Postoperative pain control in children: a guide to drug choice

Postoperative pain in children can usually be well controlled with a combination of analgesics, including acetaminophen (paracetamol), NSAIDs, opioids, and local/regional anesthesia. Recent research has shown that the dosage of acetaminophen required to provide analgesia is higher than the traditional dosages used for the regulation of elevated body temperature. Rectal administration of acetaminophen gives a lower and more variable bioavailability compared with oral administration. There is growing experience with the use of NSAIDs in children and several studies have demonstrated the relatively strong analgesic potential of these drugs. Titration of opioids to analgesic effect, and the use of nurse- and patient-controlled continuous opioid infusions in children have gained widespread use and, with proper education and supervision, are considered excellent methods of pain control. Local peripheral and central blocks decrease the need for anesthetics during surgery and provide effective postoperative pain relief.     

Non-Hodgkin's lymphoma in the elderly: a guide to drug treatment.

Adverse events are common in the elderly when they undergo potent chemotherapy and the reasons for this are various. Therefore, chemotherapy for elderly patients with non-Hodgkin's lymphoma (NHL) must differ from that for non-elderly patients. Age is one of the poor prognostic factors for NHL and the main reason for this is reduced antitumour effect due to decreased dose and increased adverse effects. However, many of these elderly patients also die from causes other than lymphoma. The usual approach to the treatment of indolent NHL is to use drugs with few adverse effects such as nucleoside analogs. Multidrug therapy is used for intermediate grade NHL and the most commonly used regimen is CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). In recent years, many clinical trials have been performed in elderly patients with NHL. The results of these trials indicate that a significantly better prognosis is achieved with anthracycline (cytostatic antibiotics) containing regimens. The elderly population will continue to grow and so it is necessary to establish more effective treatment options for NHL in the elderly.     

Secondary prevention of stroke: a practical guide to drug treatment

Stroke is a disease of the elderly and, as a result of the expected demographic changes in many industrialised countries, its incidence is likely to increase in the future. A first-ever stroke significantly increases the likelihood of further events; thus, secondary prevention is of major importance. Only a minority of recurrent strokes can be prevented by surgical or other invasive methods, meaning that most secondary preventive measures involve drug treatment, which has become increasingly sophisticated in recent years. Ischaemic stroke constitutes the vast majority of all strokes; effective secondary prevention depends on a variety of factors, of which the correct classification in terms of subtypes and aetiological mechanisms is a pivotal prerequisite, as is the assessment of the patient's cardiovascular risk profile. In addition to the evaluation of pathomechanisms, stratification of subtypes of brain infarction is mainly based on morphology seen with brain imaging techniques, which provides additional evidence for the presumed cause of the stroke. Inhibitors of platelet function and anticoagulants are the two major groups of antithrombotic drugs used for the secondary prevention of stroke. Antiplatelet agents are still indicated in the majority of patients after ischaemic stroke, especially if an arterial origin is presumed. In addition to aspirin (acetylsalicylic acid), the position of which as the first-line antiplatelet drug is increasingly being questioned, other compounds with antiplatelet activity have been developed and have proven effective in secondary stroke prevention, including ticlopidine, clopidogrel and dipyridamole. Anticoagulants are principally indicated after cardioembolic ischaemic stroke; however, their inherent bleeding risks render their use in many cases rather difficult, in particular for elderly patients. Patient compliance with the recommended treatment is of major importance, given the somewhat limited efficacy of antithrombotic agents in stroke prevention. Since 'real world' experience does not match the circumstances under which clinical trials are conducted, this article will also deal with problems not covered by specific studies, such as risk stratification for anticoagulant treatment and how to proceed in cases of unknown stroke aetiology. The management of major cardiovascular risk factors is the other mainstay of secondary stroke prevention. Recent evidence indicates that antihypertensive treatment may be as effective as antithrombotic drugs for secondary prevention of stroke. This still needs to be proven for the treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia. Nevertheless, the results of recent studies investigating the effect of HMG-CoA reductase inhibitors ('statins') on cardiovascular events strongly suggest a stroke-preventive effect.     

Narcolepsy in children: a practical guide to its diagnosis, treatment and follow-up

Narcolepsy is a neurological syndrome characterised by daytime somnolence and cataplexy which often begins in childhood. Failing to recognise the condition may lead to mislabelling a child as lazy or depressed. The diagnostic criteria for narcolepsy vary with age. In children 8 years and older a Multiple Sleep Latency Test with an average latency of less than 8 minutes, and 2 or more sleep onset REM episodes supports the diagnosis. Human leucocyte antigen (HLA) marker DQbeta1 -0602 has been associated with narcolepsy. The current evidence supports the hypothesis that transmission of narcolepsy is multifactorial. with at least two genes, one of which is non-HLA related. The goal of all therapeutic approaches in narcolepsy is to control the narcoleptic symptoms and allow the patient to continue to fully participate in personal and academic activities. This usually requires a combination of behavioural therapy along with medication. Medications for patients with excessive sleepiness are usually stimulants, including amphetamines. However, a novel wake promoting agent, modafinil, is now available. Cataplexy can be controlled by medications with noradrenergic reuptake-blocking properties, such as clomipramine and fluoxetine, through their active metabolites. Increased awareness of narcolepsy is important to allow earlier diagnosis. Research on the effects different medications have, specifically on children with narcolepsy, has been very limited.     

Controlled hypotension: a guide to drug choice

For half a century, controlled hypotension has been used to reduce bleeding and the need for blood transfusions, and provide a satisfactory bloodless surgical field. It has been indicated in oromaxillofacial surgery (mandibular osteotomy, facial repair), endoscopic sinus or middle ear microsurgery, spinal surgery and other neurosurgery (aneurysm), major orthopaedic surgery (hip or knee replacement, spinal), prostatectomy, cardiovascular surgery and liver transplant surgery. Controlled hypotension is defined as a reduction of the systolic blood pressure to 80-90 mm Hg, a reduction of mean arterial pressure (MAP) to 50-65 mm Hg or a 30% reduction of baseline MAP. Pharmacological agents used for controlled hypotension include those agents that can be used successfully alone and those that are used adjunctively to limit dosage requirements and, therefore, the adverse effects of the other agents. Agents used successfully alone include inhalation anaesthetics, sodium nitroprusside, nitroglycerin, trimethaphan camsilate, alprostadil (prostaglandin E1), adenosine, remifentanil, and agents used in spinal anaesthesia. Agents that can be used alone or in combination include calcium channel antagonists (e.g. nicardipine), beta-adrenoceptor antagonists (beta-blockers) [e.g. propranolol, esmolol] and fenoldopam. Agents that are mainly used adjunctively include ACE inhibitors and clonidine. New agents and techniques have been recently evaluated for their ability to induce effective hypotension without impairing the perfusion of vital organs. This development has been aided by new knowledge on the physiology of peripheral microcirculatory regulation. Apart from the adverse effects of major hypotension on the perfusion of vital organs, potent hypotensive agents have their own adverse effects depending on their concentration, which can be reduced by adjuvant treatment. Care with use limits the major risks of these agents in controlled hypotension; risks that are generally less important than those of transfusion or alternatives to transfusion. New hypotensive drugs, such as fenoldopam, adenosine and alprostadil, are currently being evaluated; however, they have disadvantages and a high treatment cost that limits their development in this indication. New techniques of controlled hypotension subscribe to the use of the natural hypotensive effect of the anaesthetic drug with regard to the definition of the ideal hypotensive agent. It must be easy to administer, have a short onset time, an effect that disappears quickly when administration is discontinued, a rapid elimination without toxic metabolites, negligible effects on vital organs, and a predictable and dose-dependent effect. Inhalation agents (isoflurane, sevoflurane) provide the benefit of being hypnotic and hypotensive agents at clinical concentrations, and are used alone or in combination with adjuvant agents to limit tachycardia and rebound hypertension, for example, inhibitors of the autonomic nervous system (clonidine, beta-blockers) or ACE inhibitors. When they are used alone, inhalation anaesthetics require high concentrations for a significant reduction in bleeding that can lead to hepatic or renal injury. The greatest efficacy and ease-of-use to toxicity ratio is for techniques of anaesthesia that associate analgesia and hypotension at clinical concentrations without the need for potent hypotensive agents. The first and oldest technique is epidural anaesthesia, but depending on the surgery, it is not always appropriate. The most recent satisfactory technique is a combination treatment of remifentanil with either propofol or an inhalation agent (isoflurane, desflurane or sevoflurane) at clinical concentrations. In light of the current literature, and because of their safety and ease of use, these two techniques are preferred.     

Induction of anaesthesia: a guide to drug choice

In developed countries, the choice of an anaesthetic agent for induction of anaesthesia remains based mainly on its pharmacodynamic properties. Until now, cardiovascular effects were the main factor in this decision. However, other factors, such as the depth of anaesthesia and effects on cortisol synthesis, can modify this simplistic view. A better understanding of the relationships between the pharmacokinetics and pharmacodynamics of these drugs, and the availability of new techniques, such as target-controlled infusions of anaesthetic drugs and inhalation induction, have led practitioners to the understanding that the way a drug is administered is a far more important factor for maintaining haemodynamic stability than the specific agent used. The ability of a drug to maintain spontaneous ventilation and to relax the upper airway is another factor in this decision, especially when considering difficult intubation, laryngeal mask insertion or tracheal intubation without neuromuscular blockade. Beyond the factors mentioned above, anaesthetists adapt current practice to suit patients' willingness to comply with anaesthesia and to avoid the adverse effects that are most often feared by the patient. Although most practitioners are not concerned with the cost of anaesthesia, cost-containment policies have led some institutions to restrict the use of the more expensive drugs to particular indications. However, this is too simplistic an approach for the reduction of global costs, as other direct medical costs, such as those for staffing, form a greater proportion of total costs than do direct drug costs. Cost-benefit and cost-efficacy studies of the anaesthetics used for induction of anaesthesia are needed to help anaesthetists to choose a drug based on both cost and pharmacodynamic or pharmacokinetic properties.     

A guide to drug discovery: Target selection in drug discovery

Target selection in drug discovery--defined here as the decision to focus on finding an agent with a particular biological action that is anticipated to have therapeutic utility--is influenced by a complex balance of scientific, medical and strategic considerations. In this article, we provide an introduction to the key issues in target selection and discuss the rationale for decision making.     

Engaging resistant adolescents in drug abuse treatment

In the first phase of a two-part treatment development study, families with a treatment-resistant drug-abusing adolescent (n = 42) were offered 12 sessions of Community Reinforcement and Family Training (CRAFT). This parent-focused intervention was designed to help parents facilitate their adolescents' entry into treatment, to support adolescents' subsequent behavior change, and to improve parent and family functioning. In the second phase, successfully engaged adolescents (n = 30) were offered 12 sessions of a multicomponent individual cognitive-behavioral therapy (CBT) targeting substance use and related problem behaviors. For parents and adolescents, measures were collected on pretreatment and posttreatment, with an additional follow-up assessment for parents at 3 months after treatment. Parents on CRAFT intervention experienced a significant reduction in negative symptoms, and 71% of parents were successful in engaging their resistant youths in treatment. The CBT intervention for engaged youths was associated with a statistically significant, but not clinically significant, reduction in marijuana use.     

Evaluating drug safety in children and adolescents with bipolar disorder

The safety of the use of medications in adolescents and children to treat bipolar disorder has not been extensively studied. The prevalence of bipolar disorder in children and adolescents is unknown due to the lack of completed large-scale epidemiological studies. In addition, the diagnosis of this disorder is still questionable in this age group because the same explicit diagnostic criteria used in adults potentially cannot be applied to children and adolescents since the early-onset symptoms often overlap with other disorders such as attention-deficit disorder. The safety of drugs used to treat bipolar disorder is of growing concern, particularly because this population usually requires more than one psychotropic medication to manage the disease. Common side effects seen with several agents, particularly antipsychotics, are somnolence, weight gain, extrapyramidal symptoms, dyslipidemia, type-2 diabetes, and hyperprolactinemia. This review will discuss the most advanced practice guidelines in assessing and treating bipolar disorder in children and adolescents, the safety and effectiveness of the drugs currently used based on clinical trials and post-marketing surveillance, and the risks versus benefits associated with their use.     

Delivering more effective treatment to adolescents: Improving the juvenile drug court model

Juvenile drug courts (JDC) emerged in response to a perceived need to intervene more effectively in the substance abuse-delinquency cycle. The influx of drug and alcohol offenders, lack of other juvenile justice system interventions, and positive experiences with adult drug courts helped drive interest in adapting the drug court model for juveniles. This article: (1) provides an overview of substance use and the juvenile justice system; (2) describes the current status of JDC programs; and (3) proposes a model for planning, implementing and evaluating JDCs based on adolescent drug use and treatment research as well as current JDC models. The lack of science-based JDC models and empirically sound JDC evaluations has limited the effectiveness of JDCs. The proposed model is designed to create a new generation of JDCs that maximizes the effectiveness of local resources and delivers research-based interventions to youth and families impacted by substance abuse and delinquency.     

Migraine: preventive treatment

Preventive treatment is designed to decrease headache frequency. It should be used if headaches are too frequent, disabling, or associated with worrisome neurological features or if acute treatment is overused or ineffective. The chosen drug should be given an adequate trial in the absence of interfering medications. Choose a drug based on its efficacy, adverse event profile, and the presence of coexistent conditions.     

Pharmacological treatment of depression in children and adolescents

Major depression is a common disorder during childhood and adolescence. Over the past decade, many new antidepressants have been marketed in the US. In adults, these newer agents have been shown to be as effective as the prototypic tricyclic antidepressants (TCAs). Further, when compared with the TCAs these medications are better tolerated and are safer in overdose. Although TCAs are effective in the treatment of depressed adults, controlled clinical trials have not demonstrated their efficacy in either children or adolescents. In addition, concerns about the safety of TCAs and the monoamine oxidase inhibitors has left disappointingly few pharmacological treatment options available for depressed children and adolescents. For this reason, clinicians have begun to prescribe the newer agents for this population, despite the fact that relatively little is known about their disposition, safety or effectiveness in the young. Investigators have begun to examine whether the use of newer antidepressant medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone, and venlafaxine is truly indicated for children and adolescents with major depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have been performed in depressed youths. The results of these studies have provided data for rational administration strategies for these agents. They have also provided evidence that these agents may be well tolerated in children and adolescents. Further evidence that these agents are often well tolerated when prescribed to depressed youths has been obtained from both open-label and double-blind studies. Published studies have generally shown that open-label treatment with these newer agents often leads to symptom amelioration in paediatric patients with major depression. Since high rates of placebo response are often seen in depressed children and adolescents, results from these studies cannot be interpreted to suggest that these medications have true antidepressant efficacy in this population. At present, the results of only two such studies have been published. The results of one of these trials are difficult to interpret because of methodological considerations. The other study reported that treatment with fluoxetine was superior to placebo. This paper critically reviews what has been published about the pharmacological treatment of depressed paediatric patients and provides some guidance to the use of antidepressants in this patient population, paying particular attention to what is known about the newer antidepressants as well as considering directions for future research.     

Community-acquired pneumonia in the elderly: a practical guide to treatment

The incidence of community-acquired pneumonia (CAP), an infectious disease, sharply increases among the elderly and the main risk factor for CAP in this age group is chronic comorbidity. The use of the term CAP in the elderly population should be reserved for pneumonia acquired outside of the nursing home setting, since nursing home-acquired pneumonia differs from CAP in terms of its aetiology and clinical manifestations. The main aetiology for CAP is Streptococcus pneumoniae, but atypical pathogens also play an important role as causative agents. The clinical presentations of CAP in the elderly can be different from those in younger patients, and therefore it is important to be aware of and familiar with these differences to avoid unnecessary delays in reaching the correct diagnosis. Imaging is essential to diagnose CAP and to assess its severity. Clinical and laboratory indices can be used to identify elderly patients with CAP who are at low risk for mortality and who can be treated as outpatients. The decision not to hospitalise elderly patients with CAP is contingent on a good clinical condition and the existence of home support systems. The aetiology of CAP cannot be determined on the basis of clinical manifestations, imaging or routine laboratory test results, and the initial antibiotic therapy for elderly patients with CAP should be empirical, based on accepted guidelines. In the light of developments in recent years, elderly patients with CAP, except those who are severely ill, can be treated empirically with once-daily antibiotic monotherapy in the initial phase, using a third-generation fluoroquinolone preparation, such as sparfloxacin, levofloxacin or moxifloxacin, or a new macrolide such as clarithromycin, azithromycin or dirithromycin. In addition to antibiotic therapy, it is critically important to identify and treat the physiological disturbances that accompany CAP as well as decompensation of chronic comorbid conditions. As soon as the patient's condition permits, oral antibiotic therapy should replace intravenous therapy and early discharge from the hospital should be considered. Since influenza and pneumococcus immunisation can reduce morbidity and mortality from CAP, it is important to implement regular immunisation programmes in the primary care setting.     

Sedation and analgesia in paediatric intensive care units: a guide to drug selection and use

The indications for sedation in the paediatric intensive care unit (PICU) patient are varied ranging from short term use for various procedures to prolonged administration to provide comfort during mechanical ventilation. When faced with the decision to institute sedation, the healthcare provider must make three decisions: the agent to be used, the route of delivery, and the mode of administration (intermittent versus continuous). There are several agents that have been used to provide sedation in the PICU patient including the inhalational anaesthetic agents, benzodiazepines, opioids, ketamine, propofol, chloral hydrate, phenothiazines, and the barbiturates. This review describes the various agents for sedation and discusses their advantages and disadvantages as they pertain to the PICU. Consequences of and treatment strategies for long term problems with prolonged sedation including tolerance, physical dependency, and withdrawal are reviewed.     

Perceived adverse drug reactions among non-institutionalized children and adolescents in Germany

AIMS

Little has been reported on the risks of drug use in the general child population. This study investigated perceived adverse drug reactions (ADRs) among non-institutionalized children in Germany.

METHODS

All medicines used in the last 7 days before the medical interview were recorded among the 17 450 children aged 0–17 years who participated in the 2003–06 German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Perceived ADRs were reported by the children''s parents and confirmed by trained medical professionals during the medical interview.

RESULTS

One hundred and fifty-seven medicines were involved in the occurrence of 198 perceived ADRs in 153 patients. This corresponded to 1.1% of total used drugs, 0.9% (95% confidence intervals 0.7, 1.1%) of all children, and 1.7% (1.4, 2.1%) of children treated with medications. About 40% of all perceived ADRs involved gastrointestinal disorders and 16% involved skin tissue disorders. Perceived ADRs were most frequently reported in relation to drugs acting on the nervous system (25.8%), followed by systemic anti-infectives (18.7%) and drugs acting on the respiratory system (16.2%). Risk factors for perceived ADRs included older age groups, polypharmacy (≥2) and a poor health status.

CONCLUSION

Perceived ADRs in the general child population were clustered with gastrointestinal disorders and subcutaneous tissue disorders. They appeared to be mild and at the lower limits of the range reported in other studies. Health surveys covering the use of a diverse range of drugs might be suitable for computing ADR prevalence and identifying risk factors among non-institutionalized children. They should be taken into account together with other pharmacovigilance systems.