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)

Several compounds, mainly opioid agonists such as methadone, are currently used for long term medication of heroin addicts. Nevertheless, these maintenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been demonstrated, the ability of the CB(1) antagonist, SR141716A to reduce morphine-induced addiction was investigated. The effects of SR141716A on the rewarding responses of morphine were evaluated in the place conditioning paradigm. No significant conditioned preference or aversion were observed after repeated treatment with the CB(1) antagonist alone. However, SR141716A was able to antagonize the acquisition of morphine-induced conditioned place preference. SR141716A was co-administered with morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was observed while the other were not significantly modified. In contrast, an acute injection of the CB(1) antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the withdrawal, suggesting that only chronic blockade of CB(1) receptors is able to reduce morphine-induced physical dependence. Several biochemical mechanisms could explain the reduction of opioid dependence by CB(1) antagonists. Whatever the hypotheses, this study supports the reported interaction between the endogenous cannabinoid and opioid systems, and suggests that SR 141716A warrants further investigations for a possible use in opioid addiction.
 ...
PMID:Reduction of opioid dependence by the CB(1) antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction. 1130 53

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

Addiction is a complex process that relies on the ability of an organism to integrate positive and negative properties of drugs of abuse. Therefore, studying the reinforcing as well as aversive components of drugs of abuse in a single model system will enable us to understand the role of final common mediators, such as cAMP response element-binding protein (CREB), in the addiction process. To this end, we analyzed mice with a mutation in the alpha and Delta isoforms of the CREB gene. Previously we have shown that CREB(alphaDelta) mutant mice in a mixed genetic background show attenuated signs of physical dependence, as measured by the classic signs of withdrawal. We have generated a uniform genetically stable F1 hybrid (129SvEv/C57BL/6) mouse line harboring the CREB mutation. We have found the functional activity of CREB in these F1 hybrid mice to be dramatically reduced compared with their wild-type littermates. These mice maintain a reduced withdrawal phenotype after chronic morphine. We are now poised to examine a number of complex behavioral phenotypes related to addiction in a well defined CREB-deficient mouse model. We demonstrate that the aversive properties of morphine are still present in CREB mutant mice despite a reduction of physical withdrawal. On the other hand, these mice do not respond to the reinforcing properties of morphine in a conditioned place preference paradigm. In contrast, CREB mutant mice demonstrate an enhanced response to the reinforcing properties of cocaine compared with their wild-type controls in both conditioned place preference and sensitization behaviors. These data may provide the first paradigm for differential vulnerability to various drugs of abuse.
 ...
PMID:Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse. 1171 77

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.
 ...
PMID:The truth about pain management: the difference between a pain patient and an addicted patient. 1179 14

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

Pain is unnecessary. Effective tools are available to help doctors evaluate pain in their patients. Unrelieved pain should be treated just like any other vital sign: with aggressive measures. Effective therapies are available to treat pain. Use guidelines to develop a rational plan to relieve pain. Side effects are manageable. Anticipate side effects and treat aggressively. Addiction rarely occurs. Trust your patient when they report pain. Tolerance and physical dependence can occur. Plan and you will succeed. Take the initiative and focus on relieving pain at your hospital. Your patients depend on it.
 ...
PMID:Pain management in the hospitalized patient. 1236 40

Most advances in addiction treatment to date have addressed the physical dependence and withdrawal that accompany addiction to some drugs of abuse. In contrast, it has proven more difficult to develop medications that effectively treat drug craving and relapse, the core features of addictive disorders. Current efforts focus on developing medications that prevent a drug from getting to its protein target, that mimic drug action and thereby partially alleviate drug craving, or that affect the addiction process per se. The latter approach is the most speculative, but also the most promising in terms of translating basic knowledge of addiction into clinical progress.
 ...
PMID:From neurobiology to treatment: progress against addiction. 1240 90

Patients may present to physicians with complaints of acute or chronic pain. Some of these patients will have a history of addiction to drugs or alcohol, and a few will have active addiction. Controlled-substance prescriptions, especially opioid pain medications, can be very beneficial for treatment of pain in patients. There are clear differences between physical dependence on medication, active addiction, addiction in remission, and pseudoaddiction. A search of the medical literature revealed different rates of addiction in patients with chronic pain because different criteria were used to define addiction and the types of chronic pain. It appears that rates of addiction in patient populations with chronic pain are no different than rates of addiction in the general population, according to some recent studies. "Drug-seeking behavior" may be seen with either active addiction or pseudoaddiction. A way to distinguish between these conditions is by giving the patient more pain medication and observing the patient's pattern of behavior. Some patients may be at higher risk to abuse prescription opioids, and some types of drug-seeking behavior may be more predictive of active addiction than pseudoaddiction. General guidelines can improve physicians' comfort level in prescribing opioids for patients with chronic pain, even those with a history of addiction. These include using a medication agreement or contract, setting appropriate goals with the patient, giving appropriate amounts of pain medication, monitoring with drug screens and pill counts, and documenting the case carefully. Even patients with a history of addiction can benefit from opioid pain medications if the patients are monitored appropriately.
 ...
PMID:Abuse liability in opioid therapy for pain treatment in patients with an addiction history. 1247 55

Dihydroetorphine (DHE) is one of the strongest analgesic opioid alkaloids known; it is 1000 to 12000 times more potent than morphine. Several in vitro and in vivo studies have shown that DHE is a selective mu-opioid receptor (OP(3)) agonist that also binds and activates all human recombinant mu-, delta-, and kappa-opioid receptors (OP(3), OP(1), and OP(2)). The onset of the analgesic effect of DHE in rodents is rapid, 5 to 15 min after parenteral administration; the duration of action is short, the analgesic effect disappears within 120 min after administration. By oral administration much higher doses of DHE are required to produce analgesic effects. These characteristics are accounted for by the pharmacokinetic properties of DHE in the rat, namely, by rapid distribution of DHE from the injection site to the brain and rapid metabolism by glucuronidation in the gut and liver followed by elimination into the bile. Continuous infusion and repeated administration of DHE lead to the development of tolerance to analgesia, physical dependence, and a rewarding effect in normal rats but not in animals with formalin-induced inflammation. Although formalin-induced inflammation is only one type of pain stimulus, these findings suggest that DHE addiction would be observed only in the case of pain-free conditions. Clinical reports in China show that sublingual doses of DHE, 20 to 180 microg, produce a potent analgesic effect with only mild side effects, including dizziness, somnolence, nausea, vomiting, constipation, and shortness of breath. To improve the short-lasting effect following sublingual administration, transdermal delivery of DHE via a patch has been investigated. The patch formulation of DHE produces continuous analgesic effect with minimal physical dependence and rewarding effect in rats suffering from chronic pain. This patch formulation, which is very suitable for DHE, may be viable for the treatment of severe pain and is likely to improve patients' quality of life.
 ...
PMID:Dihydroetorphine: a potent analgesic: pharmacology, toxicology, pharmacokinetics, and clinical effects. 1248 Nov 94


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