Morphine NSAIDs

Relief of pain after surgery can be achieved with a variety of techniques. An epidural infusion of a mixture of local anaesthetic and opioid provides excellent pain relief after major surgery such as laparotomy. Parenteral morphine, given intermittently by a nurse or by a patient-controlled system, will also relieve moderate or severe pain but has the attendant risk of nausea, vomiting, sedation and respiratory depression. The addition of regular paracetamol and a NSAID, given orally or rectally, will provide additional pain relief and reduce the requirement for morphine. NSAIDs are contraindicated if there is a history of gastrointestinal ulceration of if renal blood flow is compromised. 

Analgesics are divided into two groups opioids (morphine-like substances), which predominantly influence the central nervous system (CNS) and nonopioids (nonsteroidal antiinflammatory or fever-reducing drugs—NSAID), which act predominantly on the peripheral nervous system. 

Acute pain is managed with either nonopioids such as acetaminophen, NSAIDs, or, when severe, opioids such as meperidine, morphine, methadone, hydromor-phone, fentanyl, or sufentanil (Golianu et ah, 2000). The latter are generally used parenterally, and when the patient is converted to oral analgesics, agents such as codeine, oxycodone, and hydrocodone are often used. 

Within the last 10, years several new compounds were launched in the field of non-steroidal antiinflammatory drugs (NSAIDs) with a clear focus on cyclooxygenase type 2 selective compounds. In the field of opioids on the other hand no new drugs have passed phase III clinical trials. In this field innovation has been achieved through new pharmaceutical formulations of known drugs such as transdermal systems, e.g. buprenorphine patch, transmucosal systems, e.g. fentanyl lollipop, or rectal delivery systems containing e.g. morphine. These were developed in order to reduce opioid side effects, but also to overcome pharmacokinetical limitations, in particular to prolong compliance and duration of action. 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

Consider other NSAIDs or COX-2 inhibitors (it not contraindicated) or oral oxycodone (Roxicodone), morphine (Duramorph), or advance to higher level of care (parenteral analgesia and/or pain-management specialist). 

In general, pain (acute or chronic) arising from the somatic structures (skin, muscles, bones, joints) responds to NSAIDs. Acute pain arising from viscera, which is poorly localised, unpleasant, and associated with nausea is best treated with morphine but this induces dependence with prolonged use. This distinction is not, of course, absolute and a high-efficacy opioid is needed for severe somatic pain, e.g. a fractured bone. Mild pain from any source may respond to NSAIDs and these should always be tried first. 

Ketorolac is, hke several other NSAIDs, promoted as a non-narcotic analgesic. This is merely a marketing ploy, which does not reflect any special characteristics, except that it is one of many NSAIDs that can be given parent-erally. A pyrrolizine carboxylic acid derivative, it is strnc-turally and pharmacologically related to tolmetin, zomepirac, and indometacin. The trometamol salt of ketorolac enhances its solubility and allows parenteral administration single intramuscular injections are better tolerated than morphine. 

Postoperative analgesia from morphine has been shown to be the most effective if administered at the completion of the procedure (Brandsson et al 2000, Reuben et al 2001, Tetzlaff et al 2000). In these cases, it appears that the postoperative use of morphine allows the clinician to reduce both the level and the duration of other analgesics. This is not to say that the only potential benefit of morphine is in the postoperative patient. Morphine has also been shown to be of equivalent effect to corticosteroid administration in other forms of chronic arthritides (Keates et al 1999, Stein et al 1999). The reductions in inflammatory cell influx, reduced edema formation and analgesia provided with minimal systemic effects make intraarticular morphine a very attractive postoperative therapy. I most commonly use a combination of 5-15 mg morphine with 6 mg lidocaine for postoperative analgesia and have seen no untoward effects. The beneficial effects with respect to improved analgesia and ability to reduce the usage of NSAIDs remains to be proven. 

A possible relationship between the parenteral administration of the NSAID, ketorolac, and ARF has been evaluated in a multi-center study by Feldman et al. [40]. These authors found no difference in the frequency of ARF for patients receiving either ketorolac or morphine sulfate during the first 5 postoperative days however, a significant, preferential increase in ARF frequency occurred when ketorolac treatment was extended beyond 5 days. 

Furazolidone Metronidazole Minocycline Paromomycin Polymyxin B Salicylates and NSAIDs Loop diuretics Antitumor agents Miscellaneous Morphine Penicillamine Pentazocine Propranolol Propoxyphene... 

The major receptor-mediated adverse effect is water intoxication, which can occur with desmopressin or vasopressin. Many drugs, including carbamazepine, chlorpropamide, morphine, tricyclic antidepressants and NSAIDs, can potentiate the antidiuretic effects of these peptides, while lithium, demeclocycline and ethanol can attenuate the antidiuretic response to desmopressin. Desmopressin and vasopressin should be used cautiously when a rapid increase in extracellular water may impose risks (e.g., in angina, hypertension, and heart failure) and should not be used in patients with acute renal failure. Patients receiving desmopressin to maintain hemostasis should be... 

Opioid analgesics, e.g, morphine (Chapter 29), are rarely given before an operation unless the paiieni is in pain. Fentanyl and related drugs (e.g. alfcntanyh are used intravenou.sly to supplement nitrous oxide anaesthesia. These opioids are highly lipid soluble and have a rapid onset of action. They have a short duration of action because of redistribution. NSAIDs (e.g. diclofenac) may provide sufficient postoperative analgesia and do not cause respiratory depression. They can be given orally or by injection. 

These ore used particularly in the treatment of dull, poorly li alizcd (visceral) pain. Somatic pain is sharply defined and may be relieved by a weak opioid analgesic or by a non-stemitlal ami-inflammatory drug (NSAID, Chapter i2). Parenteral morphine is widely used to treat severe pain and oral morphine is the drug of choice in terminal care. 

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