Biomedical subjects

P Benfield

Publications and source records attributed to P Benfield.

At least 37 records · Page 2Linked to original sources

PubMed1996

Cefpodoxime proxetil. An appraisal of its use in antibacterial cost-containment programmes, as stepdown and abbreviated therapy in respiratory tract infections.

Cefpodoxime proxetil is an orally administered prodrug which is converted in vivo to the third generation cephalosporin cefpodoxime. Cefpodoxime has a similar spectrum of antibacterial activity to the parenteral cephalosporins ceftriaxone and cefotaxime and a long elimination half-life, which allows once- or twice-daily administration. Cefpodoxime proxetil has proven efficacy in the treatment of community-acquired pneumonia and upper respiratory tract, skin and soft tissue and urinary tract infections. It has been evaluated for use in cost-containment programmes, as stepdown (parenteral-to-oral conversion) therapy in the treatment of community-acquired pneumonia and as abbreviated therapy in upper respiratory tract infections. Substituting oral for parenteral therapy can achieve considerable savings (in acquisition, delivery and labour costs). Moreover, oral administration has advantages for the patient in terms of comfort and mobility, avoids the hazards of parenteral delivery and may allow earlier discharge from hospital, or even allow home treatment from the outset in low-risk patients. As hospitalisation is usually the major cost component in treating serious infections, considerable savings can be made in this way. Pharmacy-driven stepdown programmes in 2 US hospitals have achieved cost savings by targeting patients with community-acquired pneumonia for early conversion from intravenous ceftriaxone therapy to oral cefpodoxime proxetil. Costs were compared with those from a control group of patients who continued to receive intravenous ceftriaxone until physicians deemed that oral therapy (with various agents) was appropriate. In one study, duration of parenteral therapy in the cefpodoxime proxetil group was reduced from 6.18 to 3.82 days and duration of hospitalisation was reduced from 10.06 to 6.23 days (p < 0.02), with corresponding hospitalisation cost reductions of $US7300 per patient. However, clinical trial data relating to the efficacy of cefpodoxime proxetil as stepdown therapy in patients initially requiring parenteral antibacterials are lacking. Abbreviated (4-to 7-day) cephalosporin regimens appear to be as effective as traditional 10-day penicillin regimens in the treatment of upper respiratory tract infections. Short regimens may improve patient compliance and tolerability, thereby reducing the costs of adverse effects and treatment failures. Data from preliminary clinical studies suggest that a 5-day course of cefpodoxime proxetil is as effective as an 8-day course of amoxicillin/clavulanic acid in treating either acute otitis media or sinusitis, and as effective as a 10-day course of amoxicillin/ clavulanic acid and more effective than a 10-day course of phenoxymethyl- penicillin in the treatment of pharyngotonsillitis. Cefpodoxime proxetil tended to be better tolerated and was associated with better compliance than penicillin-based regimens. Indeed, a pharmacoeconomic study showed that a 10-day regimen of cefpodoxime proxetil was associated with lower costs for treating adverse effects and treatment failures than a 10-day regimen of amoxicillin/clavulanic acid in the treatment of acute otitis media in children. A 5-day course of cefpodoxime proxetil had a lower cost per patient treated per month free of recurrence than a 10-day course of phenoxymethylpenicillin (non-generic) or amoxicillin/clavulanic acid in the treatment of recurrent pharyngotonsillitis. Thus, evidence to date suggests that cefpodoxime proxetil has potential for use as stepdown therapy in community-acquired pneumonia and in abbreviated therapy courses in upper respiratory tract infections. These preliminary observations require confirmation in well designed studies.

Ceftizoxime↗

PubMed1995

Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in older patients with depressive illness.

The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine is an effective antidepressant in elderly patients. Its efficacy is similar to that of other frequently used antidepressants, such as the tricyclic antidepressants. However, compared with the tricyclic antidepressants, fluoxetine has a more favourable tolerability profile and is less toxic in overdose. It is associated with fewer anticholinergic, cardiovascular and CNS adverse events, but greater numbers of gastrointestinal adverse events than have been reported for the tricyclic antidepressants. This is important in elderly patients who are more at risk of developing central anticholinergic and cardiovascular effects than are younger patients. Therefore, while its position relative to other selective serotonin reuptake inhibitors requires investigation, fluoxetine represents a major advance over tricyclic antidepressant agents in the treatment of elderly patients with depression, predominantly because of its favourable tolerability profile.

Aged↗

PubMed1995

Venlafaxine. A review of its pharmacology and therapeutic potential in depression.

Venlafaxine is a phenylethylamine derivative which facilitates neurotransmission in the brain by blocking presynaptic reuptake of serotonin (5-hydroxytryptamine: 5-HT) and noradrenaline (norepinephrine). Clinical data from patients with major depression are consistent with the favourable efficacy and tolerability profile of venlafaxine predicted by pharmacodynamic studies. In patients with major depression, venlafaxine 75 to 375 mg/day administered for 6 weeks was significantly more effective than placebo, and at least as effective as imipramine, clomipramine, trazodone or fluoxetine. Venlafaxine is well tolerated, being associated with fewer anticholinergic and CNS adverse effects than tricyclic antidepressants. Unlike the tricyclic antidepressants, venlafaxine does not appear to significantly affect cardiac conduction, although there have been a few reports of modest increases in blood pressure, particularly after high doses of the drug. In conclusion, wider clinical experience is required to better characterise and confirm potential advantages of venlafaxine compared with other antidepressant agents. These advantages may include a rapid onset of action and reduced propensity to cause anticholinergic effects and cardiotoxicity compared with tricyclic antidepressants. Nevertheless, at this stage venlafaxine offers a more attractive treatment option than tricyclic antidepressants for patients with major depression, primarily because of its good overall tolerability profile.

Animals↗

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

Transnasal butorphanol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute pain management.

Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. The analgesic efficacy of transnasal butorphanol was generally superior to that of placebo in clinical trials in patients with moderate to severe postoperative pain or migraine headache. Results from single trials indicate that transnasal butorphanol provides pain relief comparable to that of intramuscular pethidine (meperidine) in postsurgical pain and comparable to or greater than intramuscular methadone in migraine headache. Moderate to severe musculoskeletal pain also appears to be responsive to transnasal butorphanol on the basis of results from 1 small noncomparative study. Tolerability of transnasal butorphanol parallels that of the injectable form, with somnolence, dizziness, nausea and/or vomiting reported most frequently. Thus, transnasal butorphanol is a novel formulation of an established analgesic which appears suitable for the short term treatment of moderate to severe pain, especially in an ambulatory setting. Transnasal butorphanol is likely to provide an alternative to oral opioid analgesics, particularly in the presence of nausea or vomiting, or to parenteral opioids when the oral route of administration is not appropriate.

Administration, Intranasal↗

PubMed1995

Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis.

Interferon-alpha-2a is a recombinant interferon with antiviral, antitumour and immunomodulatory properties. Clinical studies have demonstrated that the drug offers therapeutic benefit in patients with some forms of chronic viral hepatitis. Remission, as measured by clearance of viral DNA and hepatitis B 'e' antigen (HBeAg), and normalisation of serum alanine aminotransferase levels, is observed in approximately 30 to 45% of patients with chronic hepatitis B receiving interferon-alpha-2a (2.5 to 18MU administered 3 times/week); about 5 to 15% of untreated controls remit spontaneously every year. Complete recovery [with loss of hepatitis B surface antigen (HBsAg)] is usually noted in < 20% of treated individuals. Similar response rates have been reported in the relatively small number of children evaluated to date. Although numerous studies have shown that interferon-alpha-2a (at various dosages) induces biochemical amelioration of chronic hepatitis C in approximately 50 to 75% of patients, relapse is common. Thus, long term remission may only be observed in about 15 to 30% of treated patients. On the other hand, this disorder remits spontaneously in only a few patients. The role of interferon-alpha-2a in the treatment of chronic hepatitis D remains unclear. Although preliminary data suggest it may be beneficial, cessation of therapy is generally followed by relapse. As with other types of interferons, most patients receiving interferon-alpha-2a experience an 'influenza-like' syndrome, which tends to diminish with continuing therapy. Other effects such as fatigue, lethargy, anorexia and weight loss are usually dose-limiting. Serum neutralising antibodies develop in approximately 10 to 20% of treated patients. Thus, although response rates are less than optimal, interferon-alpha-2a is a drug of first choice amongst the limited therapeutic options available for the management of well-compensated chronic viral hepatitis B or C.

Antiviral Agents↗

PubMed1994

Streptokinase. A review of its pharmacology and therapeutic efficacy in acute myocardial infarction in older patients.

Streptokinase has been administered to many thousands of elderly patients with acute myocardial infarction. Results of large, randomised trials provide convincing evidence that intravenous streptokinase confers a distinct survival benefit in this population subgroup following myocardial infarction. The placebo-controlled ISIS-2 study demonstrated a 5-week absolute mortality reduction of 38 per 1000 patients aged 60 to 69 years administered streptokinase, compared with only 16 per 1000 for patients aged less than 60 years. Combining streptokinase with aspirin further reduces mortality, as shown by a 5-week absolute mortality reduction of 70 per 1000 patients aged 60 to 69 years administered this regimen in the ISIS-2 trial. While ideally patients should receive streptokinase as soon as possible after symptom onset, late benefit has been observed in patients presenting up to 12 hours after pain onset, as is often the case with the elderly. Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA). However, in contrast to the similar effects of streptokinase and conventionally administered rt-PA on overall survival demonstrated in previous large trials, the GUSTO study showed a lower mortality rate for accelerated rt-PA than for streptokinase in the elderly and in the total patient population. The most frequent adverse effects associated with streptokinase therapy are haemorrhagic complications, with an incidence of 0.4% for major bleeding (requiring transfusion) and 3.6% for minor bleeding among the total population in the GISSI-1 and ISIS-2 trials. An excess of stroke, particularly haemorrhagic stroke, occurring with rt-PA in GUSTO and other major mortality trials affirms the use of streptokinase as a suitable option in the elderly who are at increased risk of this complication. Significantly reduced values of end-systolic volume and regional wall motion index have been observed in elderly patients following streptokinase therapy. Overall, streptokinase and rt-PA seem to cause similar improvements in left ventricular function in this age group. Patency of occluded coronary arteries appears to be achieved in a high percentage of elderly patients following streptokinase therapy, based on a small sample. Thus, in view of the extensive clinical experience that now exists, intravenous streptokinase represents an appropriate alternative in elderly patients with acute myocardial infarction, and may be considered a first-line therapy in selected individuals, such as those with multiple risk factors for stroke or who present later than 6 hours after infarct.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1994

Aniracetam. An overview of its pharmacodynamic and pharmacokinetic properties, and a review of its therapeutic potential in senile cognitive disorders.

Aniracetam is a member of the nootropic class of drugs, which have possible cognition enhancing effects. It appears to positively modulate metabotropic glutamate receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptors, and may facilitate cholinergic transmission, effects which are possibly related to its mechanism of action. Results from trials in elderly patients with mild to moderate cognitive impairment due to senile dementia of the Alzheimer type suggest that aniracetam may be of benefit, with further trials required to confirm its efficacy profile and to define more precisely those patients most likely to respond to treatment. Aniracetam 1500 mg/day was significantly more effective than placebo in all tests at 4 and 6 months, and in a further 6-month trial was more effective than piracetam 2400 mg/day in 8 of 18 tests. Preliminary evidence in the treatment of patients with cognitive impairment of cerebrovascular origin suggests aniracetam may also be of benefit in this condition. Whilst incidence rates of adverse effects are not yet available, data from trials suggest aniracetam is well tolerated. In particular, aniracetam does not appear to cause increases in liver enzyme levels. The evaluation of drugs for patients with senile cognitive disorders is a difficult area and therapeutic options are currently limited. Preliminary evidence of the potential benefits and good tolerability profile of aniracetam support continued evaluation of its use in patients with mild to moderate senile dementia of the Alzheimer type.

Aged↗

PubMed1994

Gallopamil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in ischaemic heart disease.

Gallopamil is a methoxy derivative of verapamil. As is typical of the phenylalkylamine class of calcium antagonists, it acts on the vascular system, and on the heart and its nodal structures. In the treatment of stable angina pectoris, gallopamil is at least as effective as nifedipine and diltiazem, though apparently better tolerated than nifedipine. Typical of calcium antagonists there is little or no tolerance to the antiischaemic effects of gallopamil. Preliminary studies indicate that gallopamil, like other calcium antagonists, has cardioprotective potential. However, further investigation is required to explore the clinical relevance of the improved myocardial regional perfusion and free fatty acid utilisation in reversibly ischaemic regions, and the potential of delayed ischaemia during angioplasty that is observed during gallopamil administration. Gallopamil is well tolerated, exhibiting a low propensity for causing cardiovascular and gastrointestinal adverse effects, thus making it a suitable alternative to other calcium antagonists for the treatment of patients with ischaemic heart disease.

Animals↗

PubMed1994

Hyaluronic acid. A review of its pharmacology and use as a surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing.

Hyaluronic acid is a naturally occurring polysaccharide with distinct physicochemical properties which underlie its application as a viscoelastic tool in ophthalmological surgery. In cataract surgery the role of hyaluronic acid in facilitating procedures and protecting the corneal endothelium is well established. Some benefit has also been gained with the use of hyaluronic acid in penetrating keratoplasty, trabeculectomy, retinal reattachment and trauma surgery, although its efficacy in these indications is less well-defined in the published literature. In addition to its lubricating and cushioning properties, demonstration of some in vitro anti-inflammatory activity and a possible disease-modifying effect for hyaluronic acid in animals has prompted its investigation as a treatment in osteoarthritis and, to a much lesser extent, in rheumatoid arthritis. Hyaluronic acid 20 mg, as weekly intra-articular injections for 3 to 7 weeks, improved knee pain and joint motion in patients with osteoarthritis. Although this occurred to a greater degree than with placebo in most comparisons, the effects of hyaluronic acid was similar to those of placebo in the largest trial. In the few available comparisons with other agents, hyaluronic acid appeared equivalent to methylprednisolone 40 mg (for 3 weeks) and to a single injection of triamcinolone 40 mg. Hyaluronic acid was distinguished from other therapies by providing a sustained effect after treatment discontinuation. Together with its very good tolerability profile, these properties justify further study of hyaluronic acid in patients with osteoarthritis. Some limited evidence of improvement in patients with rheumatoid arthritis, and a possible healing effect of hyaluronic acid on tympanic membrane perforations, represent additional areas of interest for future investigation. In summary, hyaluronic acid is a well-established adjunct to cataract surgery and may prove to be a promising option in the treatment of patients with osteoarthritis. Its very good tolerability provides further impetus for examination of its potential role in an extended scope of arthritic and ophthalmological indications, and in wound healing.

Adjuvants, Pharmaceutic↗

PubMed1994

Metoprolol: a pharmacoeconomic and quality-of-life evaluation of its use in hypertension, post-myocardial infarction and dilated cardiomyopathy.

Metoprolol is a beta 1-selective adrenoceptor antagonist that is widely used in several indications. A recent investigation has also highlighted a potential role for metoprolol in selected patients with idiopathic dilated cardiomyopathy. Pharmacoeconomic and quality-of-life data for metoprolol are limited to the areas of hypertension, post-myocardial infarction and idiopathic dilated cardiomyopathy. In these settings, metoprolol has shown beneficial effects on morbidity and mortality, or closely-related end-points. Controlled release formulations offer the potential to maximise the confirmed antihypertensive benefits of metoprolol by maintaining clinically effective plasma drug concentrations within a narrow range over a 24-hour interval between doses. Recent data support the use of controlled release metoprolol at the low dose of 50 mg/day. Metoprolol is at least as effective as many other antihypertensive drugs, although compared with thiazide diuretics at relatively high doses in the MAPHY (Metoprolol Atherosclerosis Prevention in Hypertensives) trial, metoprolol was associated with a more favourable effect on mortality. Pharmacoeconomic analysis, also based on the MAPHY trial, indicates that metoprolol is more cost effective than high dose thiazide diuretics in middle-aged men with mild to moderate hypertension. However, the advantage for beta-blockade in this trial is not supported by results of other studies, and the applicability of these data to current medical practice using lower thiazide doses is therefore questionable. Quality of life in patients with mild to moderate hypertension did not deteriorate in most investigations with metoprolol. Furthermore, quality of life was similar for controlled release metoprolol and atenolol. With conventional/matrix-based sustained release metoprolol, quality of life was less satisfactory than with lisinopril but was only marginally different from that with diltiazem (at lower than usual therapeutic doses). Nevertheless, these newer agents have no proven beneficial effect on mortality, and further studies are also warranted with controlled release metoprolol 50 mg/day. When administered post-myocardial infarction, conventional metoprolol was associated with significant improvements in quality of life and was cost saving over a 3-year period. Significant improvements in quality of life were also evident for metoprolol-treated patients with idiopathic dilated cardiomyopathy. In summary, available data support the continued extensive usage of metoprolol as treatment for hypertension and as therapy post-myocardial infarction. Pharmacoeconomic data supporting an advantage for metoprolol over high dose thiazides in hypertension needs further assessment in settings reflecting usual general practice approaches to managing patients with hypertension, while differences in quality of life between metoprolol and other antihypertensive agents appear to be marginal.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiomyopathy, Dilated↗

PubMed1993

The ligand binding signatures of the rat AT1A, AT1B and the human AT1 receptors are essentially identical.

The objective of this study was to determine whether the three isoforms of recombinant Ang II receptors (rAT1A, rAT1B and hAT1), stably and individually expressed in CHO cells, could be pharmacologically distinguished by their ligand binding signatures. Competition studies were performed to characterize the inhibition of [125I]Ang II binding to each of the cell membrane preparations by an extensive series of peptide and nonpeptide Ang II analogs. Scatchard plot analyses revealed the following binding characteristics:rAT1A-Kd = 1.27 +/- 0.14 nM; rAT1B- Site 1:Kd = 0.56 +/- 0.11 nM, Site 2: Kd = 126 +/- 23 nM; and hAT1-Site 1:Kd = 1.06 +/- 0.16 nM, Site 2: Kd = 257 +/- 55 nM. The binding of [125I]Ang II in the three preparations was similarly sensitive to inhibition by GTP gamma S. The ligand binding signatures of the three receptor isoforms are essentially the same and are illustrated by the affinity and order of potency of the following ligands: L-158,809 > or = Sar1, Ile8Ang II > saralasin Ang II > or = Ang III > EXP581 > EXP3174 > losartan > or = EXP811 > GR117,289c > EXP6803 > DuP 532 > Ang I >> PD123177. In conclusion, the two rat AT1 receptor isoforms are pharmacologically indistinguishable from each other and from that of the human.

Angiotensin II↗

PubMed1993

Characterization of angiotensin AT1A receptor isoform by its ligand binding signature.

The objective of this study was to determine whether the binding signature of the cloned rat AT1A receptor transfected into Chinese hamster ovary cells could be distinguished from that of the endogenous AT1B receptor expressed in rat adrenal cortex. An extensive series of peptide and nonpeptide Ang II analogs was used for the characterization. The binding of [125I]Ang II to the recombinant AT1A receptors was quite sensitive to inhibition by GTP gamma S. Scatchard analysis of the competition of Ang II revealed two populations of binding sites (site 1: KD = 3.05 +/- 0.27 nM and a maximum binding (Bmax) of 134 +/- 26 fmol/mg protein; site 2: KD = 253 +/- 77 nM and Bmax = 1.05 +/- 0.19 pmol/mg protein). The ligand binding signature of the AT1A receptor is defined by the affinity (Ki = nM) and order of potency of the following ligands: saralasin (2.07) > Ang II (3.35) > losartan (14) > Ang III (20) > GR 117289C (28) > EXP6803 (160) > Ang I (281) > PD123177 (> 10,000). This binding signature of the cloned AT1A receptors appears to be similar to that displayed by rat adrenal cortical cells where AT1B is predominantly expressed. These findings suggest that AT1A and AT1B receptors may not be easily distinguishable by the currently available ligand agonists or antagonists. Consequently, AT1A or AT1B may be considered as isoforms rather than subtypes of the AT1 receptors.

Adrenal Cortex↗

PubMed1993

Cefprozil. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic potential.

Cefprozil is an orally active cephalosporin which has demonstrated activity against a wide range of organisms in vitro. It is particularly active against the Gram-positive organisms Streptococcus pyogenes, pneumoniae and agalactiae and against methicillin-susceptible Staphylococcus aureus. Strains of methicillin-resistant S. aureus are not susceptible to cefprozil. Cefprozil is also moderately active against Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, many Enterobacteriaceae and certain anaerobic organisms, and is relatively stable to hydrolysis by a number of beta-lactamases. In comparative trials, the clinical and bacteriological efficacy of cefprozil 500mg or 20 mg/kg administered once or twice daily has been comparable with multiple daily dosage regimens of erythromycin in patients with tonsillitis or pharyngitis, with cefaclor and amoxicillin/clavulanate in lower respiratory tract infections, with amoxicillin/clavulanate and erythromycin in skin and skin-structure infections and with cefaclor in acute uncomplicated urinary tract infections. The clinical efficacy of cefprozil is similar to that of cefaclor in patients with tonsillitis or pharyngitis but the bacteriological efficacy of cefprozil is significantly greater than that of cefaclor. Cefprozil is clinically more effective than cefuroxime axetil in the treatment of lower respiratory tract infections and demonstrated greater efficacy than cefaclor in one of 2 comparative studies when administered twice daily in patients with skin and skin-structure infections. In children with acute otitis media, cefprozil 15 mg/kg twice daily was as effective as cefaclor or amoxicillin/clavulanate 13.3 mg/kg 3 times daily and was as effective as cefixime 8 mg/kg once daily. The most frequently reported adverse effects associated with cefprozil, diarrhoea and nausea, are usually mild to moderate in severity and discontinuation of treatment is rarely necessary. Thus, cefprozil with its convenient administration regimen appears to be a suitable alternative to cefaclor, cefixime, amoxicillin/clavulanate or erythromycin for the treatment of upper and lower respiratory tract infections, skin and skin-structure infections, and otitis media in children. While cefprozil has shown similar efficacy to cefaclor in the treatment of uncomplicated urinary tract infections, well-controlled clinical trials comparing its efficacy with that of cotrimoxazole (trimethoprim+sulfamethoxazole) in this indication are required.

Animals↗

PubMed1993

Eutectic lidocaine/prilocaine cream. A review of the topical anaesthetic/analgesic efficacy of a eutectic mixture of local anaesthetics (EMLA).

Eutectic lidocaine/prilocaine cream 5% is a eutectic mixture of the local anaesthetics lidocaine (lignocaine) 25 mg/g and prilocaine 25 mg/g that provides dermal anaesthesia/analgesia following topical application. The principal indication in which eutectic lidocaine/prilocaine cream has been studied is the management of pain associated with venipuncture or intravenous cannulation, where significantly greater pain relief than placebo, with equivalent efficacy to ethyl chloride spray and lidocaine infiltration, has been demonstrated. In dermatological surgery, eutectic lidocaine/prilocaine cream offers effective pain relief in children undergoing curettage of molluscum contagiosum lesions, and in adults undergoing split-skin graft harvesting. Particular benefit has also been shown with use of eutectic lidocaine/prilocaine cream in association with treatment of condylomata acuminata in both men and women, and it appears to provide a useful alternative to lidocaine infiltration in this context. Further research in such indications as paediatric lumbar puncture, minor otological surgery, and minor gynaecological, urological and andrological procedures is likely to further broaden the profile of clinical use for eutectic lidocaine/prilocaine cream. Eutectic lidocaine/prilocaine cream has a very favourable tolerability profile, transient and mild skin blanching and erythema being the most frequent adverse events to occur in association with its application to skin. The potential for inducing methaemoglobinaemia, attributed to a metabolite of the prilocaine component of the formulation, prohibits its use in infants younger than 6 months. In summary, eutectic lidocaine/prilocaine cream is a novel formulation of local anaesthetics that has proven to be effective and well-tolerated in the relief of pain associated with various minor interventions in adults and children.

Anesthetics, Local↗

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↗

PubMed1993

Epoetin: a pharmacoeconomic review of its use in chronic renal failure and its effects on quality of life.

Epoetin (recombinant human erythropoietin) is an effective treatment for the anaemia of patients with chronic renal failure. It is well tolerated, and the risk of adverse effects that are caused by too rapid a correction of anaemia, for example hypertension, can be reduced in most cases by lower starting dosage regimens. Epoetin improves the quality of life of anaemic patients with end-stage renal disease (ESRD), and significant improvements in most parameters of the Kidney Disease Questionnaire, the Sickness Impact Profile and the Nottingham Health Profile have been reported by patients. However, acquisition costs of epoetin are high, thereby adding a considerable cost to ESRD therapy despite a reduction in blood transfusion requirements. Notwithstanding, although cost-effectiveness studies have indicated that epoetin is associated with higher costs of therapy, cost-benefit analysis indicates that these costs can be reduced markedly with low-dose regimens and may be completely recovered if patients regain employment.

Adolescent↗

PubMed1993

Misoprostol: pharmacoeconomics of its use as prophylaxis against gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs.

Misoprostol effectively prevents nonsteroidal anti-inflammatory drugs (NSAID)-induced gastric ulcer and is the only agent currently indicated for this purpose. In addition, misoprostol is effective as prophylaxis against NSAID-induced duodenal ulcer. Because of the widespread use of NSAIDs, the cost of routine misoprostol prophylaxis would be high, and thus its pharmacoeconomic evaluation is an important factor in assessing the most appropriate role of misoprostol in this group of patients. Current cost-benefit analyses undertaken in major European centres and the US have generally indicated that, depending on initial assumptions, misoprostol prophylaxis over a 3-month period is cost-saving in patients with osteoarthritis taking NSAIDs. The net savings (costs) realised were dependent on several variables, including the acquisition cost of misoprostol, silent ulcer rate and patients' compliance. Importantly, misoprostol prophylaxis was consistently more cost-beneficial in elderly patients aged greater than 60 to 65 years than in their younger counterparts. In contrast, in one study misoprostol was found to reduce patients' quality of life and, although misoprostol therapy is potentially cost-saving to society, patients generally preferred no therapy. A single study assessing the cost-effectiveness of misoprostol prophylaxis in preventing ulcerative complications concluded that primary treatment was not an economically viable option for all NSAID users. Misoprostol was most cost-effective in the prevention of recurrent or secondary gastric ulcer complications in 'high-risk' patients, for example patients aged over 60 years and patients with rheumatoid arthritis. Thus, although there are areas of interest awaiting further pharmacoeconomic investigation, misoprostol prophylaxis appears to be cost-effective in elderly and high risk patients receiving NSAIDs. Additionally, misoprostol prophylaxis is cost-saving in elderly patients with osteoarthritis requiring NSAID therapy.

Anti-Inflammatory Agents, Non-Steroidal↗