Inotropes, Vasopressors and Vasodilators

Inotropes, Vasopressors and Vasodilators Suruchi Hasija, Jatin Narula ,Vandana Maravi. ADRENERGIC RECEPTORS AND SIGNALING PATHWAYS The main control over cardiac contractility is provided by the ÃŽ ²Ã¢â‚¬â€œadrenergic signaling pathways and that over the vascular tone by both ÃŽ ±- and ÃŽ ²Ã¢â‚¬â€œadrenergic pathways. The ÃŽ ± and ÃŽ ² receptors are stimulated by catecholamines circulating in the bloodstream and those released locally from the adrenergic nerve endings. The two main subtypes of ÃŽ ²Ã¢â‚¬â€œadrenergic receptors (ÃŽ ²Ã¢â‚¬â€œARs) in the cardiovascular system are the ÃŽ ²1 and ÃŽ ²2 subtypes. Myocardial ÃŽ ²1 and ÃŽ ²2-AR stimulation leads to increased contractility, whereas vascular ÃŽ ²2-AR stimulation induces vascular smooth muscle relaxation. Drug binding to myocardial ÃŽ ²Ã¢â‚¬â€œARs activates stimulatory G protein. This leads to activation of the enzyme adenylate cyclase that catalyzes the conversion of ATP to cAMP. A cascade of intracellular reactions finally leads to the physiological effect of increased myocardial contraction or vasodilation. The ÃŽ ±Ã¢â‚¬â€œadrenergic receptors (ÃŽ ±Ã¢â‚¬â€œARs) are further classified as ÃŽ ±1 and ÃŽ ±2 subtypes. ÃŽ ±1-AR on vascular smooth muscles are the main mediators of vasoconstriction. ÃŽ ±2-AR on the neurons function in a negative feedback loop to control ÃŽ ±-adrenergic vasoconstriction. Stimulation of ÃŽ ±1-AR coupled to G protein activates phospholipase C which in turn raises intracellular Ca+2. Stimulation of ÃŽ ±2-AR coupled to inhibitory G protein inhibits adenylate cyclase, thereby lowering intracellular Ca+2. INOTROPES Inotropy or contractility is the intrinsic property of the cardiac myofibril. It defines the amount of work that the heart can perform at a given load. Contractility is primarily determined by the availability of intracellular calcium. Depolarization of the cardiac myofibril leads to the entry of a small amount of Ca+2 into the cell which triggers the release of additional Ca+2 from intracellular storage sites (sarcoplasmic reticulum). The binding of Ca+2 to troponin, displacement of tropomyosin from the binding site on actin and formation of actin-myosin crossbridges eventually leads to contraction of the myofibril. All inotropic agents act by increasing intracellular calcium. Catecholamines, phosphodiesterase inhibitors and calcium sensitizers are the broad classes of available inotropic agents. Catecholamines Catecholamines comprise the major type of available inotropic agents. Their chemical structure includes a catechol ring, catechol hydroxyl groups and variable side chains. Endogenous(present naturally in the body) catecholamines include epinephrine, norepinephrine and dopamine, and synthetic catecholamines include isoprenaline, dobutamine, dopexamine and fenoldopam. Besides acting directly on adrenergic receptors, some catecholamines may act indirectly by releasing or inhibiting reuptake of norepinephrine at the nerve terminal or by metabolism to form norepinephrine. Table 1: Site and mechanism of action of sympathomimetics Table 2: Haemodynamic effects of catecholamines and phosphodiesterase inhibitors CO=cardiac output, dp/dt=force of myocardial contraction(change in pressure/time), HR=heart rate, SVR=systemic vascular resistance, PVR=pulmonary vascular resistance, PCWP=pulmonary capillary wedge pressure, MVO2=myocardial oxygen consumption Modified from Lehmann A, Boldt J: New pharmacologic approaches for the perioperative treatment of ischemic cardiogenic shock. J Cardiothorac Vasc Anesth 19:97-108, 2005. Epinephrine Epinephrine, a naturally occurring catecholamine, is secreted from the adrenal medulla. The effects on ÃŽ ²Ã¢â‚¬â€œARs predominate at lower doses and on ÃŽ ±Ã¢â‚¬â€œARs at higher doses (> 0.1  µg/kg/min). It increases heart rate (HR), stroke volume (SV) and coronary blood flow (CBF). The rise in blood pressure (BP) results from increase in HR and cardiac output (CO). Systemic vascular resistance (SVR) decreases at low doses (ÃŽ ²2-AR effect) but increases at high doses (ÃŽ ± effect). It is metabolized in the liver by the enzymes catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO), and the metabolites are excreted in urine. It has arrhythmogenic potential. In cardiac surgical patients it is used as an infusion at 0.01-0.4  µg/kg/min to wean patients with poor ventricular function off cardiopulmonary bypass (CPB). (Tables 1 and 2) Norepinephrine Norepinephrine is the postganglionic neurotransmitter in the sympathetic nervous system. It acts on ÃŽ ±1–AR, ÃŽ ±2–AR and ÃŽ ²1–AR, and has negligible action on ÃŽ ²2–AR. The ÃŽ ²1-AR action predominates at lower doses, thereby increasing inotropy, SV and CBF. It increases BP and SVR; but decreases HR. The CO remains unchanged. It has arrhythmogenic potential. The clinical dose range is 0.01 to 0.1  µg/kg/min. Like epinephrine, it is easily oxidized. It is metabolized by COMT and MAO and taken up by the sympathetic neurons. It decreases renal, hepatic, mesenteric and splanchnic blood flow. Dopamine Dopamine is a neurotransmitter in the central and peripheral nervous system. It is the immediate metabolic precursor of norepinephrine and epinephrine. It acts on ÃŽ ±Ã¢â‚¬â€œARs, ÃŽ ²Ã¢â‚¬â€œARs and dopaminergic receptors (DA1-DA5). At 0.5-3  µg/kg/min it increases renal and mesenteric blood flow (dopaminergic effects), between 3-8  µg/kg/min it increases HR and contractility (ÃŽ ²-AR effects) and, above 8  µg/kg/min it causes vasoconstriction (ÃŽ ±-AR effects). Intravenous dopamine does not cross the blood brain barrier. It is metabolized in the liver by COMT and MAO. Isoprenaline Isoprenaline has pure ÃŽ ²Ã¢â‚¬â€œAR agonist activity. It causes an increase in HR and contractility (ÃŽ ²1-AR effect) and decreases SVR (ÃŽ ²2-AR effect). CO increases due to combined ÃŽ ²1 and ÃŽ ²2-AR effect. It dilates pulmonary, skeletal, renal and mesenteric vascular beds. It is indicated in the treatment of pulmonary hypertension, bradycardia (especially after orthotopic heart transplantation), heart block and conduction abnormalities. It is used in the dose 0.01 to 0.1  µg/kg/min. it is metabolized in the liver by COMT. It is arrhythmogenic. Dobutamine Dobutamine is primarily a ÃŽ ²1-AR agonist and has positive inotropic effects. It causes modest increase in HR (ÃŽ ²2-AR effect) and decrease in SVR (ÃŽ ²2-AR effect). The clinical dose range varies from 2-15  µg/kg/min. It is particularly indicated in patients with myocardial pump failure. Its chemical structure lacks the hydroxyl group of catecholamines. It is metabolized in the liver, although not by COMT and MAO. It increases SV, CO and CBF. The arrhythmogenic potential is less than other catecholamines. Dopexamine Dopexamine is a synthetic analog of dopamine. It has potent ÃŽ ²2-AR and dopamine agonist properties and little ÃŽ ²1-AR and ÃŽ ±-AR activity. It causes vasodilation, increase in HR and inotropy. CO and renal blood flow are increased. It is used in the dose 1-10  µg/kg/min. It undergoes methylation and sulfation in the liver and is taken up into the tissues via extraneuronal catecholamine uptake mechanisms. Unlike other catecholamines, it lacks arrhythmogenic potential. Fenoldopam Fenoldopam mesylate is a dopamine DA1 receptor agonist that causes systemic and renal arteriolar vasodilation. It increases renal blood flow at doses of 0.05-0.1  µg/kg/min and reduces BP at 0.1-0.3  µg/kg/min. Phosphodiesterase inhibitors Phosphodiesterase inhibitors act by preventing the breakdown of cAMP, thereby prolonging its physiological response. They do not act via ÃŽ ²-AR stimulation. Their addition to a catecholamine has a synergistic effect in increasing inotropy. They also produce vasodilation and are termed ‘inodilators’. They improve myocardial diastolic relaxation (positive lusitropic effect) and augment coronary perfusion. The clinically used phosphodiesterase inhibitors include amrinone, milrinone and enoximone. Amrinone Amrinone is a bipyridine derivative. It provides positive inotropy and decreases SVR. The decrease in SVR is apparent immediately after administration, whereas positive inotropy is appreciable after 10-15 minutes. They are particularly useful in heart failure by increasing forward flow. It is administered as a bolus loading dose (0.5-1.5 mg/kg) followed by infusion (5-20  µg/kg/min). The potential side effects are thrombocytopenia (2-3%), gastrointestinal upset, myalgia, fever, hepatic dysfunction, ventricular arrhythmias and allergy. Milrinone Milrinone is a derivative of amrinone and is 20 times more potent. It does not cause fever or thrombocytopenia. It is administered as a bolus loading dose (50  µg/kg over 10 minutes) followed by infusion (0.375-0.75  µg/kg/min). Enoximone Enoximone is an imidazole derivative that has more pronounced vasodilatory effect than inotropic effect. It is administered as a bolus loading dose (0.5-1 mg/kg) followed by infusion (5-10  µg/kg/min). Levosimendan Levosimendan is a new inotropic agent belonging to the class of calcium-sensitizing agents, i.e., it sensitizes the myocardium to the actions of calcium. It has vasodilating and anti-ischemic properties mediated by opening of K+-ATP channels. The haemodynamic effects include increase in SV and CO and reduction in filling pressures, mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP) and SVR. It also promotes lusitropy. It is useful in patients with compromised left ventricular function, difficulty in weaning from CPB and right ventricular failure. It is used in a loading dose of 12  µg/kg over 10 minutes followed by an infusion of 0.1  µg/kg/min. Calcium chloride Calcium ions play an important role in excitation-contraction coupling in the cardiac myofibrils. It has positive inotropic effect that is effective after CPB and in the short-term treatment of myocardial pump failure. The rise in BP occurs secondary to increased inotropy and vasoconstriction. However, it can attenuate the ÃŽ ²-AR effects of epinephrine in the postoperative cardiac surgical patients. It is administered in the dose of 2-4 mg/kg every 10 minutes. Calcium Gluconate the clinically available compound of calcium ,contains less than half of ionized calcium and has to be metabolized in the liver before action. VASODILATORS Vasodilators cause relaxation of arterial smooth muscle thereby reducing SVR and MAP. In addition, they also have venodilating property. They aid discontinuation of CPB by decreasing preload, right and left ventricular afterload, improving lusitropy and CBF. They are useful in the perioperative treatment of systemic and pulmonary hypertension, myocardial ischemia and ventricular dysfunction complicated by excessive pressure or volume overload. Sodium nitroprusside Sodium nitroprusside (SNP) acts by acting as a substrate for the formation of nitric oxide (NO) in the vascular endothelium. Binding of NO to its receptor induces a conformational change in the enzyme guanylate cyclase and production of cGMP from GTP. cGMP is the second messenger that eventually leads to vascular smooth muscle relaxation via numerous intermediate steps. SNP predominantly causes arterial and arteriolar vasodilation, but at high doses venodilation also occurs. Reflex tachycardia is apparent with its administration. SV and CO are increased only if the preload is maintained with intravenous fluids. SNP has a potential to cause ‘coronary steal’ phenomenon in patients with coronary artery disease as the epicardial coronary arteries also dilate diverting blood away from the stenosed endocardial coronary arteries. It decreases pulmonary vascular resistance (PVR) and MPAP. It abolishes hypoxic pulmonary vasoconstriction and may contribute to hypoxia. The infusion rate is 0.5  µg/kg/min, and titrated to effect. It is reconstituted in a dextrose-containing solution. SNP is sensitive to light, therefore the infusion syringe and tubing are wrapped with opaque material to prevent light induced structural breakdown of the drug. Cyanide toxicity may occur with the use of SNP above 1.5 mg/kg acute dose or 8  µg/kg/min chronic infusion. SNP is used during hypothermic CPB to promote uniform cooling by preventing cold induced vasoconstriction, to reduce the perfusion pressure, to reduce afterload by decreasing SVR and to increase pulmonary blood flow by decreasing PVR. Nitroglycerin Nitroglycerin (NTG) acts by the same mechanism as other nitrates. NTG is primarily a venodilator and reduces ventricular preload and myocardial oxygen consumption. NTG is of particular importance in patients with congestive heart failure as it unloads the left ventricle. It has modest effects on SVR and BP. It reduces PVR. The starting dose of intravenous nitroglycerin is 0.5  µg/kg/min which may be titrated to effect. Attention must be paid to the fluid status as CO may drastically reduce. At higher doses systemic vascular dilation occurs. NTG is helpful in coronary artery disease because it causes epicardial coronary artery dilation. It is metabolized in the liver. Methemoglobinemia occurs at high infusion rates. Intravenous nitroglycerin has a half-life of 1-3 minutes. Tolerance develops when administered for more than 8 hours. Nitric oxide Nitric oxide (NO) is the endothelium derived relaxing factor. Its mechanism of action has been described above. It has a very short half-life of 5 seconds. Inhaled NO promotes pulmonary vascular dilation. It can be used upto 80 parts per million (ppm) in patients with severe right ventricular failure and pulmonary arterial hypertension. As inhaled NO is rapidly taken up by the heme group of guanylate cyclase, it only acts locally in the pulmonary vascular bed causing pulmonary vasodilation. It has no systemic effects. Phenoxybenzamine Phenoxybenzamine is a non-competitive ÃŽ ±1 and ÃŽ ±2-AR blocker. It decreases PVR and SVR, thereby increasing CO. It is used to promote vasodilation during deep hypothermic circulatory arrest for uniform cooling and for the treatment of pulmonary hypertension. Phenoxybenzamine is a very potent and long acting vasodilator. It was traditionally used for afterload reduction, pulmonary vasodilatation, and in adrenal tumors such as pheochromocytoma. Phentolamine, a shorter acting agent is now more commonly used. VASOPRESSORS Vasopressors act on arteries and arterioles to increase SVR (ÃŽ ±-AR effect). They have some ÃŽ ² –AR effect also. Catecholamines such as norepinephrine, and epinephrine and dopamine at high concentrations are potent vasoconstrictors. In addition, sympathomimetics such as phenylephrine, methoxamine, ephedrine, metaraminol and mephentermine are also vasoconstrictors. They are metabolized by COMT and MAO. Phenylephrine Phenylephrine is a pure ÃŽ ±1-AR agonist and its primary action is to increase SVR. Reflex bradycardia may be seen. Vasoconstriction of renal, splanchnic and other vascular beds occurs. Coronary perfusion pressure is increased due to increase in diastolic pressure. The intravenous bolus dose is 50-100  µg and infusion rate is 0.5-1.0  µg/kg/min. Its effect is apparent in 1 minute and lasts upto 20 minutes. It is commonly used to increase SVR and therefore the perfusion pressure on CPB. Mephentermine Mephentermine has direct action on ÃŽ ±-AR and ÃŽ ²-AR, and indirect action by releasing norepinephrine at the nerve terminal. It increases CO and SVR. Its acts immediately on intravenous injection and it’s action lasts 30 minutes. It is used in 15-45 mg bolus doses and as 0.1% infusion titrated to effect. Vasopressin Vasopressin,a hormone of the anterior pituitary is a potent vasoconstrictor. It mediates vasoconstriction by inhibiting K+ ATP channels on vascular smooth muscles and blunting the rise in cGMP (due to NO and ANP) and cAMP (due to ÃŽ ²2-AR stimulation). It is one of the modalities of treating vasodilatory shock after CPB. It is used in the infusion dose of 0.01-0.1 U/min for this purpose. At higher doses it has the potential to cause renal and splanchnic vasoconstriction. It is also administered as a bolus dose of 40 U i.v. during cardiopulmonary resuscitation. Suggested reading Hoffman TM. Newerinotropesin pediatric heart failure. J Cardiovasc Pharmacol. 2011 Aug;58(2):121-5 Rognoni A, Lupi A, Lazzero M, Bongo AS, Rognoni G. Levosimendan: from basic science to clinical trials. Recent Pat Cardiovasc Drug Discov. 2011 Jan;6(1):9-15. Tavares M, Rezlan E, Vostroknoutova I, Khouadja H, Mebazaa A. New pharmacologic therapies for acute heart failure. Crit Care Med. 2008 Jan;36(1 Suppl):S112-20. Petersen JW, Felker GM. Inotropesin the management of acute heart failure. Crit Care Med. 2008 Jan;36(1 Suppl):S106-11 Ward RM, Lugo RA Cardiovascular drugs for the newborn.Clin Perinatol. 2005 Dec;32(4):979-97 Hug CC Jr. Making a choice ofinotropesandvasodilatorsin clinical situations.J Card Surg. 1990 Sep;5(3 Suppl):272-7 Stanford GG. Use of inotropicagentsin critical illness. Surg Clin North Am. 1991 Aug; 71(4):683-98.

Data Essay -- essays research papers

1. Data is something known or assumed. It is anything that fits into a DSS and is valuable. Three examples are grades for a class, a picture of wallpaper, or word of mouth about a new product or company. 2. Words, pictures, and numbers. 3. Information is acquired data that is derived from data and anything that is summarized in numerical or graphical. Information is used for "informing" some one about something. An example of information is a net income on a balance sheet, the average of grades for a class and a graph of how many people use a certain product. 4. Normative approach, subjective approach and realistic approach. The normative approach is when the DSS provides the information that a decision maker wants in order to make a particular decision. This states that the information should meet the guidelines for making the decision. The subjective approach is when the DSS has information that the designs thought would be useful. This does not mean that the information will be useful. The last approach, realistic, is when the designer asks if the decision maker will use this information or not. Each approach has its own useful data. The realistic approach is the better of all the approaches because it takes into account what the DSS will be used for and puts in the needed information. The other two approaches do not put in the information that is needed. 5. The characteristics of useful information is as follows: { Timeliness : information is up to date and st...

Reporting Practices and Ethics Essay

Introduction Reporting practices and ethical standards are the most important building blocks that are needed to build a successful health care organization or any business. These reporting practices and ethical standards prove to be the upmost important practices in any health care organization. When reviewing all the variables and factors, one considers the principals listed in the generally accepted accounting principles. There are several factors to consider and inforce these principles in an organization. To successfully implement generally accepted accounting principles and execute corporate compliance, an organization should consider in order for building a successful organization; ethics, fraud and abuse are all key components for maintaining a successful health care or business organization. A successful organization cannot be successful unless they integrate and implement the four elements for financial management. In order to implement and execute the four element of financial management for a successful organization, the four elements should be implemented and carried out in full on a daily basis for every procedure and operation within the organization. Controlling, planning, organizing, and decision making are the four components every business and/or health care organization should adopt. The four elements are the keys to every good business ethics and standards to maintain a successful organization. Four Elements of Financial Management The planning stage of the four elements of financial management proves this stage, is vital to set goals for a healthcare organization end to end with its execution of this stage and the other four elements. The next element of financial management is the controlling stage and in this important stage the organization must set goals for their organization and that each goal is executed and carried out. A perfect example of how an administrator /director/ manager in a healthcare organization can control their  organization is to conduct audits of the department they oversee. Decision making is defined as the overall performance of the other three elements and determination on wither or not the overall performance of the other elements. The success of this can be measured Decision making in conjunction with the other elements and the overall performance and success of other 3 elements ultimately determines decision making elements. Examples, if the organization exceeds the funds budgeted and find they are over budget, the decision making element comes in to play to review these items over budget and make an action plan to correct and/or prevent in the future. The four components are a vitally in financial management there are also other important principals and standards. The Generally accepted accounting principles and general financial ethical standards along with corporate compliance, ethics, or fraud and abuse are equally important separately and combined. The four functions of management help the facilities function properly and give the management the opportunity to resolve any issue or obstacle that may present as well as the opportunity to growth and make them better to perform and utilized the resources around them. Management is responsible for beginning the process for procedure or task at hand and sustaining the actual method of internal control that is set by the organization. It is important that management/ administrator/ director to oversee and maintain the budget control. The manager/admin/director overseeing the budget should be knowledgeable of how to control the budget and in order to maintain budget control, they should regulate to increase productivity and be familiar with assets, financial reporting and account summary. Every cooptation or health care organization is necessitate to meet the satisfactory operational needs, consequently cash management function helps any organization begin to create a set of policies and procedures to ensure that federal funds are not withdraw unreasonable from the organization and payments are made properly to the programs (Ethics and Compliances May 1994). According to Ethical Behavior by Companies Benefit Society and Business (November 13, 2010), when applying ethical business practices, says that business should ensure that the production of its services should be environmentally ecological and every human involve in the production should not be dangerous or harmful for them. Ethical practices involve the strong financial reporting as well as consideration  for the social and environmental impact of the business. Audit reports help the organizations know the financial condition of the organization for Health Care or any other business as well as the result of the organization’s day to day internal operations. Audits are helpful when following the practices of financial reporting practices of the organization can serve as a checks and balances and a great tool for capturing financial data, if management checks the financial audit reports often. Financial reports explain in detail how the organization is doing and prevents negative numbers on the company because it records any procedure and activity that happens in the organization (Ethics and Compliances. May 1994). According to American College of Physicians (Snyder. 2012), the environment for the delivery of health care continues to change. Sites of care are shifting, with more care provided in ambulatory settings while the intensity of inpatient care increases. Generally Accepted Accounting Principals â€Å"The phrase â€Å"generally accepted accounting principles† is a technical account term that encompasses the conventions, rules, and procedures necessary to define accepted accounting practice at a particular time. Generally accepted accounting principles (GAAP) are concerned with the measurement of economic activity, the timed when such measurements are to be made and recorded, the disclosures surrounding this activity, and the preparation and presentation of summarized economic information in the form of financial statements (Bragg, 2012). Generally accepted accounting principles also known as GAAP to understand the definition better, GAAP are guidelines that one should follow when trying to establish proper financial documents and reports. With these guidelines to follow, it was easier to maintain the financial reporting’s for all fields, including healthcare. The generally accepted accounting principles were held in the highest regard. The guidelines of the GAAP have had a high authority when it came to determining financial practices in healthcare. The GAAP influence has dwindled if not stopped. It was stated that it was not required for hospitals, nursing homes or any kind of healthcare facility to adhere to the GAAP (Taebel 1995). It has been documented that the guidelines of the GAAP has caused facilities to lose money, even though they knew what was best about recognizing costs. It has  been suggested that is not required to make decisions based off of the general accepted accounting principles. Capital costs are reimbursed according to a prospective payment system; providers are being paid a predetermined amount regardless of GAAP issues (Taebel, 1995). Conclusion There are countless of different ways that we can touch bases on to understand the importance of a cohesive financial department. It is essential to its success to be ethically compliant and to follow through with policy and procedure. It is up to the financial managers to execute and enforce proper guidelines. In conclusion, there are four elements of the financial structure that is the basis for a financial department’s success which are planning, controlling, organizing and decision making. With this information we were able to understand and summarize more in depth the importance of generally accepted accounting principles and general financial ethical standards. Finally, we were able to view examples in those respecting terms and gain understanding from them. By compiling all of these elements together can guarantee a solid financial department in any healthcare facility. References American College of Physicians (2010) Ethics in Practice: Managed Care and the Changing Health Care Environment. Retrieved 11/13/2010 from http://www.annals.org/content/ Bragg, Steven M. Wiley GAAP 2012: Interpretation and Application of Generally Accepted Accounting Principles (10th Edition). Hoboken, NJ, USA: John Wiley & Sons, 2011. ProQuest ebrary. Web1 May 2015. Ethics and Compliances Retrieved 11/13/2010 from http://www.miamivalleyhospital.org/mvhdefault.aspx?id=12746 (May 1994) Snyder L, for the American College of Physicians Ethics, Professionalism, and Human Rights Committee. American College of Physicians Ethics Manual: Sixth Edition. Ann Intern Med. 2012;156:73-104. doi:10.7326/0003-4819-156-1-201201031-00001 Taebel, S.W. (1995, October). Supreme Court ruling reduces GAAP’s authority in Medicare cases. Healthcare Financial Management, 49(10)