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.

A Painful Childhood Experience Essay example -- essays research papers

Painful Childhood Experiences In a child’s world, there is always a lot of imagination. Children create worlds of their own out of their familiar surroundings, despite what adults tell them. The only way to let them realize the truth is to make them experience it, as Rosaura from â€Å"The Stolen Party† and An-mei from â€Å"Scar† do in their lives. Liliana Heker’s â€Å"The Stolen Party† and Amy Tan’s â€Å"Scar† share a similar theme. Both stories follow the perceptions of young girls. Although Tan’s â€Å"Scar† and Heker’s â€Å"The Stolen Party† share a distinct resemblance, they also differ. Rosaura suffers the pain that others give to her, but An-mei suffers it from her loved ones, such as her grandmother. The main similarity is that both Rosaura and An-mei suffered from the painful circumstances of their lives. Rosaura convinces herself that Luciana is her friend and that she has been invited to Luciana’s birthday party as any other guests. For Rosaura, there is the proof that every afternoon she goes to Luciana’s house and they do their homework together. That is all the evidence Rosaura needs to consider herself a friend to Luciana. She even helps out with some chores during the party thinking she has some sort of â€Å"special† status in the house because of her familiarity with Luciana’s home, as Heker states, â€Å"Rosaura was the only one allowed into the kitchen. Senora Ines, Luciana’s mother also says, â€Å"You yes, but not the others, they’re much too boisterous, they might break something.† Rosaura ha...

Adam & Eve Essay -- essays research papers

It is impossible to taste the sweet without having first tasted the sour. This is one of the many lessons found within Genesis 2.0 and more specifically the story of Adam and Eve. It is also from this twisted tale of betrayal and deceit that we gain our knowledge of mankind?s free will, and God?s intentions regarding this human capacity. There is one school of thought which believes that life is mapped out with no regard for individual choice while contrary belief tells us that mankind is capable of free will and therefore has control over hisown life and the consequences of his actions. The story of Adam and Eve and the time they spent in ?paradise? again and again points to the latter as the truth. Confirming that God not only gave mankind the ability to think for himself but also the skills needed to take responsibility for those thoughts and the actions that they produced. Within the Garden of Eden God placed two exquisite trees. Each quite different in its purpose, however both proved to play an integral role in the tale of man?s beginning. Perhaps the better known of the two, the tree of knowledge of good and evil, was the only one, which God imposed a contingency upon. ?You many freely eat of every tree of the garden; but of the tree of the knowledge of good and evil you shall not eat, for in the day that you eat of if you shall die.? Is this to imply that knowledge is perhaps more important and therefore more closely guarded than life? After just a first reading this may seem to be true, however upon further analysis it becomes apparent that God?s intention was not to imply that knowledge was more significant than life, but instead that it cannot be appreciated without first possessing knowledge of both good and evil. See the man has become like one of us, knowing good and evil; and now, he might reach out his hand and take also from the tree of life, and eat, and live forever. God knew that since both Adam and Eve had now gained knowledge of both good and evil they would soon learn to really appreciate life and all it has to offer. And for this reason the couple was expelled from paradise. Had Eve ignored the serpent and refused to eat from the tree of knowledge of good and evil perhaps civilization would still exist as nirvana. However happiness and in effect perfection is relative. A beautiful spring day is only as beautiful as the worst s... .... By explicitly telling Adam and Eve to stay away from the tree of knowledge, God in effect inhibited man?s free will. All in all the actions of Eve were neither good nor evil, but instead necessary. Through her actions she brought to light the evils of the world, and as a result man is able to appreciate that which is good. Moreover one cannot blame Eve for what she did because although as we have seen God did instill upon mankind free will, he used his threats as a means of manipulating this gift. Although there were many trees in the Garden of Eden, having the tree of knowledge of good and evil forbidden created mystery for Eve, and therefore drew her to it over the tree of life. And once both Adam and Eve choose with their own free will to eat from the tree of knowledge of good and evil immortality is no longer an option. Now that man is knowledgeable enough to appreciate immortality, God removes it as an choice. In a way this story shows us the flaws of both man and God. Man in that he is tempted by that which is forbidden and does not always respect the orders of those in a position of authorit y; And God is shown to be somewhat devious and perhaps even malicious at times. Adam & Eve Essay -- essays research papers It is impossible to taste the sweet without having first tasted the sour. This is one of the many lessons found within Genesis 2.0 and more specifically the story of Adam and Eve. It is also from this twisted tale of betrayal and deceit that we gain our knowledge of mankind?s free will, and God?s intentions regarding this human capacity. There is one school of thought which believes that life is mapped out with no regard for individual choice while contrary belief tells us that mankind is capable of free will and therefore has control over hisown life and the consequences of his actions. The story of Adam and Eve and the time they spent in ?paradise? again and again points to the latter as the truth. Confirming that God not only gave mankind the ability to think for himself but also the skills needed to take responsibility for those thoughts and the actions that they produced. Within the Garden of Eden God placed two exquisite trees. Each quite different in its purpose, however both proved to play an integral role in the tale of man?s beginning. Perhaps the better known of the two, the tree of knowledge of good and evil, was the only one, which God imposed a contingency upon. ?You many freely eat of every tree of the garden; but of the tree of the knowledge of good and evil you shall not eat, for in the day that you eat of if you shall die.? Is this to imply that knowledge is perhaps more important and therefore more closely guarded than life? After just a first reading this may seem to be true, however upon further analysis it becomes apparent that God?s intention was not to imply that knowledge was more significant than life, but instead that it cannot be appreciated without first possessing knowledge of both good and evil. See the man has become like one of us, knowing good and evil; and now, he might reach out his hand and take also from the tree of life, and eat, and live forever. God knew that since both Adam and Eve had now gained knowledge of both good and evil they would soon learn to really appreciate life and all it has to offer. And for this reason the couple was expelled from paradise. Had Eve ignored the serpent and refused to eat from the tree of knowledge of good and evil perhaps civilization would still exist as nirvana. However happiness and in effect perfection is relative. A beautiful spring day is only as beautiful as the worst s... .... By explicitly telling Adam and Eve to stay away from the tree of knowledge, God in effect inhibited man?s free will. All in all the actions of Eve were neither good nor evil, but instead necessary. Through her actions she brought to light the evils of the world, and as a result man is able to appreciate that which is good. Moreover one cannot blame Eve for what she did because although as we have seen God did instill upon mankind free will, he used his threats as a means of manipulating this gift. Although there were many trees in the Garden of Eden, having the tree of knowledge of good and evil forbidden created mystery for Eve, and therefore drew her to it over the tree of life. And once both Adam and Eve choose with their own free will to eat from the tree of knowledge of good and evil immortality is no longer an option. Now that man is knowledgeable enough to appreciate immortality, God removes it as an choice. In a way this story shows us the flaws of both man and God. Man in that he is tempted by that which is forbidden and does not always respect the orders of those in a position of authorit y; And God is shown to be somewhat devious and perhaps even malicious at times.

Management on Middle Adulthood

Middle adulthood begins at the age of 40 – 60. This is a time when you can†t believe where the time went. It seems like just yesterday you were graduating from college, got married, and had children. Your children are now approaching young adulthood, pushing you into the next stage of life, middle adulthood. You look in the mirror and all the signs of middle age are starting to set in. You notice wrinkles, gray hair, flabby skin and you†re having trouble reading the menu. You begin to reassess you life. Are you happy with what you have accomplished in life so far? Do you have good family relationships? Is your career on track? Are you happy with yourself? There are many conflicts with both men and women during this period of life. One conflict very important to both men and women is the bodily issue. Our body weight starts to change. Fat seems to be redistributed to the hips, stomach and trunk; our complexions become drier and wrinkles start to appear. Our skin doesn†t seem to be as resilient as it was in our 20†³s and 30†³s. In women there is a drop in bone mass, due to the slow depletion of estrogen. Menopause is fast approaching, followed up with all the negative health complications that follow this phase. This is the beginning of a slowness of our psychomotor performance. Our reaction time to specific situations is not as quick, and our physical stamina is not as strong as it used to be. All these developments affect how men and women feel about themselves. Particularly women, begin to interpret these changes in a negative way. Some view themselves as sexually unattractive. Men, on the other hand, don†t seem to be as concerned about their physical appearance, since society has placed much of the physical importance on the women. This is a time where we need to accept these failings and move towards more important issues. This is also a time when men and women become more health conscious. We all know of the major diseases that cause premature deaths during middle adulthood, such as cancer and heart disease. When you†re a young adult, you don†t think about these health issues as you would during middle adulthood. There is more of a concern to take better care of our health, such as heathy diets, cardiovascular activity, resistance training, and not smoking. We might be better prepared for later adulthood, if we lead a healthy lifestyle. We start to realize our mortality. As most people live to be about 85, we realize that at 40, we†re almost half-way there. During this time, there may be turmoil in the family, marital distress, and general dissatisfaction with our lives. Many people during this time go through what we call the â€Å"mid-life crisis†. A mid-life crisis may be caused by many different issues. During the early 30†³s, the woman†s primary duty is child rearing and may also be pursuing a career. Most men focus on their job careers. Sometimes these two people are heading in the same direction, but may be on two different parallel roads. Men may realize their mortality and may express their turmoil and self doubts by reverting to adolescent type behavior. Some men may accept new relations with younger women as a way of dealing with their conflicts. Some women may also suffer from self doubt and their inevitable mortality during their 40†³s, but various studies have indicated that women can manifest a mid-life crisis during their early 30†³s, 40†³s and 60†³s. This is also a time when men and women assess their careers by questioning whether or not they still enjoy their career choices and their achievement in the chosen field. If not, maybe it†s time to make improvements, such as furthering your education, improving intellectually, which will make an individual more marketable. When women go through a mid-life crisis, their crisis evolves around interpersonal relationships in the family rather than aging. Men seem to be more involved with the aging factor. Women may go through the 'empty nest† syndrome. Their children are becoming young adults and leaving the ‘nest†. For some women, that have devoted most of their time to child rearing with a small amount devoted to career, this may be a very difficult time. This leaves just you and your husband. A time for reacquaintance and renewal of your relationship. As we progress into the 40†³s. we also see an emergence of more feminine/masculine aspects of self. Women start to take on a more masculine qualities, such as assertiveness and independence; while men tend to move towards a more calm, intimate status. I have touched upon some of the major conflicts of middle adulthood. For most people this can be a smooth transition and for others there may be difficulties. I believe that the 40†³s – 60†³s is a time to reassess your life, to check and balance, and to go forward to one†s later adulthood.

H&M in Fast Fashion: Continued Success Essay

Q1) Evaluate the external environment in which H&M operates in. External environment refers to the challenging and complexity in which the firm operates. It is important to highlight the factors of the external environment because it is very critical to the success of the firm. PESTEL model and Porter’s 5 Forces (P5F) models will be used to evaluate the external environment of H&M. These models will determine how challenging and attractive the environment is for H&M. 1. PESTEL PESTEL highlights 6 environmental forces namely political, economic, social, technological, ecological and legal (Johnson, et al. 2014). This model analyses the general environment that influences the industry and the organisations in it as well as how challenging the environment is to operate. 1.1 POLITICAL H&M is subjected to political pressures from the labour rights movement especially in low-wage countries. H&M has outsourced its manufacturing line to low-cost countries. H&M has no or little control over the operation in those countries. Hence, the firm would be closely scrutinised by the labour rights movement to spot any abuse in the rights of employee e.g. poor working condition. Government expansion and international trade policies would greatly impact the growth of the industry and increases competition. Threat 1.2 ECONOMIC H&M will not be spared from the increase in cotton prices and rising product cost in Asia. Economic downturn will have an impact on all the stakeholders in the environment especially the customers. Demand for luxury goods would decline for customers who are price-sensitive. They would then consider H&M competitors that offers similar goods which is are much cheaper than H&M or  go for substitutes. Threat 1.3 SOCIAL Due to the ‘fast fashion’ business, customers taste in high fashion is constantly evolving. Customers are now more educated and their demand for good quality products at low prices have increased. H&M could meet the needs of the customer as it has the advantage of being a first mover in the fast fashion business. Opportunity 1.4 TECHNOLOGICAL The emergence of technologies such as Facebook, Twitter, and YouTube allows organisations to reach out to its customers more quickly and effectively. H&M uses these online social platforms as a way to be closer to their customers as well as sharing and updating its activities to its fanbase. Opportunity 1.5 ECOLOGICAL Due to education and high awareness of the importance of conserving and going ‘green’, H&M has created a special collection of clothing line using sustainable or eco-friendly materials. Opportunity 1.6 LEGAL Legal refers to the restriction or liberalisation of legislative and regulatory constraints or changes. Organisation in the environment would not be able to avoid this particular external environment factor therefore organisation has to embrace this legal aspect. Liberalisation of the international trade has resulted in an increase of the number of suppliers globally and hence intensifying the competition among manufacturers in low-wage countries Threat From the PESTEL analysis, H&M is in a moderately competitive environment where both threats and opportunities factors are in equal balance. Therefore, H&M has to exploit the opportunities available in social, technological and ecological factors. As for the threats, H&M has to embrace them and develop strategies to overcome or steer away from them too. 2. Porter’s 5 Forces (P5F) P5F helps to identify the attractiveness of an industry in terms of 5 competitive forces namely; threat of entry, threat of substitute, power of buyers, power of suppliers and the extent of rivalry between competitors (Johnson, et al. 2014). 2.1 THREAT OF ENTRY Factor H L Case evidence Effect (High/low) Scale of experience Needs large capital to compete with the incumbents in the environment. Low Access to supply /distribution channels Plenty of suppliers available to choose from. High Expected retaliation Costly to compete with incumbent as they have the economies of scale. Low Legislation or government action Liberalisation of international trade has resulted in the increase of number of suppliers. High Differentiation There is differentiation in style and concept of the apparel industry. High High threat of new entries would indicate that the industry is attractive and and could decrease the profit margin of H&M e.g.UNIQLO. However, these competitors must have sufficient financial resources to compete with the current incumbent in the industry. These new entries would have to build up experience over time in order to be on par with existing competitors. The competitive rivalry is moderately high because the market is fragmented and there are few major incumbents in the industry. With intense rivalry e.g. Zara, each competitor is vigorously competing against the rest in order to have a market share in this apparel industry. From the P5F analysis, H&M is operating is a highly attractive market where the threats of entry is high, threats of substitute is low, power of buyer is high, power of supplier is low and high rivalry. Overall, H&M is operating in a highly competitive and attractive external environment. Therefore H&M must take steps to look into its resources and identify its strategic capabilities in order to stay ahead of the competition. Q2a) Identify and discuss the strategic capabilities of H&M. Strategic capabilities refer to the capabilities of an organisation that contributes to its long-term survival or competitive advantage (Johnson, et al. 2014). The components of strategic capabilities are resources (what the firm has) and competences (what they do well). The table below lists down all the resources and competences of H&M. This table also identifies the type of capabilities for each competences namely threshold and distinctive capabilities. Threshold capabilities refer to competences that are needed for the organisation to meet the necessary requirements to compete in a given market; and distinctive capabilities look into competences that are required to achieve competitive advantage (Johnson, et al. 2014). Resources Competences Type of capabilities Organisational resources Competent leader who has a good business acumen Distinctive Physical resources Stores position in the best location Threshold Rapid expansion into other countries and new markets Threshold Has 2206 stores in 43 countries Distinctive Ability to deliver collection within a month of initial design Distinctive Efficient integrated logistic team Distinctive Technological resources Owns its own clothing line and trends Distinctive Human resources 200 talented designers and pattern makers Distinctive Empowerment of store managers with autonomy Threshold Collaboration with famous designers to produce new collection Distinctive Innovation resources Building creative window and store displays Distinctive Created a special collection using sustainable materials (CSR) Threshold Reputational resources Pioneered in ‘fast-fashion’ business Distinctive Emphasize ‘cheap and chic’ business model Distinctive Strong branding Distinctive Culture Instils the importance of core values in employees Threshold Strong corporate culture (spirit of H&M) – Encourages experimentation, trial and error learning, decision making, initiatives, try new ideas Distinctive Information technology (IT) Efficient reporting of sales Threshold Establishment of strong social media presence Threshold Effective information sharing software Threshold Based on the table above, H&M has more distinctive capabilities than threshold. H&M now could recognise the different types of capabilities and which are the ones the organisation should focus on and turn them into sustainable competitive advantage generating above average returns. H&M has to put more effort in the distinctive capabilities such as competent leadership, physical assets such as stores, its ever-changing collection of designer clothes, integrated logistics function, its talented employees, successful collaborations, creative window display, its fast-fashion business model, strong branding and lastly its strong corporate culture. With the SWOT analysis, H&M has to continue its efforts strengthening its strength so that it would give the organisation an advantage over its rivals. As for its weaknesses, H&M could either eliminate or work on weaknesses by turning them into strengths. H&M should seize the opportunities when the time is right. Lastly, threats should be avoided or steer away from them. Identify the key issues, challenges and opportunities facing H&M. The key issues of H&M are whether their existing resources, capabilities, practices and knowledge are sufficient to keep up with competition. Another key issue is the threat of new and vigorous entrants. The answer to these is yes, H&M could keep up with the competition due to substantial resources, strategic distinctive capabilities, strong value creating activities, strong practices and knowledge. H&M challenges would be revitalising and redefining its strategic capabilities in order to be sustainable in this apparel industry. H&M has to keep up with the latest fashion trends and continue to explore other avenues to create value to its value chain activities. Another challenge is to stay ahead of its competitors especially the threats by new and vigorous new entrants, by moving fast and reaching large market based by applying a simple business model – ‘cheap and chic’. The opportunities would be v enturing into new areas where H&M has yet to explore e.g. online shopping, opening the largest store in the world on Fifth Avenue, New York. H&M has to evaluate if these opportunities could give them the competitive edge against its competitors and generating an above average returns. Based on preceding analysis, formulate and discuss appropriate strategies that you would recommend to H&M in order for it to achieve above-average returns in the future. H&M is now operating a cost leadership strategy. This strategy involves becoming the lowest-cost organisation in the industry (Johnson, et al. 2014). Cost leadership strategy is an integrated set of actions taken to produce goods or services with features that are acceptable to customers at the lowest cost (Ireland, Hoskisson and Hitt 2013) Based on preceding analysis, it is timely for H&M to review its business level strategy. Cost leadership strategy is not always the best strategy for H&M as there will always be the risk of being undercut on price especially during the economic downturn. Secondly, low cost has always been associated with cheap quality goods where products barely meet the market standard. H&M should be considering using the lock-in business strategy. This strategy is where customers become dependen t on H&M and are unable to use another supplier without substantial switching cost. With this lock-in strategy, copycats and substitutes of H&M products would have a hard time attracting customers. With customers securely locked in, H&M could charge prices which are well above cost. Lock-in strategies can be achieved in two ways mainly controlling complementary products/services and creating a proprietary industry standard (Johnson, et al. 2014). Another strategy which H&M could consider is differentiation strategies. Differentiation involves uniqueness along some dimensions that are sufficiently valued by customers to allow a price premium. Based on H&M’s strategic capabilities, one of its competitive advantage competences is having its own clothing line and trends. The fashion house could use this competency to carry out the differentiation strategy. With H&M’s large pool of over 200 talented designers and collaboration with famous top designers, customers would be willing to pay more for the latest style and fashion. With the unpredictability of the fashion industry, H&M has to be able to stay well ahead of its major competitors by reviewing its strategic capab ilities from time to time. Capabilities need to change and evolved into dynamic capabilities. Only dynamic capabilities have what it takes to be the key driver towards strategic change. Like what fashion model, Heidi Klum, from the fashion industry always said, â€Å"Today you are in but tomorrow, you might be out!† The same goes to the chosen strategy of H&M, cost leadership might  work today, but it won’t be the correct strategy tomorrow. Bibliography Ireland, R. Duane, Robert E. Hoskisson, and Michael A. Hitt. The Management of Strategy. Australia: South-Western Cengage Learning, 2013. Johnson, Gerry, Richard Whittington, Kevan Scholes, Duncan Angwin , and Patrick Regner. Exploring Strategy. Harlow: Pearson, 2014.

Critical Lens Essay on the book Night by Elie Wiesel Essay

â€Å"We must always take sides. Neutrality helps the oppressor, never the victim. Silence encourages the tormentor, never the tormented.† That quote is from Elie Wiesel in his Nobel Peace Prize Speech. I agree with the quotation. In the story Night by Elie Wiesel, many elements correspond to the quote and to the idea of silence and complicity. Wiesel says in his book that many different people were silent because they were not directly affected by the Holocaust, and thought that if they did something to try to stop it, then they themselves would get hurt. He also explained how people like Moshe the Beadle and other characters in Night who were humiliated by fellow Jews did not believe that the Holocaust was occurring. Overall, the Jews, God, and the German citizens were all silent during the Holocaust. Their silence encouraged the Nazis to gain strength and reach the magnitude of eventually massacring six million Jews. â€Å"I did not move. I was afraid,† (37) said the character Eliezer in Night. That quote refers to when his father is beaten at the concentration camp and Eliezer just stood there watching it and doing nothing to stop it. The setting of the story Night takes place in a small town of Transylvania in 1941. To this day Wiesel still feels guilty about his inaction. The silence of the victims and the lack of resistance to the Nazi threat is one way in which neutrality and silence helps the tormentors, or in this case the Nazis and never the victims who were the Jews. Even when Eliezer was being led to the fire pit and thought he was going to die, he did not try to run or escape. In the concentration camps, the Jews greatly outnumbered the Nazi soldiers. Maybe if they revolted then even though many would die in the attempt, many could still escape and the number of people who died would be insignificant to the amount of Jews who died when they did not rise up together. It is implied throughout the text that silence and passivity are what allowed the Holocaust to continue. Wiesel’s writing of Night is itself an attempt to break the silence, to tell loudly and boldly the new generation of people about the atrocities of the Holocaust. He feels that people need to know so that they can find out the warning signs and prevent anything so horrible from ever happening again. â€Å"Where is God? Where is He?† (61) someone behind Eliezer asked. This quote  from Night refers to when a child is hung in front of all the Jewish prisoners to scare them into behaving. â€Å"For more than half an hour the child in the noose stayed there, struggling between life and death, dying in slow agony under our eyes. And we had to look him full in the face. He was still alive when I passed in front of him. His tongue was still red, his eyes were not yet glazed.† (62) Behind Eliezer, he heard the same man as who said the above quotation asking: â€Å"Where is God now?† (62) And Wiesel heard a voice within himself say: â€Å"Where is He? Here He is–He is hanging here on this gallows. . . .† (62) Those quotes show that God was also silent during the Holocaust. It is the idea of God’s silence that Eliezer finds most troubling. Eliezer’s point of view during the story Night changes from not questioning why he prays, to believing that God is dead and does not care about him or any other person on earth. When a man asks, â€Å"Where is God?† (61) the only response is â€Å"total silence throughout the camp.† (61) Eliezer and his fellow Jews are left to wonder how an all-knowing, all–powerful God can allow such horror and cruelty to occur, especially to such devout worshipers. The existence of this horror, and the lack of a divine response, forever shakes Eliezer’s faith in God. At first Wiesel used to pray without questioning God’s existence. Now, Eliezer does not fast on the holy day of Yom Kippur and believes that God has died along with the boy that was hung. The silence of God shocks Eliezer and allows the Nazis to persecute them because the Jews hope for a miracle that never comes from a God who does not exist. â€Å"The opposite of love is not hate, it is indifference.† That quote is also from Elie Wiesel’s Nobel Peace Prize Speech. The German people living right next to the death camps such as Auschwitz and Buna could smell bodies being burnt, and could see the fire and smoke yet they did nothing. This is complicity, which is defined as the involvement as an accomplice in a questionable act or a crime (according to dictionary.com). The Germans were silent, and because of their silence, the tormentors and Nazis were able to further persecute their victims, who were the Jews and many other ethnic minorities that were used as scapegoats. In Night, Eliezer says, â€Å"Never shall I forget that nocturnal silence which deprived me, for all eternity, of the desire to live.† This famous quote can be interpreted to mean that  the silence of the Germans and the Allied forces is what really allowed the Jews to be murdered so heartlessly. Even though the German civilians did not do anything, Eliezer blames the Allied countries such as Great Britain and the United States for their slow response in reacting to the Nazi threat. It was said years after the Holocaust that if any powerful figure got on the BBC news radio station, telling all of the Jews to evacuate their homes and flee to Russia because all of the other Jews are disappearing, then more Jews might have been saved. Eliezer and his family were taken to Birkenau in 1944, when the war was already going on for many years. His family could have been warned and most likely saved from the Nazis. It was the neutrality and the lack of involvement of the Allied forces that led to the death of the Jews because they were not warned. In conclusion, the quote â€Å"We must always take sides. Neutrality helps the oppressor, never the victim. Silence encourages the tormentor, never the tormented† is valid because the silence of the Jews, God, the German civilians, and the Allied forces contributed to the mass murder of millions of people. All of these people in their own separate ways, due to their neutrality and silence during the Holocaust period, allowed the victims to be murdered. The Jews did not rise up against their tormentors, and therefore allowed themselves to be killed. God did not act to protect his â€Å"chosen people† and at the moment of a horrible sacrifice, God does not intervene to save innocent lives. The German people went along with Hitler’s grand scheme as puppets. Finally, the only way that the Jews could have had the opportunity of escaping their fate was if they were warned. The allies had the opportunity to warn the Jews, but didn’t, perhaps believing that other countries would warn the Jews. But they didn’t. â€Å"In Germany they came first for the Communists, and I didn’t speak up because I wasn’t a Communist. Then they came for the Jews, and I didn’t speak up because I wasn’t a Jew. Then they came for the trade unionists, and I didn’t speak up because I wasn’t a trade unionist. Then they came for the Catholics, and I didn’t speak up because I was a Protestant. Then they came for me, and by that time no one was left to speak up.† That quote is from Martin Niemoller and proves that â€Å"silence encourages the tormentor, never the tormented.†

Bas Luhrmann’s Romeo + Juliet Essay

Baz Luhrmann’s main aim from his Romeo and Juliet film was to create a film which would trickle the minds of youngsters, or what is also known as the MTV generation, who don’t enjoy watching Shakespeare’s plays. His main aim was getting the MTV generation to watch and ‘enjoy’ Shakespeare’s Romeo & Juliet without dieing of boredom. He did this by looking at the movies MTV generation watches today, which mainly includes technology, action, guns etc to get youngsters interested. What he concluded in the film which attracted youngsters was that he replaced the original assets used in the original play into modern equipment, for example, swords were changed to guns, old fashion clothes into today’s clothes etc but one thing which he kept in the original form is the dialogue, the script. He also had other aims which were to make a film so that youngsters world wide would want to watch it. The film was a success in the world as it made à ¯Ã‚ ¿Ã‚ ½98m worldwide, in America alone it made 46m so the film was a hit all over the world.  The prologue in the beginning of the film was set out to make us, the audience, understand what she is saying clearly. This was done by showing a news presenter on TV quite far away, she was wearing modern clothes but basically she was a normal news presenter to us. All she done did was read the prologue from the play. This simplifies the language used by Shakespeare as we think the words, which the news presenter is saying is in modern language but because it is set out in a modern way, we automatically presume it is in modern language and understand what she is saying. The layout of this is, a female TV presenter reading the prologue from the TV which is in a distance, but the camera slowly zooms into the TV so that at the end all we see is the news presenter reading the prologue with a picture over her left shoulder showing a broken ring and the title underneath which is ‘star crossed lovers’ all in modern day settings. The prologue also tells as that this is a story about two families who hate each other and who compete with each other to show who’s greater. The prologue, voice over, images, words, is used to guide audiences who didn’t completely understand the news presenter as it had images describing what she said, words written after it was said by the voice and images shown to describe what she meant. This simplified the whole prologue, you could almost say Baz Luhrmann was holding our hand and taking us through the prologue slowly again and again until we understood it. The images in the prologue were taken from the streets of America, they were mainly violence which is what consists in our society today. IT had fast camera action, for example, it zoomed in and from the Jesus statue, it had fast camera movements from the helicopter, from the streets, police pursues etc after each word or sentence was read out from the prologue, and if this wasn’t enough, Luhrmann put the words on the screen scrolling through or just appearing to show that audience what was said. IT had modern music in the background which includes hip hop, rock music etc to attract youngsters to watch the film without getting bored. Baz Luhrmann chose to begin like this because it was the most suitable way to keep the audience, especially the youngsters, to say ‘what happens next?’ and want to carry on watching the film without getting bored. Luhrmann’s main idea was to get the begging fast and furious to hold on to the audience and want them to understand Shakespeare’s script with them imitating what the words meant in movements, body language, how they said it etc. He used this because is most other films, the beginnings were started off with action to hold on to its audience without boring them and making want more. The gas station was the most important scene in the beginning of the film. This is because they used 170 different shots just to make up the first five minutes, this is because there was a lot of action, slow motion, fast movements, cameras zooming in and out, fast editing of certain scenes etc. IT started off with the Montague’s coming in the scene with their car in to one part of the gas station and the Capulet’s entering the scene on the other part of the gas station. The introduction of each character is set out by showing the characters and pausing them with their names on them. They introduce each side to us by zooming onto the bottom of their guns when they threaten each other, under each sides guns, their names are written which is the Capulet’s and the Montague’s. The fight starts off when the Montague’s see the Capulet’s, the Capulet’s scare the Montague’s and the Montague’s insult the Capulet’s by biting their thumb at the them. At this moment the head of the Montague’s come out and start the fight, straight away a shoot out starts and they shoot at each other. When they shoot at each other the camera uses slow motion, fast editing etc to show the audience action to get their focus on the film. The camera basically introduces the characters slowly and then uses fast editing thereafter. The music used in the film varies a lot as there was a mixture of music used, this ranged from, rock to spaghetti western. This were used in specific parts of the film. The beginning started off with classical when the dialogue was read out by a deep male voice, the part when the Montague’s are in their car is rock and hip hop, and the part where the Capulet’s are introduced is spaghetti western. There were also other sound effects used in the film when one of the Capulet’s had ‘SIN’ written on a metal plate above his tooth which was an animals voice which frightened the Montague’s. There’s also other sounds for instance ‘whoosh’ when bullets fly past their heads, music played when the characters are in slow motion etc This is all used to attract the audiences attention and to get them pumped up, the music is basically ion your face. Tybalt’s shoes makes a particular noise when he walks, this is ‘ching’, this noise particularly gets to the audience when he puts out a match in the gas station by rubbing the metal part on the match to the floor, this sends a shiver through the spines of some people which is used to get the full attention of some people or it makes them look at it in great detail. The representations of each gang is set out differently. Montague’s is introduced first and are shown as trouble makers, this is done by them being dressed up in normal casual wear, for instance, baggy colourful clothing, more open etc. The music used to show them is more of a rock type of song but it also features them listening to hip hop when one part of the music goes ‘the boys! the boys!’. They are shown to be the cool boys of the town who have a great car and ride around listening to loud music. They shout when they talk, this is to attract the audiences attention once again. They also chase off the sisters in the gas station by one of the members licking his nipple in front of them who he then confronts the Capulet’s. The Capulet’s are shown to be more serious with their gang but the representation of the Montague’s are shown as they are the hipsters of the area who are out for a laugh and a good time. This represents the Montague’s innocent in the shoot out and the Capulet’s of the more powerful side having a laugh with them with their powerful ook.