Analgesia

Ropivacaine is similar, less potent than bupivacaine but less cardiotoxic and with a longer duration of action. 

Analgesics are used to relieve pain irrespective of its cause. 

Pain is an unpleasant sensory and emotional experience in response to tissue damage, threat of tissue damage or perceived tissue damage. Experience and interpretation of pain is subjective and influenced by previous experience and an individual s physical and mental condition at the time. 

Sensory nerve endings are found throughout the body in the skin, muscles, joints, blood vessels and internal organs. These nociceptors are sensitive to the effects of potentially damaging mechanical, thermal and chemical stimuli. 

When cells are damaged they release a variety of chemical mediators, which can activate or sensitize nociceptors to other chemicals. This explains acute pain. Chronic pain is more difficult to explain, especially if it goes on beyond the initial tissue damage. Chronic pain is thought to be associated with changes to the normal physiological pain pathway. 

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Biologica.1 Activities a.ndAna.logues, The many pharmacological actions of neurotensin include hypotension, increased vascular permeabihty, hyperglycemia, increased intestinal motility, and inhibition of gastric acid secretion (120). In the brain, it produces analgesia at remarkably low doses (121). 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Dynorphin may also influence nociception at the spinal level. The levels of prodynorphin mRNA and immunoreactive dynorphin increase in the chronic inflammatory arthritic model (158). Dynorphin also inhibits morphine or P-endorphin-induced analgesia in naive animals and enhances analgesia in tolerant animals, indicating that this peptide may have a regulatory role in opioid analgesia (159). This effect does not appear to be mediated by a classical opioid receptor, since des-tyrosine dynorphin, which does not bind to opioid receptors, also antagonizes morphine analgesia (160). 

R = R = H), the first reported enkephalinase inhibitor, produced analgesia in post-myelography headache pain, but not in shock-induced pain (38). There was no tolerance or dependence observed. 

Numerous neuropeptides are beheved to be involved with the transmission or inhibition of pain, and the hope is to utilize this approach as a strategy to induce analgesia. Substance P is reported to be a transmitter of nociceptive impulses (39), and therefore antagonists should be analgesic. Capsaicin [404-86-4], C2gH2yN02, is known to deplete substance P and cause analgesia (40), but its side effects are intolerable. Antagonists to bradykinin [58-82-2], a substance known to induce pain (41), have shown some success in preclinical trials. 

Most of the time, the powerful analgesia suppHed by morphine and the other opioid analgesics is not needed. Rather, a mild analgesic, such as aspirin, the most commonly employed analgesic agent, can be used for the treatment of simple pain associated with headaches, minor muscle pain, mild trauma, arthritis, cold and flu symptoms, and fever. 

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

Neuroleptic analgesia is so called because the combination of a major tranquilizer, a neuroleptic dmg, and a potent opiate produces an anesthetic state characterized by sedation, apathy, and mental detachment (see Psychopharmacological agents) (152). Iimovar [8067-59-2] a combination of droperidol [648-72-2], C22H22FN2O2, (19) and fentanyl (9) citrate, is used for procedures that do not require muscle relaxation. However, the onset of action is slow. 

Another injectable anesthetic widely used in feline and primate practice is ketamine hydrochloride [1867-66-9]. Ketamine, a derivative of phencychdine, can be chemically classified as a cyclohexamine and pharmacologically as a dissociative agent. Analgesia is produced along with a state that resembles anesthesia but in humans has been associated with hallucinations and confusion. For these reasons, ketamine is often combined with a tranquilizer. The product is safe when used in accordance with label directions, but the recovery period may be as long as 12—24 h. 

Infusion devices have been used for diabetes, cancer chemotherapy, pain control (patient-controUed analgesia, ie, PGA), infection, Alzheimer s disease, Parkinson s, nausea, thalassemia, thromboembolism, and to treat severe spasms resulting from spiaal cord iajury (140—143). 

Anesthesia Anesthesia is a loss of sensation or feeling. Anesthesia (or "anesthetics") is often used deliberately by doctors and dentists to block pain and other sensations during surgical procedures. Treatment for pre- or postoperative pain is called analgesia. 

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet "antihistamines." This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

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