Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice

Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.     

200例门诊药房退药分析及思考

目的：了解我院门诊药房退药。隋况,提出减少退药的措施与对策。方法：收集2010年6月-2010年12月门诊药房部分典型退药案例,进行归纳分析。结果：引起患者退药的原因主要包括：药物不良反应;不合理用药;自觉药物不对症;处方差错;医院信息系统问题;改变治疗方案;患者拒绝治疗;患者转诊或死亡;用药重复或大处方;医保费用问题。结论：加强医师及药师的业务素质,加强对患者配伍禁忌及不良反应的告知,加强处方管理、医患沟通;完善退药制度,可以减少急诊退药的发生。     

A narrative review on the management of medication overuse headache: the steep road from experience to evidence

The management of medication overuse headache (MOH) is based essentially on the withdrawal of the overused drug(s). Drug withdrawal is performed according to widely differing protocols, both within and across countries; therefore, therapeutic recommendations for the acute phase of detoxification vary considerably among studies. Basically, the aims of MOH management are: (a) to withdraw the overused drug(s); (b) to alleviate withdrawal symptoms by means of a bridge therapy, which includes pharmacological and non-pharmacological support, designed to help the patient to tolerate the withdrawal process; (c) to prevent relapse. Today, there is extensive debate over the best strategies for achieving these goals and the different aspects of this debate are discussed in this review. The authors searched for the best available evidence relating to the following questions: should medication withdrawal be abrupt or gradual? Should patients receive replacement therapy? What are the most effective therapeutic programmes for controlling withdrawal symptoms? Should replacement therapy be administered routinely or as rescue therapy? Should preventive treatment be started before, during or after withdrawal? What are the most effective preventive treatments? Should patients be managed through inpatient or outpatient withdrawal programmes? What is the best approach to adopt in preventing relapses? Treatment of MOH is a difficult challenge, but may be very rewarding. Although there is still a lack of high-quality studies providing evidence-based answers to the many specific questions it raises, neurologists need to know that the combination of education with a rational use of selected therapeutic strategies may be beneficial to people with chronic headache and help to relieve their suffering.     

Alcohol withdrawal syndrome and its treatment

When alcoholics decrease or interrupt alcohol intake abruptly, they will in general experience alcohol withdrawal symptoms. Clinically in most cases it develops a vegetative syndrome with gastroenteropathy, cardiovascular diseases, neurological and psychopathological symptom. Usually alcohol withdrawal symptoms abate after four to seven days, longer courses are rare. Application of drugs is required in approximately one third to one half of the patients. A variety of drugs was suggested for the treatment of alcohol withdrawal. In the first hours of alcohol detoxification, the sensitivity of epinephrine receptors is reduced, but rises afterwards substantially. The number of NMDA-receptors increases during chronic intoxication with ethanol. The standard therapy in Europe (except of Great Britain) is an oral mono therapy with clomethiazole in a dose which depends on the severity of the symptoms. Severe withdrawal symptoms may require treatment on an intensive care unit with infusion therapy, e.g. in the context of a delirium tremens, which represents a life-threatening status. In this case, benzodiazepines have been used successfully as an alternative to clomethiazole.     

The cocaine habit

Although cocaine is considered "safe" by many drug abusers, serious psychosocial problems and medical complications, including death, can occur as the direct result of addiction to this drug. The mainstays of therapy include motivation, meticulous physical and laboratory evaluation, abstinence, and support during withdrawal. Diazepam and propranolol drugs are useful during this difficult period. Several commonly used psychotropic drugs are contraindicated. Supportive care and counseling are helpful, but a relapse is probable.     

Help substance abusers attain and sustain abstinence

Individuals struggling with substance abuse are more likely to present or return to a primary care provider who isn't an addiction specialist. These patients appear in primary care settings at various stages of readiness to change their behavior. Here we provide brief motivational interventions that can encourage a patient to enter treatment. We also detail how to recognize postabstinence symptoms that are present after acute withdrawal symptoms.     

Medication overuse and drug addiction: a narrative review from addiction perspective

Chronic headache is particularly prevalent in migraineurs and it can progress to a condition known as medication overuse headache (MOH). MOH is a secondary headache caused by overuse of analgesics or other medications such as triptans to abort acute migraine attacks. The worsening of headache symptoms associated with medication overuse (MO) generally ameliorates following interruption of regular medication use, although the primary headache symptoms remain unaffected. MO patients may also develop certain behaviors such as ritualized drug administration, psychological drug attachment, and withdrawal symptoms that have been suggested to correlate with drug addiction. Although several reviews have been performed on this topic, to the authors best knowledge none of them have examined this topic from the addiction point of view. Therefore, we aimed to identify features in MO and drug addiction that may correlate. We initiate the review by introducing the classes of analgesics and medications that can cause MOH and those with high risk to produce MO. We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. Finally, ICHD recommendations to treat MOH will be provided herein.     

Aortic emergencies

Aortic emergencies present a diagnostic and treatment challenge for emergency physicians. Both acute aortic dissection and abdominal aortic aneurysms can be difficult to recognize, and a missed or delayed diagnosis may be fatal. A high clinical suspicion and rapid patient evaluation are important. Although many patients ultimately require surgical intervention, early and aggressive attention to hemodynamic stability by the emergency physician can provide a window to definitive treatment.     

Identification and management of neonatal abstinence syndrome.

The nursing care of infants experiencing withdrawal from drug abuse through passive exposure is often challenging. These infants are at higher risk for many medical complications in addition to withdrawal itself. Often, infusion nurses play an important role in caring for an infant with drug withdrawal by providing infusion therapy for the infant's compromised medical condition, poor oral intake, and withdrawal symptoms. This article focuses on drug abuse during pregnancy, the withdrawal symptoms it may cause in the infant, ways to recognize an infant experiencing neonatal abstinence syndrome, and available scoring tools and treatment options.     

Common overuse tendon problems: A review and recommendations for treatment

There is a common misconception that symptomatic tendon injuries are inflammatory; because of this, these injuries often are mislabeled as "tendonitis."' Acute inflammatory tendinopathies exist, but most patients seen in primary care will have chronic symptoms suggesting a degenerative condition that should be labeled as "tendinosus" or "tendinopathy." Accurate diagnosis requires physicians to recognize the historical features, anatomy, and useful physical examination maneuvers for these common tendon problems. The natural history is gradually increasing load-related localized pain coinciding with increased activity. The most common overuse tendinopathies involve the rotator cuff, medial and lateral elbow epicondyles, patellar tendon, and Achilles tendon. Examination should include thorough inspection to assess for swelling, asymmetry, and erythema of involved tendons; range-of-motion testing; palpation for tenderness; and examination maneuvers that simulate tendon loading and reproduce pain. Plain radiography, ultrasonography, and magnetic resonance imaging can be helpful if the diagnosis remains unclear. Most patients with overuse tendinopathies (about 80 percent) fully recover within three to six months, and outpatient treatment should consist of relative rest of the affected area, icing, and eccentric strengthening exercises. Although topical and systemic nonsteroidal anti-inflammatory drugs are effective for acute pain relief, these cannot be recommended in favor of other analgesics. Injected corticosteroids also can relieve pain, but these drugs should be used with caution. Ultrasonography, shock wave therapy, orthotics, massage, and technique modification are treatment options, but few data exist to support their use at this time. Surgery is an effective treatment that should be reserved for patients who have failed conservative therapy.     

Delirium

Delirium is characterized by an acute change in cognition and a disturbance of consciousness, usually resulting from an underlying medical condition or from medication or drug withdrawal. Delirium affects 10 to 30 percent of hospitalized patients with medical illness; more than 50 percent of persons in certain high-risk populations are affected. The associated morbidity and mortality make diagnosis of this condition extremely important. Patients with delirium can present with agitation, somnolence, withdrawal, and psychosis. This variation in presentation can lead to diagnostic confusion and, in some cases, incorrect attribution of symptoms to a primary psychiatric disorder. To make the distinction, it is important to obtain the history of the onset and course of the condition from family members or caregivers. Primary care physicians must be able to recognize delirium so that the underlying etiology can be ascertained and addressed. The management of delirium involves identifying and correcting the underlying problem, and symptomatically managing any behavioral or psychiatric symptoms. Low doses of antipsychotic drugs can help to control agitation. The use of benzodiazepines should be avoided except in cases of alcohol or sedative-hypnotic withdrawal. Environmental interventions, including frequent reorientation of patients by nursing staff and education of patients and families, should be employed in all cases.     

The patient with daily headaches

The term "chronic daily headache" (CDH) describes a variety of headache types, of which chronic migraine is the most common. Daily headaches often are disabling and may be challenging to diagnose and treat. Medication overuse, or drug rebound headache, is the most treatable cause of refractory daily headache. A pathologic underlying cause should be considered in patients with recent-onset daily headache, a change from a previous headache pattern, or associated neurologic or systemic symptoms. Treatment of CDH focuses on reduction of headache triggers and use of preventive medication, most commonly anti-depressants, antiepileptic drugs, and beta blockers. Medication overuse must be treated with discontinuation of symptomatic medicines, a transitional therapy, and long-term prophylaxis. Anxiety and depression are common in patients with CDH and should be identified and treated. Although the condition is challenging, appropriate treatment of patients with CDH can bring about significant improvement in the patient's quality-of-life.     

Amphetamine toxicity in the emergency department.

XTC and other amphetamines are considered to be safe by the majority of partying young people who are unaware of (or unwilling to know about) the acute and chronic toxicity of these substances, and these drugs are widespread, illicit stimulants. In this article, we describe four cases of severe acute toxicity due to recreational use of amphetamines 3,4-methylene-dioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, 3,4-methylenedioxyamphetamine, 4-methylthioamphetamine or p-methoxyamphetamine, with emphasis on the presenting symptoms and acute treatment in the emergency department.     

Quel(s) antalgique(s) après le retrait du dextropropoxyphène ? Enquête auprès de médecins généralistes de la région Midi-Pyrénées

Following the announcement of the future withdrawal in Europe of drugs containing dextropropoxyphene-paracetamol (DXP-P), we performed a postal survey in a randomly selected sample of 350 general practitioners (GP) from the Midi-Pyrénées area (2.6 million inhabitants) in order to investigate which drug (s) they are willing to prescribe in anticipation of the announced withdrawal. Most of GP prescribed DXP-P in acute and chronic pain. In acute pain, GP would switch to codeine-paracetamol (59.1%) or tramadol alone or associated with paracetamol (79%), whereas they would switch to high dose paracetamol (54.7%) and tramadol alone or associated with paracetamol (74.6%) in chronic pain. Switching to other level 2 analgesic drugs after the withdrawal of dextropropoxyphene should be closely monitored because the safety profile of other drugs.     

Drugs that may cause psychiatric symptoms

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.     

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.     

Medikamentöse Migräneprophylaxe

If migraine attacks occur more frequently than 2 times a month, treatment of the acute attack with analgesics and ergotamine becomes problematic. An acute relief of migraine symptoms will be achieved only at the risk of developing a drug-induced chronic headache. Therefore, if migraine attacks occur frequently prophylactic treatment should be considered. A bewildering variety of drugs have been discussed for migraine prophylaxis in the past few decades. Only a few of them can be accepted to be effective on the basis of reliable clinical studies. Others have failed to show any superiority to placebo treatment when tested in controlled drug trials for a period long enough to rule out the placebo response, which may simulate effectiveness at the beginning of the trial. The efficacy of metoprolol and propranolol has been demonstrated beyond any doubt. It seems, however, that other beta-blocking drugs are less effective or even ineffective. In more than 20% of patients even prolonged treatment with metoprolol or propranolol does not provide sufficient relief. Flunarizine may be tried in these patients, as long as side effects do not occur or can be tolerated by the patient. Whether non-steroidal antirheumatics and dihydroergotamine can be considered as an effective and safe alternative in migraine prophylaxis is still not well established. There is, however, convincing evidence that neither clonidine, nor anti-histamines, nor barbiturates, nor antiepileptic drugs, nor anxiolytics are effective in the prophylactic treatment of migraine. Successful prophylactic treatment cannot be achieved by drug therapy alone. Any form of drug treatment should be complemented by providing the patient with detailed information about the nature of the disease and the properties of the prescribed drugs, as well as careful investigation of the patient's situation and habits and a careful search for precipitants, combined with an attempt to change the patient's habits and to avoid factors that trigger the attacks.     

Obstructive sleep apnea: novel trigger and potential therapeutic target for cardiac arrhythmias

Obstructive sleep apnea (OSA), the most common form of sleep-disordered breathing, is prevalent and frequently underdiagnosed in our community. Although presenting with predominantly respiratory symptoms, the most serious complications from OSA are cardiovascular, including arrhythmias, disease of the sinus node and conducting system, and sudden cardiac death. The acute and chronic effects of OSA on the cardiovascular system, which include major effects on autonomic function during sleep and wakefulness, are potent contributors to the development and persistence of cardiac arrhythmias. Although large randomized studies are currently lacking, treatment of OSA may be an important primary or additional therapy to supplement the use of drugs or devices in the treatment of cardiac arrhythmias.     

Withdrawal syndrome following cessation of antihypertensive drug therapy

In this study, a review of the available information concerning abrupt withdrawal of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs can produce a syndrome of sympathetic overactivity that includes nervousness, tachycardia, headache, agitation and nausea 36-72 h after cessation of the drug. A withdrawal syndrome may occur after discontinuation of almost all types of antihypertensive drugs, but mostly occurs with clonidine, beta-blockers, methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood pressure to pre-treatment levels or above, or both and/or myocardial ischaemia. Although the exact incidence of the syndrome is not known, it appears to be rare, at least in patients receiving standard doses of the above antihypertensive drugs. The best treatment is prevention. In this study regarding the withdrawal syndrome that follows cessation of antihypertensive drugs therapy, a reference to the abrupt discontinuation of the main categories of antihypertensive drugs is also attempted.