Morphine sensations

Morphine. This alkaloid exerts both a depressing and a stimulating action on the central nervous system, the depression affecting the brain especially the sensation of pain and the respiration the cerebral motoi functions are less affected. The stimulant action in the cord is best seen in the cold-blooded animals, when it may develop into tonic convulsions. In higher animals, but rarely in man, there may be some indication of this stimulant action. In cats it may also involve the motor areas, and they... 

When Montgomery and I published our article, we thought we had disproven another theory of placebo effects - the theory that placebo effects are produced by the release of endorphins in the brain. In 1978 researchers at the University of California in San Francisco discovered that when placebos reduce pain, they may stimulate the release of endorphins.18 Endorphins, the existence of which had only been discovered a few years earlier, are opioids that are produced naturally by the brain. Just like the opiates that are derived from opium - morphine and codeine, for example - endorphins reduce the sensation of pain. The University of California researchers reasoned that if placebos can mimic the effects of opiate drugs, maybe they do so by stimulating the release of the brain s endogenous opioids. 

Opium and its derivatives have been employed for centuries for the treatment of pain. Morphine was first synthesized in 1805 and has proven to be one of the most effective analgesic agents available [1], Morphine and its analogs are particularly useful because they diminish pain sensation while maintaining consciousness. However, opiates induce severe side-effects including respiratory depression, nausea, bradycardia and constipation and long-term use of opiates can cause addiction [2]. 

The problem of alleviating painful sensations is as old as mankind itself. It can probably be said with a fair degree of confidence that the isolation of morphine, the oldest of the known pain-relieving drugs, from opioid plants in the 19th century served as the initiation for the intensive development of the chemistry, pharmacology, and pharmacy. 

It is important to note that the binding of morphine to opioid receptors in the brain and spinal cord produces the sensation of pain relief it does not attack or eliminate physical causes of pain due to trauma or other injury. At the cellular and molecular level, the binding of opioids with opioid receptors sets off a cascade of events that modulate the release of neurotransmitters involved in pain signaling. 

Central nervous system depression is the usual effect of morphine, and sedation and drowsiness are frequently observed with therapeutic doses. When given in the absence of pain morphine may sometimes produce dysphora—an unpleasant sensation of fear and anxiety. The most important stimulatory effects of morphine in man are emesis and miosis. Miosis, due to stimulation of the Edinger-Westphal nucleus of the third nerve, occurs with all opioids. The combination of pinpoint pupils, coma, and respiratory depression are classical signs of morphine overdosage. Stimulation of the solitary nuclei may also be responsible for depression of the cough reflex (antitussive effect). Pharmacokinetics and metabolism... 

In addition to the development of tolerance, persistent administration of opioid analgesics has been observed to increase the sensation of pain leading to a state of hyperalgesia. This phenomenon has been observed with several opioid analgesics, including morphine, fentanyl, and remifentanil. Spinal dynorphin and activation of the bradykinin receptor have emerged as important candidates for the mediation of opioid-induced hyperalgesia. 

Typically, patients or intravenous drug users who receive intravenous morphine experience a pleasant floating sensation with lessened anxiety and distress. However, dysphoria, an unpleasant state characterized by restlessness and malaise, may sometimes occur. 

In addition, morphine appears to activate the endogenous supraspinal system that is normally activated by pain to protect the body from excessive nonessential pain stimulation. Patients report that the sensation of pain often exists, but, under the influence of morphine, they feel more at ease and comfortable. This euphoria is present in 90 to 95% of patients. Morphine may cause dysphoria in the remaining 5 to 10%. 

The effects of heroin on the CNS are related to 6-monoacetylmorphine (6-MAM) and mainly morphine. The heroin crosses the blood-brain barrier due to the acetylic groups in position 3 and 6, that increase its lipophilicity. The morphinic compounds interact with the opioid receptors, mainly the p receptors, acting as an antagonist by mimicking the endorphin effects [9], Usually the first event occurs 30 s after its administration with a typical rush followed by a succession of euphoric sensations after a few minutes the user becomes calm, satisfied, and indifferent to his surroundings after 2-4 h typical restlessness accompanied with pain and an incessant demand for heroin sets in the craving. 

Heroin was first synthesized from morphine over a century ago. Since then, it has become one of the most abused substances. Research into why it produces such powerful effects has led to the discovery of specific opiate receptors and endogenous opioids (enkephalins and endorphins). These peptides appear to be neurotransmitters involved with the sensation of pain and pleasure. A number of opiates and synthetic opioids are available and can lead to dependency, including morphine, heroin, propoxyphene (Darvon), methadone, meperidine (Demerol), pentazocine (Talwin), hy-dromorphone (Dilaudid), oxycodone (Percodan), and hydrocodone (Vicodin, Damason-P), and codeine. 

Anesthetic agents are a diverse class of chemicals which are extremely important in modern medicine. They are generally used to produce a loss of sensation to all stimuli, either in a specific anatomical area, or a total loss of consciousness. Anesthetics differ from analgesics in that analgesics such as aspirin, acetaminophen, ibuprofen, or morphine act to decrease pain, but not other sensations. Anesthetics can be broadly categorized into two general classes, local anesthetics and general anesthetics. These classes are independent as far as indication, chemical class, routes of administration, and toxicity, and thus will be considered separately. It will be noted when one compound within a class differs from the others. 

Fintsi recommended simple intravenous sedation without FNB he used promethazine and morphine sulfate (5-15 mg) and titrated the doses until the burning sensation subsided. According to him, nerve block anesthesia is not essential with this procedure, but, without the FNB, the patient is in pain during the peel and this makes it uncomfortable for both the patient and the doctor. The patient only has a vague memory of the pain. Asken reported on a study by Litton showing an accelerated heartbeat slowing down when deep sedation is combined with nerve block anesthesia. 

Sdentitic studies of opioid neurotransmitters during the 1970s have uncovered a complex and subtle system that exhibited impressive diversity in terms of endogenous ligands for only three major receptors. The opioid peptide precursors were subject to complex post-translational modifications resulting in the synthesis of multiple active peptides all of them sharing the common N-terminal sequence of Tyr-Gly-Gly-Phe-(Met or Leu), which has been termed the opioid motif. Based on the results of theses studies, the endogenous opioids have been implicated in circuits involved in the control of sensation, emotion, and affect and a role has been ascribed to them in addiction, not only to opiates such as morphine or heroin, but also to alcohol. ... 

Met-enkephalin and leu-enkephalin belong to a group of peptides called the opioid peptides, found predominantly in nerve tissue cells. Opioid peptides are molecules that relieve pain (a protective mechanism in animals that warns of tissue damage) and produce pleasant sensations. They were discovered after researchers suspected that the physiological effects of opiate drugs such as morphine resulted from their binding to nerve cell receptors for endogenous molecules. Leu-enkephalin and met-enkephalin are pentapeptides that differ only in their C-terminal amino acid residues. Substance P and bradykinin stimulate the perception of pain, an effect opposed by the opioid peptides. 

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