Biomedical subjects

Lesley J Scott

Publications and source records attributed to Lesley J Scott.

At least 19 recordsLinked to original sources

PubMed2005

Cinacalcet hydrochloride.

Oral cinacalcet hydrochloride (HCl) [Sensipar, Mimpara] is the first in a new class of therapeutic agents, the calcimimetics, and has a novel mechanism of action. It directly modulates the principal regulator of parathyroid hormone (PTH) secretion, namely the calcium-sensing receptor (CaR) on the chief cells in the parathyroid gland. Cinacalcet HCl reduces circulating PTH levels by increasing the sensitivity of the CaR to extracellular calcium. In three pivotal phase III, 26-week, randomised, double-blind, multicentre trials in chronic kidney disease (CKD) patients (n = 1136) on dialysis with uncontrolled secondary hyperparathyroidism (HPT), a significantly higher proportion of oral cinacalcet HCl 30-180 mg/day than placebo recipients achieved a reduction in intact PTH levels to < or =250 pg/mL. Cinacalcet HCl treatment also simultaneously lowered serum calcium and phosphorus, and calcium-phosphorous product levels. Notably, cinacalcet HCl proved effective in a broad range of CKD patients on dialysis with uncontrolled secondary HPT, regardless of disease severity, duration of dialysis treatment, dialysis modality, race, age, gender, or concurrent phosphate binder or vitamin D sterol use. Cinacalcet HCl (60-360 mg/day) also reduced elevated serum calcium levels by > or =1 mg/dL in 15 of 21 (71%) patients with parathyroid carcinoma in an open-label, multicentre, dose-titration trial. Cinacalcet HCl was generally well tolerated in clinical trials. Most treatment-emergent adverse events were mild to moderate in severity.

Animals↗

PubMed2005

Abacavir plus lamivudine: a review of their combined use in the management of HIV infection.

Abacavir and lamivudine (two nucleoside analogue reverse transcriptase inhibitors [NRTIs]), as separate formulations in combination with other antiretroviral agents, are effective in the reduction of HIV RNA levels in antiretroviral-naive patients with HIV infection, and are generally well tolerated. A fixed-dose combination tablet of abacavir/lamivudine (Epzicomtrade mark, Kivexatrade mark) has been developed for once-daily use and preliminary efficacy data are promising. Although further experience with this formulation is needed to fully determine its position in the management of HIV infection, a single, once-daily tablet that may be taken irrespective of food intake should aid adherence to treatment, a key factor in determining the success of an antiretroviral regimen. Thus, abacavir and lamivudine are two established components of first-line antiretroviral regimens for the management of HIV infection and the fixed-dose abacavir/lamivudine tablet has the potential to be an effective, easily adhered to and generally well tolerated component of first-line therapy.

Anti-HIV Agents↗

PubMed2005

Candesartan cilexetil: a review of its use in the management of chronic heart failure.

Candesartan cilexetil is the orally administered pro-drug of candesartan, a highly selective antagonist of the angiotensin II subtype 1 receptor that mediates the pressor activities of angiotensin II. Candesartan cilexetil is widely used for the treatment of hypertension and has recently been approved in Europe for the treatment of chronic heart failure (CHF) in patients with impaired left ventricular (LV) systolic function. Results of the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme suggest that oral candesartan cilexetil reduces morbidity and mortality in patients with CHF and LV ejection fraction (LVEF) < or =40%. There are cardiovascular benefits when candesartan cilexetil is administered as an alternative to an ACE inhibitor, or as an add-on to current treatment regimens that include an ACE inhibitor, in symptomatic CHF. While tolerability is generally good, renal monitoring is required. The recent approval of candesartan cilexetil as both add-on and alternative therapy to ACE inhibitors in patients with CHF and impaired LV systolic function recognises the cardiovascular benefits of candesartan cilexetil in both types of treatment regimens.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Paricalcitol: a review of its use in the management of secondary hyperparathyroidism.

Paricalcitol (Zemplar) is a synthetic vitamin D(2) analogue that inhibits the secretion of parathyroid hormone (PTH) through binding to the vitamin D receptor. It is approved in the US and in most European nations for intravenous use in the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure in adult, and in the US paediatric, patients. Paricalcitol effectively reduced elevated serum PTH levels and was generally well tolerated in children and adults with secondary hyperparathyroidism associated with chronic renal failure. In well designed clinical trials, paricalcitol was as effective as calcitriol and as well tolerated in terms of the incidence of prolonged hypercalcaemia and/or elevated calcium-phosphorus product (Ca x P). Thus, paricalcitol is a useful option for the management of secondary hyperparathyroidism in adults and children with chronic renal failure.

Clinical Trials as Topic↗

PubMed2005

Peginterferon-alpha-2a (40kD): a review of its use in the management of patients with chronic hepatitis B.

Subcutaneous peginterferon-alpha-2a (40kD) [Pegasys] is an effective and reasonably well tolerated treatment for the management of patients with hepatitis B e antigen (HBeAg)-negative or -positive chronic hepatitis B. It was significantly more effective than lamivudine monotherapy at inducing sustained virological response and ALT normalisation in both HBeAg-negative and -positive patients. Notably, the addition of lamivudine to peginterferon-alpha-2a (40kD) conferred no additional benefit versus peginterferon-alpha-2a (40kD) monotherapy. Moreover, in HBeAg-positive patients significantly more peginterferon-alpha-2a (40kD) recipients experienced HBeAg seroconversion than lamivudine recipients. The position of peginterferon-alpha-2a (40kD) relative to other treatment options remains to be fully determined. In the meantime, this agent appears to be a valuable new option for the management of patients with HBeAg-negative or -positive chronic hepatitis B.

Disease Management↗

PubMed2005

Dexrazoxane : a review of its use for cardioprotection during anthracycline chemotherapy.

Dexrazoxane (Cardioxane, Zinecard, a cyclic derivative of edetic acid, is a site-specific cardioprotective agent that effectively protects against anthracycline-induced cardiac toxicity. Dexrazoxane is approved in the US and some European countries for cardioprotection in women with advanced and/or metastatic breast cancer receiving doxorubicin; in other countries dexrazoxane is approved for use in a wider range of patients with advanced cancer receiving anthracyclines. As shown in clinical trials, intravenous dexrazoxane significantly reduces the incidence of anthracycline-induced congestive heart failure (CHF) and adverse cardiac events in women with advanced breast cancer or adults with soft tissue sarcomas or small-cell lung cancer, regardless of whether the drug is given before the first dose of anthracycline or the administration is delayed until cumulative doxorubicin dose is > or =300 mg/m2. The drug also appears to offer cardioprotection irrespective of pre-existing cardiac risk factors. Importantly, the antitumour efficacy of anthracyclines is unlikely to be altered by dexrazoxane use, although the drug has not been shown to improve progression-free and overall patient survival. At present, the cardioprotective efficacy of dexrazoxane in patients with childhood malignancies is supported by limited data. The drug is generally well tolerated and has a tolerability profile similar to that of placebo in cancer patients undergoing anthracycline-based chemotherapy, with the exception of a higher incidence of severe leukopenia (78% vs 68%; p < 0.01). Dexrazoxane is the only cardioprotective agent with proven efficacy in cancer patients receiving anthracycline chemotherapy and is a valuable option for the prevention of cardiotoxicity in this patient population.

Anthracyclines↗

PubMed2005

Recombinant factor VIIa (Eptacog Alfa): a review of its use in congenital or acquired haemophilia and other congenital bleeding disorders.

Recombinant factor VIIa (NovoSeven) [also known as recombinant activated factor VII or eptacog alfa] is a vitamin K-dependent glycoprotein that is structurally similar to human plasma-derived factor VIIa. It is a recombinant product, manufactured using DNA biotechnology. Intravenous recombinant factor VIIa has been evaluated in the treatment of bleeding episodes and for providing haemostasis cover during surgery in patients with certain bleeding disorders. Large, well controlled trials of recombinant factor VIIa have not been performed because of the rarity of these bleeding disorders. However, the efficacy of recombinant factor VIIa has been investigated in these patients in double-blind dose-finding or noncomparative clinical trials and worldwide compassionate-use programmes. Recombinant factor VIIa is effective and generally well tolerated in patients with haemophilia A or B with inhibitors, those with acquired haemophilia or Glanzmann's thrombasthenia. Also, recombinant factor VIIa is a treatment of choice in patients with haemophilia B with high-responding inhibitors and those with factor VII deficiency. Direct head-to-head comparisons and robust pharmacoeconomic data are required to fully determine the position of recombinant factor VIIa in relation to other therapies. Importantly though, the product appears to be relatively free of antigenicity, thrombogenicity and risk of viral transmission that, in the past, have limited the utility of blood products. Given that these characteristics are important determinants of the place of a treatment in bleeding disorders, recombinant factor VIIa provides a valuable treatment alternative in patients with haemophilia with inhibitors, platelet-refractory Glanzmann's thrombasthenia or congenital factor VII deficiency.

Factor VIIa↗

PubMed2005

Azacitidine: in myelodysplastic syndromes.

Azacitidine, a pyrimidine analogue, is an antineoplastic agent that acts mainly by causing hypomethylation of cytosine residues in newly replicated DNA and has shown efficacy in the treatment of myelodysplatic syndromes (MDS). In a randomised controlled trial in patients with MDS (n=191), subcutaneous azacitidine 75-100 mg/m2/day in 7-day cycles every 28 days with continuing supportive care produced a significantly higher response rate (including reductions in rate of transformation to acute myeloid leukaemia and transfusion requirements) than that seen with supportive care alone (60% vs 5%; p<0.001). Patients (n=49) who were switched from supportive care to azacitidine after 4 months also showed a 47% response rate. The clinical response in patients receiving azacitidine was associated with significant (p<or=0.015) improvements in several measures of health-related quality of life, including those assessing fatigue and physical functioning, compared with those in supportive care recipients. Given the grim prognosis of MDS patients, azacitidine was generally well tolerated, with common, but transient, myelotoxicity. Adverse events did not increase in severity or frequency during the course of the treatment.

Antimetabolites, Antineoplastic↗

PubMed2005

Remifentanil: a review of its use during the induction and maintenance of general anaesthesia.

Remifentanil (Ultiva), a fentanyl derivative, is an ultra-short acting, nonspecific esterase-metabolised, selective mu-opioid receptor agonist, with a pharmacodynamic profile typical of opioid analgesic agents. Notably, the esterase linkage in remifentanil results in a unique and favourable pharmacokinetic profile for this class of agent. Adjunctive intravenous remifentanil during general anaesthesia is an effective and generally well tolerated opioid analgesic in a broad spectrum of patients, including adults and paediatric patients, undergoing several types of surgical procedures in both the inpatient and outpatient setting. Remifentanil is efficacious in combination with intravenous or volatile hypnotic agents, with these regimens generally being at least as effective as fentanyl- or alfentanil-containing regimens in terms of attenuation of haemodynamic, autonomic and somatic intraoperative responses, and postoperative recovery parameters. The rapid offset of action and short context-sensitive half-time of remifentanil, irrespective of the duration of the infusion, makes the drug a valuable opioid analgesic option for use during balanced general inhalational or total intravenous anaesthesia (TIVA) where rapid, titratable, intense analgesia of variable duration, and a fast and predictable recovery are required.

Adult↗

PubMed2005

Lansoprazole: in the treatment of gastro-oesophageal reflux disease in children and adolescents.

Lansoprazole is a proton pump inhibitor that inactivates the H(+)/K(+)-ATPase pump in parietal cells, thus inhibiting gastric acid secretion and increasing intragastric pH. In an open-label, uncontrolled trial in children aged 1-11 years with gastro-oesophageal reflux disease (GORD), treatment with lansoprazole 15 or 30 mg (depending on weight) once daily for 8-12 weeks improved symptoms compared with baseline in 76% of patients (47 of 62) based on patient diaries and healed erosive oesophagitis (confirmed endoscopically) in all 27 children who had it at baseline. In adolescents aged 12-17 years with GORD, 8 weeks' treatment with lansoprazole 15 mg (in 64 patients with non-erosive disease) or 30 mg (in 23 patients with erosive oesophagitis) once daily reduced the frequency and severity of symptoms by 63% and 69% compared with baseline, based on patient diaries. In this open-label, uncontrolled trial, 96% of evaluable patients with erosive disease (21 of 22) had mucosal healing by week 8, as confirmed by endoscopy; mucosal healing did not occur after an additional 4 weeks' treatment in one patient. Lansoprazole was generally well tolerated in children and adolescents, with the most common treatment-related adverse events being gastrointestinal events and headache.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2005

Infliximab: a review of its use in Crohn's disease and rheumatoid arthritis.

Infliximab (Remicade) is a chimeric monoclonal antibody against tumour necrosis factor (TNF)-alpha that has shown efficacy in Crohn's disease and rheumatoid arthritis with a disease-modifying activity and rapid onset of action. It is administered intravenously, generally in a schedule with initial infusions at 0, 2 and 6 weeks, followed by administration once every 8 weeks. Infliximab is effective in the treatment of patients with moderately to severely active Crohn's disease with an inadequate response to other treatment options or those with fistulising disease. In combination with methotrexate, infliximab reduced signs and symptoms and delayed disease progression in patients with active, methotrexate-refractory rheumatoid arthritis and in those with early disease. The drug was generally well tolerated. Recrudescence of tuberculosis infection and worsening of heart failure and demyelinating disease are among some of the concerns with anti-TNFalpha therapy, requiring cautious use of these agents in high-risk patients. Current data suggest that infliximab may be cost effective, especially when long-term clinical outcomes and burden of the diseases are taken into account. More robust, prospective pharmaco-economic studies are required to better ascertain the cost effectiveness of infliximab. Direct head-to-head comparative trials of infliximab with other biological agents are not yet available and would be helpful in determining with greater certainty the place of infliximab in the management of these diseases. Nonetheless, infliximab, like other biological agents, is a valuable treatment option in patients with moderately to severely active Crohn's disease (including fistulising disease) or rheumatoid arthritis (including early disease).

Antibodies, Monoclonal↗

PubMed2005

Atazanavir: a review of its use in the management of HIV infection.

Atazanavir (Reyataz) is a novel protease inhibitor (PI) approved for use in combination with other antiretroviral drugs for the treatment of HIV infection. In antiretroviral therapy (ART)-experienced patients the drug is administered with low-dose ritonavir (i.e. boosted). In the US, unboosted atazanavir is also approved for use in ART-naive patients. In adult patients with HIV infection, atazanavir-containing highly active antiretroviral therapy (HAART) regimens provided marked improvements in virological and immunological markers and was generally well tolerated. Furthermore, recommended atazanavir regimens were no less effective than, and generally as well tolerated as, other HAART regimens in these patients, including regimens containing co-formulated lopinavir/ritonavir. Atazanavir may have an advantage over other PIs because of its favourable effect on lipid profiles, once-daily dosing, low capsule burden and, in patients with low prior PI exposure, a favourable resistance profile. Given these advantages and taking into consideration between-country differences in the approved indications, atazanavir is a valuable option as the PI component of HAART for the management of HIV infection in adult ART-naive patients, particularly where metabolic complications are a concern, and as a first- or second-line PI in combination with low-dose ritonavir in adult ART-experienced patients.

Anti-HIV Agents↗

PubMed2005

Eprosartan: a review of its use in the management of hypertension.

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.

Acrylates↗

PubMed2005

Intramuscular olanzapine: a review of its use in the management of acute agitation.

Intramuscular olanzapine (Zyprexa) is a rapid-acting atypical antipsychotic drug that is also indicated for use in patients with agitation associated with schizophrenia or bipolar mania, the focus of this review. Evidence from three well designed trials indicates that this formulation of olanzapine is at least as effective as intramuscular haloperidol or lorazepam in the treatment of patients with acute agitation associated with schizophrenia or bipolar mania, and has a faster onset of action. Although transient reductions in blood pressure and heart rate may occur in some patients administered intramuscular olanzapine, preliminary evidence of a general lack of clinical effect on the corrected QT (QTc) interval and a low incidence of extrapyramidal symptoms (EPS) is promising. The parenteral formulation of olanzapine appears to offer an effective, fast-acting and generally well tolerated alternative in the treatment of this significant behavioural problem.

Acute Disease↗

PubMed2005

Zonisamide: a review of its use in the management of partial seizures in epilepsy.

Zonisamide (Zonegran, Excegran) is a new-generation, broad-spectrum antiepileptic drug (AED) currently approved as adjunctive therapy for the treatment of medically refractory partial seizures in adults in the US and as adjunctive therapy or monotherapy in the control of partial and generalised seizures in adults and children in Japan and Korea. Either as adjunctive therapy or monotherapy, zonisamide effectively reduces the frequency of partial seizures, with or without secondary generalisation to tonic-clonic seizures, in adults and children with epilepsy. The drug is generally well tolerated and, additionally, has a favourable pharmacokinetic profile permitting once- or twice-daily administration. Direct head-to-head comparisons with other AEDs would be beneficial in fully defining the place of zonisamide in therapy. In the meantime, adjunctive therapy or monotherapy with zonisamide is a convenient, useful option for the management of partial seizures, including those refractory to other AEDs.

Anticonvulsants↗

PubMed2005

Risperidone: a review of its use in the treatment of bipolar mania.

Risperidone (Risperdal) is an atypical antipsychotic with high affinity for 5-hydroxytryptamine (5-HT)2A, dopamine D2 and alpha1- and alpha2-adrenergic receptors. Risperidone is now approved in the UK and the US for use in bipolar mania. Risperidone < or =6 mg/day, as monotherapy or adjunctive therapy with first-line mood stabilisers, significantly improves moderate and severe bipolar mania and improves global functioning over 3 weeks. Improvements in Young Mania Rating Scale (YMRS) scores in double-blind trials were greater with risperidone than with placebo over 3 weeks, and similar to those with haloperidol over 3 and 12 weeks. Risperidone was reasonably well tolerated. Limited data are available on the combination of risperidone and carbamazepine. Risperidone, as monotherapy or combined therapy with lithium or valproate semisodium, is an effective treatment option in bipolar mania.

Animals↗

PubMed2005

Acamprosate: a review of its use in the maintenance of abstinence in patients with alcohol dependence.

Acamprosate (Campral delayed-release tablet), a synthetic compound with a similar structure to that of the neurotransmitter GABA and the neuromodulator taurine, facilitates the maintenance of abstinence in detoxified alcohol-dependent patients. Although the precise mechanism(s) of action of the drug remains to be fully elucidated, it appears that it most likely involves beneficial modulation of the glutamatergic neurotransmitter system, including antagonism of the mGLu5 metabotropic glutamate receptor, to counteract the imbalance between the glutamatergic and GABAergic systems associated with chronic alcohol exposure and alcohol withdrawal. In several double-blind, placebo-controlled trials of up to 12 months' duration, acamprosate effectively maintained complete abstinence in detoxified alcohol-dependent patients, irrespective of disease severity or the type of psychosocial support. The drug showed better efficacy than placebo and was very well tolerated. Limited data from a relatively well designed trial indicate that the drug has similar efficacy to that of naltrexone and that combination therapy with these two agents provides better efficacy than acamprosate monotherapy, although multicentre direct head-to-head investigations are required to fully establish the potential of this combination. The drug may be particularly useful in those with hepatic impairment and/or liver disease. Thus, in combination with psychosocial and behavioural management programmes, acamprosate is a promising option for the maintenance of abstinence in alcohol-dependent patients after alcohol withdrawal.

Acamprosate↗

PubMed2005

Spotlight on remifentanil for general anaesthesia.

Remifentanil (Ultiva), a fentanyl derivative, is an ultra-short acting, nonspecific esterase-metabolised, selective mu-opioid receptor agonist, with a pharmacodynamic profile typical of opioid analgesic agents. Notably, the esterase linkage in remifentanil results in a unique and favourable pharmacokinetic profile for this class of agent. Adjunctive intravenous remifentanil during general anaesthesia is an effective and generally well tolerated opioid analgesic in a broad spectrum of patients, including adults and paediatric patients, undergoing several types of surgical procedures in both the inpatient and outpatient setting. Remifentanil is efficacious in combination with intravenous or volatile hypnotic agents, with these regimens generally being at least as effective as fentanyl- or alfentanil-containing regimens in terms of attenuation of haemodynamic, autonomic and somatic intraoperative responses, and postoperative recovery parameters. The rapid offset of action and short context-sensitive half-time of remifentanil, irrespective of the duration of the infusion, makes the drug a valuable opioid analgesic option for use during balanced general inhalational or total intravenous anaesthesia where rapid, titratable, intense analgesia of variable duration, and a fast and predictable recovery are required.

Anesthesia, General↗