Biomedical subjects

John Waugh

Publications and source records attributed to John Waugh.

12 recordsLinked to original sources

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

Anakinra: a review of its use in the management of rheumatoid arthritis.

Anakinra (Kineret) is the first biologic drug that has been developed specifically as an interleukin (IL)-1 receptor antagonist (Ra) and is derived from an endogenous IL-1Ra. The drug blocks the activity of IL-1 in synovial joints, reducing the inflammatory and joint destructive processes associated with rheumatoid arthritis (RA). In randomized, placebo-controlled trials of up to 52 weeks' duration, anakinra has shown efficacy both as monotherapy and in combination with other disease-modifying antirheumatic drugs (DMARDs) in adults with RA. It is subcutaneously administered and is generally well tolerated. Anakinra offers a useful addition to the range of drugs available for the treatment of RA.

Antirheumatic Agents↗

PubMed2004

Ciprofloxacin extended release: in the treatment of urinary tract infections and uncomplicated pyelonephritis.

Ciprofloxacin extended release (XR) is a new oral formulation of a fluoroquinolone that allows once-daily administration while maintaining therapeutic serum levels of the drug. The maximum plasma concentrations (Cmax) of once-daily ciprofloxacin XR 500 mg was higher than that of twice-daily ciprofloxacin immediate release 250 mg and the Cmax of once-daily ciproflocaxin XR 1000 mg was higher than that of twice-daily ciprofloxacin 500 mg. No accumulation of ciprofloxacin XR at steady state was observed in healthy men and all other pharmacokinetic parameters were similar to those of the immediate-release formulation. In patients with uncomplicated urinary tract infection (UTI), bacteriological eradication rates were similar in recipients of ciprofloxacin XR and immediate-release ciprofloxacin at the test-of-cure (TOC) visit, as were rates of persistence or new infection. Clinical cure rates were also similar in the two treatment groups. Bacteriological eradication occurred in 89% of ciprofloxacin XR and 85% of immediate-release ciprofloxacin recipients with complicated UTIs or acute uncomplicated pyelonephritis at the TOC visit. Clinical cure rates were also similar in the two treatment groups. black triangle Ciprofloxacin XR was generally well tolerated in patients with uncomplicated or complicated UTIs or acute uncomplicated pyelonephritis and showed similar tolerability to that of the immediate-release formulation.

Administration, Oral↗

PubMed2004

Adapalene: a review of its use in the treatment of acne vulgaris.

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favourable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.

Acne Vulgaris↗

PubMed2004

Spotlight on adapalene in acne vulgaris.

Adapalene (Differin) is a retinoid agent indicated for the topical treatment of acne vulgaris. In clinical trials, 0.1% adapalene gel has proved to be effective in this indication and was as effective as 0.025% tretinoin gel, 0.1% tretinoin microsphere gel, 0.05% tretinoin cream and 0.1% tazarotene gel once every two days; however, the drug was less effective than once-daily 0.1% tazarotene gel. It can be used alone in mild acne or in combination with antimicrobials in inflammatory acne and has proved efficacious as maintenance treatment. Adapalene has a rapid onset of action and a particularly favorable tolerability profile compared with other retinoids. These attributes can potentially promote patient compliance, an important factor in treatment success. Adapalene is, therefore, assured of a role in the first-line treatment of acne vulgaris.

Acne Vulgaris↗

PubMed2004

The paclitaxel (TAXUS)-eluting stent: a review of its use in the management of de novo coronary artery lesions.

UNLABELLED: The TAXUSExpress stent contains paclitaxel 1 microg/mm(2). On deployment, paclitaxel is slowly released into the intimal tissue of the coronary artery to prevent cell proliferation and neointimal hyperplasia. When deployed in patients with previously untreated coronary artery lesions, the paclitaxel-eluting stent (PES) effectively reduces the need for revascularization without increasing the risk of in-stent thrombosis. While long-term outcomes data and comparative efficacy and cost-benefit trials versus other drug-eluting stents are required, the PES appears to be an attractive alternative for the management of de novo coronary artery lesions. PHARMACOLOGIC PROPERTIES: The PES comprises a stainless steel stent coated with a non-erodible biocompatible polyolefin matrix containing paclitaxel 1 microg/mm(2). Paclitaxel dose dependently inhibits vascular smooth muscle cell proliferation at therapeutic concentrations as a result of binding to and stabilizing cellular microtubules. This prevents the cascade of events associated with obstructive in-stent neointimal hyperplasia. Paclitaxel was released in a controlled manner from the stent coating in in vitro studies. The higher release rate in the first 2 days after implantation (to reduce response to implantation injury) slows over the next 8-10 days. The drug is rapidly taken up by intimal cells with minimal dispersion in the plasma; it was not detected systemically after stent deployment in clinical trials. Paclitaxel is extensively bound to proteins (88-98%), and is principally metabolized in the liver, undergoing biliary clearance after systemic administration. THERAPEUTIC EFFICACY: The efficacy of the PES was compared with that of a bare-metal stent (BMS) in a number of randomized, double-blind, multicenter trials in patients with de novo coronary artery lesions. The TAXUS I and II trials used the NIR stent, while the pivotal TAXUS IV trial used the Express stent. The primary endpoints of the well designed TAXUS II and IV trials indicated superiority for the PES over the BMS. Twice as many patients receiving the BMS required target vessel revascularization at 9 months postprocedure and, 6 months following the procedure, the in-stent neointimal volume in the PES system was only one-third of that in the BMS. The incidence of cumulative major adverse cardiac events (MACE; cardiac death, myocardial infarction [MI], or target vessel revascularization [TVR]) was also significantly lower in PES than BMS recipients at 9 and 12 months postprocedure. The incidence of cardiac death and MI was low and similar between treatment groups; however, TVR was significantly reduced by the PES versus the BMS. Other secondary endpoints, such as target lesion revascularization, luminal diameter stenosis, minimal luminal diameter, and serial intravascular ultrasound measurements from one or both trials supported these results. Preliminary analysis of the subgroup of patients with diabetes mellitus in the TAXUS IV trial suggested that the PES was also effective in diabetic patients who receive oral medications. The group receiving insulin was too small to draw meaningful conclusions. TOLERABILITY: Because of the small paclitaxel dosages and the mainly local uptake, systemic adverse events associated with the PES are considered unlikely. The incidences of cardiac death and MI were very low and similar in both groups. Local events such as in-stent aneurysms, incomplete stent apposition, or in-stent thrombosis occurred at a similar rate in PES and BMS recipients. There has been no evidence of late thrombosis in PES recipients followed for 2 years. The rate of late luminal loss in the 5mm of vessel proximal and distal to the stent edges was significantly lower in PES than BMS systems. PHARMACOECONOMIC CONSIDERATIONS: Initial deployment costs associated with the PES are likely to be offset by savings in repeat procedures, according to a cost-effectiveness analysis in the UK.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis.

Specifically formulated for nebulisation using the PARI LC PLUS reusable nebuliser, tobramycin solution for inhalation (TSI) [TOBI] provides a high dose of tobramycin (an aminoglycoside antibacterial with good activity against Pseudomonas aeruginosa) to the lungs of patients with cystic fibrosis, while maintaining low serum concentrations of the drug, thus reducing the risk of systemic toxicity. Intermittent (28-day on/28-day off) treatment with TSI 300 mg twice daily significantly (p < 0.001) improved lung function and sputum P. aeruginosa density compared with placebo (randomised double-blind trials), and was significantly (p = 0.008) more effective than colistin for improvement in forced expiratory volume in 1 second (small nonblind trial) in patients aged > or =6 years with cystic fibrosis and chronic P. aeruginosa infection. Improvements in lung function were most marked in adolescent patients (aged 13-17 years) in placebo-controlled trials. Improvements were maintained for up to 96 weeks in patients in an open-label extension study. Fewer TSI than placebo recipients required parenteral antipseudomonal agents or hospitalisation. In addition, TSI 300 mg twice daily for 28 days reduced P. aeruginosa density in the lower airways of patients aged <6 years with early colonisation and cystic fibrosis, although TSI is not currently indicated in this patient group. A decrease in tobramycin susceptibility of P. aeruginosa isolates and an increase in fungal organisms (Candida albicans and Aspergillus species) during prolonged intermittent treatment with TSI 300 mg twice daily was not associated with adverse clinical outcome. There was no evidence of selection for the most resistant isolates. TSI is generally well tolerated, with no renal toxicity or hearing loss in clinical trials, although transient mild or moderate tinnitus occurred more frequently in TSI than placebo recipients. Bronchospasm after administration of TSI was transient and occurred with a similar incidence to that with placebo; TSI is preservative free and specifically formulated for the lung in terms of osmolality and pH. In conclusion, TSI provides an effective means of delivering tobramycin to the lungs of patients with cystic fibrosis with chronic P. aeruginosa infection, improving lung function and sputum P. aeruginosa density in these patients without the nephrotoxicity or ototoxicity of parenteral aminoglycosides. Further data on the potential for and clinical significance of increased tobramycin resistance and fungal colonisation during TSI treatment would be beneficial, as would longer-term data. In the meantime, TSI represents a valuable option for suppressive antipseudomonal therapy in patients with cystic fibrosis.

Administration, Inhalation↗

PubMed2003

Escitalopram : a review of its use in the management of major depressive and anxiety disorders.

UNLABELLED: Escitalopram is the therapeutically active S-enantiomer of RS-citalopram, a commonly prescribed SSRI. The R-enantiomer is essentially pharmacologically inactive. Escitalopram 10 or 20 mg/day produced significantly greater improvements in standard measurements of antidepressant effect (Montgomery-Asberg Depression Rating Scale [MADRS], Clinical Global Impressions Improvement and Severity scales [CGI-I and CGI-S] and Hamilton Rating Scale for Depression [HAM-D]) in patients with major depressive disorder (MDD) than placebo in several 8-week, placebo-controlled, randomised, double-blind, multicentre studies. Symptom improvement was rapid, with some parameters improving within 1-2 weeks of starting escitalopram treatment. In addition, escitalopram showed earlier and clearer separation from placebo than RS-citalopram, at one-quarter to half the dosage, in 8-week, placebo-controlled trials; had significantly better efficacy than RS-citalopram in a subgroup of patients with moderate MDD in a 24-week trial; and produced sustained response and remission significantly faster than venlafaxine extended release in patients with MDD. Escitalopram reduced relapse rate compared with placebo and increased the percentage of patients in remission in long-term trials (up to 52 weeks). Consistently significant improvements for all efficacy parameters were also observed in patients with generalised anxiety disorder, social anxiety disorder and panic disorder treated with escitalopram for 8-12 weeks in individual, randomised, placebo-controlled, double-blind investigations. The good tolerability profile of escitalopram is predictable and similar to that of RS-citalopram. Such adverse events as nausea, ejaculatory problems, diarrhoea and insomnia are expected but, with the exception of ejaculatory problems and nausea, which is mild and transient, these were generally no more frequent than with placebo in fully published clinical trials. No adverse events not previously seen in acute trials were reported with long-term use. CONCLUSIONS: Escitalopram, the S-enantiomer of RS-citalopram, is a highly selective inhibitor for the serotonin transporter, ameliorates depressive symptoms in patients with MDD at half the RS-citalopram dosage, has a rapid onset of symptom improvement and has a predictable tolerability profile of generally mild adverse events. Like RS-citalopram, escitalopram is expected to have a low propensity for drug interactions, a potential benefit in the management of patients with comorbidities. In combination, these properties place escitalopram, like other SSRIs, as first-line therapy in patients with MDD. Escitalopram is indicated for use in patients with panic disorder in Europe and, should further evidence confirm early findings that escitalopram reduces anxiety, the drug may well find an additional role in the management of anxiety disorders.

Animals↗

PubMed2003

Topiramate: as monotherapy in newly diagnosed epilepsy.

Topiramate is an antiepileptic drug that has a broad spectrum of antiseizure effects, which appear to be the result of several neurostabilising pharmacological mechanisms. These include blockade of ion channels, potentiation of GABA neuroinhibition and glutamate receptor antagonism at non-NMDA receptors, as well as mild inhibition of carbonic anhydrase. Topiramate monotherapy dose dependently reduced the number of patients who met seizure related exit criteria in children (aged > or =6 years) and adults with epilepsy. This effect was also observed in patients who had previously experienced partial onset seizures and for those who had experienced generalised tonic clonic seizures. Six-month and 1-year seizure-free rates were dose-dependently reduced. In epilepsy, topiramate monotherapy 100 or 200 mg/day was as effective as carbamazepine 600 mg/day or valproate 1250 mg/day as measured by time to study exit for any reason, time to first seizure and percentage of patients seizure-free in the final 6 months of treatment (mean treatment duration 244 days). Adverse events associated with topiramate monotherapy that were dosage related included paraesthesia, weight loss and diarrhoea. Renal calculi were also reported in both fully published trials.

Animals↗

PubMed2003

Losartan: in the reduction of stroke risk in patients with hypertension and left ventricular hypertrophy.

Losartan binds selectively to the angiotensin II subtype 1 receptor, blocking the activity of angiotensin II. Losartan 50-100 mg/day was compared with atenolol 50-100 mg/day in patients with essential hypertension and left ventricular hypertrophy (LVH) [n = 9,193] in the randomized, double-blind Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Two substudies compared these drugs in patients with diabetes mellitus (n = 1,195) or isolated systolic hypertension (ISH) [n = 1326]. The target BP (<140/90 mm Hg) was achieved in approximate, equals 45% of losartan and atenolol recipients in the LIFE study. Significant regression of LVH occurred with losartan versus atenolol in the LIFE study, as well as in the diabetes mellitus and ISH substudies. In the LIFE study, although BP reduction was similar for the two treatments, the risk of a cardiovascular event (the composite of cardiovascular death, stroke, and myocardial infarction; primary endpoint), stroke, or new-onset diabetes mellitus was significantly lower with losartan than with atenolol. Losartan was generally well tolerated in patients with hypertension and LVH in the LIFE study. Significantly fewer losartan than atenolol recipients discontinued treatment because of adverse events, drug-related adverse events, or serious, drug-related adverse events.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Flunisolide HFA.

Flunisolide is a synthetic corticosteroid approved for the treatment of persistent asthma and delivered by means of a metered-dose inhaler (MDI). A new formulation of flunisolide, using hydrofluoroalkane (HFA) as a propellant, has been developed to comply with the mandated worldwide phase-out of ozone-depleting chlorofluorocarbon (CFC) propellants. Aerosol particle size in the new flunisolide HFA solution is smaller than the flunisolide CFC suspension (1.2 vs 3.8 microm mass median aerodynamic diameter). Aerosol particle size is a key element in determining lung deposition and the regional distribution of inhaled medication within the lung. In addition, the flunisolide HFA MDI has been redesigned to include a built-in spacer. These features have improved distal lung deposition. Flunisolide HFA, at one-third the dosage (170 and 340 microg twice daily), had similar efficacy to flunisolide CFC (500 and 1000 microg twice daily) and significantly greater efficacy than placebo in a randomized, double-blind, placebo-controlled, 12-week study in patients with mild to moderate asthma. Flunisolide HFA was well tolerated in all trials. A long-term study found no suppression of adrenal function and minimal systemic effects were observed both in adults and children.

Aerosol Propellants↗

PubMed2002

Travoprost.

Travoprost is a synthetic ester prodrug of a prostaglandin F(2alpha) analogue used in the treatment of open-angle glaucoma and ocular hypertension. Intraocular travoprost 0.004% once daily was significantly more effective at reducing intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension than placebo or timolol 0.5% twice daily and was at least as effective as latanoprost 0.005% once daily in randomised, double-blind studies. When used as adjunctive therapy with timolol 0.5% twice daily in patients with elevated IOP not adequately controlled by timolol alone, travoprost 0.004% showed significant additional IOP reduction in a randomised double-blind trial. Travoprost 0.004% was well tolerated in clinical trials. The majority of adverse events such as ocular hyperaemia and eyelash changes were mild and resolved without treatment.

Adult↗