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Assessing fluid balance Urine output monitoring and 24-hour fluid balance This is an important part of the clinical evaluation of charts are essential in unwell patients order wellbutrin sr 150mg overnight delivery. Daily weights are patients with a variety of illnesses purchase wellbutrin sr 150 mg amex, which may affect the useful in patients with fluid overload particularly those Chapter 1: Fluid and electrolyte balance 3 with renal or cardiac failure. Oliguria (urine output cardiac failure, and these patients may require in- below 0. A lowurine output may be due to prere- Further investigations and management depend on the nal (decreased renal perfusion due to volume depletion underlying cause. Baseline and serial U&Es to look for or poor cardiac function), renal (acute tubular necrosis renal impairment (see page 230) should be performed. In previously fit patients, particularly if there is raymay show cardiomegaly and pulmonary oedema. However, the management is hypoxia due to underlying lung disease or pulmonary verydifferent in fluid overload or in oliguria due to other oedema. In cases of doubt (and where Hypernatraemia appropriate following exclusion of urinary obstruction) afluidchallengeof∼500mLofnormalsalineoracolloid Definition (see page 9) over 10–20 minutes may be given. Incidence previous history of cardiac disease, elderly or with renal This occurs much less commonly than hyponatraemia. Patients should be reassessed regularly (initially usually within 1–2 hours) as to the effect of treatment on Sex fluid status, urine output and particularly for evidence M = F of cardiac failure: r If urine output has improved and there is no evidence Aetiology of cardiac failure, further fluid replacement should be This is usually due to water loss in excess of sodium loss, prescribed as necessary. Those r If the urine output does not improve and the patient at most risk of reduced intake include the elderly, infants continues to appear fluid depleted, more fluid should and confused or unconscious patients. The normal physiological response to a rise in extracel- r If hypotension persists despite adequate fluid replace- lular fluid osmolality is for water to move out of cells. Pa- ment, this indicates poor perfusion due to sepsis or tients become thirsty and there is increased vasopressin 4 Chapter 1: Principles and practice of medicine and surgery release stimulating water reabsorption by the kidneys. Urine output and plasma Changes in the membrane potential in the brain leads to sodium should be monitored frequently. The under- impaired neuronal function and if there is severe shrink- lying cause should also be looked for and treated. Cellsalsobegintoproduceorganicsolutes allowedtodrinkfreelyasthisisthesafestwaytocorrect after about 24 hours to draw fluid back into the cell. Patients may be irritable or tired, pro- is less hypertonic than the plasma so this will help to gressing to confusion and finally coma. Signs of fluid over- load suggest excessive administration of salt or Conn’s normal saline (0. There may be neurological worsening hyperglycaemia which can alter the osmo- signs such as tremor, hyperreflexia or seizures. Complications Prognosis Hypernatraemicencephalopathyandintracranialhaem- The mortality rate of severe hypernatraemia is as high as orrhage (may be cerebral, subdural or subarachnoid) 60% often due to coexistent disease, and there is a high may occur in severe cases. Hyponatraemia Investigations Definition r The diagnosis is confirmed by the finding of high Aserumsodium concentration <135 mmol/L. Serum glucose and urine sodium, potassium and osmolality should also be re- Incidence quested. If there is raised urine osmolality, this is a sign Occurs relatively commonly, with 1% of hospitalised pa- that the kidneys are responding normally to hyperna- tients affected. Hyponatraemia with Congestive cardiac failure, cirrhosis, r In psychogenic polydipsia, patients drink such large fluid overload nephrotic syndrome Renal failure volumes of water that the ability of the kidney to ex- Severe hypothyroidism crete it is exceeded. The brain is most sensi- Opiates, ecstasy tive to this and if hyponatraemia occurs rapidly oedema develops, leading to raised intracranial pressure, brain- stem herniation and death. If hyponatraemia develops it is acute or chronic and whether there is fluid depletion, more slowly, the cells can offset the change in osmolality euvolaemia or fluid overload. This reduces the degree r Acute hyponatraemia is usually due to vomiting and of water movement and there is less cerebral oedema. The severity depends on the ceases and the kidneys rapidly excrete the excess water degree of hyponatraemia and the rapidity at which (up to 10–20 L/day). In severe cases, the patient may have seizures water there needs to be the following: r or become comatose. It is important to take a careful Adequate filtrate reaching the thick ascending loop of drug history, including the use of any illicit drugs such Henle (where sodium is extracted to produce a dilute as heroin or ecstasy. This is impaired in renal failure and hypo- of fluid depletion or fluid overload (see page 2). Investigations r Adequate active reabsorption of sodium at the loop of To determine the cause of hyponatraemia the following Henle and distal convoluted tubule, this is impaired tests are needed: the plasma osmolality, urine osmolality by all diuretics. Almost all of the body’s potassium stores are intracellu- r Urine osmolality helps to differentiate the causes of lar, with a high concentration of potassium maintained hyponatraemia with a low plasma osmolality.

These serve as important carriers of nitrogen from the periphery (skeletal muscle) to the intestine and liver cheap wellbutrin sr 150 mg without prescription. In the small intestine generic wellbutrin sr 150 mg on-line, glutamine is extracted and metabolized to ammonia, alanine, and citrulline, which are then conveyed to the liver via the portal circulation (Harper et al. Nitrogen is also removed from amino acids by deamination reactions, which result in the formation of ammonia. A number of amino acids can be deaminated, either directly (histidine), by dehydration (serine, threonine), by way of the purine nucleotide cycle (aspartate), or by oxida- tive deamination (glutamate). These latter two processes are important because glutamate and aspartate are recipients of nitrogen by transamination from other amino acids, including alanine. Glutamate is also formed in the specific degradation pathways of arginine and lysine. Thus, nitrogen from any amino acid can be funneled into the two precursors of urea synthesis, ammonia and aspartate. Urea synthesis takes place in the liver by the cyclic pathway known as the Krebs-Henseleit cycle. The remaining part of the cycle involves the resynthesis of arginine using nitrogen from ammonia and aspartate. Thus, although arginine is the direct precursor of urea, it is not consumed in the process, as the nitrogen excreted as urea is all derived from ammonia and aspartate. After synthesis, the urea is carried by the circulation from the liver to the kidney, where it is excreted into the urine. Although the excretion of urea dominates nitrogen excretion as a whole, significant quantities of ammonium ions are also excreted. There are some metabolic pathways, notably the purine nucleotide cycle, whereby purine nitrogen is converted to ammonium ions. It is generally believed that much of the ammonia produced by this cycle in skeletal muscle is transported in the blood as glutamine. Some of this glutamine is metabolized in the kidneys, where the enzyme glutaminase leads to the release of ammonium ions and glutamate. This glutamate, after losing its amino group, is then utilized in the synthesis of glucose in the kidney. The generation of ammonium ions from glutamine has a specific role in acid–base homeostasis, as ammonium ion excretion serves as the main vehicle for the excretion of excess hydrogen ions to prevent acidosis. Carbon Metabolism For most amino acids, removal of the amino nitrogen group generates their ketoacid analogues. Many of these are already in a form for entry into the pathways of oxidative metabolism (Figure 10-3). All the others have specific degradation systems that give rise to intermediates that can be metabolized in these oxidative pathways. This is particularly true in non-growing adults, who on average consume, and therefore oxidize, about 10 to 15 percent of their dietary energy as protein (Appendix Table E-17). The contribution of protein to energy needs may be significant during periods of energy restriction or following the utilization of the body’s limited endogenous carbohydrate stores. Protein oxidation also has been shown to rise considerably in highly traumatized or septic individuals, which results in large amounts of body protein loss; this loss can compro- mise recovery or even lead to death (see below) (Klein, 1990). It is much less in periods of chronic starvation because of various metabolic adaptations related to ketone utilization, or on protein-restricted diets. Whether glucose or fat is formed from the carbon skeleton of an amino acid depends on its point of entry into these two pathways. The carbon skeletons of other amino acids can, however, enter the pathways in such a way that their carbons can be used for gluco- neogenesis. This is the basis for the classical nutritional description of amino acids as either ketogenic or glucogenic (i. Some amino acids produce both products upon degradation and so are considered both ketogenic and glucogenic (Figure 10-3). It has been argued that the majority of hepatic amino acid catabolism is directed in an obligatory fashion to glucose synthesis (Jungas et al. This cycle also involves the peripheral synthesis of glutamine, an amino acid that is utilized in substantial quantities by the intestinal cells in which it is used for energy and for the synthesis of proline, citrulline, and nucleic acids. A significant proportion of the glucose synthesized in the liver is due to recapture and recycling via the liver of 3-carbon units in the form of lactate derived from anaerobic glucose breakdown in muscle (the Cori cycle). Hepatic gluconeogenesis also occurs via the glucose–alanine cycle (a direct parallel of the Cori cycle) and the glucose–glutamine cycle. Since the nitrogen donors may be either glucogenic or ketogenic amino acids, these cycles function as mechanisms for transporting nitrogen from the periphery to the liver as well as for glucose production. The cycle involving glutamine transport from the periphery to the gastrointestinal tract is also vital to the synthesis of arginine and proline and is critical to the preven- tion of the build up of excessive ammonia in the circulation. Nonprotein Pathways of Amino Acid Nitrogen Utilization Although in general the utilization of dietary amino acids is dominated by their incorporation into protein and their role in energy metabolism, amino acids are also involved in the synthesis of other nitrogenous com- pounds important to physiological viability as shown in Table 10-5. Some pathways have the potential for exerting a substantial impact on the utili- zation of certain amino acids, and may be of potential significance for the requirements for these amino acids. This is particularly true for glycine, which is a precursor for six nitrogenous compounds, as shown in Table 10-5.

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Colorectal Cancer The World Cancer Research Fund and American Institute for Cancer Research (1997) reviewed the literature linking foods buy 150mg wellbutrin sr amex, nutrients wellbutrin sr 150 mg sale, and dietary patterns with the risk of human cancers worldwide. Data from five case-control studies showed an increase in colorectal polyps and colorectal cancer risk across intakes of sugars and foods rich in sugars (Benito et al. The subgroups studied showed an elevated risk for those consum- ing 30 g or more per day compared with those eating less than 10 g/d. Others have concluded that high consumption of fruits and vegetables, as well as the avoidance of foods containing highly refined sugars, are likely to reduce the risk of colon cancer (Giovannucci and Willett, 1994). In many of the studies, sugars increased the risk of colorectal cancer while fiber and starch had the opposite effect. One investigator suggested that the positive association between high sugars consumption and colorectal cancer reflects a global dietary habit that is generally associated with an increased risk of colorectal cancer and may not indicate a biological effect of sugars on colon carcinogenesis (Macquart-Moulin et al. Burley (1997) concluded from a review of the available literature that there was insufficient evidence to conclude whether sugars had a role in colon cancer. At a time when populations are increasingly obese, inactive, and prone to insulin resistance, there are theoretical reasons that dietary interventions that reduce insulin demand may have advantages. In this section of the population, it is likely that more slowly absorbed carbohydrate foods and low glycemic load diets will have the greatest advantage. Data from long-term clinical trials on the effects on energy intake are lacking and further studies are needed in this area. Because not all micronutrients and other nutrients such as fiber were not examined, the association between added sugars and these nutrients it is not known. While it is recognized that hypertriglyceridemia can occur with increasing intakes of total (intrinsic plus added) sugars, total sugars intake can be limited by minimizing the intake of added sugars and con- suming naturally occurring sugars present in nutrient-rich milk, dairy prod- ucts, and fruits. Intake Assessment Median intakes of added sugars were highest in young adults, particu- larly adolescent males (35. At the 95th percentile of intake, added sugars intakes were as high as 52 tsp (208 g or 832 kcal) for men aged 19 to 50 years. Interaction of dietary sucrose and fiber on serum lipids in healthy young men fed high carbohydrate diets. Studies in human lactation: Milk composition and daily secretion rates of macronutrients in the first year of lactation. Insulin resistance of puberty: A defect restricted to peripheral glucose metab- olism. Energy and macronutrient content of human milk during early lactation from mothers giving birth prematurely and at term. Effects of growth hormone releasing hormone on insulin action and insulin secretion in a hypopituitary patient evaluated by the clamp technique. Glucose metabolism during fasting through human pregnancy: Comparison of tracer method with respiratory calorimetry. Ketosis, weight loss, uric acid, and nitrogen balance in obese women fed single nutrients at low caloric levels. Measurement of “true” glucose production rates in infancy and childhood with 6,6-dideuteroglucose. The effects of physiologic amounts of simple sugars on lipoprotein, glucose, and insulin levels in normal subjects. A quantitative assess- ment of plasma homocysteine as a risk factor for vascular disease: Probable benefits of increasing folic acid intakes. Thermogenic capacity of brown adipose tissue is reduced in rats fed a high protein, carbohydrate-free diet. Balance of carbohydrate and lipid utilization during exercise: The “crossover” concept. Glycemic index in the diet of European outpatients with type 1 diabetes: Relations to glycated hemoglobin and serum lipids. Reassessing the effects of simple carbohydrates on the serum triglyceride responses to fat meals. Prediction of glycemic response to mixed meals in noninsulin-dependent diabetic subjects. Low glycaemic index starchy foods improve glucose control and lower serum cholesterol in diabetic children. Effect of source of dietary carbohydrate on plasma glucose, insulin, and gastric inhibitory polypeptide responses to test meals in subjects with noninsulin-dependent diabetes mellitus. The 24- hour excursion and diurnal rhythm of glucose, insulin, and C-peptide in normal pregnancy. Glucose kinetics in nondiabetic and diabetic women during the third trimester of pregnancy. Oxi- dation and metabolic effects of fructose or glucose ingested before exercise. Changes in brain weights during the span of human life: Relation of brain weights to body heights and body weights.

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Some treatment medications are used to help the brain Medications are being developed to inter- • Nicotine replacement adapt gradually to the absence of the fere with these triggers to help patients sus- therapies (available as a patch purchase 150 mg wellbutrin sr free shipping, abused drug generic wellbutrin sr 150 mg with visa. They can help • Varenicline How do behavioral therapies treat patients focus on counseling and other psy- n Opioid Addiction chotherapies related to their drug treat- drug addiction? Gaining the ability to stop abusing drugs is just one part of a long and complex recovery process. When people enter treatment for a sub- stance use disorder, addiction has often taken over their lives. The compulsion to get drugs, take drugs, and experience the effects of drugs has dominated their every waking moment, and abusing drugs has taken the place of all the things they used to enjoy doing. It has disrupted how they function in their family lives, at work, and in the z Cognitive Behavioral Therapy seeks to help patients recognize, avoid, community, and has made them more likely to suffer from other seri- and cope with the situations in which they are most likely to abuse drugs. Because addiction can affect so many aspects of a per- son’s life, treatment must address the needs of the whole person to be z Contingency Management uses positive reinforcement such as providing successful. This is why the best programs incorporate a variety of reha- rewards or privileges for remaining drug free, for attending and participating bilitative services into their comprehensive treatment regimens. Treatment counselors may select from a menu of services for meeting z Motivational Enhancement Therapy uses strategies to evoke rapid and the specific medical, psychological, social, vocational, and legal needs internally motivated behavior change to stop drug use and facilitate treat- of their patients to foster their recovery from addiction. For more information on substance use disorder treatment, z Family Therapy (especially for youth) approaches a person’s drug see Principles of Drug Addiction Treatment: A Research-Based problems in the context of family interactions and dynamics that may con- Guide (www. Special initiatives target students and teachers as well as designated populations and ethnic groups. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2014. From coca leaves to crack: the effects of dose and routes of administration in abuse liability. Dynamic mapping of human cortical development during childhood through early adulthood. The interrelationship between substance use and precocious transitions to adult statuses. Monitoring the Future national survey results on drug use: 1975-2013: Overview, key findings on adolescent drug use. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Facilitation of sexual behavior and enhanced dopamine efflux in the nucleus accumbens of male rats after D-amphetamine behavioral sensitization. Homologies and differences in the action of drugs of abuse and a conventional reinforcer (food) on dopamine transmission: an interpretive framework of the mechanism of drug dependence. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. The health consequences of involuntary exposure to tobacco smoke: a report of the Surgeon General. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2006. Department of Health and Human Services, Centers for Disease Control and Prevention; 2007: Also available at: http://www. Global Health in the 21st Century, published by Jossey-Bass, New York, edited by C Everett Koop, Clarence E Pearson and M Roy Schwarz, 2000. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. Tobacco and alcohol are generally the most commonly used drugs amongst South African youth. Although polysubstance abuse is common in South Africa, cannabis is the most commonly used illicit substance amongst youth (Peltzer 2003). A study by Reddy et al in 2010 reported that 12% of South African learners had ever used at least one illegal drug such as heroin, mandrax and cocaine. Given the medical and social harm caused by these drugs, it is important to understand the extent of their use amongst sub populations and explore the effective ways to combat them.

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Duration – Depending on indication and clinical response Contra-indications buy wellbutrin sr 150 mg with visa, adverse effects cheap 150mg wellbutrin sr overnight delivery, precautions – Do not administer to patients allergic to cephalosporins or penicillins (risk of cross-sensitivity). Contra-indications, adverse effects, precautions – Do not administer to patients with allergy to cephalosporins or penicillins (cross-sensitivity may occur) and to neonates with jaundice (risk of bilirubin encephalopathy). Contra-indications, adverse effects, precautions – Do not administer to children under 1 year. In these events, stop treatment immediately; • gastrointestinal disturbances, peripheral and optic neuropathies. If used during the 3rd trimester, risk of grey syndrome in the newborn infant (vomiting, hypothermia, blue-grey skin colour and cardiovascular depression). In these events, stop treatment immediately; • gastrointestinal disturbances, peripheral and optic neuropathies. Duration – Change to oral treatment as soon as possible Contra-indications, adverse effects, precautions – Do not administer to patients with closed-angle glaucoma, prostate disorders; to elderly patients with dementia (e. Dosage – Severe staphylococcal and/or streptococcal infections Neonate 0 to 7 days (< 2 kg): 10 mg/kg/day in 2 divided infusions Neonate 0 to 7 days (≥ 2 kg): 15 mg/kg/day in 3 divided infusions Neonate 8 days to < 1 month (< 2 kg): 15 mg/kg/day in 3 divided infusions Neonate 8 days to < 1 month (≥ 2 kg): 30 mg/kg/day in 3 divided infusions Child 1 month and over: 30 mg/kg/day in 3 divided infusions (max. Duration – Cellulitis, erysipelas: 7 to 10 days; pneumonia: 10 to 14 days; severe cutaneous anthrax: 14 days; necrotizing infections: according to clinical evolution. Contra-indications, adverse effects, precautions – Do not administer to patients with allergy to lincosamides or history of pseudo-membranous colitis. Do not use oral cloxacillin for completion treatment following parenteral therapy. Contra-indications, adverse effects, precautions – Do not administer to penicillin-allergic patients. Dosage and duration – The dosage range is variable, depending on the severity of symptoms and clinical response. Every 6 hours, discharge the content remaining in the electric syringe and prepare a new syringe for 6 hours. Remarks – Diazepam is subject to international controls: follow national regulations. Maximum dose: 150 mg/day Duration – Maximum 2 to 3 days; change to oral treatment as soon as possible. Contra-indications, adverse effects, precautions – Do not administer to patients with bradycardia, ill defined arrhythmia, coronary artery disease. Remarks – When administering nifurtimox-eflornithine combined therapy, the dosage of nifurtimox in children and adults is 15 mg/kg/day in 3 divided doses at 8-hour intervals. If the implant is inserted later (in the absence of pregnancy), it is recommended to use condoms during the first 7 days after the insertion. Contra-indications, adverse effects, precautions – Do not administer to patients with breast cancer, severe or recent liver disease, unexplained vaginal bleeding, current thromboembolic disorders. Remarks – Implants provide long term contraception, their efficacy is not conditioned by observance. Contra-indications, adverse effects, precautions – Administer with caution to patients with hepatic or renal impairment, cardiac disorders (bradycardia, heart rhythm disorders, etc. Stop treatment in the event of anaphylactic reaction, hepatic disorders or severe skin reaction. Remarks – For cryptococcocal meningitis, when amphotericin B is not available or not tolerated, fluconazole may be administered alone during the induction phase (same doses as the oral route). Duration – According to clinical response; – If prolonged use is required, change to oral treatment 3 hours after the last injection. Contra-indications, adverse effects, precautions – Do not administer in other types of oedema, especially those due to kwashiorkor. Given the risk of renal and auditory toxicity, do not prolong treatment unnecessarily. Contra-indications, adverse effects, precautions – Do not administer to patients with allergy to aminoglycosides o auditory and vestibular damage. Contra-indications, adverse effects, precautions – May cause: • vein irritation; • severe tissue damage (necrosis) in the event of extravasation. Remarks – 50% glucose solution is too viscous, concentrated and irritant to be used in children. If ready-made 10% glucose solution is not available: add 10 ml of 50% glucose per 100 ml of 5% glucose to obtain a 10% glucose solution. Contra-indications, adverse effects, precautions – Do not administer to patients with cardiac disorders (cardiac failure, recent myocardial infarction, conduction disorders, bradycardia, etc. Remarks – Haloperidol decanoate is a long-acting form used in the long-term management of psychotic disorders in patients stabilised on oral treatment (100 mg every 3 to 4 weeks). Start with an initial dose of 250 Iu/kg and adjust dosage according to coagulation tests.

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