Parasympathetic Nervous System - Assignment Example

Pharmacology Module 2 Pharmacology Module 2 Workbook Activity For each body system list the effect of activating the parasympathetic and sympathetic nervous systems in the first two columns, then in the third column, describe a clinical symptom or condition that may be observed in someone with a highly activated parasympathetic nervous system. System Sympathetic Affect Parasympathetic Affect Clinical Condition CVS 1. Heart rate Increased 2. Vasoconstriction of vessels of skin 3. Vasodilatation of skeletal and cardiac vessels 1. Hear rate Decreased 2. Vasodilatation of vessels Bradycardia Respiratory System 1. Increased respiratory rate 2. Bronchodilatation Constriction of Bronchiolar Muscles Difficulty in Breathing Urinary Tract 1. Relaxation of bladder Walls 2. Constriction of sphincters 1. Contraction of bladder Walls 2. Relaxation of Sphincter Polyurea Genital Tract 1. Ejaculation 1. Penile Erection Excessive Erection Eye Contraction of pupil Relaxation of Pupil Mydriasis GIT 1. Relaxation of smooth muscles 2. Contraction of Sphincters 1. Contraction of smooth Muscles 2. Relaxation of Sphincters Increased Secretions 1. Diarrhea 2. Stomach Acidity Skin 1. Excessive sweat Glands Secretion 2.Pilomotor Erection No prominent effects Dry, hot Skin Workbook Activity 2 For each drug; in the first column, identify ONE paramedic indication, then in the subsequent columns, list the molecular target involved in the identified interaction, the type of interaction (i.e. agonist / antagonist / allosteric modulator / inhibitor), and briefly explain how this interaction of the drug with the molecular target accounts for the observed therapeutic effect for that indication. Drug Paramedic Indication Drug Target Type of Interaction Therapeutic Effect Salbutamol Asthma β2 adrenergic Receptor Agonist Bronchodilatation by activating beta-2 receptors in the lung. Adrenaline Shock Both Alpha and Beta Adrenergic Receptors Agonist Used Primarily in Cardiovascular Shock, Helps by activating Alpha receptors in the heart to increase its activity, also in the Lungs by activating beta-2 receptors in Asthma Fentanyl Analgesia Opioid receptors Agonist Not usually used now but acts mainly on the opiod receptors to cause Analgesia Ondansetron Nausea, Vomiting 5HT3 Serotonin Receptors Antagonist Used mainly during surgeries and chemotherapy and helps in decreasing Nausea and Vomiting Midazolam Seizures GABA receptors Agonist Emergency management of Seizures/Epilepsy, Act by activating GABA inhibitory receptors thus decreasing nerve impulse conduction and treating seizures Ipratropium Asthma Muscarinic Receptors Antagonist Acts at the Muscarinic Receptors in the lung to cause bronchodilatation and treating Acute Asthma Atropine Parasympathetic Poisoning Muscarinic Receptors Antagonist Used as a mydriatic agent in eye, also used in the emergency management of excessive parasympathetic activity in case of poisoning Adenosine Cardiac Arrhythmias Potassium and Calcium channels in heart Agonist at first while antagonist at the second receptor Used mainly in Cardiac Arrhythmias due to its affects on the Potassium (Agonist) and Calcium Channels (Antagonist) Ketamine Anesthesia NMDA receptor Antagonist Used to induce anesthesia in which the person remains conscious but is unresponsive (Dissociative Anesthesia) Naloxone Opioid poisoning Opioid Receptors Antagonist Used majorly in the emergency management of opium poisoning because of its rapid blocking of opioid receptors and reversing the affects Aspirin Anti Inflammatory Several Receptors in the body Agonist at some and antagonist at others Used in the treatment of Pyrexia and Inflammation Work Book activity 3 In this workbook learning activity you will need to recreate and complete the following table in your workbook, considering the drugs used in your clinical practice as a paramedic: In the first column, list FIVE receptors from different classes, then list their endogenous agonist(s) in the second column. In the third column give an example of ONE drug that is a clinically relevant SELECTIVE agonist OR antagonist for each of the receptors Receptor Endogenous Substrate Selective agonist or antagonist  used in paramedic practice Alpha adrenergic Receptor Epinephrine, Nor-epinephrine Albutarol, Salbutamol Beta- Adrenergic Receptors Epinephrine Propranolol Serotonin 5HT receptors Serotonin Almotriptzam, eletriptan, Zolmitriptan Histamine H 1, 2 & 3 Receptors Histamine Diphendramine, Promethazine GABA Receptors GABA Midazolam, Diazepam Workbook Activity 4 1. Consider drugs that are antagonists of β adrenergic receptors and briefly explain how they produce clinically useful effects. Ans. The drugs that are usually used as Beta-adrenergic receptor antagonist are Propranolol, Nadolol, Esmolol, Timolol and Carvedilol etc. the major affects of these drugs in the body are produced mainly by their actions on the beta 1 and 2 receptors. These drugs which have an antagonist action on the receptors are used mainly in the diseases associated the Heart. Their actions on heart are caused by the blockade of beta receptors which in turn has several major affects such as decreased heart rate, decreased oxygen demand of the heart and decreased blood pressure. Decreased heart rate makes these drugs useful in the treatment of cardiac arrhythmias where as decreased heart and blood pressure which helps in decreasing the oxygen consumption and demand of the heart have useful affects in treating diseases such as angina pectoris and myocardial infarction. Decreased blood pressure helps in hypertension thus their beta blocking affects produce clinically useful affects mainly by decreasing workload on heart. 2. Considering the actions of β-adrenoceptors in the body identified in part (1), would it be the most appropriate treat uncomplicated hypertension in 68 year old patient with moderate asthma and renal impairment with atenolol, metoprolol or propranolol? Briefly explain the reasons for your decision. Ans. 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). Workbook Learning Activity for Module 3 1. Diagram of metabolism of Paracetamol alongwith the indication of major enzymes. 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. Metabolic Pathway of Paracetamol (Acetaminophen) (Image courtesy of Muslimvillage.com) 2. Explain how the metabolism of paracetamol contributes to the hepatotoxicity caused by this drug. Ans. 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 end product of oxidation but since this NAPQI is toxic to the human body, it undergoes either conjugation with glucoronic acid or sulfation to form conjugated non toxic end products. This is what happens normally in the body. But when there is an overdose of this drug, there is an increased rate of metabolism too. This overdose resulting in an increased rate of metabolism further results in the excessive production of NAPQI, successively the stores of the glucoronic acid required to conjugate this toxic metabolite keep on decreasing and this pathway gets saturated resulting in the accumulation of this product which is toxic. When NAPQI keeps on accumulating in the hepati system it deteriorates hepatic system and its functionality by binding to the macro/micro molecules of the hepatic cells resulting in their injury and necrosis thus resulting in hepatic injury. 3. Explain the mechanism of action of N-acetylcysteine as an antidote for the treatment of paracetamol overdose. Ans. N-acetylcysteine when enters the body acts a precursor of the depleted glutathione which is the main source for the conjugation of toxic metabolits of paracetamol. Hence, providing the body with enough glutathione to compensate for the depleted source and making it readily available to detoxify NAPQI. Activity 2 1. Explain briefly the mechanism of action of opioid agonists, such as morphine. Ans. Opioid agonists have many mechanisms of actions but their mainly their actions are that of anelgesics. These agonists acts on specific opioid receptors in the body namely kappa, mu, delta receptors. These receptors are located mainly in the CNS where they alter the activity of the brain i.e. mainly depresses CNS function. Other locations where these recpetors might be present are GIT and spinal cord. Morphine, which is a strong opioid agonist mediates its actions mainly via mu receptors. The major mechanism of action through which these receptors operates is that they are G-protein coupled receptors and when morphine attaches to them they send signals through G-protein coupled channels to decrease the amount of adenylate cyclase enzyme. Which in turns reduces the production of cAMP from ATP. This reduction in the amounts of c AMP causes the blockade of calcium channels and opening of potassium channels. This blockade and opening of different channels leads to increased negativity inside the neurons leading them to a state of hyperpolarization. Theus nerve impulse conduction is reduced and the signals required to conduct pain are not generated. Also, another proposed action of these opioids is that they mainly change the perception of pain in the brain. 2. List the physiological effects observed with opioid overdose. Ans. The major physiological affects of oopiod overdose are mainly related to the central nervous system however, other systems are also affected. The major affects are: a) Euphoria b) Cognitive impairement c) Respiratory depression d) Anelgesia e) Constipation f) Anti tussive affect g) Muscular rigidity h) Hypothermia i) Tachycardia (Katzung 2009 , p 547-548) 3. Explain the pharmacological basis for the treatment of opioid overdose with naloxone, including the time-course of naloxone treatment. Ans. Naloxone being a direct antagonist of opioids acts on the receptors of opioids and makes them unavailable for the agonists to bind to. Furthermore, naloxone is a competitive antagonists which means that if introduced in higher quantities, it can rapidly displace already bound opioids from the receptors and reverse their affects (Rang& Dale 2007, p.334-339).. The time course of naloxone treatment is usually till the reversal of symptoms of tixicity. PART 2 1. Explain briefly the mechanism of the pharmacokinetic interaction between amiodarone and warfarin. Comment on the potential clinical implications of this interaction. Ans. Amiodarone is supposed to interfere with the cytochrome P450 enzyme system and inhibits its activity. One of the enzymes, CYP2C9 is of significance when we’re to see the interaction of this drug with the pharmacokinetics of Warfarin as warfarin is metabolized by this enzyme (Rang& Dale 2007, p.334-339).. The inhibition of this enzyme leads to the increased concentrations of warfarin in the plasma due to decreased metabolism and may ,ead to its toxicity of worsen the adverse affects e.g. bleeding disorders etc. 2. Explain briefly the mechanism of the pharmacokinetic interaction between St Johns wort and midazolam. Comment on the potential clinical implications of this interaction. Ans. Unlike the two drugs mentioned above, the interaction between st. john’s wart and midazolam is quiet opposite since st, john’s wart is a potent inducer of the P450 enzyme system (Rang& Dale 2007, p.334-339).. This induction leads to decreased plasma amounts of midazolam as this drug is metabolized by the same system. This could lead to decreased efficacy of the drug and may require dosage adjustments. References 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: .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: . (Accessed on 15th Apr. 2012). Read More