Tolvaptan for the treatment of heart failure: a review of the literature.
Expert Opin Pharmacother. 2011 Mar 15;
Authors: Ambrosy A, Goldsmith SR, Gheorghiade M
Introduction: It has been > 25 years since it was firs…

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Lubiprostone for the treatment of opioid-induced bowel dysfunction.

Expert Opin Pharmacother. 2011 Mar 9;

Authors: Wong BS, Camilleri M

Introduction: Opioid-induced bowel dysfunction (OBD) is a prevalent condition that leads to reduced opioid use, human suffering and a high burden and cost on the healthcare system. Opioid-induced constipation (OIC) is the most troublesome aspect of OBD, for which standard laxatives are often ineffective. A major unmet need is effective and safe OIC treatment without inhibiting opioid analgesia or inducing opioid withdrawal symptoms. Recent data indicate that lubiprostone, a locally acting type 2 chloride channel activator, approved for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation, may be effective in treating OBD. Areas covered: The areas covered are: i) an overview of clinical trials of lubiprostone in the treatment of OBD based on peer-reviewed literature and congress materials from 2005 to 2010; and ii) an evaluation of the efficacy and potential mechanisms of action of lubiprostone in the treatment of OBD. Expert opinion: Lubiprostone has potential in treating OBD and deserves additional study. Lubiprostone’s ability to promote fluid secretion locally at the apical membrane of intestinal epithelial cells ensures it does not provoke opioid withdrawal or compromise analgesia. Lubiprostone seems safe for long-term use in CIC patients, and a similar safety profile is anticipated in OBD.

PMID: 21385112 [PubMed - as supplied by publisher]

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Memantine in dementia: a review of the current evidence.

Expert Opin Pharmacother. 2011 Mar 9;

Authors: Herrmann N, Li A, Lanctôt K

Introduction: As the world’s population ages, the incidence of Alzheimer’s disease (AD) is projected to double every 20 years. Understanding the pathogenesis of AD and developing effective treatments is a public health imperative. Memantine is a low- to moderate-affinity, non-competitive NMDA receptor antagonist that is currently approved for the treatment of moderate to severe AD. Areas covered: We discuss the current evidence, emphasizing more recent studies examining the effects of memantine in AD. We also look at the gaps in the current knowledge; the studies that will be required to fill these gaps are also discussed. The present paper reviews: the pharmacology of memantine; evidence for its use in moderate to severe AD, as well as in mild to moderate AD; adverse events related to memantine use; its effects specifically on behaviours including aggression and agitation; the pharmacoeconomics of memantine; and the use of memantine in other dementias. Memantine has shown modest benefits in cognition, function, global and behavioural measures, and has shown little potential for drug-drug interactions. Expert opinion: For the treatment of moderate to severe AD, memantine should be offered as a therapeutic option, either on its own, or in combination with a cholinesterase inhibitor.

PMID: 21385152 [PubMed - as supplied by publisher]

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Modern treatment of patients at risk: still a HOPE for ACE inhibitors?

Expert Opin Pharmacother. 2011 Feb 16;

Authors: Angeli F, Reboldi G, Verdecchia P

Indications for angiotensin-converting enzyme (ACE) inhibitors include heart failure, postmyocardial infarction, diabetes mellitus and proteinuric chronic renal disease. ACE inhibitors provided life-saving benefits in patients with heart failure or left ventricular systolic dysfunction. On the other hand, there are conflicting data regarding the ability of ACE inhibitors to reduce the incidence of cardiovascular events in patients with vascular disease and preserved left ventricular systolic function. Results of the main randomized clinical trials that evaluated the benefit of ACE inhibitors in patients with vascular disease are discussed in this editorial. In particular, the different prognostic impact of ACE inhibitors in high-risk patients with and without heart failure or preserved left ventricular systolic function is examined in detail. The possible impact of lipids and statins on the effect of ACE inhibitors is also discussed. In our opinion, the available data indicate that ACE inhibitors should continue to be used in all patients with documented coronary artery disease or different phenotypes of high vascular risk, even in a context of modern and aggressive preventive strategies.

PMID: 21323501 [PubMed - as supplied by publisher]

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Medical management of ascites.

Expert Opin Pharmacother. 2011 Feb 10;

Authors: Leung W, Wong F

Introduction: Ascites is a common complication of advanced cirrhosis that has a significant negative impact on survival. This review updates the reader on the medical management of ascites. Areas covered: This review explores the pathophysiology of ascites formation in cirrhosis; the current mainstays of medical management (treating the underlying cause of cirrhosis, avoiding nephrotoxic agents, sodium restriction, and combination diuretic therapy); potential novel agents, such as vasoconstrictors and vaptans; and albumin infusions. The literature research covers all aspects of medical management of ascites from the English literature, concentrating on publications from the past 10 years. It provides a thorough understanding of how the correction of pathophysiology of ascites formation helps to improve ascites; knowledge on the monitoring of patients with cirrhosis and ascites receiving medical management, and on prophylaxis against potentially life-threatening complication such as spontaneous bacterial peritonitis; and potential new treatments for ascites. Expert opinion: Management of patients with cirrhosis and ascites requires careful attention to fluid and electrolyte balance and avoidance of complications. Recognition of refractory ascites allows for the use of second-line treatments. All patients with cirrhosis and ascites should be considered for liver transplantation.

PMID: 21306283 [PubMed - as supplied by publisher]

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Management of varices in cirrhosis.

Expert Opin Pharmacother. 2011 Jan 27;

Authors: Thalheimer U, Triantos C, Goulis J, Burroughs AK

Introduction: Acute variceal bleeding is a medical emergency and one of the main causes of mortality in patients with cirrhosis. Timely and effective treatment of the acute bleeding episode results in increased survival, and appropriate prophylactic treatment can prevent bleeding or rebleeding from varices. Areas covered: We discuss the prevention of development and growth of varices, the primary and secondary prophylaxis of bleeding, the treatment of acute bleeding, and the management of gastric varices. We systematically reviewed studies, without time limits, identified through Medline and searches of reference lists, and provide an overview of the evidence underlying the -treatment options in the management of varices in cirrhosis. Expert opinion: The management of variceal hemorrhage relies on nonspecific interventions (e.g., adequate fluid resuscitation, airway protection) and on specific interventions. These are routine prophylactic antibiotics, vasoactive drugs and endoscopic treatment. Procedures such as the placement of a Sengstaken-Blakemore tube or a transjugular intrahepatic portosystemic shunt (TIPS) can be lifesaving. The primary and secondary prophylaxis of bleeding is based on nonselective beta-blockers and endoscopy, even though TIPS or, less frequently, surgery have a role in selected cases.

PMID: 21269241 [PubMed - as supplied by publisher]

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Opioids in chronic non-cancer pain.

Expert Opin Pharmacother. 2011 Jan 22;

Authors: Chan BK, Tam LK, Wat CY, Chung YF, Tsui SL, Cheung CW

Introduction: The use of chronic opioid therapy for chronic non-cancer pain is growing and is now accepted as an effective treatment modality. Areas covered: Although there are guidelines and reviews for chronic opioid therapy for chronic non-cancer pain patients, physicians may still have concerns and be reluctant to prescribe strong opioids for chronic non-cancer pain. Common issues and concerns when prescribing opioid for chronic pain management are reviewed and discussed. The literature search was done using Medline with key words ‘chronic non-cancer pain’, ‘chronic opioid therapy’, ‘effectiveness’, ‘opioid tolerance’, ‘opioid-induced hyperalgesia’, ‘adverse effect’, ‘opioid dependency’, ‘addiction’, ‘monitoring’, ‘opioid contract’ and various combinations with these key words. Studies from 1990 – 2010 have been included. This article helps readers to update, clarify and understand the common concerns when using opioid for chronic non-cancer pain. Clinical effectiveness and adverse effects with chronic opioid therapy, opioid tolerance and opioid-induced hyperalgesia, opioid dependency and addiction, monitoring during chronic opioid use, and opioid contact are discussed in detailed. Expert opinion: Not much strongly positive data supports the long-term use of opioids for pain relief, and the evidence for an improvement in functional activity is inconclusive. With careful selection of patients, meticulous prescription and monitoring protocol, chronic non-cancer pain patients who are likely to benefit from potent opioids should not be prevented from obtaining this treatment.

PMID: 21254859 [PubMed - as supplied by publisher]

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Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia.

Expert Opin Pharmacother. 2011 Jan 22;

Authors: Saloustros E, Tryfonidis K, Georgoulias V

Introduction: Neutropenia poses a serious threat to patients on chemotherapy. It exposes them to the risk of infection – including potentially fatal infections – and also leads to delays in treatment and reductions in dose intensity, which can compromise the possibility of a favorable outcome. Areas covered: The use of granulocyte colony-stimulating factors (G-CSF) and antibiotics to prevent febrile neutropenia (FN) and to ameliorate cancer chemotherapy-induced myelosuppression is discussed, based on a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. We consider that the treatment of FN, with the emphasis on careful attention to the patient, prompts antibiotic therapy and good hospital care. Expert opinion: We would argue that antibiotic prophylaxis should be offered routinely to patients receiving cytotoxic chemotherapy for acute leukemia and for patients with solid tumors and lymphoma receiving high-dose chemotherapy. In patients undergoing cyclical standard-dose myelosuppressive chemotherapy, we believe that prophylaxis is indicated during the first cycle of chemotherapy in which there is an expectation of grade 4 neutropenia (< 500 neutrophils). However, although the use of antibiotics and haematopoietic growth factors may improve quality of life by reducing the risk and consequences of FN, further study of the magnitude of their effects is needed.

PMID: 21254862 [PubMed - as supplied by publisher]

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Beyond efficacy: pharmacokinetic differences between clopidogrel, prasugrel and ticagrelor.

Expert Opin Pharmacother. 2011 Jan 22;

Authors: Giorgi MA, Cohen Arazi H, Gonzalez CD, Di Girolamo G

Introduction: Clinical nonresponse to clopidogrel has been associated with variability in response. This has led to the development of other P2Y12 receptor inhibitors, such as prasugrel and ticagrelor, with different pharmacokinetic characteristics that influence their pharmacodynamics. Areas covered: Clopidogrel response variability is attributable to its complex pharmacokinetics and is vulnerable to genetic polymorphisms in genes involved in absorption, metabolism and drug-drug interactions (i.e., proton pump inhibitors). Prasugrel which has a simpler metabolism, leading to greater bioavailability, seems to be less affected by genetic or drug-drug interactions and achieves a greater antiplatelet effect. Ticagrelor is the most novel compound approved with a simpler metabolism. Both prasugrel and ticagrelor reached their antiplatelet effect faster and to a much greater extent than clopidogrel. All these differences observed in kinetics explain, to some degree, the efficacy and safety profile observed in clinical trials for these molecules associated with other antiplatelet agents (aspirin, gpIIb/IIIa inhibitors) and anticoagulants. Expert opinion: Clopidogrel is still the best standard of care. However, the pharmacokinetic advantages of both prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for the appropriate subject.

PMID: 21254864 [PubMed - as supplied by publisher]

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Changing anticoagulant paradigms for atrial fibrillation: dabigatran, apixaban and rivaroxaban.

Expert Opin Pharmacother. 2011 Jan 22;

Authors: Giorgi MA, Cohen Arazi H, Gonzalez CD, Di Girolamo G

Introduction: Vitamin K antagonists (VKAs) are the main therapeutic agents used to prevent embolic events in patients with atrial fibrillation (AF). Despite their proven efficacy, VKAs are underused and have several limitations. In recent years, there has been great interest in the development of new oral anticoagulants with a more efficient pharmacological profile, first tested in venous thromboembolism prevention and later in AF. Areas covered: The authors review the pharmacological differences between dabigatran, rivaroxaban and apixaban, and potential subgroups of patients in whom these new drugs would constitute a possible alternative to VKA therapy. Pharmacodynamic and pharmacokinetic data from each compound are analyzed in respect to their potential use in AF. This article provides an exhaustive review of the current status of this topic and the controversies still regarding each drug. Expert opinion: Apixaban and rivaroxaban are under evaluation for thromboembolic prevention in AF; dabigatran was recently approved for this indication. Therefore, it is important to know the characteristics of these drugs as a potential alternative to VKAs.

PMID: 21254865 [PubMed - as supplied by publisher]

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Treatment of central sensitization in patients with ‘unexplained’ chronic pain: what options do we have?

Expert Opin Pharmacother. 2011 Jan 22;

Authors: Nijs J, Meeus M, Oosterwijck JV, Roussel N, Kooning MD, Ickmans K, Matic M

Introduction: Central sensitization accounts for chronic ‘unexplained’ pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. Areas covered: This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Expert opinion: Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2?) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that – theoretically – desensitize the CNS in humans. To provide a comprehensive treatment for ‘unexplained’ chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization.

PMID: 21254866 [PubMed - as supplied by publisher]

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Anticoagulant use in cancer patients.

Expert Opin Pharmacother. 2011 Feb;12(3):351-62

Authors: Trujillo-Santos J, Monreal M

Introduction: The development of venous thromboembolism (VTE) in patients with cancer adversely affects their prognosis. Several autopsy- and population-based studies have clearly shown a negative impact of VTE on patient outcome in cancer patients. Areas covered: An up-to-date review of VTE prophylaxis and treatment in cancer patients is provided with some insights on areas of uncertainty to be answered in the near future. Particular attention is paid to recent cohort studies, randomized clinical trials and consensus guidelines. Expert opinion: Cancer patients at a higher risk for VTE may be identified with five variables easily available before initiation of chemotherapy. Long-term treatment with low-molecular-weight heparin (LMWH) demonstrated a superior efficacy over vitamin K antagonists. The intensity and duration of anticoagulant therapy should be tailored to the risk of VTE recurrences or bleeding in an individual patient.

PMID: 21254944 [PubMed - in process]

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Adjuvant analgesics in acute pain.

Expert Opin Pharmacother. 2011 Feb;12(3):363-85

Authors: Lui F, Ng KF

Introduction: Despite its central role in acute pain management, the exclusive use of opioids has been challenged recently in view of its immediate and long-term side effects. Development of chronic postsurgical pain syndromes, hyperalgesia and immunomodulation are some particular concerns as they may be related to opioid exposure, intertwined with patient characteristics and other factors. Application of a multimodal approach, administration of preventive analgesia and paradigm shift in surgical techniques all mandate a revisit of evidence-based perioperative pain management. Areas covered: Adjuvant analgesics are drugs indicated for primary non-pain conditions, but have been found efficacious in analgesia either when used alone or in combination with other analgesics. Among a diverse group of adjuvant analgesics, systemic administration of ketamine, magnesium, gabapentinoids, steroids, ?2 agonists and lidocaine are reviewed, with recent evidence compared with earlier systematic reviews or meta-analyses from a Medline search (1990 – Apr 2010). Expert opinion: For acute pain management, adjuvant analgesics in appropriate doses and monitored care are beneficial in improving analgesic efficacy and reduce opioid-related side effects with good safety and tolerability. However, the quest for an optimal regime for administration and individualizing treatment remains.

PMID: 21254945 [PubMed - in process]

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Ivabradine: recent and potential applications in clinical practice.

Expert Opin Pharmacother. 2011 Feb;12(3):443-50

Authors: Riccioni G

Introduction: Published data indicate that heart rate is an independent strong predictor of cardiovascular and all-cause mortality in men and women of all ages, with and without cardiovascular disease, including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine is a pure heart-rate-lowering agent with well-documented antianginal and anti-ischemic properties comparable to well-established anti-anginal agents. Areas covered: This short review explores recent results with ivabradine, a new medication that lowers heart rate by selectively inhibiting the I (f) current. This review also describes future potential applications. Expert opinion: Measurement of heart rate represents an important component of the assessment of patients with coronary artery disease and chronic heart failure, and should be viewed in the same light as other risk factors, because a high heart rate has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias and left ventricular function. Ivabradine has anti-ischemic and antianginal efficacy equivalent to that of ?-blockers and calcium channel antagonists in the treatment of chronic stable angina pectoris. Recently ivabradine has been shown to improve cardiac outcomes in stable coronary artery disease and left ventricular systolic dysfunction in patients who have heart rates of ? 70 bpm and in patients with stable angina.

PMID: 21254949 [PubMed - in process]

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Biologic properties and clinical uses of rifaximin.

Expert Opin Pharmacother. 2011 Feb;12(2):293-302

Authors: Dupont HL

Introduction: Rifaximin is increasingly being used to treat acute and chronic gastrointestinal infections and disorders. The drug exerts its beneficial effect through a variety of gut-selective mechanisms involving the host intestinal microbiota. Areas covered: Abstracts of all publications listed in PubMed on the topic of rifaximin are reviewed to determine their potential value in the understanding of mechanisms of rifaximin activity. The author’s extensive file on the drug is also used in the review. Expert opinion: Rifaximin inhibits a broad spectrum of bacteria in the bile-rich small bowel and susceptible bacteria in the aqueous colon, and alters microbial virulence and epithelial cell function. The different mechanisms of action of rifaximin potentially explain the use of the drug in widely varied diseases and syndromes.

PMID: 21226639 [PubMed - in process]

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