Pain relief, opiates

Complete C-fibre inhibitions can be produced under normal conditions but opiates do not always produce a complete analgesia in some clinical situations, especially when the pain arises from nerve damage. Reasons for this are suspected to be excessive NMDA-mediated activity which is hard to inhibit and the mobilisation of cholecysto-kinin in the spinal cord which can act as a physiological antagonist of opiate actions. The idea that pre-emptive analgesia aids post-operative pain relief by preventing the pain-induced activation of these systems is becoming popular. 

The difference in opiate pharmacology between people with and without pain also applies to addiction. The drug-seeking behaviour synonymous with drug addiction does not occur in patients given opiates for pain relief in childbirth, operations or heart attacks (Porter and Jick, 1980). Clearly, drug addicts are not in pain, and it has consequently been argued that medical use of opiates does not produce addicts (McQuay, 2001). 

Pain Action Unknown but may stimulate opioid sites, sedation and analgesia Dose Adults. Self administered inhalation (generally 25-50% w/ oxygen) until pain relief or pt drops mask/falls asleep Peds. Same as adult (onset w/in 2-5 min) Caution [ , ] Do not use after full meal Contra EtOH intox AMS following head injury COPD, thoracic trauma Disp Supplied in blue cylinders SE N/V, Light-headedness, AMS and hallucinations Interactions T CNS depression Wf opiates, EtOH, sedatives EMS Do not strap mask to pt s face, allow pt to hold the mask to their face dosing is self-limiting when pt drops mask d/t CNS depression typically used for bums and fractures... 

There are many peripheral organs that possess enkephalin opiate receptors the ileum, the most distal part of the small intestine, and the vas deferens are the most significant. The receptors in the ileum are responsible for the antidiarrheal activity of opiates. This is also the explanation for the severe constipation that may occur when people use opiates for pain relief. 

Opiates act on a variety of receptors. The three most important subtypes are the mu, delta, and kappa opiate receptors (Fig. 13—25). The brain makes its own endogenous opiate-like substances, sometimes referred to as the brain s own morphine. They are peptides derived from precursor proteins called pro-opiomelanocortin (POMC), proenkephalin, and prodynorphin. Parts of these precursor proteins are cleaved off to form endorphins or enkephalins, stored in opiate neurons, and presumably released during neurotransmission to mediate endogenous opiate-like actions (Fig. 13-25). However, the precise number and function of endogenous opiates and their receptors and their role in pain relief and other central nervous system (CNS) actions remain largely unknown. 

PHYSICAL DEPENDENCE A condition that may occur after prolonged use of an opiate, but differing from addiction because the user is dependent on the drug for pain relief, rather than emotional or psychological relief. 

Methadone and opiates were first used for pain relief, and are still chiefly used in that area of medicine. It is important to remember that methadone and other opiates do not exert their pain control by altering a person s sensitivity to pain. Rather, methadone and other opiates interfere with the transmission of pain impulses from the nervous system to the brain. They accomplish this by a variety of methods. First, they decrease the transmission of nerve signals that conduct pain messages from various parts of the body to the spine. Secondly, they prevent production of neurochemicals that transfer this pain information to the spine. Finally, they mimic the actions of endorphins, which are the body s own pain-controlling chemicals. While methadone and other opiates work quite well to control pain, they do not affect touch, vision, or hearing. 

Opioids are known to alter mood states. For example, opiates such as morphine produce euphoria and pain relief. Prolonged use of and withdrawal from opiates produce depressive-like symptoms as well. Based on the mood-altering effects of opiates, the role of endogenous opiates in psychiatric symptoms of various diseases has been studied. In addition, endogenous opioids are believed to play a role in neuronal circuitry responsible for reward and pleasure. Therefore, it is thought that perhaps the anhedonia observed in depressed patients is due to dysregulation of endogenous opioids in neuronal reward circuitry. 

Q4 Constipation can be a troublesome side effect of opiates used for pain relief, for example morphine and codeine. It is also a side effect of some calcium channel blocking agents, antacids containing aluminium compounds and iron salts used in the treatment of anaemia. 

The pharmacological uses of vitamin K are in the treatment of (rare) vitamin K deficiency prophylaxis in newborn infants (Section 5.4.1), and as an antidote to overcome anticoagulant toxicity. Because of its cytoxic effects, menadione has been used in cancer chemotherapy. It also potentiates the analgesic actions of salicylates and opiates, and has been used to enhance pain relief in cancer patients. 

In common with other phenolic opiate analgesics, buprenorphine shows low peroral potency, suggesting a high first-pass metabolism effect indeed, work in rats has shown this to be the case. Intravenous studies have estimated that the extraction ratio of buprenorphine is 85% and that peroral systemic availability is consequently expected to be 15% or less. Although absorption from the mouth is slow and, therefore, not as useful as parenteral administration in the treatment of acute pain, it offers a major bioavailability advantage over the peroral route for this drug. If required, the patient can be given a parenteral dose of buprenorphine to achieve rapid pain relief and... 

In Chapter 10 we discussed the use of opiate drugs in the treatment of pain. But the use of opiates for pain relief is usually reserved for severe cases. Many effective painkillers are available over the counter, and aspirin is the most widely known and used. Acetylsalicylic acid (aspirin) is closely related to a chemical found in the bark of the willow and other trees (salicylic acid). Willow bark was used in the treatment of painful conditions and fever by the ancient Greeks and by Native Americans. Salicylic acid was isolated and used as a pain reliever in Europe, but it causes severe stomach distress. It was not until the late 19th century that acetylsalicylic acid was synthesized and named aspirin by the. Bayer Company of Germany. Aspirin has come to be one of the most important drugs in medicine. It is marketed under the brand names Anacin, Bufferin, and Excedrin to name just a few, and more than 10,000 tons of aspirin are consumed in the United States every year (Julien, 2005). 

Chronic pain Surgery, NSAIDs, opiates, tricyclic antidepressants, antiepileptic drugs Sedation, pain relief... 

It is important to appreciate that the opiates are not the only compounds which are of use in the relief of pain and that there are several other classes of compounds, including aspirin, which combat pain. These compounds, however, operate by different mechanisms from those employed by the opiates, and therefore relieve a different, sharper kind of pain. The opiates have proved ideal for the treatment of deep chronic pain and work in the central nervous system (CNS). 

---