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

This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established.
 ...
PMID:Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol. 1044 36

The potentiation of morphine analgesia by dextromethorphan raises the issue of whether dextromethorphan also potentiates those actions of morphine that lead to abuse. Clinical pharmacology experiments indicated that dextromethorphan does not potentiate the euphorigenic and miotic actions of morphine. Morphine suppresses the dysphoric action of dextromethorphan. A second set of experiments indicated that dextromethorphan does not alter the response to naloxone-precipitated withdrawal. In a third set of experiments, dextromethorphan did not alter the morphine-induced depression in the slope of the increase in minute volume in response to breathing increased CO2. In contrast to potentiation of analgesia, dextromethorphan does not enhance the euphorigenic, physical dependence, and respiratory depressant actions of morphine. These findings indicate that dextromethorphan does not enhance the abuse potential of morphine and that the potentiation of analgesia appeared to be selective.
J Pain Symptom Manage 2000 Jan
PMID:Abuse potential of morphine/dextromethorphan combinations. 1068 36

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.
 ...
PMID:[Tolerance and dependence on opioid analgesics: experimental and clinical aspects]. 1096 10

Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G-protein-coupled receptors and subsequent binding of regulatory proteins called beta-arrestins. Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu-opioid receptor to the development of morphine antinociceptive tolerance and the subsequent onset of physical dependence. Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic morphine treatment, and that these animals fail to develop antinociceptive tolerance. However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug.
 ...
PMID:Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. 1113 73

Three major types of opioid receptors, designated mu, delta, and kappa, are widely expressed in the CNS. Development of selective receptor ligands and recent cloning of each receptor have contributed greatly to our increasing knowledge of the neuropharmacological profile of each opioid receptor type. It is of interest to note that they include noncompetitive and allosteric interactions among their types. This review focuses on the functional interaction among these opioid receptor types that contribute to opioid dependence. Various studies provide arguments to support substantial roles for mu-opioid receptors and the possible involvement of delta-opioid receptors in the development of physical and psychological dependence on morphine. Noradrenergic transmission originating in the locus coeruleus is most likely to play the primary causal role in the expression of physical dependence on morphine. In contrast, many studies have pointed to the mesolimbic dopaminergic pathway projecting from the ventral tegmental area to the nucleus accumbens as a critical site for the initiation of psychological dependence on opioids. It is noteworthy as the broad existence of opposing interactions between mu/delta- and kappa-receptors in the brain. The activation of kappa-receptors leads to the suppression of unpleasant mu/delta-mediated side effects such as the rewarding effect. Considering the functional interaction among opioid receptor types, the co-administration of morphine-like compounds with kappa-receptor agonists may constitute a preferable and superior approach to the treatment of pain with fewer side effects.
 ...
PMID:Regulations of opioid dependence by opioid receptor types. 1131 10

At a recent seminar on pain management in Atlanta, researchers reported that health care providers do poorly when it comes to recognizing and managing the pain suffered by patients with AIDS. This lack of adequate attention is reflected in the lack of relevant studies about pain management in the medical literature. As with cancer, AIDS pain increases with disease progression. However, patients with AIDS tend to be more depressed than cancer patients, and have a higher rate of suicidal thoughts. Experts at the seminar discussed the obstacles involved in treating pain in AIDS patients who have a history of substance abuse. According to one study, pain medication addiction is rare in patients. Providers must distinguish between tolerance and physical dependence. Guidelines for managing pain in substance abusers include respecting the patient's reports of pain, and setting clear goals and conditions for opioid therapy. Using a team approach that recognizes pharmacological and non-pharmacological interventions, and that pays attention to psychosocial issues will also lead to greater success in treating patients with pain. The most common painful illnesses are HIV-related headaches, herpes simplex, peripheral neuropathy, back pain, herpes zoster, and throat pain.
 ...
PMID:Clinicians not providing necessary pain relief for AIDS patients. 1136 81

Today, a wide range of efficient analgesic and non-analgesic drugs for the treatment of back pain are available. However, drugs should never be the only mainstay of a back pain treatment program. Non-steroidal antiinflammatory drugs (NSAID) are widely used in acute back pain. NSAIDs prescribed at regular intervals are effective to reduce simple back pain. The different NSAIDs are effective for the reduction of this pain. They have serious adverse effects, particularly at high doses, in the elderly, and on long-term administration. The new cyclooxygenase II-inhibitors have less gastrointestinal complications. But the long-term experiences are limited up to now. Considerable controversy exists about the use of opioid analgesics in chronic noncancer pain. Many physicians are concerned about the effectiveness and adverse effects of opioids. Other clinicians argue that there is a role for opioid therapy in chronic noncancer pain, e. g. especially in chronic low back pain. There is a low incidence of organ toxicity in patients who respond to opioids. The incidence of abuse and addiction is likewise relatively low. The potential for increased function and improved quality of life seems to outweigh the risks. However, there is a lack of randomised controlled trials (RCT) on opioid therapy in a multimodal pain treatment approach. Clinical experience and some studies suggest administration of sustained release opioids because of better comfort for the patient and less risks for addiction. The opioids should be selected due to the specific side effects of the different drugs. For patients with pre-existing constipation transdermal fentanyl should be preferred. Antidepressant medications have been used for the treatment of chronic back pain, though there is only little scientific evidence for their effectiveness. There is no evidence for the use of antidepressants in acute low back pain. Trials of muscle relaxants for patients with acute back pain have used a wide range of agents, e. g. benzodiazepines. They mostly reduce acute back pain, but they have significant adverse effects including drowsiness and psychological and physical dependence even after relatively short treatment. Benzodiazepines are not indicated in the treatment of chronic back pain. Drugs are sometimes necessary for the patients to begin and persevere a multimodal treatment program. Drug therapy should be terminated as soon as other treatment strategies succeed. Unfortunately, no studies exist evaluating the place of analgesics within a multimodal treatment program.
 ...
PMID:[Treatment of low back pain--significance, principles and danger]. 1179 51

Pain is undertreated in all parts of the world. Multiple barriers exist that prevent valid treatment of the pain patient. This paper will provide definitions of pain, addiction, physical dependence, tolerance, and pseudoaddiction that health professionals need to understand in order to treat pain. It will address how to differentiate between a pain patient and an addict when evaluating the patient for treatment. The physiological benefits of using long- versus short-acting opioids will be presented. With proper education of the medical community, patients should receive humane and compassionate treatment of their chronic pain syndromes.
Eur J Pain 2001
PMID:The truth about pain management: the difference between a pain patient and an addicted patient. 1179 14

Fentanyl has been shown to be a potent analgesic with a lower propensity to produce tolerance and physical dependence in the clinical setting. The present study was designed to investigate the mechanisms of fentanyl- or morphine-induced antinociception at both supraspinal and spinal sites. In the mouse tail-flick test, the antinociceptive effects induced by both fentanyl and morphine were blocked by either the mu1-opioid receptor antagonist naloxonazine or the mu1/mu2-opioid receptor antagonist beta-funaltrexamine (beta-FNA) after s.c., i.c.v. or i.t. injection. In contrast, both fentanyl and morphine given i.c.v. or i.t. failed to produce antinociception in mu1-deficient CXBK mice. These findings indicate that like morphine, the antinociception induced by fentanyl may be mediated predominantly through mu1-opioid receptors at both supraspinal and spinal sites in mice. We also determined the ED50 values for s.c.-, i.c.v.- and i.t.-administered fentanyl- or morphine-induced antinociception in mice. The ED50 values for s.c.-, i.c.v.- and i.t.-administered fentanyl-induced antinociception were 73.7, 18.5 and 1.2-fold lower than that of morphine, respectively. The present data clearly suggest the usefulness of peripheral treatment with fentanyl for the control of pain.
 ...
PMID:Possible involvement of mu1-opioid receptors in the fentanyl- or morphine-induced antinociception at supraspinal and spinal sites. 1215 Jan 99

Administration of opioids to alleviate moderate to severe acute pain and chronic cancer pain is an established management process. However, advancements in clinical pharmacologic research have shown that opioids are also effective in chronic noncancerous pain. Many patients properly treated for prolonged periods with opioids develop tolerance and subsequently, physical dependence. This process is not necessarily harmful to the patient and will not cause the patient to develop an addiction (properly defined as psychologic dependence). For many patients who have been on opioid therapy for months or years, analgesic effectiveness tragically becomes less. In addition, opioid-induced constipation can be severe and cause pain; patients do not develop tolerance to this adverse reaction. Therefore, such issues become a management problem and require additional intervention. Currently, many different classes of drugs can serve as effective adjuncts to opioids for treatment of pain. Adding adjunctive medication to opioid therapy improves pain management primarily by nonopioid mechanisms of action. Clinical outcomes of such combinations include greater analgesia and attenuation of opioid-induced adverse reactions such as nausea and vomiting, constipation, sedation, and respiratory depression. Adjuncts include acetaminophen, antiarrhythmics, anticonvulsants, antidepressants, antipsychotics, baclofen, benzodiazepines, capsaicin, calcium channel blockers, clonidine hydrochloride, central nervous system stimulants, corticosteroids, local anesthetics, N-methyl-D-aspartate receptor antagonists, nonsteroidal antiinflammatory drugs, pentoxifylline, and scopolamine. Some adjuncts (eg, acetaminophen) are routinely used today, whereas others (eg, nifedipine [calcium channel blocker]) are used on a limited basis but have great potential for more widespread application. All professionals (eg, nurses, pharmacists, physicians, physicians' assistants, social workers, members of the clergy) involved in treating patients with unresolved pain recognize this to be an extraordinary and delicate time. It is when patients are likely to request physicians to provide some method to accelerate their death. Thus, inadequate analgesia can become a suicidogen, ie, any factor that causes a patient to want to commit suicide. Incorporation of adjuncts to opioid therapy can serve to lessen pain and improve quality of life for a suffering patient.
 ...
PMID:Adjuncts to opioid therapy. 1235 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>