calculations, the formula: pKa = -log Ka is used, where pKa is equal to “the negative log of the acid dissociation constant, Ka”. (Volland, 2005) The use of HCL in the solution is evidence of the need to balance the pH levels of Clonidine when using the drug in intravenous or intramuscular injections in the patient for treatment. (c) A statement of the probable shelf life of the molecule. The shelf life of the oral Clonidine Hydrochloride tablets and the Clonidine HCL solution for IM & IV injections can be taken to be determinant on the means and method of storage. Direct sunlight, extreme temperatures, and other conditions like humidity can influence the deterioration of the medicines if they are exposed directly to heat, light, or moisture. Sandoz, a pharmaceutical manufacturer, estimates the shelf life of the tablets at 24 months. (Sandoz, 2011) The Clonidine HCL injection solution from Pharma Force has a manufacturers label recommending storage at 20 to 25 degrees Celsius, with a factory expiration date established by the date of production and stamped on the package individually. (DailyMed, 2011) If using these pharmaceuticals in a medical facility from a storage room, the doctor or nurse should make a regular habit of checking the lot number and manufacturer’s expiration date on all medicines. The shelf life for the Clonidine solution should be longer than the tablets due to the exposure to heat and humidity, but this requires that the seals and packaging material remain unbroken. Quinapril (a) A discussion of the potential degradation reactions of the molecule. Quinapril is metabolized by the liver primarily when administered in tablets such as Accupril, though medical reports suggest as much as 97% of an IV dose of Quinaprilat is eliminated through the kidneys. (Drug Bank, 2011) Clinical research suggests that food can be a detrimental contraindication for the use of Quinapril in patients. Patients are advised to avoid high-fat and high-salt in foods, as well as the herbs “bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice”. (Drug Bank, 2011) As Quinapril is a regulator of heart activity and hypertension in patients, these additional food and dietary restrictions are required to avoid the effects of strain, stress, and high blood pressure that may become stimulated through the effects of the diet. The usage instructions for Accupril suggest that it is required to avoid the use of ACE inhibitors in combination with Quinapril, as this can lead to additional head and neck Angioedema in patients as a side effect. (Daily Med, 2011) (b) The pH rate profile of the molecule and an explanation of the basis for the profile. The pH calculation for Quinapril involves the measurement of “the concentration of the hydronium ion in moles per liter” through the use of a negative algorithm. (Chem Purdue, 2011) In calculating the pH rate of the molecule Quinapril (C25H30N2O5), the formula to use is: pH = - log [H3O+] Quinapril is found in tablets (quinapril hydrochloride) of 5 mg, 10 mg, 20 mg, or 40 mg that are used for oral administration in patients, with the most common commercial form marketed under the brand name Accupril. (RxList, 2011) Quinapril is manufactured by Pfizer, Sun, Teva, Sandoz, Ranbaxy, and other drug producer under a combination of generic names and proprietary brands, though the use of tablets is more common for administration than IM or IV solutions. The pH calculation will be based on a sterile water solution of pKw = 14. In calculating the pH rate of Quinapril, two values are given for the pKa: Quinapril (C25H30N2O5): pKa = 3.2 and 5.5. (Spark, 2011) Molecule: C25H30N2O5 Initial concentration = 0.1 Ka1 = 0.00063095734448019 ( pKa1 = 3.2 ) pKw: 14 From this the pH rate for Quinapril (C25H30N2O5) is = 2.1172439414191 This calculation is based upon the formula pKw = -log Kw, where the negative log of the water ion product (Kw) is used to calculate the pH rate of Quinapril in sterile water. (Volland, 2005) Repeating the previous calculation of pH for Quinaprilat using the second pKa value of 5.5, leads to the values of a pH rate for Quinapril (C9H9Cl2N3) = 3.2512213813064 Molecule: C9H9Cl2N3 Initial concentration = 0.1 Ka1 = 3.1622776601684E-06 ( pKa1 = 5.5 ) pKw: 14 In these calculations, the formula: pKa = -log Ka is used, where pKa is equal to “the negative log of the acid dissociation constant, Ka”. (Volland, 2005) From this range of values, it can be determined that the pH balancing of Quinapril with HCL is used in order to make the solution of a neutral acidity for medical use in tablets or injection. In these calculations, the pKa value of 3.2 is taken from analysis of Quinapril and the pKa value of 5.5 is used in reference to Quinaprilat. (Spark, 2011) In this instance, the difference in chemical composition between the two agents resulted in a difference of pH of approximately 1.4 between the versions. (c) A statement of the probable shelf life of the molecule. According to Aurobindo Pharma Ltd., the manufacturer of Quinapril Hydrochlorothiazide 20/25 mg film-coated tablets, the shelf life of their product is three years. (Aurobindo, 2011) Most manufacturers should have a similar expiration date, but will label this directly on the packaging materials with a lot number representing the time of production. The manufacturers also recommend not leaving the tablets in extreme conditions of heat, sunlight, or humidity for best results in usage. Medical health practitioners should always directly read the label, lot number, and expiration date of any medicine such as Quinapril before administering them directly to patients, and to watch for expired or damaged packages in the clinic environment when directly responsible for patient care. Sources Cited Aurobindo Pharma Ltd. (2011). Quinapril/Hydrochlorothiazide 20/25 mg film-coated tablets. EMC, Datapharm Communications Ltd., 2011. Retrieved from http://www.medicines.org.uk/EMC/medicine/24954/SPC/Quinapril+Hydrochlorothiazide+20+25+mg+film-coated+tablets/ Buchanan, M. L. et al. (2009). Clonidine Pharmacokinetics in Pregnancy. DMD, April 2009, Vol. 37, No. 4., pp. 702-705. Retrieved from http://www.cac.psu.edu/jbe/twocont.html DailyMed (2011). CLONIDINE HYDROCHLORIDE injection, solution [PharmaForce, Inc.]. U.S. National Library of Medicine, National Institutes of Health, Health & Human Services, 2011. Retrieved from http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6e562c90-2e37-47ac-9c3f-12460f96dc33 DailyMed (2011). ACCUPRIL (quinapril hydrochloride) tablet, film coated [Parke-Davis Div of Pfizer Inc]. U.S. National Library of Medicine, National Institutes of Health, Health & Human Services, 2011. Retrieved from http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=12730 DrugBank (2011). Clonidine. Drug Bank Version 3.0, 2011. Retrieved from http://drugbank.ca/drugs/DB00575 DrugBank (2011). Quinapril. Drug Bank Version 3.0, 2011. Retrieved from http://drugbank.ca/drugs/DB00881 Foye, William O.; Lemke, Thomas L.; & Williams, David A. (2011). Foye's principles of medicinal chemistry. Lippincott Williams & Wilkins, 2007. Retrieved from http://books.google.co.in/books?id=NHQQBMM-qMEC Purdue Chem (2011). pH, pOH, pKa, and pKb. Chemistry Department, Purdue University, 2011. Retrieved from http://www.chem.purdue.edu/gchelp/howtosolveit/Equilibrium/Calculating_pHandpOH.htm The Rx List (2011). Accupril. RxList Inc., 2011. Retrieved from http://www.rxlist.com/accupril-drug.htm Sandoz (2011). SPC: Clonidine 25mcg Tablets BP. EMC, Datapharm Communications Ltd., 2011. Retrieved from http://www.medicines.org.uk/emc/medicine/21711/SPC/clonidine%2025mcg%20tablets%20bp/ Spark Holland (2005). DETERMINATION OF QUINAPRIL AND TWO METABOLITES BY TANDEM ONLINE SPE USING SYMBIOSIS™ PHARMA. EMC, Spark System Solutions BV, November 2005. Retrieved from http://www.medicines.org.uk/EMC/medicine/24954/SPC/Quinapril+Hydrochlorothiazide+20+25+mg+film-coated+tablets/ Volland, Dr. Walt (2005). Definition of pH, pOH, "p", sample calculations. Online Introductory Chemistry, April 12, 2005. Retrieved from http://www.800mainstreet.com/acid_base/definitions-ph.html Spark Holland (2005). DETERMINATION OF QUINAPRIL AND TWO METABOLITES BY TANDEM ONLINE SPE USING SYMBIOSIS™ PHARMA. EMC, Spark System Solutions BV, November 2005. Retrieved from http://www.medicines.org.uk/EMC/medicine/24954/SPC/Quinapril+Hydrochlorothiazide+20+25+mg+film-coated+tablets/ Read More