Opioid analgesics central nervous system

Severe pain should be treated with an opioid such as morphine, hydromorphone, methadone, or fentanyl. Moderate pain can be treated effectively in most cases with a weak opioid such as codeine or hydrocodone, usually in combination with acetaminophen. Meperidine should be avoided owing to its relatively short analgesic effect and its toxic metabolite, normeperidine. Normeperidine may accumulate with repeated dosing and can lead to central nervous system side effects including seizures. 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Tramadol is an opioid analgesic and when given to patients who are also receiving imipramine (a tricyclic antidepressant), there is an increased risk of central nervous system toxicity. The risk of occurrence of sedation is increased. 

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. 

De Souza, E.B., Schmidt, W.K., Kuhar, M.J. Nalbuphine an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic, J. Pharmacol. Exp. Ther. 1988, 244, 391-402. 

Opioid analgesics such as oxycodone act directly on the central nervous system by stimulating opioid receptors in the brain. This action affects how the pain is perceived and can alter the user s emotional response to the pain. 

Katzung PHARMACOLOGY, 9e > Section V. Drugs That Act in the Central Nervous System > Chapter 31. Opioid Analgesics Antagonists > ... 

Opioids are compounds that bind one or more of the many different opioid receptors in the body. Opioids act primarily on the central nervous system. The selectivity of a given opioid for the various opioid receptors determines its characteristic activity. While many opioids are powerful analgesics, opioids often cause physical dependence and have tolerance issues. Sedation and decreased rate of breathing are also side effects associated with opioids. Despite their problems, opioids are generally the drug of choice for treating severe, acute pain. 

All agonists in this therapeutic group decrease the sensation of painful stimuli, which is their main clinical application. They tend to subdue dull, persistent pain rather than sharp pain, but this difference is to some extent dose dependent. The major difference between the non-opioid analgesics such as aspirin and the opiates is that the former reduce the perception of peripherally mediated pain, by reducing the synthesis of local hormones that activate the pain fibres, whereas the latter attenuate the affective reaction to pain without affecting the perception of pain. This clearly suggests that the site of action of the opiate analgesics is in the central nervous system. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Analgesics are classed as narcotic (which act in the central nervous system and cause drowsiness, i.e. opioids) and non-narcotic (which act chiefly peripherally, e.g. diclofenac). 

Heroin s primary toxic principle is its profound ability to depress the central nervous system (CNS). Opioid analgesics bind with stereospecific receptors at many sites within the CNS. Heroin, similar to other opioids, exerts its pharmacologic effect by acting at mu, kappa, and delta receptors in the brain. Although the precise sites and mechanisms of action have not been fully determined, alterations in the release of various neurotransmitters from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effect. Activities associated with the stimulation of opiate receptors are analgesia, euphoria, respiratory depression, miosis, and reduced gastrointestinal motility. 

Morphine is the prototype for the class of natural and synthetic opioid analgesics and its toxicity stems mainly from its extensive effect on the central nervous system (CNS), principally that of a descending depression. Opioids interact with stereospecific and saturable binding sites mostly located in the CNS. Interaction with the opioid receptors mimics the actions of endogenous enkephalins and endorphins. Morphine is a pure opiate agonist and exerts its activity primarily on the mu receptor. Activity also appears to involve an alteration in the release of neurotransmitters, such as the inhibition of acetylcholine, norepinepherine, and dopamine. These actions result in the therapeutic effects of analgesia, sedation, euphoria, and decreased gastrointestinal motility however, in toxic amounts they can lead to... 

Narcotic analgesics (narcotic agonists) such as opioids act on the central nervous system to treat moderate and severe pain, suppress respiration and coughing by acting on the respiratory and cough centers in the medulla of the brain stem. All narcotic analgesics relieve pain. All except meperidine (Demerol) are also antitussive (cough suppression) and antidiarrheal. 

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