Biomedical subjects

R N Brogden

Publications and source records attributed to R N Brogden.

At least 163 records · Page 9Linked to original sources

PubMed1982

Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections.

Trimethoprim, which has been widely available for several years in combination with sulphamethoxazole as co-trimoxazole, is now available for use alone in the treatment of acute uncomplicated urinary tract infections. Trimethoprim, which is active against a wide range of Gram-positive and Gram-negative aerobic bacteria, is readily absorbed by the oral route and is widely distributed in body fluids and tissues. In therapeutic trials, trimethoprim 200 to 400mg daily has been shown to be comparable in efficacy with co-trimoxazole, ampicillin 2g, cephalexin 2g, oxolinic acid 1.5g and nitrofurantoin 200mg daily in the treatment of acute urinary tract infection. Similarly, in long term prophylaxis of recurrent urinary tract infection, trimethoprim 100mg daily given as a single dose at night was comparable with nitrofurantoin 50 to 100mg, methenamine 1g, oxolinic acid 375mg or co-trimoxazole (80mg trimethoprim/400mg sulphamethoxazole) each given as a single daily dose. Emergence of acquired resistance has been infrequent during years of therapeutic use of co-trimoxazole. Nevertheless, results of serial laboratory surveys suggest that resistance to trimethoprim among enterobacteria is increasing. However, at present, there is no conclusive evidence that there will be a more rapid increase following the introduction of trimethoprim for use alone in the treatment of urinary tract infections. At the dosages used, trimethoprim has generally been well tolerated and in studies comparing it with co-trimoxazole overall, skin rashes and gastrointestinal upset have occurred less frequently with trimethoprim than with co-trimoxazole.

Bacteria↗

PubMed1982

Amoxapine: a review of its pharmacology and efficacy in depressed states.

Amoxapine is an N-demethylated dibenzoxazepine closely related in the neuroleptic loxapine. Its tricyclic structure appears to give it antidepressant properties resembling imipramine and amitriptyline. In uncontrolled trials it was shown to have antidepressant activity in usual doses up to 200 to 400mg daily. In placebo and double-blind controlled studies comparing amoxapine with the standard tricyclic antidepressants imipramine and amitriptyline, it was shown to be comparable in efficacy with a possibly somewhat faster onset of improvement of selected symptoms of depression in some studies. Because of the small study groups and lack of placebo control, many reports do not show statistically significant differences of treatment over standard drugs. To date there have been no studies comparing amoxapine with electroconvulsive therapy. Side effects were qualitatively similar to standard drugs with a suggestion that in standard doses or overdose myocardial effects are mild. However, the final place of amoxapine in the therapy of depressed states is still to be decided.

Amoxapine↗

PubMed1982

Tinidazole in anaerobic infections: a review of its antibacterial activity, pharmacological properties and therapeutic efficacy.

Tinidazole, like the structurally-related drug metronidazole, was initially introduced for treating protozoal infections. However, both these nitroimidazole compounds are also active in vitro against most clinically important obligate anaerobes. Most of the clinical experience with tinidazole to date has involved prophylactic use to prevent postoperative anaerobic infection. Prospective placebo-controlled studies demonstrated that a single dose of tinidazole administered orally prior to elective colorectal surgery significantly reduced postoperative infection. Similarly, when given intravenously prior to appendectomy, tinidazole reduced the incidence of postoperative infection in some subgroups of patients. Although results of non-blinded studies with prophylactic tinidazole were encouraging when used in women undergoing gynaecological surgery (mainly hysterectomy), results from double-blind placebo-controlled studies in this situation have been somewhat equivocal. Thus, although the overall weight of evidence suggests that the drug is effective in this area of use, further study is needed to clarify its role in preventing anaerobic infection following gynaecological surgery compared with other antibiotics which can also be used for this purpose. Relatively few studies have been conducted with tinidazole in the treatment of established anaerobic infections, and this is an area needing further investigation. The drug is well tolerated when administered orally or intravenously.

Anaerobiosis↗

PubMed1982

Zimelidine: a review of its pharmacological properties and therapeutic efficacy in depressive illness.

Zimelidine is a new antidepressant, which is structurally unrelated to the tricyclic and tetracyclic antidepressants. The pharmacological profile of zimelidine is different to that of other antidepressants in that it appears to owe the major part of its activity to the inhibition of serotonin uptake within the central nervous system. It appears that the demethylated metabolite, norzimelidine, may be responsible for most of the pharmacological activity. Studies to date suggest that zimelidine has overall efficacy comparable with that of amitriptyline, desipramine, maprotiline and doxepin in depressive illness, but at dosages which have achieved a similar overall clinical improvement zimelidine does not cause sedation, and anticholinergic side effects are mild and occur infrequently. Preliminary evidence suggests that zimelidine is effective against concomitant anxiety in depressed patients, and that it may also be useful in treating phobic anxiety. Zimelidine appears less likely to cause serious cardiotoxicity, in therapeutic dosages or an overdosage, than the tricyclic antidepressants, but it has not been studied in patients with cardiovascular disease. Sleep disturbance has occurred significantly more frequently during zimelidine therapy than during therapy with other sedative antidepressants, but whether this simply reflects the absence of sedation with zimelidine, or an effect on sleep as such, is presently unclear. Zimelidine appears to be effective and well tolerated in elderly patients. Thus, some aspects of the drug's profile (e.g. apparent low incidence of anticholinergic effects or drowsiness) may offer potential advantages in some patients; however, clinical experience with zimelidine to date has been limited, and further well designed studies are required to define the role of the drug more clearly in treating depressive illness compared with other antidepressants, and particularly to define whether some types of depression may respond more readily to zimelidine than to other antidepressants.

Antidepressive Agents↗

PubMed1982

Ranitidine: a review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases.

Ranitidine is a new histamine H2-receptor antagonist which, unlike cimetidine, does not contain an imidazole group. On a weight basis, ranitidine is 4 to 10 times more potent than cimetidine in inhibiting stimulated gastric acid secretion in humans. Therapeutic trials comparing ranitidine and cimetidine have demonstrated that ranitidine 150 mg twice daily is an effective alternative to cimetidine 1000 mg daily in 4 divided doses in increasing the rate of healing of duodenal and gastric ulcers over a period of 4 to 6 weeks. Ranitidine, given as a single 150 mg dose at night, decreases the incidence of ulcer recurrence. Preliminary studies in the Zollinger-Ellison syndrome and in patients intolerant of, or unresponsive to cimetidine, indicate that ranitidine controls the gastric hyperacidity and heals most ulcers, including those which failed to respond to months of treatment with cimetidine 1 to 1.6 g daily. Ranitidine, unlike cimetidine, has no antiandrogenic effects and does not alter hepatic metabolism of drugs. Ranitidine is well tolerated. Preliminary reports of the resolution of cimetidine-induced adverse effects following substitution of ranitidine, suggest that ranitidine may be of value in patients intolerant of cimetidine. However, wider clinical experience with ranitidine is needed to determine the clinical relevance of these reports.

Animals↗

PubMed1982

Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic.

Domperidone is a dopamine antagonist that does not readily enter the central nervous system. Given parenterally or orally it increases gastric emptying of liquids and increases lower oesophageal sphincter pressure in healthy subjects. The antiemetic and pharmacodynamic profile of domperidone is similar to that of metoclopramide, although domperidone has a lower propensity to cause extrapyramidal side effects. Domperidone effectively alleviates symptoms of chronic postprandial dyspepsia and nausea and vomiting due to a wide variety of underlying causes and in some studies has been superior to metoclopramide. Vomiting associated with the administration of moderately emetic cytotoxic drugs is controlled in the majority of patients. Alleviation of the dose-limiting peripheral side effects (nausea and vomiting) of the anti-Parkinsonian drugs bromocriptine and levodopa, enables a higher optimum dose, with consequent improvement in Parkinsonian symptoms. Domperidone does not aggravate the extrapyramidal side effects of neuroleptic drugs. Control of cytotoxic-induced, and postprandial nausea and vomiting in children has been achieved with domperidone without evidence of extrapyramidal side effects. Indeed, side effects have seldom occurred with therapeutic doses of domperidone.

Antiemetics↗

PubMed1981

Fenbufen: a review of its pharmacological properties and therapeutic use in rheumatic diseases and acute pain.

Fenbufen is a phenylalkanoic acid derivative with analgesic and anti-inflammatory activity. The anti-inflammatory activity appears to reside in the metabolites. Published data indicate that fenbufen 600 to 1000mg daily is comparable in effectiveness to therapeutic doses (3 to 4g) of aspirin, indomethacin (75 to 100mg) or phenylbutazone (300 to 400mg) in rheumatoid arthritis, but generally causes fewer side effects. At a daily dosage of 600mg, fenbufen is comparable with aspirin 3.6g or indomethacin 75mg in osteoarthritis. Initial studies suggest that fenbufen 600 to 900mg daily is at least as effective as ibuprofen 1200 to 1800mg of fenoprofen 1800 to 2400mg daily. It has not been compared with naproxen or sulindac in adequate numbers of patients. Fenbufen is effective when given twice daily and there is some evidence that once daily dosage is adequate in known responders to the drug. As with other non-steroidal alkanoic acid drugs, gastrointestinal complaints are the most frequently reported side effects, but there have been no reports of peptic ulcer to date.

Animals↗

PubMed1981

alpha-Methyl-p-tyrosine: a review of its pharmacology and clinical use.

alpha-Methyl-p-tyrosine is an orally active inhibitor of catecholamine synthesis which inhibits the hydroxylation of tyrosine to dopa. At dosages of 600 to 3500 mg daily it is effective in controlling the hypertensive episodes and symptoms of catecholamine excess in phaeochromocytoma during preparation for surgery. Limited published experience suggests that it is effective in controlling hypertension and symptoms in malignant phaeochromocytoma, but further long term experience is needed. Concomitant administration of phenoxybenzamine and propranolol may be desirable in some patients and treatment with phentolamine is usually necessary to control hypertension during manipulation of the tumour.

Adrenal Gland Neoplasms↗

PubMed1981

Temazepam: a review of its pharmacological properties and therapeutic efficacy as an hypnotic.

Temazepam is a benzodiazepine drug which is a minor metabolite of diazepam. In clinical studies using subjective evaluation methods it was effective for maintaining sleep and increasing total sleep time. However, sleep laboratory studies did not show a significant effect on some sleep parameters, especially sleep induction. Temazepam has a relatively short half-life (about 5 to 11 hours, longer in some subjects and in the elderly), and no active metabolites of clinical importance, and thus may be considered more suitable for use as an hypnotic than longer acting drugs such as diazepam, nitrazepam or flurazepam when residual sedative effects the next day are not desirable. Indeed, few residual effects on morning performance appear to occur with usual single doses of temazepam, although at the upper end of the recommended dosage range (30 mg or more) some evidence of impaired psychomoter and cognitive function in the morning has been reported. Whether or not temazepam is likely to produce "hangover" with repeated night-time administration needs further clarification. While a call for a large number of controlled trials may not be justifiable in evaluating a new hypnotic, a few well designed additional comparative studies in insomniac subjects are needed to assess adequately the relative merits of temazepam (particularly with regard to sleep onset) compared with other benzodiazepine hypnotics, especially those which are short- or intermediate-acting.

Animals↗

PubMed1981

Trazodone: a review of its pharmacological properties and therapeutic use in depression and anxiety.

Trazodone is a triazolopyridine derivative with antidepressant activity, that is chemically unrelated to other currently available antidepressants. Its pharmacological properties differ from those of most other antidepressants. Trazodone exhibits antiserotonin activity in animal studies, but its mechanism of action in depressive illness in humans is not clear. It has an overall therapeutic efficacy comparable with imipramine and amitriptyline in depressive illness but, at dosages which have achieved a similar overall clinical improvement, trazodone causes fewer anticholinergic side effects than the tricyclic antidepressants. Trazodone appears also to have activity against the concomitant anxiety in depressed patients and in limited studies was comparable with diazepam and chlordiazepoxide in anxiety neurosis. Trazodone has been reported to be of value in tremors and chronic alcoholism. Studies in animals, limited human studies and the low incidence of cardiovascular side effects in controlled therapeutic trials, suggest that trazodone is less likely than imipramine to cause cardiotoxicity at therapeutic doses, but the effects of overdosage are not known at present. Trazodone appears to be well tolerated by the elderly, seldom aggravates psychotic symptoms and does not produce neurological side effects.

Aged↗

PubMed1981

Penbutolol: a preliminary review of its pharmacological properties and therapeutic efficacy in hypertension and angina pectoris.

Penbutolol is a non-selective beta-blocking drug with 'moderate' intrinsic sympathomimetic (partial agonist) properties, and a relatively narrow dose-response range. In many other aspects its pharmacological profile resembles that of propranolol. Significant beta-blockade, as demonstrated by reduction in heart rate during exercise in healthy subjects, persists for at least 24 hours after penbutolol administration, and thus the recommended dosage schedule in both hypertension and angina involves single daily doses (20 or 40mg daily) in most patients, with a divided dose (40mg twice daily) if a higher dose is needed. However, most angina prophylaxis studies to date have not been designed to clearly demonstrate that the beneficial effects of beta-blockade with a single dose of penbutolol extend throughout a 24-hour dosing interval. Further studies are needed to provide such evidence. As might be expected, penbutolol appears to be about as effective as usual doses of propranolol in both mild to moderate hypertension and in angina, but much of the clinical experience with the drug is in unpublished form and is thus somewhat difficult to evaluate in detail. The choice of a beta-blocking drug should be based on a knowledge of the characteristic pharmacodynamic and pharmacokinetic properties of the individual drugs within this group, and on careful consideration of how these properties might be used to benefit the individual patient. As is the case with most other beta-blocking drugs, penbutolol has some specific properties (e.g. relatively narrow dose-response range minimising the difficulty of dose titration, moderate intrinsic sympathomimetic activity) which may be used to advantage in certain patients.

Angina Pectoris↗

PubMed1981

Triazolam: a review of its pharmacological properties and therapeutic efficacy in patients with insomnia.

Triazolam is a triazolobenzodiazepine with hypnotic properties, advocated for use in acute or chronic insomnia, situational insomnia in hospitalised patients, and insomnia associated with other disease states. As triazolam has a relatively short half-life of about 2 to 3 hours in healthy subjects and has only 1 short acting active metabolite, alpha-hydroxytriazolam, it would seem more suitable as an hypnotic than longer acting drugs such as flurazepam, nitrazepam or flunitrazepam, particularly when residual sedative effects on the day after ingestion are undesirable. Thus, with usual hypnotic doses of triazolam (0.25 or 0.5 mg) impairment of psychomotor and cognitive function is generally not carried over into the day after ingestion, although at doses of 1 mg or greater, residual effects may appear. In short term comparative studies triazolam was clearly superior to a placebo, and was at lest as effective as flurazepam, or other benzodiazepines such as nitrazepam or diazepam, in hastening sleep onset, reducing nocturnal awakenings, and increasing sleep duration. In other studies it was often superior to chloral hydrate, methyprylone or quinalbarbitone (secobarbital). In a small number of patients with chronic insomnia receiving extended treatment with triazolam in a clinical setting or in some sleep laboratory studies, no evidence of tolerance occurred; however, some evidence of reduced effect with repeated administration has been reported in one sleep laboratory study. Thus, a definitive statement about the likelihood of tolerance occurring on repeated administration is difficult to make at this time.

Animals↗

PubMed1981

Piroxicam: a review of its pharmacological properties and therapeutic efficacy.

Piroxicam is an N-heterocyclic carboxamide of 1,2 benzothiazine 1,1 dioxide with analgesic and anti-inflammatory activity. It has an extended half-life of about 40 hours and is suitable for once daily administration. Published studies indicate that piroxicam 20mg daily is comparable with aspirin 3 to 6g. indomethacin 75 to 150mg, phenylbutazone 400mg, naproxen 500mg, ibuprofen 1200 to 2400mg and diclofenac 75mg in rheumatoid arthritis. In osteoarthritis, piroxicam 20mg daily is comparable in efficacy with aspirin 2.6 to 3.9g, indomethacin 75mg, naproxen 500mg and fenbufen 600mg but is generally better tolerated than aspirin or indomethacin in patients with arthritic diseases. Piroxicam 20mg was at least as effective as indomethacin 75mg in a study in ankylosing spondylitis. As with other non-steroidal anti-inflammatory drugs gastrointestinal complaints are the most frequently reported side effects and their frequency and severity appears to be dose-related.

Animals↗

PubMed1981

Amoxycillin/clavulanic acid: a review of its antibacterial activity, pharmacokinetics and therapeutic use.

Clavulanic acid is a beta-lactamase inhibitor produced from Streptomyces clavuligerus, which when combined with certain beta-lactam antibiotics extends their activity against bacteria which owe their resistance to the production of beta-lacatamases. In combination with amoxycillin it extends the antibacterial activity of amoxycillin to include beta-lactamase-producing strains, which are otherwise resistant, as well as amoxycillin-resistant species such as Bacteroides fragilis. The addition of clavulanic acid to amoxycillin occasionally extends (but does not decrease) the susceptibility of amoxycillin-sensitive bacteria. Clavulanic acid is adequately absorbed after oral administration and its basic pharmacokinetic characteristics are similar to those of amoxycillin. Preliminary therapeutic trials suggest that amoxycillin plus clavulanic acid is effective in urinary tract infections caused by amoxycillin-resistant organisms and in lower respiratory tract infections unresponsive to previous routine antibiotic therapy, in hospitalised patients. It is generally well tolerated; nausea, vomiting, diarrhoea and skin rash being the most frequently reported adverse effects.

Amoxicillin↗

PubMed1981

Cefoperazone: A review of its in vitro antimicrobial activity, pharmacological properties and therapeutic efficacy.

Cefoperazone is a new 'third generation' semisynthetic injectable cephalosporin. It has a broad spectrum of antibacterial activity which includes Pseudomonas aeruginosa (unlike older cephalosporins), along with the Enterobacteriaceae and other Gram-negative bacteria, Gram-positive bacteria and anaerobic bacteria. Unlike other cephalosporins, cefoperazone is excreted to a considerable extent by extrarenal mechanisms. Given by intravenous or intramuscular injection, cefoperazone is effective against a wide variety of infections caused by Gram-negative or Gram-positive aerobes, including infections of the biliary tract, and in many anaerobic infections. It is generally well tolerated, diarrhoea and skin rashes being the most frequently reported side effects.

Anti-Bacterial Agents↗

PubMed1980

Miconazole: a preliminary review of its therapeutic efficacy in systemic fungal infections.

Miconazole is an imidazole antifungal drug which has recently become available for systemic use. Its antifungal activity has been well studied and it is active in vitro against a wide range of fungi. Published and unpublished reports of the use of miconazole in conditions such as systemic or mucocutaneous candidosis, coccidioidomycosis, fungal meningitis, and paracoccidioidomycosis (which seems especially responsive) have often been encouraging, particularly in view of the serious, refractory nature of the conditions treated, but in most areas of use experience is limited. There are few effective drugs available for treating most systemic fungal infections, and if further studies confirm the encouraging results often seen to date, miconazole will be an important addition to the limited choices available for such conditions.

Animals↗

PubMed1980

Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis.

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It has been studied in osteoarthritis, pain resulting from musculoskeketal sprains and strains and from minor surgery and cancer. The duration of its analgesic effect is longer than that of aspirin and diflunisal is effective when given twice daily. Diflunisal is not metabolised to salicylic acid and has a lesser effect than aspirin on platelet function in vivo. In osteoarthritis, diflunisal appears comparable in efficacy to moderate doses of aspirin (2 to 3g daily), but is better tolerated. It has not been compared with the most active phenylalkanoic acid derivatives such as naproxen in adequate numbers of patients. Diflunisal is comparable with glafenine in pain and with propoxyphene/paracetamol combinations and oxyphenbutazone in pain and in musculoskeletal strains and sprains. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects.

Diflunisal↗

PubMed1980

Colestipol: a review of its pharmacological properties and therapeutic efficacy in patients with hypercholesterolaemia.

Colestipol is an anion exchange resin with bile acid sequestering properties resembling those of cholestyramine, another lipid-lowering binding resin. In daily doses of 15 to 30g colestipol reduces total plasma cholesterol concentrations (primarily low density lipoprotein cholesterol) by about 15 to 30%, but plasma triglyceride concentrations may be unchanged or in some patients increased. Thus, like cholestyramine, colestipol is of benefit in patients with primary hypercholesterolaemia without associated hypertriglyceridaemia (type IIa hyperlipoproteinaemia). Colestipol is odourless and tasteless, and is said by some to be more readily tolerated by patients than cholestyramine, leading to improved compliance, but such data has not been documented in most studies. Side effects of colestipol treatment are primarily gastrointestinal in nature since the drug is essentially unabsorbed. As with cholestyramine, colestipol may bind with other concomitantly administered drugs reducing their absorption or enterohepatic recirculation; dosage intervals of other concurrent medications should be adjusted to minimise the potential for such an interaction.

Colestipol↗