Intramuscular aripiprazole : a review of its use in the management of agitation in schizophrenia and bipolar I disorder

An intramuscular formulation of the atypical antipsychotic aripiprazole (Abilify) has been developed and is approved in the EU for use in agitation and disturbed behaviour associated with schizophrenia. In the US, it is approved for the treatment of agitation associated with schizophrenia or bipolar I disorder (manic or mixed). In large, well designed trials, intramuscular aripiprazole was an effective and generally well tolerated treatment for agitation associated with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder. Intramuscular aripiprazole was more effective than placebo in these patient populations and was noninferior to intramuscular haloperidol in those with agitation associated with schizophrenia and its related disorders. Aripiprazole is associated with a low risk for extrapyramidal symptoms (EPS), cardiac effects, hyperprolactinaemia, weight gain and other metabolic disturbances. Head-to-head trials comparing intramuscular aripiprazole with other intramuscular atypical antipsychotics are required before the relative position of each of these agents can be fully determined. In the meantime, intramuscular aripiprazole, with its favourable tolerability profile, is a valuable treatment option for agitation in patients with schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I disorder.     

Alteplase: a review of its use in the management of acute ischaemic stroke

Alteplase (Actilyse?, Activase?) is a recombinant tissue-type plasminogen activator that activates plasminogen directly to plasmin. It is the only pharmacological treatment currently approved for patients with acute ischaemic stroke. This article reviews the efficacy and tolerability of alteplase, focusing on data relevant to treatment between 0 and 4.5 hours after onset of stroke, and summarizes its pharmacological properties. Well designed clinical trials showed that alteplase administered within 3 hours (in the NINDS trial) and between 3 and 4.5 hours (in the ECASS III trial) after stroke onset significantly improved clinical outcomes at 90 days relative to placebo. Alteplase was generally well tolerated in these trials, with no significant difference observed between alteplase and placebo recipients in the 90-day mortality rates, despite significantly higher incidences of any and symptomatic intracranial haemorrhages in alteplase recipients. These results were generally supported by those of the SITS-MOST and SITS-ISTR observational studies, which showed that alteplase was effective and generally well tolerated when administered within 4.5 hours of stroke onset in routine clinical practice. However, results from SITS-ISTR indicated that the safety and functional outcomes were generally less favourable when alteplase was administered 3-4.5 hours after stroke onset than within 3 hours of stroke onset. Additionally, results from pooled analyses of randomized clinical trials indicated that the benefit of alteplase therapy over placebo decreased as the time between stroke onset and treatment initiation increased, with no significant benefit observed when treatment was initiated >4.5 hours after stroke onset. Moreover, the odds of mortality increased as the time between stroke onset and treatment initiation increased. Thus, the greatest benefit of alteplase therapy is gained with early treatment. Based on these results, current EU labelling and treatment guidelines recommend that alteplase should be administered as early as possible within 4.5 hours of symptom onset in patients with acute ischaemic stroke. However, recent results from a meta-analysis and IST-3 suggest that some patients may benefit from treatment up to 6 hours after stroke onset. Patients for whom alteplase therapy is contraindicated as per current EU licensing criteria, such as those aged >80 years, may also benefit from therapy. Further randomized trials of alteplase administered >4.5 hours after stroke in selected patients are required to confirm these findings.     

Ticagrelor: a review of its use in the management of acute coronary syndromes

Ticagrelor (Brilique?; Brilinta?), a cyclopentyl-triazolo-pyrimidine antiplatelet agent, is the first oral antagonist of the P2Y(12) receptor to offer reversible receptor binding. It is indicated in the EU for the prevention of atherothrombotic events in adults with acute coronary syndromes (ACS) [unstable angina pectoris, ST-segment elevation myocardial infarction [STEMI] or non-STEMI), including those managed medically or with percutaneous coronary intervention or coronary artery bypass grafting (CABG). Ticagrelor provides selective and reversible inhibition of adenosine diphosphate-induced platelet aggregation, with a faster onset and offset of action than that of clopidogrel, and is effective in the treatment of patients with ACS, with or without ST-segment elevation. In the large, randomized, double-blind, multicentre PLATO trial conducted in this patient population, ticagrelor was more effective than clopidogrel in terms of preventing ischaemic events over 12 months, providing a significantly lower risk of the primary composite endpoint of myocardial infarction, stroke or death from vascular causes, and was associated with an overall mortality benefit. The risk of major bleeding with ticagrelor, including bleeds related to CABG, did not differ from that seen with clopidogrel in this study, although ticagrelor was associated with more non-CABG-related major bleeds and fatal intracranial bleeding, albeit the latter bleeding events were rare. Further long-term and comparative efficacy and tolerability data are required to definitively position ticagrelor with respect to other antiplatelet agents, including prasugrel. However, the clinical data currently available indicate that ticagrelor is a promising option for the treatment of patients with ACS and may be of particular use in those at high risk of ischaemic events or unresponsive to clopidogrel.     

Levosimendan: a review of its use in the management of acute decompensated heart failure

Levosimendan (Simdax) is a calcium-sensitising drug that stabilises the troponin molecule in cardiac muscle, thus prolonging its effects on contractile proteins, with concomitant vasodilating properties. Intravenous levosimendan (12-24 microg/kg loading dose followed by 0.1-0.2 microg/kg/min for 24 hours, adjusted for response and tolerability) is approved for the short-term treatment of acute severe decompensated heart failure. Cardiac output increased by about 30% and pulmonary capillary wedge pressure and systemic vascular resistance decreased by about 17-29% in patients with decompensated heart failure receiving intravenous levosimendan. In large, well controlled trials in patients with decompensated heart failure, intravenous levosimendan was significantly more effective than placebo or dobutamine for overall haemodynamic response rate (primary endpoint). Significant benefits were also seen for mortality (versus placebo or dobutamine) and for the combined risk of worsening heart failure or death (versus dobutamine). Improvements in key symptoms (dyspnoea and fatigue) have not been consistently demonstrated. Hospitalisation costs were similar for levosimendan and dobutamine; the total incremental (hospitalisation plus drug) cost per life-year saved (extrapolated to 3 years) for levosimendan relative to dobutamine was estimated at Euro 3205 (year of costing 2000). Levosimendan is generally well tolerated, with an adverse event profile at recommended dosages similar to that in patients receiving placebo. Cardiac rate/rhythm disorders and headache were the most common events. At higher dosages, patients receiving levosimendan had higher rates of sinus tachycardia than those in placebo recipients. More patients receiving dobutamine than those receiving levosimendan experienced angina pectoris/chest pain/myocardial ischaemia or rate/rhythm disorders. CONCLUSION: Intravenous levosimendan is an effective calcium-sensitising drug with vasodilatory and inotropic effects, and superior efficacy/tolerability to those of intravenous dobutamine in patients with acute decompensated heart failure. It may be associated with reduced mortality compared with both placebo and dobutamine. Levosimendan is generally well tolerated and may have less potential for cardiac rate/rhythm disorders than dobutamine. While evidence from well designed trials confirming the improved mortality over dobutamine and investigating haemodynamic efficacy and mortality versus other positive inotropes is required, intravenous levosimendan appears to be a useful addition to the treatment options for acute decompensated heart failure in patients with low cardiac output.     

Celecoxib: a review of its use in the management of arthritis and acute pain

Celecoxib (Celebrex), the first cyclo-oxygenase (COX) 2-selective inhibitor (coxib) to be introduced into clinical practice, has been available for almost a decade. It is approved in one or more countries worldwide for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (in patients aged > or =2 years) and ankylosing spondylitis (AS), the management of acute pain in adults, the treatment of primary dysmenorrhoea and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis.Celecoxib remains an effective and useful altenative to nonselective NSAIDs in the treatment of acute or chronic musculoskeletal pain. In the latter setting, it offers the prospect of improved gastrointestinal (GI) tolerability and, in patients not taking aspirin for cardioprophylaxis, a GI safety advantage. Currently available evidence of an increase in cardiovascular (CV) risk with celecoxib is inconsistent; any increase in risk is likely to be small and similar to that with nonselective NSAIDs. As with all NSAIDs, the potential GI, CV and renal risks of celecoxib must be weighed against the potential benefits in each individual; it is a rational choice for patients at low CV risk who require NSAID therapy, especially those at increased risk of NSAID-induced GI toxicity, but also those unresponsive to, or intolerant of, other NSAIDs. If selected, celecoxib, like all NSAIDs, should be used at the lowest effective dose for the shortest possible duration.     

Ropivacaine: a review of its use in regional anaesthesia and acute pain management

Ropivacaine (Naropin) is the pure S(-)-enantiomer of propivacaine, and is a long-acting amide local anaesthetic agent, eliciting nerve block via reversible inhibition of sodium ion influx in nerve fibres.Ropivacaine is a well tolerated regional anaesthetic effective for surgical anaesthesia as well as the relief of postoperative and labour pain. The efficacy of ropivacaine is similar to that of bupivacaine and levobupivacaine for peripheral nerve blocks and, although it may be slightly less potent than bupivacaine when administered epidurally or intrathecally, equi-effective doses have been established. Clinically adequate doses of ropivacaine appear to be associated with a lower incidence or grade of motor block than bupivacaine. Thus ropivacaine, with its efficacy, lower propensity for motor block and reduced potential for CNS toxicity and cardiotoxicity, appears to be an important option for regional anaesthesia and for the management of postoperative and labour pain.     

Oxycodone/Ibuprofen combination tablet: a review of its use in the management of acute pain

Oxycodone/ibuprofen 5 mg/400 mg (Combunox) is an oral fixed-dose combination tablet with analgesic, anti-inflammatory and antipyretic properties. It is approved in the US for the short-term (up to 7 days) management of acute, moderate-to-severe pain and is the first and only fixed-dose combination containing ibuprofen and oxycodone. A single dose of oxycodone/ibuprofen 5 mg/400 mg provided better analgesia than low-dose oxycodone or ibuprofen administered alone in most trials and appears to be more effective than a single dose of some other fixed-dose combination analgesics. It is generally well tolerated after single or multiple doses and short-term use is not expected to produce any of the serious adverse effects typically associated with the long-term use of opioids or NSAIDs. Thus, oxycodone/ibuprofen 5 mg/400mg is an effective, convenient treatment option for the short-term management of acute, moderate-to-severe pain.     

Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia

Azacitidine (Vidaza?) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties. The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone. The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML). The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS. Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials, peripheral cytopenias were the most commonly occurring adverse event in azacitidine recipients, with gastrointestinal adverse events (e.g. nausea, vomiting and diarrhoea) and injection-site reactions among the most commonly occurring non-haematological adverse events. In conclusion, azacitidine is an important agent for use in the treatment of patients with MDS/AML.     

Zolpidem: a review of its use in the management of insomnia

Zolpidem (Ambien, Stilnox, Myslee, an imidazopyridine, is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia. Zolpidem improves sleep in patients with insomnia. Its overall tolerability is favourable when administered according to the manufacturer's prescribing information, with a low propensity to cause clinical residual effects, withdrawal, dependence or tolerance. In addition, most evidence suggests that the drug is associated with minimal rebound insomnia. In the only clinical trials that investigated the use of a hypnosedative drug in an 'as-needed' regimen, zolpidem produced a global improvement in sleep. Thus, zolpidem continues to be a useful therapeutic option in the pharmacological treatment of patients with insomnia.     

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.     

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

Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Results of large (n > 100) randomised double-blind studies in patients with mild, moderate or severe hypertension demonstrated that the antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single daily dose or in 2 divided doses) is significantly greater than that of placebo and at least as good as that of enalapril. In placebo-controlled trials, eprosartan achieved mean reductions from baseline in trough sitting systolic blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7 mm Hg. Response rates associated with once daily administration of eprosartan 400 to 800 mg were approximately double those with placebo. Overall, eprosartan was well tolerated with a similar tolerability profile to that of placebo. In comparative trials, in which the incidence of persistent dry cough was evaluated as the primary end-point, enalapril was several-fold more likely to induce this adverse event than eprosartan (the difference being statistically significant regardless of study population and definition of cough). In conclusion, the angiotensin II receptor antagonist eprosartan is a well tolerated and effective antihypertensive agent that is administered once or twice daily without regard to meals. Eprosartan has a low potential for serious adverse events, and the drug has not been associated with clinically significant drug interactions. Unlike ACE inhibitors such as enalapril, eprosartan does not have a high propensity to cause persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic option in the management of patients with hypertension.     

Manidipine: a review of its use in the management of hypertension

Manidipine is a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. In addition, manidipine does not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation. It has a gradual onset of action and a long duration of action enabling once daily administration. Furthermore, manidipine dilates both the efferent and the afferent renal arterioles and appears to have beneficial renal effects unrelated to its antihypertensive effect. Once-daily oral manidipine is an effective and generally well tolerated antihypertensive agent for younger and elderly adult patients with mild-to-moderate hypertension. In particular, in a large double-blind trial, the incidence of ankle oedema was significantly lower in manidipine than in amlodipine recipients. Manidipine is also effective in hypertensive patients with comorbidities, such as type 2 diabetes mellitus and/or renal impairment, and appears to improve insulin sensitivity without affecting metabolic function. Thus, manidipine represents a first-line treatment option for patients with essential mild-to-moderate hypertension.     

Orlistat: a review of its use in the management of obesity

Orlistat (Xenical) is a reversible inhibitor of gastric and pancreatic lipases. In conjunction with a hypocaloric diet and moderate exercise, orlistat is an effective drug for use in the management of obesity in adults with or without comorbidities. Recent data have shown that orlistat is also effective as a component of weight management strategies in obese adolescents. In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome. Orlistat is generally well tolerated. Thus, orlistat is an option for the treatment of obese patients with or without type 2 diabetes and also has a role in the management of obese patients with the metabolic syndrome, associated comorbidities or concomitant disorders.     

Ciclesonide: a review of its use in the management of asthma

Ciclesonide (Alvesco) is an inhaled corticosteroid used in the preventative treatment of persistent bronchial asthma in adults, adolescents and, in some countries, children. The drug is delivered by a non-chlorofluorocarbon hydrofluoroalkane (HFA) metered-dose inhaler (MDI). In the lungs, ciclesonide is converted to an active metabolite, which is responsible for the beneficial effects of the drug in patients with asthma. Ciclesonide and its active metabolite have low systemic bioavailability and therefore have a low potential to produce systemic adverse events. Inhaled ciclesonide delivered by HFA-MDI is effective in the prophylactic treatment of persistent asthma in adults, adolescents and children, and is generally well tolerated. In general, ciclesonide improves lung function and reduces asthma symptoms and rescue medication use in adults and adolescents with asthma of varying severity. The drug is generally no less effective than other inhaled corticosteroids with regard to maintaining or improving lung function and may have a more favourable tolerability profile than some other agents in this class. Ciclesonide has also shown efficacy in paediatric patients with asthma. Data on its long-term effects on other clinical outcomes, such as asthma exacerbations, would be of interest. Further comparative and long-term studies would also be beneficial in order to definitively position ciclesonide with respect to other inhaled corticosteroids. In the meantime, ciclesonide offers an effective and well tolerated first-line preventative treatment option for persistent asthma.     

Pranlukast: a review of its use in the management of asthma

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. CONCLUSIONS: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.     

Lacidipine: a review of its use in the management of hypertension

Lacidipine (Caldine, Lacimen, Lacipil, Midotens, Motens) is a once-daily, orally-administered, lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity, resulting in a lack of reflex tachycardia. It has a long duration of action and a high degree of vascular selectivity. In addition to calcium channel-modulated vasodilation, lacidipine displays antioxidant activity greater than that of other dihydropyridine calcium antagonists. In randomised, well-controlled trials, lacidipine 2-6 mg orally once daily had antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). Lacidipine was effective in elderly patients (including those with isolated systolic hypertension), African Nigerian patients and patients with concurrent type 2 diabetes mellitus. During long-term treatment for 4 or 5 years in patients with isolated systolic hypertension or essential hypertension, the incidence of cardiovascular events and mortality with lacidipine was similar to that with chlorthalidone or atenolol. The European Lacidipine Study on Atherosclerosis (ELSA), in which 2334 patients with hypertension were randomised to 4 years of therapy with lacidipine 4-6 mg/day or the beta-blocker atenolol 50-100 mg/day, demonstrated significantly lower atherosclerotic progression and plaque formation with lacidipine compared with atenolol in patients completing the full 4 years of the study. Between-group differences in favour of lacidipine for the primary efficacy variable (mean change in carotid artery intima-media thickness) did not reach statistical significance in the intent-to-treat population. The tolerability profile of lacidipine (headache, flushing, pedal oedema, dizziness and palpitations) is similar to that of other dihydropyridine calcium antagonists, but with a lower incidence of peripheral oedema. Data from the ELSA study suggest that the incidence of serious adverse events during long-term lacidipine therapy is similar to that with atenolol. CONCLUSION: Lacidipine is an effective, well tolerated, once-daily, oral antihypertensive agent that can be used in a wide variety of patients. As with other members of its class, lacidipine has shown potentially beneficial antiatherosclerotic effects, although definitive data with respect to possible superiority over other drug classes are still required. Therefore, lacidipine is an attractive therapy for the long-term management of essential hypertension.     

Glucosamine: a review of its use in the management of osteoarthritis

Glucosamine occurs naturally in all human tissues. It stimulates the synthesis of glycosaminoglycan, proteoglycan and hyaluronic acid, although the precise mechanism of action remains to be established. Formulated as glucosamine sulphate (Dona) and various others), glucosamine has been evaluated for its efficacy in relieving the symptoms of osteoarthritis and its disease-modifying potential.In two large randomised, double-blind, multicentre studies in patients with osteoarthritis, oral or intramuscular glucosamine for 4-6 weeks was associated with a greater decrease in symptom severity (as assessed by the Lequesne index) than placebo. In addition, there was a greater proportion of responders (defined as patients with a >or=3-point reduction in the Lequesne index, along with a positive overall assessment by the investigator) at the end of the treatment period with glucosamine than with placebo. In two large 4-week trials, oral glucosamine produced similar improvements to ibuprofen in the Lequesne index in one study and in articular pain scores in the other study. In a smaller 8-week comparative trial, oral glucosamine therapy achieved a significantly greater improvement in articular pain score than ibuprofen, and the investigators rated treatment efficacy as 'good' in a significantly greater proportion of glucosamine than ibuprofen recipients. In comparison with piroxicam, glucosamine significantly improved arthritic symptoms after 12 weeks of therapy and remained effective 8 weeks after treatment was discontinued. Beneficial effects of long-term oral glucosamine therapy in preventing joint space narrowing and improving symptoms were shown in two 3-year placebo-controlled trials in a total of 414 patients with osteoarthritis. Statistically significant differences favouring glucosamine were noted in the per-protocol and intention-to-treat analyses for the primary endpoints for both joint structural changes and symptom modification. Glucosamine has a tolerability profile similar to that of placebo and is better tolerated than ibuprofen or piroxicam. In particular, glucosamine recipients had a markedly lower incidence of gastrointestinal disturbances than those receiving ibuprofen. Other adverse events reported in both glucosamine and ibuprofen recipients were pruritus or skin reactions, flushing and fatigue. In general, a lower incidence of withdrawal from clinical trials was reported for glucosamine recipients than either ibuprofen or piroxicam recipients.CONCLUSION: In short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. Glucosamine may therefore prove to be a useful treatment option for osteoarthritis.     

Aliskiren: a review of its use in the management of hypertension

Aliskiren (Tekturna) is an orally active, nonpeptidic inhibitor of renin, the enzyme involved in the initial and rate-limiting step of the renin-angiotensin system (RAS). In the US, aliskiren is approved for the treatment of hypertension and may be used alone or in combination with other antihypertensive agents.Monotherapy with aliskiren 150-300mg once daily was effective in lowering blood pressure (BP) and providing 24-hour BP control; it was generally well tolerated when administered for up to 1 year to patients with mild to moderate hypertension. In the short term (1-3 months), the BP-lowering effect of aliskiren 150-300mg once daily was significantly greater than that of hydrochlorothiazide (HCTZ) 12.5-25mg once daily and noninferior to, or significantly greater than, that of ramipril 5-10mg once daily. It was similar to that of valsartan 160-320mg once daily and losartan 100mg once daily, and similar to, or significantly greater than, that of irbesartan 150mg once daily. Aliskiren provided significant additional BP-lowering effects when combined with HCTZ 12.5-25 mg/day, ramipril 5-10 mg/day, amlodipine 5mg once daily or valsartan 160-320 mg/day; combination therapy was well tolerated. Long-term administration of aliskiren-based therapy was superior to HCTZ- and ramipril-based therapies in lowering BP after 6 months, and was similarly well tolerated.The ultimate role of aliskiren will be determined by the results of target organ protection studies, which are ongoing, and a cardiovascular outcome trial, which is planned. Nonetheless, by offering a new approach to the blockade of the RAS, aliskiren provides a useful addition to the therapeutic options available to treat patients with mild to moderate hypertension.     

Amisulpride: a review of its use in the management of schizophrenia

Amisulpride (Solian), a substituted benzamide derivative, is a second-generation antipsychotic that preferentially binds to dopamine D2/D3 receptors in limbic rather than striatal structures. High dosages preferentially antagonise postsynaptic D2/D3 receptors, resulting in reduced dopamine transmission, and low dosages preferentially block presynaptic D2/D3 receptors, resulting in enhanced dopamine transmission. Amisulpride (200-1200 mg/day) was at least as effective as haloperidol and as effective as risperidone or olanzapine, in studies of up to 1 year in patients with schizophrenia manifesting predominantly positive symptoms. Amisulpride (50-300 mg/day) was significantly more effective than placebo in studies of up to 6 months in patients manifesting predominantly negative symptoms. Quality of life was also improved significantly more in patients receiving amisulpride than in those receiving haloperidol in 4- and 12-month studies in patients with predominantly mixed symptoms. Amisulpride was generally well tolerated in clinical trials. In patients with predominantly positive symptoms, amisulpride appeared to be better tolerated than haloperidol and was tolerated as well as risperidone and olanzapine. The incidence of extrapyramidal adverse effects with amisulpride was lower than with haloperidol but was generally similar to risperidone or olanzapine. Weight gain with amisulpride was less than that with risperidone or olanzapine and, unlike these agents, amisulpride does not seem to be associated with diabetogenic effects. Plasma prolactin levels are increased during amisulpride therapy and amenorrhoea occurs in about 4% of women. The incidence of adverse events with low dosages of amisulpride (< or = 300 mg/day) in patients with predominantly negative symptoms was similar to that observed with placebo. In conclusion, oral amisulpride (200-1200 mg/day) is at least as effective as haloperidol, and as effective as risperidone or olanzapine, in the treatment of patients with schizophrenia manifesting predominantly positive symptoms. In the treatment of patients manifesting predominantly negative symptoms, low dosages of amisulpride (50-300 mg/day) are significantly more effective than placebo. Amisulpride appears to be better tolerated than haloperidol, causing a lower incidence of extrapyramidal adverse effects and an improved quality of life. Compared with risperidone or olanzapine, amisulpride is more likely to cause hyperprolactinaemia, but has a lower propensity to cause weight gain and does not seem to be associated with diabetogenic effects. Thus, amisulpride is an effective and well tolerated option for the first-line treatment of patients with acute schizophrenia as well as for those requiring long-term maintenance therapy.