Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Buprenorphine was administered as sublingual tablets to 70 patients suffering from chronic pain of malignant or non-malignant origin. Daily doses ranging from 0.4 mg to 3.2 mg were administered and good analgesia was reported by the majority of patients. The most common unwanted effects were drowsiness/sleepiness, nausea and/or vomiting and sweating which appeared to be dose related but the incidence of dizziness was not related to daily dose. The incidence of all these unwanted effects except drowsiness/sleepiness decreased after the first week's treatment. No buprenorphine related changes in vital signs or laboratory values were observed and no signs of tolerance or physical dependence were seen in the short term period after discontinuation of treatment. A significant positive correlation between buprenorphine plasma concentration and daily dose was observed but there was no correlation between plasma levels and pain relief.
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PMID:A long-term open, clinical and pharmacokinetic assessment of sublingual buprenorphine in patients suffering from chronic pain. 401 31

Xorphanol is a new mixed agonist-antagonist from the morphinan class of analgesics. On the basis of animal experiments, the physical dependence liability of xorphanol is predicted to be of a low order in man. Conceptually, xorphanol is of interest since in vitro experiments have revealed anti-naloxone properties and resistance to antagonism by opioid antagonists. At the practical level, xorphanol is a well tolerated, orally active analgesic that provides effective pain relief clinically.
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PMID:Xorphanol. 403 50

A 70 year old hypertensive patient who had undergone a gastrectomy experienced withdrawal symptoms 10 h after a second epidural injection of morphine (150 micrograms X kg-1) for postoperative analgesia. A clonidine treatment had been stopped 129 h earlier. These symptoms disappeared shortly after a third epidural injection of morphine. Clonidine was then reintroduced. The later progressive interruption of epidural morphine analgesia did not introduce any further symptoms of withdrawal. Since physical dependence on a drug is related to repeated and prolonged administration of that drug, opiate withdrawal symptoms were highly unlikely after epidural morphine used to relieve immediate postoperative pain. Abrupt discontinuation of a long-term treatment by clonidine may produce a withdrawal syndrome, but clinical and biological signs usually occur earlier than noted in this case. Recent experimental and clinical data has provided support for the existence of a complex presynaptic regulation of noradrenergic transmission in the central nervous system, both alpha 2 and opiate receptors being implicated. The activation of such presynaptic receptors inhibits further transmitter release. Suddenly stopping the chronic administration of alpha 2 or opiate agonists was responsible for a rebound excitation of these noradrenergic neurons, inducing a withdrawal syndrome. The related withdrawal symptoms may have resulted from an interaction between the discontinuation of clonidine and the decrease in morphine activity. Practitioners should be warned of this possible side-effects.
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PMID:[Withdrawal syndrome during epidural administration of morphine after stopping treatment with clonidine]. 609 36

Electrical stimulation of the brainstem abolishes pain, while continued stimulation induces tolerance to the analgesic effect. Analgesic drugs producing tolerance also induce physical dependence, suggesting that the phenomenon of tolerance is associated with addiction. There is evidence that the neural mechanism for stimulation-produced analgesia is related to the release of opiate substances within the brain. We therefore propose that repeated or protracted brain stimulation elicits dependence upon the endorphins released by electrical stimulation of the neurons themselves. To investigate this possibility, rats were given repetitive bursts of analgesic electrical brain stimulation for two hours. Immediately thereafter, they were injected with the opiate antagonist, naloxone. Behaviors associated with low grade opiate withdrawal were observed. These data suggest that prolonged analgesic stimulation can result in naloxone-precipitated behaviors similar to the behaviors exhibited during opiate withdrawal.
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PMID:Opiate withdrawal behavior after focal brain stimulation. 654 76

The chemistry, pharmacokinetics, pharmacology, clinical efficacy, adverse effects, physical dependence and tolerance, drug interactions, dosing, and cost of zomepirac sodium (Zomax, McNeil) are reviewed. Zomepirac is a new nonsteroidal anti-inflammatory agent (NSAIA) approved for the treatment of mild to moderately severe pain. The drug is well absorbed when given orally. It undergoes extensive biotransformation in the liver. Zomepirac shares the pharmacology of the other NSAIAs by decreasing prostaglandin synthesis. The efficacy of zomepirac has been demonstrated primarily in acute forms of pain with associated inflammatory processes including postdental-extraction, postpartum, and postoperative pain. Many of these studies have been single-dose evaluations. Zomepirac sodium 100 mg has been reported to be approximately equivalent to one to two tablets of aspirin-phenacetin-caffeine (APC) with codeine 30 mg. In two studies, zomepirac sodium 100 mg compared favorably with morphine sulfate 8 and 16 mg i.m. It has been shown to be superior to aspirin 650 mg in oral-surgery patients. In osteoarthritis, daily doses of zomepirac sodium 400-600 mg are approximately equivalent to aspirin 3200-4800 mg. Zomepirac has side effects similar to high-dose aspirin. Zomepirac is associated with an increased incidence of urogenital symptoms such as dysuria and pyuria. Because of tumorigenicity in rats, the drug is contraindicated in children, pregnant women, and nursing mothers. The drug has not demonstrated any potential for physical dependence, withdrawal, or tolerance. Zomepirac may provide a suitable alternative to aspirin, narcotic/NSAIA combinations, and narcotics in the treatment of mild to moderately severe pain. It is unlikely that zomepirac will replace narcotics in more severe types of pain.
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PMID:Evaluation of zomepirac sodium. 702 15

Zomepirac sodium (Zomax) is a new orally effective nonopioid analgesic that can relieve mild to severe pain. It is more effective than aspirin or codeine alone and is as effective as analgesic combinations containing codeine or other narcotics. Given orally, zomepirac has provided analgesia comparable with usual intramuscular doses of morphine in postoperative pain. With long-term use, neither tolerance to its analgesic effect nor psychic or physical dependence has been demonstrated. Like aspirin, zomepirac has anti-inflammatory and antipyretic actions and inhibits the synthesis of prostaglandins. Zomepirac is generally well tolerated with both short-term and long-term use; gastrointestinal reactions are the most frequently occurring side effects.
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PMID:Zomepirac sodium. A new nonaddicting analgesic. 724 89

Ninety-eight patients completed a double-blind, multidose, randomized parallel study in which buprenorphine (Temgesic) was compared to morphine. Drugs were administered at approximately equipotent intramuscular doses for a maximum of three days for the relief of moderate to severe postoperative pain. The two drugs exhibited similar profiles with pain relief evident at 1/2 hour, peaking at 1 hour, and decreasing to slight relief at 4-5 hours, with no significant differences for time to remedication. The most frequent side effect was somnolence. One patient suffered sudden chest pain shortly after an injection of morphine, and one patient had moderate hypoventilation after buprenorphine; both patients recovered uneventfully. Overall, both drugs provided good or excellent analgesia in 80 per cent of the patients in this unique multidose/observational study. Thus, these data and the reported lack of withdrawal symptoms and the absence of physical dependence liability suggest that buprenorphine may have a role in the management of chronic pain.
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PMID:Multidose/observational, comparative clinical analgetic evaluation of buprenorphine. 726 31

Flupirtine is a novel non-opiate centrally acting analgesic agent with muscle relaxant properties, advocated for use in a number of pain states. Preliminary evidence suggests that flupirtine 100 to 200mg orally or 150mg rectally 3 to 4 times daily (maximum daily dose 600mg) is more effective than placebo in relieving moderate acute pain of various types. For the relief of pain due to surgery, traumatic injury, dental procedures, headache/migraine and abdominal spasms, flupirtine has proved at least as effective as the opiate analgesics codeine, dihydrocodeine and pentazocine, the nonsteroidal anti-inflammatory agents suprofen, diclofenac and ketoprofen, as well as dipyrone and paracetamol (acetaminophen). Although evidence to support a role in the treatment of chronic pain is limited, flupirtine has been found as effective as pentazocine in short term trials of patients with muscular or neuralgiform pain, dysmenorrhoea, soft tissue rheumatism or cancer pain. The safety profile of flupirtine has not yet been fully established, although initial evidence suggests that adverse reactions, while frequent, are usually minor in nature. The most common reactions are drowsiness, dizziness, dry mouth and various gastrointestinal complaints. In comparison with opiate drugs, flupirtine appears to produce fewer central nervous system effects, no respiratory or cardiovascular depression, and no overt tolerance or physical dependence on prolonged administration. If these initially favourable results are confirmed in larger long term trials, then flupirtine would appear to represent an effective analgesic for the relief of moderate pain, particularly that of musculoskeletal origin.
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PMID:Flupirtine. A review of its pharmacological properties, and therapeutic efficacy in pain states. 768 75

Propiram is an orally administered opioid analgesic with partial morphine-like agonist and weak antagonist properties. Analgesic efficacy of propiram, usually 50 or 100mg, appears comparable to that of standard dosages of other oral opioid drugs [i.e. pentazocine, pethidine (meperidine)] in patients with acute pain of moderate to severe intensity arising from various gynaecological and surgical procedures, and may be superior to codeine in gynaecological and postoperative dental pain. Some evidence of a more rapid onset of action for propiram than for these opioid agents, and a longer duration of action for propiram than for codeine, is encouraging but remains to be substantiated in more extensive clinical use. The tolerability profile of propiram resembles those of others in its class, with drowsiness, nausea and vomiting, and dizziness experienced most frequently in controlled trials. The apparently low propensity of propiram for development of physical dependence and psychotomimetic effects requires confirmation with wider clinical experience. Available data thus indicate that propiram is an effective, orally administered opioid analgesic suitable for providing relief of acute moderate to severe pain arising from various surgical or gynaecological procedures, and that the drug is likely to become a useful alternative in such conditions where opioid analgesia is appropriate.
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PMID:Propiram. A review of its pharmacodynamic and pharmacokinetic properties, and clinical use as an analgesic. 769 33

1. The opioid activity of the amphibian peptide, [Lys7]dermorphin, was studied in rats and mice. When administered intracerebroventricularly (i.c.v.), intravenously (i.v.) or subcutaneously (s.c.) it produced a long lasting analgesia. Its antinociceptive potency exceeded that of morphine 290 times by i.c.v. injection, and 25-30 times by peripheral administration. 2. The dose-response curves of [Lys7]dermorphin antinociception were shifted to the right by the pretreatment with naloxone (0.1 mg kg-1, s.c.) or with the mu 1-selective antagonist, naloxonazine (10 mg kg-1, i.v. 24 h before peptide injection). 3. The peptide also displayed potent antinociceptive effects in a chronic inflammatory pain model (rat Freund's adjuvant arthritis). In this pain model, systemic administration of the peptide raised the nociceptive threshold more in inflamed than in healthy paw. 4. High central and peripheral doses of [Lys7]dermorphin in rats produced catalepsy. The cataleptic response was antagonized by naloxone but left unchanged by naloxonazine pretreatment. 5. In rats and mice, central or peripheral administration of [Lys7]dermorphin induced a significantly slower development of tolerance to the antinociceptive effect than did morphine. 6. Upon naloxone precipitation of the withdrawal syndrome, [Lys7]dermorphin-dependent mice made fewer jumps and lost less weight than the morphine-dependent animals. Withdrawal hyperalgesia did not develop in [Lys7]dermorphin-dependent mice. 7. In conclusion, [Lys7]dermorphin seems to be a unique opioid peptide having a high penetration into the blood-brain barrier despite its low lipid solubility. This peptide causes fewer side-effects than other opioids and appears less likely than morphine to cause physical dependence in rats and mice.
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PMID:Production of antinociception by peripheral administration of [Lys7]dermorphin, a naturally occurring peptide with high affinity for mu-opioid receptors. 771 29


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