**1. Introduction**

*Pain is inevitable, suffering is optional.*

*(Dalai Lama)*

Pain-related complaints represent as many as 70% of presenting concerns for patients in the A&E departments or GP setting [1–3]. A wide variety of options are available for the treatment of pain, from which the most known and used are the analgesics.

The approach to patients in pain should use a division of pain patients into four specific treatment groups: acute pain, chronic pain, recurrent pain and chronic pain of malignancy. In this chapter we will address mostly to the acute pain management.

Pain treatment should be initiated promptly, titrated to an acceptable level of relief, and continued during the cause's investigation. It is inappropriate to delay analgesics use until a diagnosis has been made. There is no evidence that the administration of adequate doses of opioid analgesia to establish patient comfort impairs the medical ability to rich a diagnose of an emergency condition. To the contrary,

administration of analgesia may enhance the accuracy of physical examination and patient assessment [4, 5].

The medications useful in treating acute pain are similar to those used in treating other types of pain [1]. The World Health Organisation (WHO) analgesic ladder (**Figure 1**) developed for treating patients with cancer pain also provides a useful approach to treat acute pain. At the lowest level (mild pain) are recommended nonopioid analgesics such as paracetamol or/plus nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g. ibuprofen). Such drugs have an analgesic ceiling; above a certain dose, no further analgesia effect is expected [1]. For moderate pain, are recommended combining paracetamol and/or a NSAID with an opioid (a weak opioid). The inclusion of paracetamol limits the amount of opioids that should be used within 24 hour period, with many benefits which will be discussed later in the chapter. For severe level of pain, a strong opioid such as morphine is a better choice; such opioids have no analgesic ceiling. Most postoperative or trauma patients initially respond better to a morphine-equivalent opioid. By the moment the patient is eating, drinking and ready for discharge, a combination of oral analgesics including opioids and paracetamol plus/minus NSAID are most of the time an adequate option.

Not all types of pain respond equally to the same medication. Usually NSAIDs and steroids are highly effective in controlling soft tissue and bone pain. Bone pain may be helped partially by opioids [1]. But overall, the combination of NSAIDs, paracetamol and opioids is synergistic in treating the most types of pain. Opioid analgesics are useful in controlling somatic and visceral pain. Neuropathic pain, often described as pain with a burning and hyperaesthesia characteristic, which responds well to a diverse group of drugs, called adjuvants, including low dose of antidepressants (amitriptyline), anticonvulsants (carbamazepine and clonazepam), antiarrhythmics (mexiletine), baclofen and alfa-adrenergic agonists (clonidine). Opioids may also be helpful [1]. Most of the time, analgesia is improved after 1–2 days of using adjuvant drugs. Adjuvants were not developed initially as analgesics but recent studies show they poses benefits in a better pain control. Drugs that control pain by different mechanisms of action may be synergistic, when used together. Also, by lower doses of two or more different agents, the patient may have better pain control with fewer side effects. This is the basic background for the multimodal analgesia concept.

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*Analgesics*

**2.1 Paracetamol**

other analgesics [2].

distribution [6].

respectively) [6, 9].

are contraindicated.

ment of hepatic necrosis.

*DOI: http://dx.doi.org/10.5772/intechopen.94319*

and is an effective analgesic and antipyretic.

Paracetamol is the first-line agent for the treatment of both acute and chronic pain. It is one of the pain killers with the highest profile of safety and is a first pharmacologic option for controlling pain in children and adults. It has a high toxicto-therapeutic ratio and has very few significant drug interactions compared with

It can be given orally, rectally or parentally, has small anti-inflammatory activity,

Paracetamol is the active metabolite of the earlier (more toxic) drugs acetanilide and phenacetin. The recommended dose in adults is 0.5–1 g oral, iv or rectal every

Paracetamol has a CNS action, where inhibits prostaglandin synthesis. In clinical doses it has insignificant peripheral anti-inflammatory action. Unlike morphine, paracetamol has no apparent biding sites, and unlike NSAIDs it does not inhibit peripheral cyclo-oxygenase activity. But however, his mechanisms of action include, beside central COX-2 inhibition [2, 7], inhibition of a central cyclo-oxygenase, COX-3, that is selectively susceptible to paracetamol, and modulation of descending serotonergic pathways that suppresses spinal cord nociceptive transmission. There is also evidence of agonism at the cannabinoid receptor CB1 [2, 8]. There are, other evidences that paracetamol may inhibit prostaglandin endoperoxidase H2 produc-

The most recent Cochrane review [9] of RCTs of single-dose oral analgesic for acute postoperative pain in adults reported a NNT of 3·6 with 1 g paracetamol, when morphine 10 mg IM has 2.9, ibuprofen 400 mg - 2.4 and codeine 60 mg - 16.7. Efficiency of paracetamol is improved in combinations with other analgesics, such as 400 mg ibuprofen, 60 mg codeine and 10 mg oxycodone (NNT 1·5, 2·2 and 1·8

So, paracetamol is an effective analgesic, with potency somewhat less than standard dose of morphine. Paracetamol is an efficient adjunct to opioid analgesia, and regular administration after surgery produce an opioid sparing effect, because reduce opioid requirements by 20–30%. Paracetamol proved to be an integral component of multimodal analgesia in combination with NSAIDs and opioids. Paracetamol has less side effects than the NSAIDs and can be used when the latter

A significant concern regarding paracetamol use relates to the development of hepatotoxicity; however, current data suggest this is unlikely to develop at therapeutic doses [10]. However, doses of more than 150 mg/kg of paracetamol taken within 24 hours may result in severe liver damage, hypoglycaemia and acute tubular necrosis, especially when associated with dehydration and chronic malnutrition [11]. Individuals taking enzyme-inducing agents are more susceptible. So, important caution should be taken in overdoses due to the risk of liver damage and less frequently renal damage. Nausea and vomiting, the only early features of poisoning, usually settle within 24 hours. Persistence beyond this time, often associated with the onset of a right-side subcostal pain and tenderness, usually indicates develop-

Although paracetamol has been in use since 1880, its pharmacologic mecha-

nism of action is not fully known. It has a rapid absorption from the small intestine after oral administration. Paracetamol has lower protein binding than NSAIDs (and hence fewer potential drug interactions) and higher volume of

4–6 hours when necessary, without exceeding a total daily dose of 4 g [6].

tion at the cellular level, independent of cyclooxygenase activity [2, 6].

**2. Nonopioid analgesic agents**

**Figure 1.** *WHO analgesic ladder.*
