Biomedical subjects

P Benfield

Publications and source records attributed to P Benfield.

65 records · Page 4Linked to original sources

PubMed1989

Flunarizine. A reappraisal of its pharmacological properties and therapeutic use in neurological disorders.

Flunarizine is a class IV calcium antagonist with a pharmacological profile which suggests its therapeutic potential in a number of neurological and cerebrovascular disorders. It is an effective prophylactic treatment for common or classic migraine in children and adults, and it appears at least as effective as a number of other agents which act by different pharmacological mechanisms, including pizotifen (pizotyline), cinnarizine, methysergide, nimodipine, metoprolol, propranolol, aspirin and cyclandelate. Flunarizine is also effective in reducing the frequency of seizures, when used as an 'add-on' treatment, in some patients with partial or generalised epilepsy resistant to maximal therapy with a combination of several conventional antiepileptic drugs. Placebo-controlled studies show that flunarizine is effective in the treatment of vertigo and associated symptoms of either peripheral or central origin, and in the treatment of cerebrovascular insufficiency where psychological symptoms, rather than vertigo, are the primary symptoms. In the treatment of vertigo, flunarizine appears at least as effective as cinnarizine and more effective than nicergoline, betahistine dichlorhydrate, pentoxifylline (oxpentifylline) and vincamine. Flunarizine therefore is useful in the prophylaxis of migraine, an effective treatment for vertigo and a worthwhile alternative as 'add-on' therapy in patients with epilepsy resistant to conventional drugs.

Animals↗

PubMed1988

Bevantolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris.

Bevantolol is a new beta-adrenoceptor antagonist which possesses a relatively high degree of selectivity for beta 1-adrenoceptors. It is devoid of intrinsic sympathomimetic activity and possesses only weak local anaesthetic properties. Interestingly, bevantolol has been shown to cause a lowering effect on peripheral vascular resistance. Available clinical data indicate that bevantolol, given once or twice daily, is an effective agent in the management of mild to moderate hypertension and stable angina pectoris. In hypertension bevantolol has been shown to be of comparable therapeutic efficacy to both atenolol and propranolol, while in patients with angina pectoris the drug compared favourably with atenolol. During short and long term administration bevantolol has been well tolerated and few patients have withdrawn from treatment because of adverse effects. However, although the properties of bevantolol may offer theoretical advantages in some patients, only a few comparative studies have been reported, and thus it is presently unclear what advantages bevantolol may offer over existing treatments for hypertension or angina pectoris.

Adrenergic beta-Antagonists↗

PubMed1988

Sulconazole. A review of its antimicrobial activity and therapeutic use in superficial dermatomycoses.

Sulconazole is a substituted imidazole antimicrobial agent structurally related to other drugs in this group. It possesses a broad spectrum of activity in vitro against dermatophytes, yeasts and some Gram-positive bacteria. The efficacy and safety of sulconazole 1% cream has been demonstrated in controlled clinical studies in patients with superficial dermatophyte or yeast infections. In these trials, sulconazole generally displayed similar efficacy to clotrimazole, econazole and miconazole, although in a few studies sulconazole produced better and/or quicker improvement than clotrimazole or miconazole in small numbers of patients with tinea pedis. Further studies in larger groups of patients are needed to confirm these encouraging preliminary findings. Thus, sulconazole is an effective and well tolerated alternative to other topical imidazole drugs in the treatment of superficial fungal infections of the skin.

Animals↗

PubMed1988

Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Ciprofloxacin is one of a new generation of fluorinated quinolones structurally related to nalidixic acid. The primary mechanism of action of ciprofloxacin is inhibition of bacterial DNA gyrase. It is a broad spectrum antibacterial drug to which most Gram-negative bacteria are highly susceptible in vitro and many Gram-positive bacteria are susceptible or moderately susceptible. Unlike most broad spectrum antibacterial drugs, ciprofloxacin is effective after oral or intravenous administration. Ciprofloxacin has been most extensively studied following oral administration. It attains concentrations in most tissues and body fluids which are at least equivalent to the minimum inhibitory concentration designated as the breakpoint for bacterial susceptibility in vitro. The results of clinical trials with orally and intravenously administered ciprofloxacin have confirmed the potential for its use in a wide range of infections, which was suggested by its in vitro antibacterial and pharmacokinetic profiles. It has proven an effective treatment for many types of systemic infections as well as for both acute and chronic infections of the urinary tract. Ciprofloxacin generally appeared to be at least as effective as alternative orally administered antibacterial drugs in the indications in which they were compared, and in some indications, to parenterally administered antibacterial therapy. However, further studies are needed to fully clarify the comparative efficacy of ciprofloxacin and standard antibacterial therapies. Bacterial resistance to ciprofloxacin develops infrequently, both in vitro and clinically, except in the setting of pseudomonal respiratory tract infections in cystic fibrosis patients. The drug is also well tolerated. Thus, as an orally active, broad spectrum and potent antibacterial drug, ciprofloxacin offers a valuable alternative to broad spectrum parenterally administered antibacterial drugs for use in a wide range of clinical infections, including difficult infections due to multiresistant pathogens.

Animals↗

PubMed1988

Bromperidol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in psychoses.

Bromperidol is a close structural analogue of haloperidol. Both agents possess similar pharmacodynamic properties which are consistent with central antidopaminergic activity. The available clinical data from non-comparative and comparative trials have shown that bromperidol possesses antipsychotic activity. Its overall efficacy was slightly greater than chlorpromazine and perphenazine, and similar to or slightly better than haloperidol in a small number of comparative studies. Bromperidol frequently displayed a faster onset of action than these comparative agents and there have been reports of bromperidol causing an activating effect. However, extrapyramidal side effects occurred with similar frequency and severity after bromperidol compared with the 3 reference drugs. Data from additional controlled clinical trials are required to confirm the comparative antipsychotic efficacy of bromperidol and to assess whether it possesses any advantages in certain sub-types of schizophrenia.

Clinical Trials as Topic↗

PubMed1988

Colloidal bismuth subcitrate. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease.

Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. However, CBS has the advantage of slower ulcer relapse rates than those seen after initial healing with the H2-antagonists. It has been postulated that this effect may be partly due to the antibacterial properties of CBS against Campylobacter pylori, a bacterium found in the gastric mucosa and gastric metaplasia within the duodenum of most patients with peptic ulcer and closely associated with gastritis. However, the role of C. pylori in the aetiology of peptic disease is far from clear. The mechanism by which CBS heals ulcers has not been fully elucidated, but several actions may be involved. CBS and mucus form a glycoprotein-bismuth complex in vitro. This provides a diffusion barrier to HCl and may, therefore, provide a protective coating in the ulcer crater which allows healing of the lesion to occur. Prostaglandin E2 production is also stimulated by CBS with subsequent secretion of alkali into the mucus layer. In addition, CBS has a direct inhibitory effect on C. pylori. Administration of CBS results in low levels of bismuth absorption. Most of the ingested bismuth is excreted as bismuth sulphide, causing blackening of the faeces, and the small amount absorbed is excreted in the urine. Bismuth intoxication (encephalopathy) has been reported with prolonged administration of bismuth salts, and there has been 1 report of similar intoxication in a patient receiving unusually high doses of CBS for a prolonged period. However, no such intoxication has been reported with CBS used at its recommended dosage in the acute treatment of peptic ulcer disease, and no other serious adverse effects have been associated with CBS. Tissue accumulation during prolonged therapy seems likely, and the safety of CBS during long term maintenance therapy has not been established. The lack of effect on gastric acid secretion is seen as an added advantage for CBS, since prolonged drug-induced hypochlorhydria has been postulated to have potentially detrimental effects. Thus, while the role of C. pylori in peptic ulceration requires further clarification, CBS would appear to have an important place in the treatment of peptic ulcer disease with the advantage of relatively slow relapse rates after initial healing and treatment discontinuation.

Anti-Ulcer Agents↗

PubMed1987

Esmolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Esmolol is a relatively cardioselective beta-adrenoceptor antagonist. Since esmolol is rapidly metabolised by blood-borne esterases, it has a very short half-life (about 9 mins) and a short duration of action. In this respect esmolol is unique amongst currently available beta-adrenoceptor antagonists, and it is anticipated that it will be particularly useful in critical care situations where administration by continuous intravenous infusion should permit a level of control over beta-adrenoceptor antagonism that has previously been unattainable. In perioperative settings, esmolol attenuates tachycardia induced by a variety of surgical stimuli such as endotracheal intubation, sternotomy and aortic dissection, suggesting a clinical use of the drug to prevent potentially serious complications in surgical patients with cardiovascular disease. Additionally, clinical studies have shown that titrated dosages of esmolol achieved therapeutic response rates of 66 to 79% in patients with supraventricular tachyarrhythmias, which favourably compared with response rates achieved with propranolol. In most of these patients esmolol produced a reduction in ventricular rate which was well maintained during infusion but disappeared within 30 minutes following esmolol withdrawal. Preliminary studies involving small numbers of patients have reported that esmolol exerts significant antihypertensive effects in patients with postoperative hypertension, and beneficial effects in patients with myocardial ischaemia and infarction, but support for these results is required from additional large, well-controlled studies. Esmolol has been generally well tolerated, and although hypotension has occurred in up to 44% of patients it resolved during or soon after the infusion of esmolol. Thus, esmolol is the first titratable beta-adrenoceptor antagonist able to be rapidly 'switched on' and 'off', a property that is expected to offer a major contribution to safety in critical care patients requiring beta-adrenoceptor antagonism for short durations.

Adrenergic alpha-Antagonists↗

PubMed1986

Aldose reductase inhibitors and late complications of diabetes.

Neuropathy and retinopathy are two potentially serious late complications of diabetes. There is accumulating evidence that the development of these conditions is closely related to increased activity of the polyol pathway, which occurs in certain tissues as a consequence of long term hyperglycaemia. Symptomatic diabetic neuropathy may appear as one of many forms and is frequently accompanied by pain. Diabetic retinopathy is a progressive degeneration of the retina that represents one of the major causes of blindness in the developed world. A good prognosis for either of these conditions is believed to rely on early diagnosis and optimisation of glycaemic control as they become less reversible with progression of cellular damage. A new approach to the treatment of these and other late complications of diabetes may be offered by recently developed drugs, such as sorbinil, that inhibit the enzyme aldose reductase. In various animal models of late complications of diabetes sorbinil and other aldose reductase inhibitors have been shown to reverse some of the biochemical and physiological changes believed to underlie these complications. These include prevention or reversal of the accumulation of sorbitol and depletion of myo-inositol in nerve, lens and renal glomeruli. Sorbinil also counteracts the slowing of nerve conduction velocities, reverses the structural changes of Sipple stages I and II cataracts and prevents proteinuria in diabetic rats. Orally administered sorbinil is absorbed rapidly and reaches steady state plasma concentrations after 6 to 10 days' administration. Its elimination half-life is long (38-52 hours) and much greater than that of another aldose reductase inhibitor, tolrestat (10-12 hours). Within the dose range 50-250 mg about one-third of administered sorbinil appears in the urine as unchanged drug. In the small number of clinical studies of diabetic patients with neuropathies sorbinil has demonstrated limited therapeutic effects. There is now a requirement for studies of its prophylactic use and its therapeutic use in patients with diabetic neuropathy in the early stages of development.

Aldehyde Reductase↗

PubMed1986

Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders.

During the intervening years since metoprolol was first reviewed in the Journal (1977), it has become widely used in the treatment of mild to moderate hypertension and angina pectoris. Although much data have accumulated, its precise mechanisms of action in these diseases remain largely uncertain. Optimum treatment of hypertension and angina pectoris with metoprolol is achieved through dose titration within the therapeutic range. It has been clearly demonstrated that metoprolol is at least as effective as other beta-blockers, diuretics and certain calcium antagonists in the majority of patients. Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations. Addition of a diuretic may improve the overall response rate in hypertension. Several controlled trials have studied the effects of metoprolol administered during the acute phase and after myocardial infarction. In early intervention trials a reduction in total mortality was achieved in one moderately large trial of prolonged treatment, but in another, which excluded patients already being treated with beta-blockers or certain calcium antagonists and where treatment was only short term, mortality was significantly reduced only in 'high risk' patients. Overall results with metoprolol have not demonstrated that early intervention treatment in all patients produces clinically important improvement in short term mortality. Thus, the use of metoprolol during the early stages of myocardial infarction is controversial, largely because of the requirement to treat all patients to save a small number at 'high risk'. This blanket coverage approach to treatment may be more justified during the post-infarction follow-up phase since it has been shown that metoprolol slightly, but significantly, reduces the mortality rate for periods of up to 3 years. Metoprolol is generally well tolerated and its beta 1-selectivity may facilitate its administration to certain patients (e.g. asthmatics and diabetics) in whom non-selective beta-blockers are contraindicated. Temporary fatigue, dizziness and headache are among the most frequently reported side effects. After a decade of use, metoprolol is well established as a first choice drug in mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients. Further study is needed in less well established areas of treatment such as cardiac arrhythmias, idiopathic dilated cardiomyopathy and hypertensive cardiomegaly.

Adult↗

PubMed1986

Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

Fluvoxamine is a new antidepressant which potently and specifically inhibits neuronal reuptake of serotonin. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from facilitation of serotoninergic neurotransmission as a result of reuptake inhibition. Studies suggest that fluvoxamine has overall therapeutic efficacy comparable with that of imipramine and clomipramine in depressive illness. It causes fewer anticholinergic-type and cardiovascular side effects than the tricyclic antidepressants but it is associated with a higher incidence of nausea and vomiting. Elderly patients also respond well to fluvoxamine. Studies are now required to compare fluvoxamine with other second generation antidepressants and to establish whether some types of depressive illness respond more readily to fluvoxamine than other agents. Thus, in patients with depressive illness, fluvoxamine offers a suitable alternative to tricyclic antidepressants and may be especially valuable in patients with concomitant cardiovascular disease, and those unresponsive to or unable to tolerate tricyclic antidepressants.

Animals↗

PubMed1986

Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.

Fluoxetine is a new antidepressant which enhances serotoninergic neurotransmission through potent and selective inhibition of neuronal reuptake of serotonin. Metabolism by N-desmethylation occurs in man yielding desmethylfluoxetine, which also inhibits serotonin reuptake. Both the parent compound and metabolite possess elimination half-lives of several days facilitating the maintenance of steady-state plasma concentrations during long term treatment. Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients. Geriatric patients also responded as well to fluoxetine as to doxepin. The symptomatic improvement in patients with unipolar depression during short term fluoxetine treatment has been satisfactorily maintained when therapy was extended for at least 6 months: the relapse rate was low and similar to that of imipramine. Preliminary data have shown that patients with bipolar depression gained similar therapeutic benefit from fluoxetine or imipramine. Other preliminary trials have indicated that fluoxetine may be useful in obsessive-compulsive disorders. Usual doses of fluoxetine cause significantly fewer anticholinergic-type side effects than tricyclic antidepressants. Nausea, nervousness and insomnia are the most frequently reported fluoxetine-related adverse effects, but these have usually not been severe. Therapeutic doses of fluoxetine do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease and fluoxetine has been relatively safe in the small number of patients who have taken overdoses. It has not been clearly established whether some types of depression may respond more readily to fluoxetine than other antidepressants, and its overall therapeutic efficacy has not been compared with other second generation antidepressants. Thus, with its different and perhaps improved side effect profile compared with older tricyclic antidepressants, fluoxetine offers properties that could be used to advantage in many patients with depression.

Animals↗