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1

J, Meredith T., World Health Organization, Commission of the European Communities., and International Program on Chemical Safety., eds. Antidotes for poisoning by paracetamol. Cambridge: Published by Cambridge University Press on behalf of the World Health Organization and of the European Commission, 1995.

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2

Paracetamol (acetaminophen): A critical bibliographic review. 2nd ed. London: Taylor & Francis, 2001.

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3

Paracetamol (acetaminophen): A critical bibliographic review. London, UK: Taylor & Francis, 1996.

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4

N, Gregg, and Great Britain. Health and Safety Executive., eds. Paracetamol: Criteria document for an occupational exposure limit. London: HSE Books, 1994.

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5

En Prozac is mijn paracetamol: Zestien en depressief. [Schiedam]: Scriptum, 2010.

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6

Ricardo, Royder Yáñez, and Cruz Catata Teodora, eds. Mentisán, paracetamol o wira wira?: Jóvenes, salud e interculturalidad en los barrios mineros de Potosí. La Paz: PIEB, Programa de Investigación Estratégica en Bolivia, 2006.

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7

National Register of Foreign Collaborations (India) and India. Dept. of Scientific & Industrial Research., eds. Technology in Indian paracetamol industry: A status report prepared under the National Register of Foreign Collaborations. New Delhi: Govt. of India, Dept. of Scientific & Industrial Research, Ministry of Science and Technology, 1994.

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8

Paracetamol. Royal Society of Chemistry, 2002.

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9

Joe, Smith. Paracetamol. Independently Published, 2018.

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10

executive, Health and safety. Paracetamol. Health and Safety Executive (HSE), 1994.

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11

Dan, Micon. Paracetamol. Independently Published, 2018.

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12

Goody, Bob. War & Paracetamol. Burning Eye Books, 2021.

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13

Fermin, Solana. Paracetamol 500. Casa Editorial Hum, 2014.

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14

Mallet, Christophe, and Alain Eschalier. The rediscovery of paracetamol. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0004.

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The chapter describes experiments performed by Bernard B. Brodie and Julius Axelrod in an article published in 1948 and entitled ‘The fate of acetanilide in man’. This was an important breakthrough in the history of paracetamol (acetaminophen), which was synthesized in 1878 but only clinically used in 1955. We highlight how this article historically catalysed the rehabilitation (also called ‘the rediscovery’) of this popular over-the-counter painkiller. Demonstrating that paracetamol was the key active metabolite of acetanilide (an antipyretic/analgesic used at that time), and discarding the false idea that paracetamol causes methaemoglobinaemia, Brodie and Axelrod paved the way for this molecule to become nowadays the most sold analgesic worldwide, one which is still the subject of scientific publications.
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15

WOODHAMS. Standby Cpd: Paracetamol Overdose. Class Publishing, 2017.

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16

Levine, Michael. Management of acetaminophen (paracetamol) poisoning. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0318.

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Acetaminophen overdose remains common, and is one of the most frequent reasons for liver transplant in the United States. Toxicity results from the metabolism to a toxic metabolite, N-acetyl-para-benzoquinoneimine. This chapter begins with a brief discussion of the history and epidemiology of acetaminophen overdose, followed by a discussion on the pharmacokinetics and pharmacodynamics. The risk factors, clinical presentation, and treatment strategies presented.
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17

Bannwarth, Bernard, and Francis Berenbaum. Systemic analgesics (including paracetamol and opioids). Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0029.

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Apart from non-steroidal anti-inflammatory drugs (NSAIDs), there are only two categories of systemic analgesics, namely paracetamol (acetaminophen) and opioids, that are currently available worldwide for clinical use. Paracetamol is poorly effective in relieving pain and improving function in patients with symptomatic osteoarthritis (OA). Furthermore, its safety profile is less favourable than classically thought. In fact, there is evidence paracetamol acts as a weak inhibitor of the cyclooxygenase enzymes. Given that paracetamol poses a lower risk of severe adverse events than NSAIDs while being better tolerated than opioids, it is usually considered as the first-line systemic analgesic for OA. Commonly prescribed opioids are primarily agonists of the mu receptors, thereby producing similar desirable (analgesia) and untoward effects. Meta-analyses of short-term clinical trials showed that, on average, the modest clinical benefits of opioids did not outweigh the side effects in patients with knee or hip OA. Accordingly, most current guidelines support the use of opioids for selected OA patients only (e.g. patients who have not had an adequate response to other treatment modalities and are not candidates for total joint arthroplasty). In view of the limited efficacy and/or potential harms of available analgesics, particular attention was paid to novel painkillers, especially nerve growth factor (NGF) antagonists. Although these agents provided clinically meaningful improvements in pain and physical function in patients with hip or knee OA, they lead to severe side effects, including rapidly destructive arthropathies and neuropathies. Thus, if approved for marketing, NGF antagonists would be reserved for selected and well-defined patients with OA.
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18

Group, Research, and The Acetaminophen Research Group. The 2000-2005 World Outlook for Acetaminophen (paracetamol). 2nd ed. Icon Group International, 2000.

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19

Parker, Philip M. The 2007-2012 World Outlook for Acetaminophen (paracetamol). ICON Group International, Inc., 2006.

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20

ICON, Group International Inc. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in Oceana. Icon Group International, 2001.

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21

ICON, Group International Inc. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in Europe. Icon Group International, 2001.

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22

Parker, Philip M. The 2007-2012 Outlook for Acetaminophen (paracetamol) in India. ICON Group International, Inc., 2006.

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23

Inc, ICON Group International. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in Africa. Icon Group International, 2001.

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24

Inc, ICON Group International. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in Asia. Icon Group International, 2001.

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25

Parker, Philip M. The 2007-2012 Outlook for Acetaminophen (paracetamol) in Japan. ICON Group International, Inc., 2006.

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26

Inc, ICON Group International. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in Latin America. Icon Group International, 2001.

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27

Parker, Philip M. The 2007-2012 Outlook for Acetaminophen (paracetamol) in Greater China. ICON Group International, Inc., 2006.

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28

ICON, Group International Inc. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in the Middle East. Icon Group International, 2001.

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29

Parker, Philip M. The 2007-2012 Outlook for Acetaminophen (paracetamol) in the United States. ICON Group International, Inc., 2006.

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30

Borman, Marilyn. Acetylcysteine: A Potent Medicine That Is Used to Treat Paracetamol Overdose. Independently Published, 2019.

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31

Banerjee, Ashis, and Clara Oliver. Toxicology. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198786870.003.0017.

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Toxicology questions frequently appear in the Intermediate FRCEM short-answer question (SAQ) paper and a general knowledge of poisoning and its associated management is required. This chapter covers the basic principles of poisoning and drug elimination. It also focuses on common toxidromes to aid diagnosis and their associated management. In addition, this chapter also provides detailed information and management for the commonest poisoning agents such as paracetamol, salicylates, tricyclic antidepressants, and carbon monoxide. Paracetamol overdose is one of the commonest presentations of poisoning to the emergency department, the treatment guidelines for which have recently changed. This chapter provides the basic pathophysiology of paracetamol toxicity and details the current management guidance.
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32

ICON, Group International Inc. The 2000-2005 Outlook for Acetaminophen (Paracetamol) in North America and the Caribbean. Icon Group International, 2001.

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33

Stacey, Victoria. Toxicology. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199592777.003.0017.

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34

Vry, Dogad. Paracetamol: Medication for the Treatment of Fever, Pains, Migraine Attack, Menstrual Cramp and Joint Pains. Independently Published, 2018.

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35

Hegarty, Rob, and Fevronia Kiparissi. Drug-induced liver injury. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198759928.003.0058.

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The chapter on drug-induced liver injury discusses the definition, clinical manifestations, and then management of this frequently challenging to diagnose situation. It also covers in more detail the management of paracetamol overdose.
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36

Coloring, ParacetamolVs. Coloring Book and Poster Collection: High on Paracetamol Polarized Light Photomicrograph of Thin Layer of Parace Fantasy. Independently Published, 2019.

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37

Sjøgren, Per, Frank Elsner, and Stein Kaasa. Non-opioid analgesics. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199656097.003.0096.

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Non-opioid analgesics encompass the non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol (acetaminophen). The NSAIDs include acetylsalicylic acid (ASA, aspirin), dipyrone (metamizole), and numerous other drugs in diverse classes. The NSAIDs have potent anti-inflammatory, analgesic and antipyretic activity, and are among the most widely used drugs worldwide. In palliative medicine, they represent the first step of the World Health Organization’s analgesic ladder used for mild pain and they are an important supplement to opioids and adjuvant drugs at higher steps of the ladder. The disadvantages of non-opioid analgesics include a ceiling effect for pain relief and the risk of side effects. NSAIDs are also associated with an increased risk of adverse gastrointestinal, renal, and cardiovascular effects and hepatotoxicity can result from overdosing with paracetamol. This chapter describes the clinical pharmacology of NSAIDs, their classification, molecular mechanisms of action and adverse effects, as well as some recent developments aimed at designing effective anti-inflammatory agents with improved safety and tolerability profiles.
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38

Prout, Jeremy, Tanya Jones, and Daniel Martin. General therapeutics. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199609956.003.0007.

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Drugs used during the perioperative period may have implications for both the patient and the environment. Drugs may cause toxicity such as propofol infusion syndrome or dependency problems in the long-term. Perioperative anaphylaxis, the triggers, recognition and management is detailed. Management of patients with acute poisoning is included with general assessment and supportive management as well as specific antidotes. The clinical consequences of paracetamol poisoning are discussed in detail.
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39

Jolly, Elaine, Andrew Fry, and Afzal Chaudhry, eds. Clinical pharmacology and therapeutics. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199230457.003.0005.

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Chapter 5 covers the basic science and clinical topics relating to clinical pharmacology and therapeutics which trainees are required to learn as part of their basic training and demonstrate in the MRCP. It covers pharmacodynamics, pharmacokinetics, drug metabolism and prescribing in special circumstances, drug interactions, adverse drug reactions, drug development, paracetamol poisoning, salicylate poisoning, lithium toxicity, digoxin toxicity, carbon monoxide poisoning, ethylene glycol poisoning, and tricyclic antidepressant poisoning.
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40

Dashfield, Adrian. Acute pain. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198719410.003.0040.

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This chapter discusses the management of acute pain. It begins with an introduction which describes the benefits of acute pain management and the measurement of pain. Analgesic drugs are then described, including paracetamol, non-steroidal anti-inflammatory drugs, and opioids (including their comparative efficacy). Patient-controlled analgesia, epidural analgesia, and continuous peripheral nerve blockade are described. Transcutaneous electrical nerve stimulation and acupuncture are discussed. The management of the patient with a substance misuse disorder is discussed. The chapter concludes with a discussion of non-opioid adjuvant analgesics.
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41

Dashfield, Adrian. Acute pain. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198719410.003.0040_update_001.

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This chapter discusses the management of acute pain. It begins with an introduction which describes the benefits of acute pain management and the measurement of pain. Analgesic drugs are then described, including paracetamol, non-steroidal anti-inflammatory drugs, and opioids (including their comparative efficacy). Patient-controlled analgesia, epidural analgesia, and continuous peripheral nerve blockade are described. Transcutaneous electrical nerve stimulation and acupuncture are discussed. The management of the patient with a substance misuse disorder is discussed. The chapter concludes with a discussion of non-opioid adjuvant analgesics.
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42

Raine, Tim, James Dawson, Stephan Sanders, and Simon Eccles. Prescribing. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199683819.003.0004.

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Prescribing – general considerationsHow to prescribe – best practiceDrug interactionsReporting adverse drug reactionsSpecial considerationsControlled drugsEnzyme inducers and inhibitorsEndocarditis prophylaxisNight sedationSteroid therapyTopical corticosteroidsEmpirical antibiotic treatmentClostridium difficile (C. diff)Prescribing medicines is rarely taught well in medical school, yet it is one of the first tasks you’ll be asked to do on day one. Even the most experienced of doctors will only know by heart the dose and frequency of a maximum of 30–40 drugs, so do not worry if you cannot even remember the dose of paracetamol; for adults it’s 1g/4–6h PO max 4g/24h in divided doses (...
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43

Foo, Joanne, Benazir Saleem, and Philip G. Conaghan. Analgesics. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0078.

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Pain is one of the commonest presenting symptoms of musculoskeletal disorders and may be one the hardest to treat successfully. The available analgesic options provide different modes of action and their ranks continue to expand with new agents, some with multiple target action. This chapter reviews currently available analgesics (paracetamol and opioids) used for managing musculoskeletal pain and the agents used for neuropathic pain, including their mechanism of action, pharmacokinetics and side effects. The role of neuroleptic agents is reviewed, and a brief outline of some newer therapies for the treatment of pain such as tapentadol, and a potential therapy, anti-nerve growth factor monoclonal antibodies.
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44

Beaulieu, Pierre. Mechanisms of action of acetaminophen for pain treatment. Edited by Paul Farquhar-Smith, Pierre Beaulieu, and Sian Jagger. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198834359.003.0046.

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The landmark paper discussed in the chapter, published by 2008 by Mallet et al., reports on the mechanisms of action of acetaminophen for pain treatment. Acetaminophen, also known as paracetamol (N-acetyl-para-aminophenol), has analgesic and antipyretic properties and has superior tolerance, compared to non-steroidal anti-inflammatory drugs, making it appropriate for widespread use in patients. However, despite many years of use worldwide and numerous studies, acetaminophen’s mechanism of action is still uncertain. The article by Mallet et al. is a landmark paper because it reconciled many observations made at the time to propose a plausible mechanism of action of acetaminophen in pain treatment.
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45

Moonesinghe, Ramini, and Sue Mallett. Acute pain in patients with renal or hepatic impairment. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199234721.003.0015.

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The metabolism and excretion of many analgesic drugs will be altered in the presence of renal or hepatic impairment. Some analgesic drugs can cause renal or hepatic damage. Protein binding of drugs may be altered by hepatic reduction in production or uraemic displacement from binding sites. In renal disease, paracetamol is the simple analgesic of choice. Morphine can be used with care in mild to moderate renal disease, but fentanyl or oxycodone may be better alternatives. Non-steroidal anti-inflammatory drugs should be avoided in renal disease. In hepatic disease with significant impairment, doses of morphine must be reduced and the dosage interval lengthened. Fentanyl should be avoided in severe hepatic disease.
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46

Devlin, Hugh, and Rebecca Craven. Central nervous system. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198759782.003.0012.

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The central nervous system (CNS) in relation to dentistry is the topic of this chapter. Nerve conduction is described, then the physiology of facial and dental pain and processing of afferent pain nerve impulses in the cerebral cortex. We discuss abnormal sensations of allodynia and paraesthesia. Pain control with non-steroidal anti-inflammatory drugs or paracetamol is explained. The function of the cranial nerves and the autonomic nervous system are described. We explain the nerve pathways involved in salivation, lachrymation, and taste sensation. We propose some techniques for treating the nervous patient, e.g. modelling, systematic desensitization, and feedback. Effective local anaesthesia is essential in gaining the cooperation of nervous patients. The major types of local anaesthetics are compared. The techniques for inferior alveolar and superior alveolar nerve blocks are described as are drugs commonly used in dental sedation. There are final sections on drug problems encountered in dental practice and on dementia.
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47

Axelsson, Bertil. The Incurable Cancer Patient at the End of Life: Medical Care Utilization, Quality of Life and the Additive Analgesic Effect of Paracetamol in Concurrent ... from the Faculty of Medicine, 1013). Uppsala Universitet, 2001.

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48

Bonnet, Francis, Marc E. Gentili, and Christophe Aveline. Post-surgical analgesia and acute pain management. Edited by Jonathan G. Hardman. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0046.

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Postoperative and acute pain remains uncontrolled in many instances, leading to the risk of development of chronic pain syndromes. After tissue damage, activation of postsynaptic NMDA receptors, also induced by opioid administration, plays a key role in postoperative pain sensitization, allodynia, and hyperalgesia. Pain intensity may depend on sex, age, anxiety, and genetic factors but in clinical practice, surgical procedure is the main determinant of pain, although pain may vary from one patient to one another. Serial pain measurements are mandatory to assess pain intensity and to guide pain treatment. They are based on unidimensional simple pain scales. Multimodal analgesia combining opioid and non-opioid agent and regional block or infiltration is the rule postoperatively, although evidence is sometimes lacking to support all the combinations commonly used. Opioids should be used on demand while other agents are administered systematically. Non-steroidal anti-inflammatory drugs decrease opioid demand as well as paracetamol although to a less extend. Antihyperalgesic agents including NMDA blockers (ketamine) and α‎2-δ‎ ligands (gabapentin, pregabalin) have an opioid-sparing effect and may prevent the occurrence of chronic pain syndrome after surgery. Regional blocks and infiltration provide good quality analgesia but the balance between advantages and drawbacks of central block need to be evaluated carefully for each surgical procedure.
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49

Hansen, Tom G. Acute paediatric pain management. Edited by Jonathan G. Hardman and Neil S. Morton. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199642045.003.0073.

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Paediatric pain management has made great strides in the past few decades in the understanding of developmental neurobiology, developmental pharmacology, the use of analgesics in children, the use of regional techniques in children, and of the psychological needs of children in pain. The consequences of a painful experience on the young nervous system are so significant that long-term effects can occur, resulting in behavioural changes and a lowered pain threshold for months after a painful event. Accurate assessment of pain in different age groups and the effective treatment of postoperative pain are constantly being refined, with newer drugs being used alone and in combination with other drugs, and continue to be explored. Systemic opioids, paracetamol, non-steroidal anti-inflammatories, and regional anaesthesia alone or combined with additives are currently used to provide effective postoperative analgesia. These modalities are often best utilized when combined as a multimodal approach to treat acute pain in the perioperative setting. The safe and effective management of pain in children includes the prevention, recognition, and assessment of pain; early and individualized treatment; and evaluation of the efficacy of treatment. This chapter discusses selected topics in paediatric acute pain management, with more specific emphasis placed on pharmacology and regional anaesthesia in the treatment of acute postoperative pain management.
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50

Wenham, Claire Y. J., and Philip G. Conaghan. Osteoarthritis—management. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0140.

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Osteoarthritis (OA) is a common condition which often causes pain and functional limitation, significantly impacting on a person's quality of life. A comprehensive assessment of the impact of OA should be performed before selecting therapies and treatment goals. Current recommended therapies include a combination of pharmacological and non-pharmacological therapies, which should be considered for all people with OA, regardless of anatomical site of involvement. Non-pharmacological treatments include education, muscle strengthening and aerobic exercises, weight loss if appropriate, splints and devices, and aids. Pharmacological therapies include paracetamol, oral and topical non-steroidal anti-inflammatory drugs, topical capsaicin, intra-articular corticosteroid injections, and opioids. Many existing therapies have only a small analgesic effect size and, in the case of drug therapies, may be associated with important side effects, so an individual's symptoms and comorbidities must be taken into account when selecting therapies. For those who do not respond to these treatments, surgery such as a total joint arthroplasty may be required. There is a strong need for new analgesic treatments for OA. As it is becoming increasingly clear that the sources of pain in OA are complex and multifactorial, future treatments for OA will need to target both peripheral and central pain mechanisms.
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