Atenolol, Metaprolol and Propranolol have affects on both the beta 1 and beta 2 adrenergic receptors which makes them favorable in the treatment of uncomplicated hypertension but a patient with asthma and renal impairment should not be given these drugs as they have beta-2 blocking affects too. The beta-2 blocking affects of these drugs could trigger an attack of asthma in an asthmatic patient due to the absence of beta-2 mediated bronchodilatation. Also, in renal impairment these drugs could lead to worsening of the disease (Katzung 2009 , p 175-177).The metabolism of paracetamol occurs mainly in the liver after it is absorbed from the gastric system, the rate at which paracetamol is absorbed from the GIT depends mainly on the fact that how fast is the rate of emptyming of stomach. After the drug reaches the liver it undergoes the process of metabolism which include the process of conjugation and activation of the drug. The amount of drug that raches the systemic circulation after being absorbed and metabolised is 75% of the total. Main process of metabolism occurs in the hepatic system however, some minor metabolism and brakdown process occurs in the renal system too. In these two systems, the drug undergoes three main processes of metabolism namely 1) Glucoronidation, 2) oxidaion and 3) Sulfation. Oxidation is the process which yields the useful and activated product. The activated product N-acetyl-p-benzoquinonemimime is mainly toxic for the body but this product is then conjugated with glutathione to form a conjugated and non toxic product which is then excreted mainly in the urine.The other two metaolic pathways that include glucoronidation and Sulfation are usually of not that much importance as they mainly yield inactivated products. Glucoronidation involves an enzyme UDP-Glucoronyltransferase which is the main enzyme catalysing this reaction. While in Sulfation, only small quantities of paracetamol is usually converted to a product called N-acetyl-p-benzoquinonemimie by two major enzymes groups of the P450 family namely CYP3A4 and CYP2E1. The activated product is then conjugated and converted to a less/non toxic mteabolite. The matebolism of paracetamol as described earlier occurs in the liver where it is first activated and then conjugated by the processes of sulfation and conjugation. The first process which involves its metabolism is the process of oxidation which results in the formation of NAPQI, the activated toxic
HOWLAND, R. D., MYCEK, M. J., HARVEY, R. A., CHAMPE, P. C., & MYCEK, M. J. (2006). Pharmacology. Philadelphia, Lippincott Williams & Wilkins.
KATZUNG, B. G., MASTERS, S. B., & TREVOR, A. J. (2009). Basic & clinical pharmacology. New York, McGraw-Hill Medical. http://www.accessmedicine.com/resourceTOC.aspx?resourceID=16.
Algren, D. Adam.2008. "Review of N-acetylcysteine For the Treatment of acetaminophen (paracetamol) Toxicity in Pediatrics." [Online]. Available at: <www.who.int/selection_medicines/committees/subcommittee/2/acetylcysteine_rev>.Pdf. (Accessed on 12 April. 2012)
Coleman, M. D. (2005) Human Drug Metabolism: An Introduction. Chichester, England: John Wiley. Print.
Dale, M.M., Rang, H. P. 2007. Rang & Dales pharmacology .6th ed. Edinburgh: Churchill Livingstone Press. Print.
Jones, A.L. (1998) Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: a critical review. Journal of Clinical Toxicology 36: 277–85
Laura, James. P, Philip Mayeux, and Jack.A Hinson.(2003) "Acetaminophen-Induced Hepatotoxicity ." Drug Metabolism and Disposition: Vol 31(12), [Online]. Available at: http://dmd.aspetjournals.org/content/31/12/1499.full. (Accessed on 13th April 2012).
Lemke, Thomas L., David, A. Williams. 2007. Foyes principles of medicinal chemistry. 6th ed. Philadelphia, Lippincott Williams & Wilkins. Print.
Vale, J.A, Proudfoot, A.T. (1995). Paracetamol (acetaminophen) poisoning: Lancet, 346: 547–52.
Zhou, S, Chan, E, Pan, S.Q, Huang, M. 2004 "Pharmacokinetic interactions of drugs with St John’s wort. A Journal of Psychopharmacology: National Centre for Biotechnology Information.18 (2). [Online] Available at: <http://www.ncbi.nlm.nih.gov/pubmed/15260917>. (Accessed on 15th Apr. 2012).
Please type your essay title, choose your document type, enter your email and we send you essay samples