**3. Opioids**

that influence neurotransmitters (e.g., antidepressants, antiepileptic drugs), and treatment with opioids is reserved for patients with refractory neuropathic pain. There are no truly effective medicines for certain types of pain; thus, a better understanding of the existing ones [opioids: methadone and tramadol; antidepressants: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin‐noradrenalin reuptake inhibitors (SNRIs); anticonvulsants: gabapentin and pregabalin] or the search for new or perhaps the

The usual approach is to start with a nonopioid analgesic such as a nonsteroidal anti‐inflam‐ matory drug (NSAID) or acetaminophen for mild‐to‐moderate pain. If this is inadequate, the next step may be to add an antidepressant. If there is a component of neuropathic pain, then a trial of one of the anticonvulsant analgesic agents could be the option. If these steps are inadequate, then an opioid analgesic may be added. In an individual patient, one or several mechanisms may be at play in the etiology of the pain and more than one agent may be neces‐ sary for pain control; thus, it may be appropriate to use a combination of agents with different

This chapter focuses on pharmacotherapeutic options for patients with chronic, no cancer

Nonselective NSAIDs act inhibiting both the COX‐1 and the COX‐2 enzymes, leading this mechanism of action to both the therapeutic and toxic effects associated with their use. They are extensively prescribed to treat acute and chronically painful conditions. Complications with the use of these agents range from minor gastric complaints (nausea, abdominal pain, etc) to serious complications (gastric ulcers, bleeding, etc). These drugs inhibit platelet aggre‐ gation and increase bleeding time. The introduction of COX‐2 selective NSAIDs in the mar‐ ket did not lead to a more effective and safer therapy, and cardiovascular complications associated with these agents culminated in the withdrawal of rofecoxib and valdecoxib from

Both COX‐2 selective and nonselective NSAIDs can also cause adverse renal outcomes in chronic use [3, 5]. So, risks associated with prolonged NSAIDs use must be addressed, as well

A weak acid drugs NSAIDs are, a plasma‐gastrointestinal tract recirculation process through pancreatic/intestinal juices must be expected, although a systematic overview of the literature made no mention of this phenomenon. Due to the high concentration of sodium bicarbonate, pancreatic juice pH is above 8. This fact makes the transfer of an acidic drug from blood to the pancreatic lumen possible. Once in the duodenum, the accumulated drug in the pancreatic juice is available for reabsorption, resulting in a perceptible multiple peak plasma concentra‐ tion‐time profile. This phenomenon was evidenced by our group in a study carried out in healthy volunteers after ketoprofen administration [6]. In this work, no evidence of secondary

pain and possible drug‐drug interactions that can result from a combined therapy.

mechanisms of action in an effort to obtain adequate pain control [3].

oldest form of medicine (cannabis) is needed.

34 Pain Relief - From Analgesics to Alternative Therapies

**2. NSAIDs and acetaminophen**

as the benefits, on a patient‐by‐patient basis.

the market in 2004 [3, 4].

There has been a dramatic change in the way pain specialists view the use of opioid drugs for the management of chronic, no cancer pain. There is growing recognition that some patients can be provided opioid drugs for prolonged periods without evidence of tolerance and toxic‐ ity. Serious adverse effects are rare, and addiction is rare, particularly, if there is no history of chemical dependency.
