Biomedical subjects

M I Wilde

Publications and source records attributed to M I Wilde.

30 records · Page 2Linked to original sources

PubMed1996

Ebrotidine.

Ebrotidine is the first of a new generation of H2 receptor antagonists with gastroprotective activity It stimulates epithelial cell proliferative activity and produces beneficial physicochemical changes in the gastric mucus that contribute to its gastro-protective action against ethanol-, aspirin- or stress-induced gastric mucosal damage The antisecretory properties of ebrotidine are similar to those of ranitidine and approximately 10-fold greater than those of cimetidine This drug exhibits anti-Helicobacter pylori activity that is synergistic with a number of antibacterial agents; it inhibits the urease enzyme and the proteolytic and mucolytic activities of H. pylori, and counteracts the inhibitory effects of H. pylori lipo-polysaccharide Ebrotidine is as effective as ranitidine for the treatment of patients with gastric or duodenal ulcers or erosive reflux oesophagitis Ebrotidine therapy results in significantly better ulcer healing rates than ranitidine treatment in patients who smoke.

Animals↗

PubMed1996

Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications.

The use of ondansetron, a selective serotonin 5-HT3 receptor antagonist, is well established in patients with nausea and vomiting associated with cancer chemotherapy, radiotherapy or anaesthesia and surgery. The wide distribution of 5-HT3 receptors in the body and the role of these receptors in disease have provided the rationale for investigation of ondansetron in novel applications. Preliminary data have shown ondansetron to have clinical benefit in patients with nausea and vomiting associated with drug overdosage or poisoning, anti-infective or antidepressant therapies, uraemia or neurological trauma, and in patients with pruritus. Patients with gastrointestinal motility disorders (e.g. carcinoid syndrome, irritable bowel syndrome, diarrhoea associated with cryptosporidiosis or diabetes, and chronic refractory diarrhoea) have also shown some improvement when treated with ondansetron, as have patients with certain pain or CNS-related disorders [e.g. alcohol (ethanol) dependence, opiate withdrawal, vertigo, cerebellar tremor and Parkinson's disease treatment-related psychosis]. In contrast to conventional antiemetics, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions. Furthermore, unlike dopamine receptor-blocking neuroleptics, ondansetron does not appear to worsen the symptoms of Parkinson's disease. Thus, in addition to its established indications, preliminary results suggest that ondansetron may be beneficial in a number of novel applications. This drug may represent a treatment alternative in patients with refractory disease, or an effective treatment of conditions for which current therapies are either poorly tolerated or not available. Further investigation of ondansetron in a range of potential new applications appears to be warranted.

Animals↗

PubMed1996

Tamsulosin. A review of its pharmacological properties and therapeutic potential in the management of symptomatic benign prostatic hyperplasia.

Tamsulosin is the first subtype-selective (alpha IA) alpha 1 adrenoceptor antagonist with specificity for prostatic alpha 1 adrenoceptors (alpha 1A adrenoceptors are thought to be involved in prostatic smooth muscle contraction) to become available for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH). With tamsulosin, the incidence of adverse events commonly associated with alpha 1 adrenoceptor antagonism is similar to that with placebo (except for ejaculation disorders) and alfuzosin. The incidence of other adverse events is similar with tamsulosin and placebo. Furthermore, blood pressure and heart rate are not significantly affected by tamsulosin in patients with symptomatic BPH. In contrast, blood pressure is significantly reduced by alfuzosin compared with tamsulosin. Tamsulosin is available as a controlled release formulation suitable for once daily administration; dose titration is not required. The overall efficacy of this agent administered at a dosage of 0.1 to 0.4 mg/day in Japan, 0.4 mg/day in Europe and 0.4 to 0.8 mg/day in the US to patients with symptomatic BPH is greater than that of placebo was similar to that of alfuzosin or prazosin in the 2 available studies. Efficacy was primarily assessed by changes in maximum and average urinary flow rates, residual urinary volume and total symptom scores. Improvements in these parameters in short term trials (< or = 13 weeks) appear to be maintained in the longer term (< or = 60 weeks). Quality-of-life effects also appear to be similar with tamsulosin and alfuzosin. In conclusion, the pharmacodynamic properties of this agent appear to translate into tolerability and administration advantages over other alpha 1 adrenoceptor antagonists. If future investigations confirm its promising efficacy and tolerability, tamsulosin will be ideally placed as a valuable therapeutic option for patients with symptomatic BPH and in patients awaiting surgery or in those unable to undergo surgery.

Adrenergic alpha-Agonists↗

PubMed1996

Sertraline. A pharmacoeconomic evaluation of its use in depression.

Depression is a common condition that is often unrecognised, misdiagnosed and/or undertreated. It is associated with substantial direct, indirect and intangible costs. The indirect costs of lost earnings/productivity and premature death account for the majority of these costs; drug costs account for only about 1 to 2% of total costs and about 10 to 12% of direct costs. Thus, better recognition and appropriate treatment of depression would increase the direct costs associated with this illness, but would also have the potential to greatly reduce indirect costs and consequently the overall cost of depression. Because of their higher acquisition costs relative to tricyclic antidepressants (TCAs), there has been much debate about whether the use of sertraline or other selective serotonin reuptake inhibitors (SSRIs) for first-line treatment of depression can be justified. While these agents have similar efficacy to TCAs, they are better tolerated and have a lower risk of death on overdosage. Despite the large economic burden of depression on society, pharmacoeconomic data on sertraline and antidepressant drugs in general are scarce. Most of the available studies on sertraline are limited to considerations of direct costs and do not assess costs from a societal perspective. In addition, a number of studies have significant methodological problems which limit determination of meaningful conclusions. Nonetheless, data from 2 more recent studies with fewer methodological problems than earlier studies indicated that sertraline was more cost-effective than TCAs because of fewer psychiatrist consultations, and less costly than fluoxetine because of fewer absences from work and fewer medical consultations. The cost-utility ratio of maintenance therapy of depression with sertraline appears to fall within the range of accepted cost-utility ratios of common healthcare interventions. Thus, studies to date have generally shown that overall treatment costs with sertraline and other SSRIs are no greater than those for TCAs; this is despite the lower acquisition costs of the latter agents. Therefore, it is clear from these data that it is misleading to classify antidepressant agents as expensive or inexpensive based solely on their acquisition costs. Sertraline, therefore, can be considered as a first-line alternative to TCAs and other SSRIs for the treatment of depression on both clinical and pharmacoeconomic grounds.

1-Naphthylamine↗

PubMed1995

Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression.

Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology. The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence of dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1995

Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations.

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1995

Paroxetine. A pharmacoeconomic evaluation of its use in depression.

There has been intense debate about whether the use of paroxetine or other selective serotonin reuptake inhibitors (SSRIs) as alternatives to tricyclic antidepressants for first-line treatment of depression can be justified, considering their higher acquisition costs. The rationale for using paroxetine in the treatment of depression lies in its more favourable tolerability profile than tricyclic antidepressants and its lower risk of death on overdosage. Depression is one of the most common psychiatric disorders and is associated with substantial direct, indirect and intangible costs. Indirect costs account for the majority of costs associated with depression, while drug costs account for only 9 to 25% of direct costs. Therefore, increased recognition and treatment of depression has the potential to greatly reduce the overall cost of this disease. Pharmacoeconomic data on paroxetine and other SSRIs in the treatment of depression are scarce. Available studies are limited to considerations of direct costs alone and are primarily based on retrospective data from clinical trials. Nevertheless, in terms of costs per successfully-treated patient, available data suggest that the treatment costs associated with paroxetine are similar to those of amitriptyline and possibly less than those of imipramine. Paroxetine treatment costs also appear to be similar to those of amitriptyline and imipramine in terms of expected costs per patient. While one group of investigators suggested that the overall cost of administering paroxetine may also be less than that for fluoxetine and sertraline when drug costs and labour costs associated with dosage adjustment are taken into account, more data are required before conclusions on the relative pharmacoeconomic merits of SSRIs can be made. Despite the lower risk of death from overdosage with SSRIs, switching from an established tricyclic antidepressant to a newer tricyclic or related antidepressant in an attempt to avoid suicide appears to be more cost effective than switching to an SSRI. Thus, evidence available to date indicate that despite higher acquisition costs paroxetine and other SSRIs are no more costly than tricyclic antidepressants when total costs per successfully treated patient or expected costs per patient are considered. With its favourable tolerability profile and low risk of death on overdosage, paroxetine should therefore be considered as an effective alternative to tricyclic antidepressant agents as a first-line treatment of depression.(ABSTRACT TRUNCATED AT 400 WORDS)

Antidepressive Agents, Second-Generation↗

PubMed1994

Omeprazole. An update of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole, a gastric acid pump inhibitor, dose-dependently controls gastric acid secretion: the drug has greater antisecretory activity than histamine H2-receptor antagonists. Omeprazole 20 to 40 mg/day is more effective than histamine H2-receptor antagonists in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. Available data suggest that omeprazole 10 to 40 mg/day is also more effective than ranitidine in the maintenance therapy of duodenal ulcer and reflux oesophagitis. The drug is also effective in patients with duodenal ulcer, gastric ulcer or reflux oesophagitis poorly responsive to histamine H2-receptor antagonists. The efficacy of omeprazole 20 mg/day appears to be similar to that of lansoprazole 30 mg/day in the short term treatment of duodenal ulcer, gastric ulcer and reflux oesophagitis. However, most available studies have been reported in abstract form only, and 2 of 3 studies in patients with duodenal ulcer have shown greater healing rates at 2 (but not 4) weeks with lansoprazole. Helicobacter pylori eradication decreases duodenal ulcer relapse rates and appears to be associated with improved duodenal ulcer healing rates. Evidence also suggests that H. pylori eradication is associated with reduced gastric ulcer relapse rates. Omeprazole monotherapy may suppress but does not eradicate H. pylori infection. Eradication rates with omeprazole 20 or 40 mg twice daily plus amoxicillin usually up to 2 g/day (3 g/day in a few studies) for 2 weeks appear to be similar to those of standard triple therapy (bismuth salt plus metronidazole, plus tetracycline or amoxicillin) or omeprazole plus clarithromycin, although eradication rates vary widely. Omeprazole plus amoxicillin appears to be better tolerated than triple therapy and represents a first-line treatment alternative in patients with H. pylori-associated peptic ulcer disease. Omeprazole plus amoxicillin plus metronidazole appears to be more effective than omeprazole plus amoxicillin in patients with metronidazole-sensitive H. pylori infection. Omeprazole remains a treatment of choice in patients with Zollinger-Ellison syndrome. The dosages should be adjusted according to individual response. However, relatively low dosages of 10 to 40 mg/day may be sufficient in some patients. The drug has also shown promise in the treatment of children with severe reflux oesophagitis, in patients with reflux oesophagitis and coexisting systemic sclerosis, and in the prevention of aspiration pneumonia. Evidence suggests that omeprazole is more effective than ranitidine in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage who continue to take NSAIDs, especially in patients with large gastric ulcers; however, completion of ongoing studies is required to verify this.(ABSTRACT TRUNCATED AT 400 WORDS)

Gastric Acid↗

PubMed1994

Enalapril: a review of quality-of-life and pharmacoeconomic aspects of its use in heart failure and mild to moderate hypertension.

Enalapril is an angiotensin converting enzyme (ACE) inhibitor with an established clinical profile. In patients with symptomatic heart failure, enalapril reduces overall mortality, death from progressive heart failure and hospitalisation rates. In those with asymptomatic left ventricular dysfunction, enalapril decreases the combined risk of death and development of heart failure, and the risk of death and hospitalisation. The effects of enalapril in reducing hospitalisation rates in symptomatic patients translate into net savings in healthcare costs in heart failure. Enalapril also produces modest benefits in quality-of-life (QOL) parameters in patients with symptomatic heart failure as shown in well controlled studies. Its effects appear similar to those of hydralazine plus isosorbide dinitrate. The influence of enalapril on quality of life in patients with asymptomatic disease is minimal but not deleterious. Enalapril generally either maintains or slightly improves quality of life from baseline in patients with mild to moderate hypertension. The drug appears to have a QOL profile that is more favourable than that of propranolol and similar to those of most other comparator drugs, as assessed by subjective measures of quality of life. Clarification is required of its QOL profile relative to that of captopril, in view of conflicting results in the literature. The effects of enalapril on cognitive and psychomotor function appear to resemble those of comparator agents. Thus, enalapril has modest beneficial effects on the quality of life of patients with symptomatic heart failure, while generally maintaining quality of life in patients with asymptomatic left ventricular dysfunction or mild to moderate hypertension. Enalapril is a cost-effective treatment in heart failure that would be expected to yield considerable cost savings in this therapeutic area.

Cost-Benefit Analysis↗

PubMed1993

Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia.

Alfuzosin, a new quinazoline derivative, acts as a selective and competitive antagonist of alpha 1-adrenoceptor-mediated contraction of prostatic, prostatic capsule, bladder base and proximal urethral smooth muscle, thereby reducing the tone of these structures. Consequently, urethral pressure and resistance, bladder outlet resistance, bladder instability and symptoms associated with benign prostatic hyperplasia are reduced. A limited range of clinical studies have shown oral alfuzosin to be more effective than placebo (in studies of < or = 6 months duration), to have sustained effects on long term administration (< or = 30 months), and to be comparable with the alpha 1-adrenoceptor antagonist prazosin, in the symptomatic treatment of benign prostatic hyperplasia. This is reflected in increases in urinary flow rate and decreases in symptom score and residual urinary volume. The most marked improvements occur in patients with severe pretreatment urinary flow abnormalities. Furthermore, preliminary results suggest a beneficial effect of alfuzosin on quality of life in patients with benign prostatic hyperplasia. The overall incidence of adverse effects appears similar to that with placebo, and the incidence of vasodilatory-related adverse effects appears lower than that with prazosin. The relative selectivity of alfuzosin for alpha 1-adrenoceptors in the genitourinary tract compared with receptors in the vasculature is a potential advantage over other alpha-adrenoceptor antagonists, including prazosin, as the symptoms of benign prostatic hyperplasia may be reduced by alfuzosin at doses that have minimal vasodilatory effects, thereby minimising postural hypotension and syncope. However, vasodilatory-related adverse effects are the most common adverse effects that occur with alfuzosin, and dose and first-dose hypotensive relationships, especially in the elderly, cannot be excluded at this stage in the clinical use of alfuzosin. The full potential of alfuzosin in the symptomatic treatment of benign prostatic hyperplasia will be clarified by further long term comparative studies (with large patient numbers) against placebo and other alpha 1-adrenoceptor antagonists. Nevertheless, oral alfuzosin 7.5 to 10 mg/day in divided doses appears to be a promising first-line agent for symptomatic treatment of noncomplicated mild to moderate benign prostatic hyperplasia in patients with a high dynamic component to their obstruction. In addition, alfuzosin offers an alternative to prostatectomy (the current 'gold standard') in patients who require surgery but are unfit for this treatment, and in patients requiring symptomatic relief while awaiting surgery.

Adrenergic alpha-Antagonists↗

PubMed1993

Fluvoxamine. An updated review of its pharmacology, and therapeutic use in depressive illness.

Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake into presynaptic neurones. The overall antidepressant efficacy of fluvoxamine 100 to 300 mg/day for 4 to 6 weeks in once daily or divided dosage regimens appears to be at least comparable to that of imipramine and similar to that of clomipramine, dothiepin, desipramine, amitriptyline, lofepramine, maprotiline, mianserin and moclobemide. The efficacy of fluvoxamine has been maintained for up to 1 year, but long term data are limited, and there are no comparative studies of fluvoxamine with other selective serotonin reuptake inhibitors. In some studies, fluvoxamine appeared to have an earlier beneficial effect on suicidal ideation and/or anxiety or somatic complaints compared with imipramine, dothiepin and maprotiline. Gastrointestinal adverse effects, especially nausea, are commonly reported with fluvoxamine but are generally mild to moderate in severity. The tolerability profile of fluvoxamine appears to be more favourable than that of tricyclic antidepressants in terms of cardiotoxic and anticholinergic adverse effects, sedation, weight gain and death from overdosage. Thus, fluvoxamine is an effective and well tolerated antidepressant agent that is becoming established as an alternative to older agents in patients with mild, moderate or severe depression. Fluvoxamine may be particularly beneficial in potentially suicidal patients with severe depression, in those with an underlying compulsive personality or cardiovascular disorder, in patients with coexistent anxiety or agitation, and in the elderly.

Animals↗

PubMedDate not supplied

Terazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia.

Terazosin selectively antagonises alpha 1-adrenoceptor-mediated contraction of the prostate, prostatic capsule, proximal urethra and bladder base, and consequently reduces urethral pressure, bladder outlet resistance and urinary symptoms associated with symptomatic benign prostatic hyperplasia. The efficacy of terazosin is reflected in increases in peak urinary flow rate, and reductions in obstructive and irritative symptom scores compared with placebo, and reductions in residual urinary volume from baseline. Clinical improvements begin to occur within 2 weeks and have been sustained for up to 2 years. The most marked treatment effects tend to occur in patients with more severe pretreatment urinary flow abnormalities. The relatively long duration of action of terazosin, allowing once-daily administration, offers a potential clinical advantage over other alpha 1-adrenoceptor antagonists although formal compliance studies have not been reported. Terazosin is generally well tolerated, but caution is recommended at treatment initiation and when dosage adjustments are made due to an increased risk of postural hypotension and related adverse effects at these times; such a risk has also been observed with several other alpha 1-adrenoceptor antagonists. Although publication of clinical trial results with terazosin is still evolving, this drug shows promise in the treatment of patients with mild to moderate symptomatic benign prostatic hyperplasia for whom surgery is not absolutely indicated. Terazosin also shows promise as a nonsurgical treatment alternative in patients with severe symptoms who are unfit for surgery and also in those who are on long waiting lists for surgery.

Adrenergic alpha-Antagonists↗