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Biomedical subjects

A Markham

Publications and source records attributed to A Markham.

At least 19 recordsLinked to original sources
PubMed1999

Cilostazol.

Cilostazol is an antiplatelet agent with vasodilating properties that has been used in the treatment of patients with peripheral ischaemia such as intermittent claudication. The drug inhibits platelet aggregation induced by ADP, collagen and arachidonic acid. Unlike aspirin (acetylsalicylic acid), cilostazol inhibits both primary and secondary aggregation. It also acts as a vascular vasodilator by inhibiting calcium-induced contractions while having no direct effect on contractile proteins. In double-blind randomised trials, patients with intermittent claudication receiving cilostazol showed significant improvements versus placebo in terms of time to initial pain and maximal walking or absolute claudication distance; these findings were confirmed by cilostazol patients' positive responses on subscales measuring physical functioning and quality of life. In a 24-week randomised double-blind trial in patients with intermittent claudication, cilostazol 100mg twice daily produced significant improvements in pain-free and maximum walking distances, compared with pentoxifylline (oxpentifylline) 400mg 3 times daily and placebo. Cilostazol has been well tolerated, with the most common adverse events being headache, diarrhoea, abnormal stools and dizziness.

Cilostazol↗
PubMed1999

Long-acting isosorbide mononitrate.

Elantan long (EL) is the only long-acting isosorbide mononitrate formulation based on a controlled membrane principle. 30% of the dose is available for immediate release and the remaining 70% is gradually released over time. After oral administration, isosorbide mononitrate EL has a quick onset of action (30 minutes) and effects are evident for up to 17 hours. The antianginal effects of once-daily isosorbide mononitrate EL 50 to 100mg were generally similar to those of conventional isosorbide mononitrate or isosorbide dinitrate 10 to 20mg twice or 3 times daily, or sustained-release nifedipine 20mg twice or 3 times daily. Patients tended to show a better response with once-daily isosorbide mononitrate EL 50mg than with bupranolol 100mg. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate EL than with twice or 3 times daily regimens of conventional isosorbide mononitrate or isosorbide dinitrate. Tolerance did not develop after 13 months of once-daily administration of isosorbide mononitrate EL. No rebound increase in incidence of ischaemic episodes was observed after discontinuation of the drug.

Angina Pectoris↗
PubMed1999

Finasteride: a review of its use in male pattern hair loss.

UNLABELLED: The 5alpha-reductase inhibitor finasteride blocks the conversion of testosterone to dihydrotestosterone (DHT), the androgen responsible for male pattern hair loss (androgenetic alopecia) in genetically predisposed men. Results of phase III clinical studies in 1879 men have shown that oral finasteride 1 mg/day promotes hair growth and prevents further hair loss in a significant proportion of men with male pattern hair loss. Evidence suggests that the improvement in hair count reported after 1 year is maintained during 2 years' treatment. In men with vertex hair loss, global photographs showed improvement in hair growth in 48% of finasteride recipients at 1 year and in 66% at 2 years compared with 7% of placebo recipients at each time point. Furthermore, hair counts in these men showed that 83% of finasteride versus 28% of placebo recipients had no further hair loss compared with baseline after 2 years. The clinical efficacy of oral finasteride has not yet been compared with that of topical minoxidil, the only other drug used clinically in patients with male pattern hair loss. Therapeutic dosages of finasteride are generally well tolerated. In phase III studies, 7.7% of patients receiving finasteride 1 mg/day compared with 7.0% of those receiving placebo reported treatment-related adverse events. The overall incidence of sexual function disorders, comprising decreased libido, ejaculation disorder and erectile dysfunction, was significantly greater in finasteride than placebo recipients (3.8 vs 2.1%). All sexual adverse events were reversed on discontinuation of therapy and many resolved in patients who continued therapy. No other drug-related events were reported with an incidence > or =1% in patients receiving finasteride. Most events were of mild to moderate severity. Oral finasteride is contraindicated in pregnant women because of the risk of hypospadias in male fetuses. CONCLUSIONS: Oral finasteride promotes scalp hair growth and prevents further hair loss in a significant proportion of men with male pattern hair loss. With its generally good tolerability profile, finasteride is a new approach to the management of this condition, for which treatment options are few. Its role relative to topical minoxidil has yet to be determined.

Alopecia↗
PubMed1999

Oral delayed-release mesalazine: a review of its use in ulcerative colitis and Crohn's disease.

UNLABELLED: Oral delayed-release mesalazine is an enteric-coated formulation which releases mesalazine in the terminal ileum and colon. Up to 74% of patients with mild to moderately active ulcerative colitis experience endoscopic or symptomatic improvement (including remission) or both when treated with oral delayed-release mesalazine 2.4 to 4.8 g/day. There is a trend towards a better response in patients receiving higher daily dosages of oral delayed-release mesalazine, especially in patients with active distal disease. In patients with left-sided ulcerative colitis, oral balsalazide 6.75 g/day appears to be more effective than oral delayed-release mesalazine 2.4 g/day, but a higher dosage of oral delayed-release mesalazine 4.8 g/day may provide additional benefit in these patients. Oral delayed-release mesalazine 0.8 to 4.4 g/day appears to be as effective as sulfasalazine 2 to 4 g/day, prolonged-release mesalazine 1.5 g/day or balsalazide 3 g/day in maintaining remission in patients with ulcerative colitis. The optimal dosage of oral delayed-release mesalazine for the maintenance of remission is unclear. However, oral delayed-release mesalazine 1.6 g/day with rectal mesalazine 4g, administered twice weekly, was more effective than oral drug alone in maintaining remission in patients at high risk of relapse. In patients with left-sided or distal disease oral olsalazine 1 g/day appeared to be superior to oral delayed-release mesalazine 1.2 g/day for maintenance of symptomatic remission. Limited data in patients with Crohn's disease have shown oral delayed-release mesalazine 0.4 to 4.8 g/day to be an effective therapy for active disease (remission in up to 45% of patients) and for quiescent disease (relapse in 34% of recipients over a duration of up to 12 months). Preliminary data indicate that oral delayed-release mesalazine 2.4 g/day is effective in preventing postoperative recurrence of Crohn's disease. Oral delayed-release mesalazine is effective and well tolerated in sulfasalazine-intolerant patients with ulcerative colitis or Crohn's disease. CONCLUSIONS: Oral delayed-release mesalazine is effective in patients with mild to moderately active or quiescent ulcerative colitis. Available data suggest that patients with left-sided or distal ulcerative colitis are likely to require higher daily dosages of oral delayed-release mesalazine or supplementation with rectal mesalazine. Oral delayed-release mesalazine also appears to be effective in active and quiescent Crohn's disease. The drug is well tolerated and it appears to be effective in sulfasalazine-intolerant patients.

Administration, Oral↗
PubMed1999

Fluvastatin: a review of its use in lipid disorders.

UNLABELLED: Fluvastatin is an HMG-CoA reductase inhibitor used to treat patients with hypercholesterolaemia. Since fluvastatin was last reviewed in Drugs, trials have shown its efficacy in the secondary prevention of coronary heart disease (CHD) events and death and have expanded knowledge of its effects in primary CHD prevention and its mechanisms of activity. In addition to reducing total (TC) and low density lipoprotein (LDL-C) cholesterol, fluvastatin has antiatherogenic, antithrombotic and antioxidant effects, can improve vascular function, and may have immunomodulatory effects. Although fluvastatin interacts with bile acid sequestrants (requiring separation of doses), its pharmacokinetics permit oral administration to most patient groups. Fluvastatin is well tolerated, with adverse effects usually mild and transient. Use of fluvastatin to reduce lipids in patients with primary hypercholesterolaemia is well established. Its effects are similar in most patient groups, with 20 to 80 mg/day reducing LDL-C by 22 to 36%, triglycerides (TG) by 12 to 18% and apolipoprotein B by 19 to 28% and increasing high density lipoprotein cholesterol by 3.3 to 5.6%. Attempts to find fluvastatin dosages with efficacy equivalent to that of other HMG-CoA reductase inhibitors produce variable results, but larger per-milligram fluvastatin dosages are needed when patients switch from other HMG-CoA reductase inhibitors. Combinations of fluvastatin with fibric acid derivatives and bile acid sequestrants produce additive effects. Small noncomparative studies suggest fluvastatin reduces LDL-C in patients with hypercholesterolaemia secondary to kidney disorders by < or = 40.5% and with type 2 diabetes mellitus by < or = 32%. Three large randomised, double-blind trials show fluvastatin can help prevent CHD events or death and slow disease progression in patients with CHD with or without hypercholesterolaemia. In the Fluvastatin Angiographic Restenosis trial in patients undergoing balloon angioplasty, fluvastatin 80 mg/day for 40 weeks reduced the postangioplasty rate of deaths plus myocardial infarctions (1.5% vs 4% with placebo, p < 0.025) without altering vessel luminal diameters. In the Lipoprotein and Coronary Atherosclerosis Study in patients with coronary artery stenosis, luminal diameter reduced to a significantly lesser extent after fluvastatin 20 mg twice daily than placebo after 2.5 years (-0.028 vs -0.01 mm, p < 0.005). The Lescol in Symptomatic Angina study found reductions in all cardiac events or cardiac death in patients after 1 year of fluvastatin 40 mg/day (1.6% vs 5.6% for placebo, p < 0.05). CONCLUSIONS: An evolving pattern of data suggests that, in addition to its well established efficacy and cost effectiveness in reducing hypercholesterolaemia, fluvastatin may now also be considered for use in the secondary prevention of CHD.

Fatty Acids, Monounsaturated↗
PubMed1999

Mirtazapine: a review of its use in major depression.

UNLABELLED: Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) which has predominantly been evaluated in the treatment of major depression. The drug had equivalent efficacy to tricyclic antidepressants and it was at least as effective as trazodone in the majority of available short term trials in patients with moderate or severe depression, including those with baseline anxiety symptoms or sleep disturbance and the elderly. A continuation study also showed that sustained remission rates were higher with mirtazapine than with amitriptyline and that the drugs had similar efficacy for the prevention of relapse. There is some evidence for a faster onset of action with mirtazapine than with the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). Mirtazapine was more effective than the SSRI fluoxetine at weeks 3 and 4 of therapy and it was also more effective than paroxetine and citalopram at weeks 1 and 2, respectively, in short term assessments (6 or 8 weeks). Preliminary data suggest that the drug may be effective as an augmentation or combination therapy in patients with refractory depression. Anticholinergic events and other events including tremor and dyspepsia are less common with mirtazapine than with tricyclic antidepressants. There was a greater tendency for SSRI-related adverse events with fluoxetine than with mirtazapine, but, overall, mirtazapine had a similar tolerability profile to the SSRIs. Increased appetite and bodyweight gain appear to be the only events that are reported more often with mirtazapine than with comparator antidepressants. In vitro and in vivo data have suggested that mirtazapine is unlikely to affect the metabolism of drugs metabolised by cytochrome P450 (CYP)2D6, although few formal drug interaction data are available. CONCLUSIONS: Mirtazapine is effective and well tolerated for the treatment of patients with moderate to severe major depression. Further research is required to define the comparative efficacy of mirtazapine in specific patient groups, including the elderly and those with severe depression. Clarification of its efficacy as an augmentation therapy and in patients with refractory depression and its role in improving the efficacy and reducing the extrapyramidal effects of antipsychotic drugs would also help to establish its clinical value. The low potential for interaction with drugs that are metabolised by CYP2D6, including antipsychotics, tricyclic antidepressants and some SSRIs, may also make mirtazapine an important option for the treatment of major depression in patients who require polytherapy. Mirtazapine also appears to be useful in patients with depression who present with anxiety symptoms and sleep disturbance.

Antidepressive Agents, Tricyclic↗
PubMed1999

Piperacillin/tazobactam: an updated review of its use in the treatment of bacterial infections.

UNLABELLED: Piperacillin/tazobactam is a beta-lactam/beta-lactamase inhibitor combination with a broad spectrum of antibacterial activity encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases. Evidence from clinical trials in adults has shown that piperacillin/tazobactam, administered in an 8:1 ratio, is an effective treatment for patients with lower respiratory tract, intra-abdominal, urinary tract, gynaecological and skin/soft tissue infections, and for fever in patients with neutropenia. Combination regimens of piperacillin/tazobactam plus an aminoglycoside are used to treat patients with severe nosocomial (hospital-acquired) infections. In clinical trials, piperacillin/tazobactam was significantly more effective than ticarcillin/clavulanic acid in terms of clinical and microbiological outcome in patients with community-acquired pneumonia. In patients with intra-abdominal infections, clinical and bacteriological response rates were significantly higher with piperacillin/tazobactam than with imipenem/cilastatin (administered at a dosage lower than is recommended in countries outside Scandinavia). Piperacillin/tazobactam in combination with amikacin was at least as effective as ceftazidime plus amikacin in the treatment of ventilator-associated pneumonia and was significantly more effective than ceftazidime plus amikacin in the empirical treatment of febrile episodes in patients with neutropenia or granulocytopenia. In other trials, the efficacy of piperacillin/tazobactam was similar to that of standard aminoglycoside-containing and other treatment regimens in patients with intra-abdominal, skin/soft tissue or gynaecological infections. Piperacillin/tazobactam is generally well tolerated. The most frequent adverse events are gastrointestinal symptoms (most commonly diarrhoea) and skin reactions. The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given in combination with an aminoglycoside than when given as monotherapy. CONCLUSION: Because of the broad spectrum of antibacterial activity provided by piperacillin/tazobactam, it is useful for the treatment of patients with polymicrobial infections caused by aerobic or anaerobic beta-lactamase-producing bacteria. Piperacillin/tazobactam appears to have a particularly useful role in the treatment of patients with intra-abdominal infections and, in combination with amikacin, in the treatment of patients with febrile neutropenia, especially given the current prevalence of Gram-positive infections in this group.

Bacterial Infections↗
PubMed1999

Sildenafil: a review of its use in erectile dysfunction.

UNLABELLED: Sildenafil is an oral therapy for erectile dysfunction of a broad range of causes. By selectively inhibiting phosphodiesterase type 5, it allows corpus cavernosum smooth muscle to relax, potentiating erections during sexual stimulation. Blood pressure is reduced transiently by sildenafil, but more marked hypotension may occur during concurrent administration of sildenafil and organic nitrates; this combination is contraindicated. Sildenafil is rapidly absorbed, with dose-proportional peak plasma concentrations within 1 hour of administration. The elimination half-life is 3 to 5 hours. Dosages usually begin at 50mg taken when needed =1 hour before sexual activity no more than once daily. The maximum dose is 100mg when needed once daily and lower doses (e.g. 25mg) may be used in elderly patients and those with hepatic or renal impairment or receiving cytochrome P450 enzyme CYP3A4 inhibitors, such as ritonavir, saquinavir, ketoconazole, erythromycin or cimetidine. More than 3000 patients with erectile dysfunction of organic (e.g. diabetes or spinal cord injury), psychogenic or mixed origin received sildenafil 5 to 100mg or placebo in fixed- or titrated-dose trials. Sildenafil was associated with dose-related improvements in the frequency, hardness and duration of erections and in patients' abilities to achieve and maintain erections adequate for successful sexual intercourse. In titrated-dose trials, the most commonly effective doses were 50 or 100mg, although lower doses were effective in some patients. Sildenafil was significantly more effective than placebo in erectile dysfunction of all tested causes. The efficacy of sildenafil was not affected by patient age (> or < or =65 years) or by antihypertensive or antidepressant medications. The drug was effective in patients with severe erectile dysfunction. Efficacy was maintained in long term (1-year) studies. Sildenafil also appears to improve the quality of life of both patients and their sexual partners. Common adverse events associated with sildenafil were transient and mild or moderate and included headache, flushing, dyspepsia, nasal congestion and abnormal vision. Tolerability was maintained in long term (< or =1 year) studies. No serious sildenafil-related adverse events occurred in clinical trials; cardiovascular events seen in postmarketing surveillance generally occurred in patients with other known risk factors. CONCLUSIONS: Sildenafil is an effective oral treatment in men with erectile dysfunction. It was significantly superior to placebo in improving erections and allowing successful penetrative sexual intercourse. Although its place in disease management is still emerging and there are contraindications to its use, if preliminary positive reports are confirmed, sildenafil will be the pre-eminent first-line therapy for erectile dysfunction.

Clinical Trials as Topic↗
PubMed1998

Cytogenetics and the surgeon: an invaluable tool in diagnosis, prognosis and counselling of patients with solid tumours.

BACKGROUND: Cytogenetic studies have become an important part of tumour characterization. In a minority of tumours cytogenetic and/or molecular studies may be of help for diagnosis, selection of treatment protocols and predicting outcome. METHODS: This article reviews the literature on solid tumour translocations and established family cancer syndromes. In addition, the potential importance of genetics in management of patients with breast, ovarian and pancreatic carcinoma is reviewed. RESULTS AND CONCLUSION: Cytogenetic analysis of tumours may help confirm the diagnosis when conventional histology demonstrates no evidence of differentiation along a particular tissue pathway. For patients with well defined cancer syndromes, cytogenetic and molecular analysis offers the prospect of screening to reduce the risk of malignant disease. For many malignancies the underlying genetic anomalies are gradually being elucidated. Further studies designed to demonstrate the significance of these findings can only be undertaken if tumour material is collected and stored in optimal conditions for cytogenetic and/or molecular biological studies.

Age of Onset↗
PubMed1998

Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone.

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.

Antineoplastic Agents↗
PubMed1998

Pramipexole. A review of its use in the management of early and advanced Parkinson's disease.

UNLABELLED: Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a worsening of the Parkinson's disease), dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pramipexole and placebo recipients. CONCLUSIONS: Pramipexole is effective as adjunctive therapy to levodopa in patients with advanced Parkinson's disease. However, the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The efficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.

Antiparkinson Agents↗
PubMed1998

Fexofenadine.

The nonsedating histamine H1 receptor antagonist fexofenadine is the active metabolite of terfenadine. It reduced the allergic response in animal models of allergy and did not prolong the QT interval (QTc) in dogs or rabbits at plasma concentrations many times higher than those seen after administration of therapeutic dosages. Similarly, relative to placebo, fexofenadine did not affect mean QTc in patients given dosages of up to 480 mg/day for 2 weeks or in volunteers who received up to 800 mg/day for 6 days or 240 mg/day for 12 months. In a double-blind clinical trial, oral fexofenadine 120 or 180mg once daily controlled symptoms in patients with seasonal allergic rhinitis as effectively as cetirizine. Other double-blind clinical trials showed that fexofenadine 40 to 240mg twice daily was significantly more effective than placebo. Fexofenadine 180 or 240mg once daily was significantly more effective than placebo in patients with chronic idiopathic urticaria. The drug was well tolerated in these clinical trials, with an adverse event profile similar to that seen with placebo. The most common adverse events were headache, throat irritation, viral infection, nausea, dysmenorrhoea, drowsiness, dyspepsia and fatigue.

Animals↗
PubMed1998

Sumatriptan. An updated review of its use in migraine.

UNLABELLED: Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. CONCLUSIONS: Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.

Administration, Intranasal↗
PubMed1998

Montelukast.

Montelukast is a selective antagonist of the leukotriene D4 (LTD4) receptor. In patients with asthma, montelukast 5 to 250 mg/day attenuated LTD4-induced bronchoconstriction and, at a dosage of 10 mg, significantly reduced early and late airway response to allergen (dust mite extract) relative to placebo. In studies evaluating the effects of various dosages of montelukast on exercise-induced bronchoconstriction the optimal dose of the drug was found to be 10 mg. Montelukast 10 mg/day controlled asthma significantly more effectively than placebo in a 3-month randomised double-blind study. In a 9-month open extension of this trial, during which patients were randomised to treatment with montelukast 10 mg/day or beclomethasone (approximately 400 micrograms/day), daytime symptom score and beta-agonist use decreased to a similar extent in each group. In a further study, treatment with montelukast 10 mg/day permitted clinically significant tapering of corticosteroid dosage in patients with stable asthma. Montelukast (5 mg/day) has also demonstrated efficacy in childhood asthma. The tolerability profile of montelukast was similar to that of placebo in placebo-controlled clinical trials in adults and children; the most common adverse event was headache.

Acetates↗
PubMed1998

Telmisartan.

Telmisartan is a nonpeptide angiotensin II receptor antagonist which selectively and insurmountably inhibits the angiotensin II AT1 receptor subtype without affecting other receptor systems involved in cardiovascular regulation. Oral telmisartan dose-dependently reduced blood pressure (BP) in various animal models of hypertension. In transgenic rats, telmisartan reduced cardiac hypertrophy and glomerulosclerosis. When administered at dosages of 40 to 160 mg once daily to patients with mild to moderate hypertension, telmisartan significantly reduced systolic and diastolic BP compared with placebo and was at least as effective as atenolol 50 or 100 mg and lisinopril 10 to 40 mg. One study showed telmisartan 80 mg/day to be more effective than enalapril 20 mg/day. In 2 studies that used ambulatory BP monitoring, once daily telmisartan provided better control of diastolic BP for the full dosing interval than losartan potassium 50 mg or amlodipine 5 or 10 mg. In a single study in patients with severe hypertension, a telmisartan-based regimen had antihypertensive efficacy similar to that of an enalapril-based regimen. Telmisartan had a tolerability profile similar to that of placebo in clinical studies.

Angiotensin Receptor Antagonists↗
PubMed1998

Theophylline. A review of its potential steroid sparing effects in asthma.

UNLABELLED: Theophylline is generally considered to be a bronchodilatory drug. However, recent pharmacodynamic studies indicate that it has anti-inflammatory effects. It reduced eosinophil survival rates in vitro, and reduced eosinophil accumulation in bronchial tissue in patients with atopic asthma. Theophylline has also been shown to reduce T cell proliferation and accumulation. These changes were mirrored by improved pulmonary function in patients with asthma in studies that evaluated this parameter. Three randomised double-blind studies have evaluated the potential role of theophylline as an anti-inflammatory treatment in patients with asthma not controlled by low doses of inhaled corticosteroids. Patients were randomised to receive low dose theophylline (400 to 750 mg daily) plus low dose inhaled corticosteroids, or an increased dose of inhaled corticosteroids. Clinical pulmonary function improved to the same or a greater extent in patients who received low dose inhaled corticosteroids plus theophylline than in those treated with high dose inhaled corticosteroids plus placebo. Where reported, the dosages of theophylline used in these studies resulted in serum theophylline concentrations of approximately 9 to 10 mg/L. Approximate monthly costs were provided in one study: these were $60 (year and currency not specified) for theophylline plus budesonide 800 micrograms/day, compared with $100 for budesonide 1600 micrograms/day, and $155 for a regimen of budesonide 800 micrograms/day and salmeterol 100 micrograms/day. CONCLUSIONS: Low dose theophylline has been shown to reduce requirements for inhaled corticosteroid therapy in patients with asthma and may reduce overall treatment costs.

Adrenal Cortex Hormones↗
PubMed1997

Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients.

Lisinopril, the lysine analogue of enalaprilat, is a long-acting angiotensin converting enzyme (ACE) inhibitor which is administered once daily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in elderly patients with hypertension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure < or = 90 mm Hg) to > or = 8 weeks' lisinopril treatment. Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day. Dosages usually need to be lower in patients with significant renal impairment. In congestive heart failure, lisinopril 2.5 to 20 mg/day increases exercise duration, improves left ventricular ejection fraction and has no significant effect on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisinopril reduced mortality and left ventricular dysfunction when given for 42 days starting within 24 hours of the onset of infarction symptoms. Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (-25.5%). Economic studies suggest that lisinopril is cost saving compared with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less expensive of the successful ACE inhibitor regimens for acute myocardial infarction. In other trials, patients with diabetic nephropathy and hypertension improved or did not deteriorate during lisinopril treatment. Blood pressure was controlled and reductions or trends towards reductions in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than those in patients receiving atenolol. Lisinopril appears to reduce mortality in diabetic patients after myocardial infarction and may also improve neuropathy associated with diabetes. Lisinopril is well tolerated and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to the incidence of adverse events in these age groups. Drug interactions occur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, thus, an effective treatment for elderly patients with hypertension, congestive heart failure and acute myocardial infarction and has shown promising benefits in patients with diabetic nephropathy.

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