Dihydropyridines from the first to the fourth generation: better effects and safety

Dihydropyridines are among the most widely used drugs for the management of cardiovascular disease. Introduced in the 1960s, dihydropyridines have undergone several changes to optimise their efficacy and safety. Four generations of dihydropyridines are now available. The first-generation (nicardipine) agents have proven efficacy against hypertension. However, because of their short duration and rapid onset of vasodilator action, these drugs were more likely to be associated with adverse effects. The pharmaceutical industry responded to this problem by designing slow-release preparations of the short-acting drugs. These new preparations (second generation) allowed better control of the therapeutic effect and a reduction in some adverse effects. Pharmacodynamic innovation with regard to the dihydropyridines began with the third-generation agents (amlodipine, nitrendipine). These drugs exhibit more stable pharmacokinetics, are less cardioselective and, consequently, well tolerated in patients with heart failure. Highly lipophilic dihydropyridines are now available (lercanidipine, lacidipine). These fourth-generation agents provide a real degree of therapeutic comfort in terms of stable activity, a reduction in adverse effects and a broad therapeutic spectrum, especially in myocardial ischaemia and potentially in congestive heart failure.     

Advances in the treatment of epilepsy.

Significant advances have been made in the diagnosis and treatment of epilepsy over the past decade. With the advent of electroencephalographic video monitoring, physicians are now able to reliably differentiate epilepsy from other conditions that can mimic it, such as pseudoseizures. In addition, neuroimaging has changed the way treatment for difficult epilepsy is approached. As a result, the classification systems that have been in use since the early 1980s are currently being revised. A broader range of treatment options for epilepsy is now available. Many new antiepileptic drugs have become available in recent years, including felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine and zonisamide. These medications offer options for patients with epilepsy whose seizures cannot be controlled using the classic agents. Several classic antiepileptic drugs have been modified and reformulated. The ketogenic diet has resurfaced as a treatment option in certain types of epilepsy. The vagus nerve stimulator, approved in 1997, represents a completely new treatment modality for patients with seizures not controlled by medications. Epilepsy surgery is now a well-documented and effective treatment for some patients with intractable epilepsy.     

Overview of French databases available for studying anticancer drugs in real‐life setting

Considering their novelty and cost, post‐marketing evaluation is highly relevant for new anticancer drugs. Identify and characterize available and potentially useful databases for post‐marketing evaluation of these specific drugs is necessary. A review was conducted to identify available and accessible databases to study the post‐marketing evaluation of drugs in real‐life care setting. Databases identified have been classified into medico‐administrative databases, medical record databases, and databases resulting from ad hoc collections. Taking as examples databases available in France, each type was described as well as its strengths and limits for a potential use in the oncology field. Record linkage of medico‐administrative databases could cover almost the whole population and is now used to evaluate anticancer drugs (e.g., Système National des Données de Santé). Large medical record databases are still lacking, but efforts are currently made to give access to hospital data warehouses for research purposes. Finally, databases resulting from ad hoc collections are also available for some cancer localizations and allow to obtain highly valuable clinical and biological data. A range of important and valuable databases exist but, individually, none is enough to answer to all questions from health authorities, healthcare professionals, and patients. In order to obtain a complete overview on utilization, associated health outcomes and costs of these drugs, it seems necessary to better interlink available databases.     

Medications for weight reduction

Comparatively few drugs are available for the treatment of overweight patients, and their effectiveness is limited to palliation of the chronic disease of obesity. Nevertheless, drug development that is now underway is more rapid than in the past, and we anticipate the discovery of safe and effective pharmacologic strategies for the management of obesity and its serious complications.     

New drug therapy of chronic obstructive pulmonary disease

The progression of chronic obstructive pulmonary disease(COPD) can be inhibited by smoking cessation. As adjunct drugs, nicotine replacement therapy and an antidepressant bupropion are found to improve the abstinence rate from smoking. The mainstay of drug therapy of COPD consists of bronchodilators. Inhaled long-acting anticholinergic agents are in development. Inhaled long-acting beta 2-agonists are newly available. Theophylline has weak antiinflammatory effects. The significance of corticosteroids and mucolytic drugs in stable COPD is yet to be elucidated. In severely hypoxemic patients with COPD long-term domicillary oxygen therapy improves the survival rate. There is no drug therapy which can prevent the long-term deterioration of pulmonary function in patients with COPD. New class of drugs are now in development.     

New antithrombotics for the intensive care unit setting: GP IIb/IIIa inhibitors, low-molecular-weight heparins, and direct thrombin inhibitors

Thromboembolic disease (TED) is a frequent problem encountered by clinicians in the intensive care unit (ICU). Traditionally, unfractionated heparin (UFH) has been used in the treatment and prophylaxis of TED. However, newer antithrombotic agents have evolved as effective alternatives to UFH. Low-molecular-weight heparins are effective for both the treatment and prophylaxis of TED. Lepirudin is useful for patients with TED and a history of heparin-induced thrombocytopenia. The platelet glycoprotein IIb/IIIa inhibitors are synergistic with UFH for the treatment of acute coronary syndromes and percutaneous coronary interventions (PCI). Several drugs are now available to clinicians for the treatment and prophylaxis of TED.     

Using cannabinoids in pain and palliative care

Interest in the use of cannabinoids in a clinical setting is gradually increasing, particularly in patients where more conventional treatments have failed. They have been reported as offering perceived benefits in a wide range of conditions, but the major interest at present is centred on their place in pain management and in the palliation of symptoms secondary to terminal cancer and neurological disease. The potential benefits include symptomatic relief for patients suffering from intractable neuropathic pain, anorexia, anxiety and muscle spasm. There is clear consensus that cannibinoids should not be used as a first-line monotherapy, but should be considered as valuable adjuvants to more commonly indicated therapeutic options in the management of palliative care patients. Scientific evidence documenting the benefits of the canibinoids nabilone and sativex is accumulating, but needs to be evaluated carefully in the light of the paucity of available data. Both drugs are usually used under the guidance of specialist units. Nabilone and Sativex are now controlled drugs, and are frequently used outside of their licensed indication (control of chemotherapy-induced nausea and vomiting) and hence particular care needs to be taken in evaluating the rational for their use. Sativex has been recently licenced for use in the management of patients with multiple sclerosis.     

Rivaroxaban for the prevention of venous thromboembolism following major orthopedic surgery: the RECORD trials

Patients undergoing total hip or knee arthroplasty face an increased risk for venous thromboembolism in the days and weeks following surgery. Hence, the routine application of prophylactic strategies is currently recommended. These include parenteral anticoagulants such as the low-molecular-weight heparins or fondaparinux and oral anticoagulants such as warfarin. New anticoagulant drugs are rapidly becoming available, including drugs that are administered orally, at fixed doses and without laboratory monitoring. Rivaroxaban is the first of a new class of anticoagulants: the selective, direct Factor Xa inhibitors. It has completed clinical evaluation in the setting of major orthopedic surgery and is now approved in many countries for the prevention of venous thromboembolism in patients undergoing total knee and hip arthroplasty. In this paper, we will review the trial data now supporting the clinical use of rivaroxaban and will discuss the potential role of this agent in daily clinical practice.     

Recent advances in antiarrhythmic drug research: studies in chronic canine myocardial infarction-ventricular tachyarrhythmia models

Several chronic canine myocardial infarction-ventricular tachyarrhythmia models are now available for the evaluation of new antiarrhythmic drugs. The available models fulfill many, but not all of the requirements for an ideal chronic arrhythmia model. Sustained arrhythmias can be initiated in these animals using routine methods of programmed pacing. Presumably, the mechanism for these arrhythmias is localized re-entry, similar to that in patients with previous myocardial infarction and chronic coronary artery disease. However, these models are not suitable for determining whether a new drug will abolish spontaneously-occurring ventricular extrasystoles. In addition, these models are of unproven value in the study of acute spontaneously-occurring sudden death, although recently initiated, provocative work may shed further light on this subject. Most importantly, the available models do seem well-suited to the evaluation of new drugs intended for use of chronic coronary artery disease patients at risk for sustained re-entrant ventricular tachycardia or fibrillation. Notably, the results of preliminary electropharmacologic studies in these canine models parallel closely those findings reported in human patients with sustained life-threatening ventricular tachyarrhythmias. Therefore, increased use of these chronic models for new antiarrhythmic drug testing appears promising.     

Pain, analgesics, and the cardiovascular system

Original Article Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most used medications in the world. Ordinarily considered to be safe and effective when used according to labeling instructions, their safety for patients with cardiovascular disease is now being reassessed.     

Pharmacological treatment of acute coronary syndromes

Many trials have examined the efficacy of medications used in acute coronary syndromes. This paper reviews those now recommended in patients with unstable angina and non-ST-segment elevation myocardial infarction. There are currently seven groups of drugs that are used in the management of such patients.     

Prevention and treatment of viral infections: problems and current recommendations

Childhood immunization unfortunately has ceased to be an important focus of preventive medicine in the United States. Although smallpox is no longer a problem, vaccination against poliomyelitis, measles, and rubella is still very much needed. Immunization is also available for hepatitis B, influenza, and rabies and can be carried out in children or adults under selected circumstances. The antiviral drugs now being used have limited roles, although new drugs on the horizon seem promising.     

Management principles of gastrointestinal bleeding

There is now a multitude of technologic and pharmacologic options available to clinicians caring for patients with gastrointestinal (GI) bleeding; however, drugs and technology are no substitute for understanding and properly executing the basic management principles of GI bleeding. This article focuses on the most common causes of GI bleeding and emphasizes the importance of the primary care provider's role in the management of these patients. Also, by answering questions we are commonly asked as gastroenterology consultants, we hope to provide insight into current diagnostic and therapeutic options and the most appropriate use of these options.     

Epinephrine kinetics in septic shock – a means to understand variable catecholamine efficiency?

It is well-established that the hemodynamic response to infusing catecholamines, the most frequently applied drugs for circulatory support during shock states, may vary markedly within and between individuals. In this context it is striking that only scarce data are available on the pharmacokinetics of catecholamines in critically ill patients. Furthermore, the existing literature comprises fairly equivocal observations. Abboud and colleagues now report that, in patients with septic shock, epinephrine kinetics are linear and its clearance directly depends on body weight and is inversely related to the severity of the disease. The authors conclude that the endogenous adrenal axis hormones do not assume any additional importance.     

Cancer chemotherapy. Current status, coming innovations

A wide number of agents are now available for chemotherapeutic treatment of cancer. The agents fall into four categories: the alkylating agents, the antimetabolites, the anti-tumor antibiotics, and the mitotic inhibitors. Various combinations of the agents are used to gain greater treatment efficacy and reduce resistance, and chemotherapy used as an adjunct to surgery can give added benefit in some cases. Since successful chemotherapy depends on using active drugs, new assays to predict drug responsiveness are being developed. Toxicity of cytotoxic drugs remains a major problem, although attempts at modification hold promise. Clinical trials, the mainstay for evaluating efficacy and toxicity of chemotherapy, must be carefully analyzed to interpret results meaningfully.     

Treatment of patients with lipid disorders in the primary care setting: new treatment guidelines and their implications

Coronary heart disease (CHD) remains a major cause of morbidity and mortality throughout North America. The role played by lipid abnormalities is now well established, and primary care physicians can play a major role in reversing the increasing prevalence of CHD by following the recommended guidelines of the National Cholesterol Expert Panel (NCEP ATP-III). While many physicians are aware of the importance of lowering lipid levels, a large number of patients still fail to reach their treatment goals. It is therefore important to identify patients at risk of developing coronary events due to abnormal lipid profiles and to quickly implement effective prevention programs. Although diet and other lifestyle modifications should form the basis of lipid management, the addition of lipid-modifying drugs is often necessary. Several lipid-modifying agents are available, but the proven efficacy and good tolerability of statins has increasingly made them the drugs of choice.     

Cabazitaxel in castration resistant prostate cancer with brain metastases: 3 case reports

Prostate cancer is the most common non-cutaneous malignancy for men. The skeleton is the most common metastatic site but, following an improvement in survival, metastases in uncommon sites are being found more frequently in clinical practice, especially brain metastases. Despite the new drugs now available for metastatic castration resistant prostate cancer, no clinical evidence exists about their effectiveness on brain metastases. We describe the clinical history of 3 patients treated with cabazitaxel plus whole brain radiotherapy. These case reports demonstrate that cabazitaxel is highly active and well tolerated in brain metastases.