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In general 100 mg kamagra chewable, drugs in categories A and B were more likely than those in C and D to have been marketed for a long time order kamagra chewable 100mg free shipping, and both were more likely to have at least one fatal case of liver injury and reported cases of positive rechallenge kamagra chewable 100 mg fast delivery. However buy kamagra chewable 100 mg with visa, in categories C and D with one to 12 cases reported, it is still not clear whether these agents are really hepatoxic drugs. Category A Although drugs in this category (n = 48) were supposed to have >50 case reports of liver injury associated with the use of these drugs, 81% of the drugs had >100 cases reported. In Table 1, the category A drugs are illustrated with the indication and/or class of drug. Treatment with these drugs should motivate physicians to guide patients about potential symptoms of liver injury when taking these drugs and about prompt discontinuation if these symptoms occur. All except one entity (estrogens-progestins) or 98% had at least one convincing case that was associated with fatal outcome. All of these drugs except telithromycin had been approved for marketing for more than 15 years and 63% for more than 35 years [9]. The most common types of drugs were antimicrobials among 33% of the drugs, followed by drugs acting on the central nervous system (12. Although antimicrobials were the most common agents among drugs, antimicrobials were also the most common agents in categories B (30%), C (19%) and D (27%). There is unfortunately not enough room to discuss many of these well-documented hepatotoxic agents. As mentioned in the abstract, azathioprine and infliximab have in one study been found to be associated with the highest risk of liver injury [9]. Both hepatocellular and cholestatic injury has been described due to azathioprine [8,9]. Despite the common problem of hepatotoxicity with azathioprine, there is a lack of studies with a significant number of well-characterized patients with this type of liver injury. Drugs that, according to analysis of data in LiverTox [8], have been associated with more than 100 cases of drug-induced liver injury. This seems particularly true for drugs with reports of documented rechallenge, which had been reported in at least one case in 38% of the drugs [9]. In comparison with category A drugs, which almost exclusively had been associated with fatality, approximately 50% of category B drugs had been associated with a fatal outcome. Thus, in drugs with less frequent reporting of liver injury in category B, only 38% had rechallenge reported vs. Drugs in category B (>12 and >40 cases) that, according to analysis of data in LiverTox [8], have been associated with >30 published case reports of drug induced liver injury. Categories C, D and E Overall, 222/353 (63%) of drugs in LiverTox® with hepatotoxicity fall into categories C and D. Compared with category D, with only one to three cases reported, category C (<12 and >4 case reports) drugs were more likely to have rechallenge reports, with 26% vs. A positive rechallenge is usually defined with biochemical criteria, showing recurrence of liver test abnormalities upon readministration of the drug, due to either intentional or inadvertent re-exposure [4,5]. This is generally considered to be the gold standard of the diagnosis of drug-induced liver injury. A documented positive rechallenge provides more evidence of the hepatotoxicity of a Int. Given the frequency of case reports with drugs in categories A and B, there seems little doubt that drugs in these categories can lead to hepatotoxicity and little need to do a strict causality assessment of reports with these drugs. However, in category C, consisting of 4–11 case reports, the hepatotoxicity of some drugs can be put into question. Thus, it can be concluded that these drugs do not have a well-documented hepatotoxicity, although liver injury with their use cannot be excluded. The poorly documented exclusion of competing causes, as well as the use of other concomitant drugs, made a causality assessment difficult. It is very important that observations of hepatotoxicity of new drugs should lead to well-documented case reports with detailed clinical and biochemical information. Table 3 illustrates the five most common drugs associated with liver injury in at least three prospective studies. In India, anti-tuberculous drugs (58%), anti-epileptics (11%), olanzapine (5%), and dapsone (5%) were the most common causes [16]. The 10 most frequently implicated drugs were: amoxicillin-clavulanate, flucloxacillin, erythromycin, diclofenac, sulfamethoxazole/Trimethoprim, isoniazid, disulfiram, Ibuprofen and flutamide [12–14,21]. Drugs with an intermediate risk were amoxicillin-clavulanic acid and cimetidine, with a risk of one per 10 per 100,000 users [24]. The limitations of this study were the retrospective design with a lack of complete data regarding diagnostic testing and a lack of data on over-the-counter drugs and herbal agents [24]. Amoxicillin-clavulanate-induced liver injury was found in one of 2350 outpatient users, which was higher among those who were hospitalized already, one of 729. This might be due to a detection bias, with more routine testing of the liver in the hospital, but it cannot be excluded that sicker patients are more susceptible to liver injury from this drug. The incidence rates were higher than previously reported, with the highest being one of 133 users for azathioprine and one of 148 for infliximab. Acknowledgments: No specific grants were obtained for research work presented in this paper and no funds for publishing in open access. Discrepancies in liver disease labeling in the package inserts of commonly prescribed medications. Categorization of drugs implicated in causing liver injury: Critical assessment based upon published case reports. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: Current status and challenges. Drug-induced liver injury: An analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Single-center experience with drug-induced liver injury from India: Causes, outcome, prognosis, and predictors of mortality. The increased risk of hospitalizations for acute liver injury in a population with exposure to multiple drugs. A review of epidemiologic research on drug-induced acute liver injury using the general practice research data base in the United Kingdom. Acute and clinically relevant drug-induced liver injury: A population based case-control study. Sigurdsson and Gudmundur Thorgeirsson 1Solvangur Health Center of Hafnarfjo¨ rdur, 2Department of Family Medicine, University of Iceland, 3Department of Medicine, National University Hospital of Iceland.

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Management Cocaine intoxication: Initial management includes en- Incidence/prevalence suring a clear airway and ventilation if needed discount kamagra chewable 100 mg free shipping. Amphetamineandderivatives(includingecstasy)arethe 1 Seizures are treated with diazepam or lorazepam cheap kamagra chewable 100 mg online. Chapter 15: Alcohol and drugs of abuse 525 Pathophysiology 1 Seizures and agitation are treated with diazepam or Amphetamines are stimulant drugs with cardiovascular buy kamagra chewable 100mg amex, lorazepam buy 100 mg kamagra chewable mastercard. Multi- 2 Hypertension should be treated with diazepam or ple doses, taken to maintain euphoria, can lead to intox- if this is ineffective, intravenous glyceryl trinitrate ication, and feelings of anxiety and paranoia. The excre- tion of amphetamine depends on urine pH – acid urine increases its clearance. Ecstasy abuse Definition Clinical features Ecstasy is a semi-synthetic derivative of amphetamine Physical effects of an amphetamine-intoxicated state in- with hallucinogenic properties. A history should be taken of re- usually comes in tablets or capsules, which may have centandpreviousrecreationaldruguse,includingmeth- logos or pictures on them. Occasionally it is and social history should be taken, as well as a medical found in a powder form that is smoked or snorted. Incidence/prevalence Complications Ecstasy use continues to rise, doubling in the last 5 Medical complications include seizures, coma, tach- years. Acute ecstasy, with rates approaching 30% in university stu- hepatic failure has been reported. There have been over 200 deaths from the drug in tions include paranoia, eating disorders, hallucinations 15 years. If physical side-effects highly variable, but in addition idiosyncratic responses are present, U&Es, liver function tests, creatine kinase appear to occur, both in naıve and chronic users. Clinical features r Effects begin within an hour and usually last 4–6 Management hours, but may persist for 48 hours with very high In more than mild toxicity, patients should have cardiac doses. Increasedthirstcanbemarked,suchthatex- 5 Metabolic acidosis should be corrected with sodium cessive water intake occurs, leading to hyponatraemia. Mood effects are 6 Narrow complex tachycardias are treated with intra- of euphoria, and ecstasy is unique in its ability to make venous β-blockers. A psychiatric and social his- Overview of acute poisoning tory should be taken, as well as a medical history and examination. Definition Acute poisoning may result from accidental self- ingestion, deliberate self-harm or medical error. Complications Deaths: These appear to be due to cardiac arrhythmias, fulminant liver failure and neuroleptic malignant syn- Incidence/prevalence drome, which may cause acute renal failure, dissemi- Common presentation to A&E, commonest cause of nated intravascular coagulation and metabolic acidosis. Neuropsychiatric complications include memory and concentration loss, insomnia, hallucinations and flash- Age backs. Aetiology Many different substances are involved in poisoning, es- Management pecially in children (see Table 15. In severe toxicity, initial management includes ensuring aclear airway, and ventilation if needed. Clinical features 1 All patients should have cardiac, pulse, blood pressure Acutepoisoningshouldbeconsideredinanypatientpre- and temperature monitoring. A full physical examination glyceryl trinitrate, but in refractory hypertension con- should be made. Principles of management: Other neurological features include altered behaviour, r Reduction of absorption by emptying the stomach seizures, hallucinations, motor disturbances. However, r Cardiovascular system: Altered heart rate, arrhyth- lavage or induced emesis is contraindicated following mias, blood pressure instability. The patient must have an intact cough reflex dice, vomiting and diarrhoea, alcohol may be smelt or a cuffed endotracheal tube to protect the airway. Alternatively activated charcoal is useful for certain r Eyes: Miosis (constriction of the pupil is seen with drugs, ideally within 4 hours of ingestion dependent opiates and organophosphates) or mydriasis (dilation on the drug. Following an accidental These will depend on the presentation and the availabil- overdose social circumstances need to be considered ity of a reliable history. Patients presenting fol- mayhavetobeinvestigatedandmanagedasanacutecon- lowing deliberate ingestion require a psychiatric eval- fusional state or coma. Appropriate investigations may uation prior to discharge in order to assess their risk include of further self-harm and to identify and manage any r plasma paracetamol and salicylate levels. Accidental or deliberate overdose of paracetamol, caus- r blood gases to detect respiratory failure or metabolic ing liver damage. Complications Incidence These depend on cause and clinical state but may include Currently the commonest drug used for deliberate over- hypothermia, rhabdomyolysis and convulsions. In significant over- dose a prothrombin time, liver and renal function tests and a lactate should be checked and repeated at 24 hours. P-450 Mixed function oxidase Prothrombin time measured 24 hours post ingestion is the best marker for liver damage. Toxic Intermediates Glutathione Hepatocyte Management macromolecules r Activated charcoal is given if the patient presents within 1 hour of ingestion and >12 g (6 g in the high risk treatment group) or ≥150 mg/kg have been in- gested, whichever is the smaller. Mercaptopuric acid Cell death r N-acetylcysteine (a glutathione precursor) is given by intravenous infusion if the plasma paracetamol level is Figure 15. It is maxi- mally effective before 8 hoursfollowing ingestion but Aetiology may be of value up to and beyond 24 hours. In older appropriate to start N-acetylcysteine prior to blood patients it is usually a form of deliberate self-harm; levels are known if very high doses have been taken or however, it may be accidental due to combination drug if presentation is delayed. Prognosis Normally toxic metabolites are inactivated by conjuga- If acute hepatic failure occurs, mortality is <50% with tion with glutathione. Liver failure leads Salicylate poisoning to encephalopathy, haemorrhage, hypoglycaemia, cere- bral oedema and death. Clinical features Aetiology There are often no early symptoms following paraceta- Ingestion of salicylates is usually accidental in toddlers; mol overdose, patients may present with nausea, vom- it is now rare as paracetamol and ibuprofen have become iting and pallor, which usually settle within 24 hours. Right subcostal pain and tenderness may then develop, Deliberate self-harm with aspirin is also unusual. Other features in- Pathophysiology clude hypotension, arrhythmias, excitement, delirium Salicylates have a direct effect on the central respi- and coma. This hyperventilation leads to respiratory hyperpyrexia, vasodilation and tachycardia. In severe alkalosis, which is compensated for by renal excretion overdose disorders of consciousness occur progressing of bicarbonate and potassium. Thecombinationofthemetabolicandrenaleffects Cerebral oedema and pulmonary oedema, which may be result in a metabolic acidosis. Investigations Blood glucose, blood gases, U&Es, prothrombin time Clinical features and bicarbonate levels should be measured. Treatment Patients may appear asymptomatic even in the pres- is based on plasma salicylate levels (>500 mg/L (3. Gastrointesti- Activated charcoal may be considered in conscious pa- nal haemorrhage may require blood replacement and tientswithin1hourofingestionandconsumptionabove metabolic acidosis should be corrected. Symptomatic patients with moderate (3–5 mg/L or Haemodialysis is used if plasma salicylate level is 700 55–90 µmol/L) or severe (>5 mg/L or 90 µmol/L) mg/L (5. Patients who have not developed symptoms by 6 hours following ingestion are unlikely to have had a significant overdose and do not require further Iron overdose monitoring. Aetiology Iron poisoning is usually seen in childhood and results Tricyclic antidepressant overdose from accidental ingestion of iron-containing medica- Definition tions such as vitamin preparations mistaken for sweets.

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The form should be submitted as soon as possible generic kamagra chewable 100mg with mastercard, but no later than 3 weeks before your ceremony kamagra chewable 100 mg on-line. Any form submitted after this deadline will not be processed and graduation will be deferred until the next appropriate set of ceremonies cheap kamagra chewable 100 mg on line. A registration fee of £40 is payable on first graduation from The University of Edinburgh in respect of life membership of the General Council safe 100 mg kamagra chewable, the statutory body comprising all of the University’s graduates. Students who, for any reason, do not wish to attend a ceremony (graduate in absentia) may do so but must still complete an online graduation registration form in order to receive their award certificate. Please be aware that if it is your intention to graduate at the above ceremony, any outstanding debts to the University must be paid to the Finance Office 21 days prior to the Graduation Ceremony. The Disability Office can assess your requirements and request adjustments and support you may need or negotiate specific assessment and exam arrangements. Assessment will be through an online journal review and basic statistics multiple choice questions. Online assessment (participation in interactive modules, discussion boards and group work) will constitute the other 10% of the overall course grade and is taken to represent a formative assessment of learning throughout the programme. The discursive paper will cover unusual clinical scenarios, difficult patient consultations and aspects of good and bad communication, possibly involving video clips. Online assessment through discussion boards and group work (wikis) will constitute the other 10% of the overall course grade and is taken to represent an assessment of learning throughout the programme. Online assessment through discussion boards and group work (wikis) will constitute the other 30% of the overall course grade and is taken to represent a formative assessment of learning throughout the programme (more details in programme proposal document). This is a written assignment critically reviewing a specific current global health problem. Online assessment in the form of discussion boards/ tutorials and group work and participation will constitute the other 50% of the overall course grade. This is taken to represent a formative assessment of learning throughout the programme. The written assignment should review aspects of palliative care management and should be considered in a specific clinical scenario. Summative works will be approximately 3,000 words in total and will be approved by the Health Informatics Programme Committee, on the recommendation of the Course Convener. This will be a reflective piece of around 2,000-2,500 words entitled, for example: "Take a learning outcome from your own clinical area and discuss how you would teach, assess and evaluate it; explaining and justifying the reason for your choices". This will be a written case assignment based on a particular patient- focused ethical situation and submitted online. Discussion boards and tutorial contributions will constitute the other 30% of the overall course grade which is also taken to represent a formative assessment of learning throughout the programme. Online assessment through participation in discussion boards, group work (wikis) and interactive materials will constitute the other 10% of the overall course grade and is taken to represent a formative assessment of learning throughout the programme. Within each specialty module students will be assessed by means of:  Critical appraisal of recent journal articles (50%) through a combination of online journal clubs and written online journal article appraisal forms. Students will be encouraged to produce either a short PowerPoint presentation, podcast or audio lecture that can be put online for peer and tutor assessment. This piece should be written in a style appropriate for a general medical (non-specialist) audience. The formatting should be suitable for formal publication and should contain an appropriate review of the literature. Tutors and fellow students will grade presentations with marks allocated in a 60% (tutor) to 40% (student) ratio. Writing skills, awareness of issues relating to plagiarism and referencing will be introduced. Students will be expected to actively use these tools throughout the course to create pieces of solo and group work, for example making presentations, reviewing journal articles and writing short review articles. The tools and resources available to perform thorough and accurate literature researching both within the University library services and on the internet will be introduced. How to conduct literature appraisal and the concept of evidence- based medicine will also be discussed. Students will receive some initial information on statistics that will be developed in later modules. The University’s librarians and a team for transferable skills will be working to tailor this module to students’ needs. Intended learning outcomes At the end of this course candidates should be able to conduct a literature search and critically review research and statistics used in clinical research. Online assessment (participation in interactive modules, discussion boards and group work) will constitute the other 10% of their overall course grade and is taken to represent a formative assessment of learning throughout the programme. Course description This programme aims to ensure that practitioners have a sound understanding of basic pharmacology principles and practices. Pharmacodynamic and pharmacokinetics principles will be taught using clinical examples. Reasons for individual variation, drug monitoring, and types of adverse drug reactions will be discussed using interactive and problem-based scenarios. Students will also learn and reflect on medication compliance: why medication errors occur and how safe prescribing guidelines can be formulated. Students will gain a good understanding of the mechanisms of action and effects of recreational misused drugs. They will discuss common clinical toxicology and poisoning case scenarios, developing analytical reasoning to aid diagnostic and management decisions. Intended learning outcomes At completion of this course the candidate should have sufficient understanding of the basic principles of pharmacology to guide prescribing in a general medical setting. Students should be able to diagnose and initiate appropriate treatment for common clinical toxicology presentations and understand why good prescribing practices are required to ensure patient safety. The basic framework of medicines management—internationally, nationally and locally—should be appreciated. Course description This programme aims to ensure that practitioners have a sound anatomical and physiological basis for treatment of common medical conditions encountered in adult acute and general medicine. Intended learning outcomes On completing this course the candidate should understand the anatomy, physiology and pathological processes that are important for the common diseases encountered in general medicine. Existing University of Edinburgh anatomy, physiology and pathology online e-learning tools will be utilised in combination with core reading (available in e-book format) as well as external resources to guide students through the various body systems. Course description This course aims to ensure that practitioners have a sound understanding of the laboratory techniques used to aid in the diagnosis of common general medical problems. Key clinical cases will be used to improve understanding in each of the disciplines; microbiology, haematology and biochemistry. Students will discuss how to interpret a blood film, diagnose coagulation disorders, make a microbiological diagnosis and conduct simple biochemistry assays.

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