Tuesday, April 19, 2011

Opioid analgesics: ways to improve the treatment of pain syndromes

The most effective pain relievers are opiates (opium alkaloids) and their synthetic analogs - opioid analgesics. The most severe and acute pain, causing the shock reaction, or moderate, but persistent, exhausting the patient's pain can be stopped in the first place with opioid analgesics. Alternative to them in severe cases can only serve as general anesthetics (nitrous oxide, ketamine), and in some situations - for clonidine and local anesthetics. In outpatient practice, the principal cause of the suffering of patients is a chronic pain syndrome in incurable cancer in the terminal stage. In this situation, opioid analgesics are absolutely non-alternative means of therapy. To take full anesthesia and the increase of comfort being in the last weeks or months of life of these patients a physician must navigate the modern medical forms and be able to competently apply them.

Major achievement for pharmacology of analgesics in the 70's and 80's. XX century was the discovery of opiate receptors, a demonstration of their heterogeneity, deciphering the molecular structure and effector mechanisms, the discovery of endogenous ligands - opioid peptides, of which the best known enkephalins, endorphins and dynorphin. Formulated the concept antinociceptive system. It implies that pain impulses causes simultaneous excitation of several brain structures that inhibit further transmission of pain impulses. The main structures of antinociceptive systems are okolovodoprovodnoe gray matter of the midbrain, a large core of the joint, and the giant paragigantokletochnoe nucleus of the reticular formation of medulla oblongata. Axons of neurons in these nuclei are sent down the dorsolateral cord spinal cord, resulting in superficial layers of dorsal horn neurons. These descending fibers in contact with the neurons of posterior horns of the spinal cord, release of serotonin, norepinephrine and GABA.

Many of them modulate nociceptive impulses, highlighting the enkephalins or other opioid peptides, which stimulate opioid receptors [1-3].

Opiate receptors are found in the peripheral areas of painful afferent C-fibers, they are available on the terminals of C fibers in the posterior horns of the spinal cord, located in the same neurons are gelatinous substance, and besides - in the brain structures involved in the transmission and perception of pain signals . There are three major types of opioid receptors - m (mu), k (kappa) and d (delta), relating to the family of serpentine receptors related to G-protein. These major types of opioid receptors are also divided into subtypes (m1, m2, k1, k2, k3), which can differ not only in structure, but also mediated their reactions. Creation of highly selective drugs may be useful, for example, a selective agonist of m1-receptor may cause analgesia without respiratory depression (realized by m2-receptors). Most opioid analgesics have a marked analgesic effect due to affinity and agonism (mimetic action) in relation to m-receptors. Commonly used synthetic opioids has analgesic effects due to preferential excitation of k-opioid receptors [1,4,5].

Was recently discovered so-called orphan receptors (opiate receptors - ODA). These receptors have a lower affinity for morphine than other types of opiate receptors, they have not yet found an endogenous ligand is unknown, and prospects of application of agonists or antagonists. Table 1 summarizes the effects that are mediated by the main types of opioid receptors.

1 comment:

  1. Side effects of hydrocodone include nausea, vomiting, stomach ache, drowsiness or dizziness, shallow breathing, slow heartbeat, feeling light headed, fainting, confusion, unusual thoughts or behavior, seizure or convulsions, loss of appetite, itching, anxiety, mood swings, blurred vision and jaundice. Allergic reactions like hives, difficulty in breathing, swelling of lips, tongue, throat and face is also possible. It also has withdrawal effects like insomnia, restlessness, confusion and anxiety.

    Agustin Legido