Biomedical subjects

R N Brogden

Publications and source records attributed to R N Brogden.

At least 37 records · Page 2Linked to original sources

PubMed1996

Verapamil: a review of its pharmacological properties and therapeutic use in coronary artery disease.

Verapamil has well proven efficacy in the treatment of patients with hypertension, and early studies indicated its efficacy in the treatment of coronary artery disease. The efficacy of verapamil relative to placebo in patients with stable angina pectoris is confirmed, and the drug is at least as effective as nifedipine, propranolol or metoprolol and of similar efficacy to bepridil and nicardipine when administered as a conventional or sustained release formulation. Verapamil is the first calcium antagonist to be shown in a double-blind study to significantly reduce mortality and reinfarction rate after acute myocardial infarction in patients without heart failure. In these patients, the reduction in mortality achieved with verapamil was similar to that reported with beta-adrenoceptor antagonists, suggesting that verapamil may be a suitable alternative to beta-blockers as secondary prevention in patients intolerant of these drugs. Recurrence of stenosis in patients who successfully undergo percutaneous transluminal coronary angioplasty (PTCA) limits the usefulness of the procedure. Verapamil has recently been shown to significantly reduce the rate of restenosis in patients with stable angina at risk of recurrence, although these initial results require confirmation. Verapamil, therefore, is effective in the treatment of patients with stable angina pectoris, appears to be an alternative to beta-blockers in selected patients as late start secondary prevention after acute myocardial infarction and has a potential role in preventing recurrent stenosis after PTCA, if initial results are confirmed.

Angina Pectoris↗

PubMed1996

Aceclofenac. A review of its pharmacodynamic properties and therapeutic potential in the treatment of rheumatic disorders and in pain management.

Aceclofenac is a phenylacetic acid derivative with anti-inflammatory and analgesic properties similar to those of diclofenac. However, preclinical studies suggest that the potential of aceclofenac to cause gastrointestinal damage is less than that of diclofenac. Double-blind comparative trials indicate that the efficacy of aceclofenac is at least equivalent to that of ketoprofen and similar to that of indomethacin and diclofenac in patients with rheumatoid arthritis, similar to that of diclofenac and piroxicam in patients with osteoarthritis of the knee and similar to that of tenoxicam, indomethacin and naproxen in patients with ankylosing spondylitis. The analgesic efficacy of aceclofenac 100mg is more prolonged than that of paracetamol (acetaminophen) 650mg. If the apparently improved gastrointestinal tolerability of aceclofenac compared with diclofenac is confirmed by wider clinical experience, aceclofenac will have the potential to become a preferred initial drug in an individualised NSAID regimen in patients with rheumatic disorders.

Animals↗

PubMed1996

Cefuroxime axetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Cefuroxime axetil is an oral cephalosporin which is rapidly hydrolysed to the active parent compound, cefuroxime. Cefuroxime has a broad spectrum of in vitro antibacterial activity which encompasses methicillin-sensitive staphylococci and the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and group A beta-haemolytic streptococci. Cefuroxime has broad spectrum activity against the beta-lactamase positive respiratory pathogens H. influenzae and M. catarrhalis; it is also active against penicillin-susceptible and -intermediate strains of S. pneumoniae. In clinical trials, cefuroxime axetil (administered twice daily) has been evaluated in the treatment of upper and lower respiratory tract infections and has demonstrated similar efficacy to established antibacterial agents, including amoxicillin/clavulanic acid and cefaclor. Five days' treatment with cefuroxime axetil was recently shown to be as effective as 10 days' treatment with either cefuroxime axetil or amoxicillin/clavulanic acid in patients with acute otitis media or acute bronchitis. Cefuroxime axetil was at least as effective as phenoxymethylpenicillin (penicillin V) in the treatment of patients with group A beta-haemolytic streptococcal tonsillopharyngitis. A number of studies have evaluated the efficacy of cefuroxime axetil as the oral component of intravenous to oral sequential therapy in hospitalised patients with lower respiratory tract infection. In each study patients received parenteral cefuroxime for approximately 2 days followed by cefuroxime axetil for 5 to 10 days. In comparative studies, cefuroxime sequential therapy was as effective as amoxicillin/ clavulanic acid sequential therapy and full courses of parenteral cefuroxime, cefotiam or cefoperazone. Adults with urinary tract infections and skin infections were also effectively treated with cefuroxime axetil, as were adults and adolescents with early stage lyme disease. Cefuroxime axetil is associated with a low incidence of adverse events, with gastrointestinal disturbances being the most frequently observed. Thus, cefuroxime axetil is an effective and convenient treatment for a wide range of infections and may be considered a therapeutic option when empirical treatment of community-acquired infections is required. Moreover, given the promising results of several intravenous/oral sequential treatment studies, cefuroxime axetil may also become established as an oral component of sequential treatment regimens.

Age Factors↗

PubMed1995

Nilvadipine. A review of its pharmacodynamic and pharmacokinetic properties, therapeutic use in hypertension and potential in cerebrovascular disease and angina.

Nilvadipine, a calcium antagonist of the dihydropyridine class, selectively blocks calcium channels in vascular smooth muscle. Compared with nifedipine, the prototype of the dihydropyridines, nilvadipine has a longer duration of action. The antihypertensive efficacy of nilvadipine appears to be comparable with that of nicardipine and nitrendipine, enalapril and captopril and hydrochlorothiazide/triamterene, although further clinical experience is required to establish the claimed advantages nilvadipine may have over the other dihydropyridine derivatives currently used to treat hypertension. Preliminary studies suggest that nilvadipine may also be useful in the treatment of patients with stable exertional or variant angina. Studies conducted in Japan indicate that nilvadipine improves symptoms resulting from cerebral infarction in some patients, but further comparative studies are required to confirm these results. The tolerability of nilvadipine appears to be comparable with that of nicardipine and better than that of nifedipine with respect to flushes, oedema and liver function abnormalities. As is typical of calcium antagonists, there is no evidence of tolerance to the antihypertensive effects of nilvadipine. The drug is equally effective in treating hypertension in elderly and younger patients and does not appear to adversely affect glucose or lipid metabolism. Thus, provided its apparently good tolerability is confirmed by wider clinical experience, it should be a suitable alternative to other calcium antagonists when used alone or in conjunction with other drugs for the majority of patients with mild to moderate hypertension.

Aging↗

PubMed1995

Goserelin. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in prostate cancer.

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which during long term administration reduces circulating levels of gonadotrophins (luteinising hormone and follicle stimulating hormone) and sex hormones. Goserelin is administered subcutaneously as a biodegradable depot formulation incorporating 3.6mg of the drug, which is released continuously over 4 weeks. In men with untreated advanced prostate cancer, monthly goserelin 3.6mg has been confirmed as similar in efficacy to surgical castration and diethylstilbestrol (stilboestrol) 3mg daily taken orally. Goserelin is better tolerated than diethylstilbestrol and appears to have a more favourable effect on quality of life than surgical castration. Treatment of prostate cancer with a combination of goserelin and an antiandrogen remains controversial as a result of inconsistent findings, despite extended data from a large trial which indicated an advantage for the combined regimen over surgical castration with respect to duration of time to progression and survival. Combination therapy also minimises the initial increase in signs and symptoms (disease flare) that occurs in up to 4% of patients at the beginning of treatment with a GnRH analogue. Surgical castration remains the treatment of choice in patients at risk of metastatic compression of the spinal cord or ureteric obstruction. However, goserelin is an effective alternative to surgery, or estrogen therapy, in men with previously untreated advanced prostate cancer. Goserelin seems to be preferred to surgery by the majority of patients given a choice of treatment, and importantly in a palliative care situation where there are no survival advantages for treatment alternatives, it appears to have a more beneficial effect on the quality of life than surgery.

Absorption↗

PubMed1995

Pentoxifylline (oxpentifylline). A review of its therapeutic efficacy in the management of peripheral vascular and cerebrovascular disorders.

Pentoxifylline (oxpentifylline) has been used widely in the treatment of intermittent claudication, a prevalent condition in the elderly population. The exact mechanism(s) of action of the drug are unclear, but may be related to identified effects on white blood cell function and haemorrheological parameters. Clinical trials which conform best with European and North American guidelines have shown that 6 months' oral therapy with pentoxifylline 1200 mg/day significantly improves walking distances in patients with intermittent claudication. Patients most likely to benefit from treatment are those with an ankle/arm blood pressure ratio < or = 0.8 and a history of disease > 1 year. However, it remains unclear whether pentoxifylline or any other conservative treatment approach (including physical training) offers long term benefit, as studies comparing the development of intermittent claudication after several years of treatment with the natural course of the disease are still lacking. In patients with more severe vascular disease, intravenous administration of pentoxifylline (1200 mg/day for 21 days) decreased rest pain in patients with critical limb ischaemia. Oral administration (1200 g/day for up to 6 months) increased the healing of venous ulcers of the leg when used as an adjunct to standard compression bandaging. However, further studies are required to confirm these initial findings. The efficacy of pentoxifylline in the treatment of cerebrovascular disease has been evaluated in controlled clinical trials. Most notably, long term therapy (1200 mg/day) may slow the progression of dementia in patients who meet the clinical diagnostic criteria for 'multi-infarct' dementia and who also have clinical and neuroradiological evidence of cerebrovascular disease. The drug is effective in decreasing the risk of transient ischaemic attacks, but there are insufficient data to determine its value in the prevention and treatment of stroke. Pentoxifylline is well tolerated, with gastrointestinal effects reported in fewer than 3% of treated patients. However, the incidence of adverse events may be higher in elderly patients and/or those receiving concomitant medications. In summary, pentoxifylline is the most established agent when drug therapy is deemed appropriate in patients with intermittent claudication. Moreover, a promising new development for the drug is in the management of cerebrovascular dementia, an area where few therapeutic options are currently available.

Aged↗

PubMed1995

Torasemide. An update of its pharmacological properties and therapeutic efficacy.

The pharmacological properties and therapeutic use of the high-ceiling loop diuretic torasemide (torsemide) were previously reviewed in Drugs in 1991, the following being a re-examination of the role of the drug in the light of data that have subsequently become available (particularly in the management of oedematous disorders). Torasemide produces a more prolonged water and electrolyte excretion than equipotent diuretic doses of furosemide (frusemide), but does not increase kaliuresis to the same extent. Dosages of torasemide of 2.5 to 5 mg/day do not affect plasma renin activity or aldosterone release to a clinically significant extent, although torasemide 20mg increases plasma renin levels, angiotensin II activity and urinary dopamine and prostaglandin E excretion. Studies published since the previous review have confirmed the efficacy of low dosages of torasemide (2.5 to 5 mg/day) in the treatment of hypertension, and have shown it to be effective when administered orally at a dosage of 5 to 20 mg/day in the management of congestive heart failure. Dosages of up to 400 mg/day increased urinary volume excretion and natriuresis in patients with chronic renal failure. Bodyweight and peripheral oedema were reduced by torasemide 10 to 200 mg/day as monotherapy, and 5 to 20 mg/day when coadministered with spironolactone, in patients with nephrotic syndrome. Dosages of 10 to 40 mg/day, either as monotherapy or in conjunction with an aldosterone antagonist, reduced ascites, oedema and bodyweight in patients with hydropically decompensated liver failure. Adverse effects due to torasemide are usually mild and transient in nature. No evidence of ototoxicity has been demonstrated in humans, and torasemide does not appear to affect blood glucose levels, serum uric acid concentrations, or serum potassium levels at dosages below 5 mg/day. Thus, additional evidence has accumulated for the clinical efficacy of torasemide in the management of mild to moderate essential hypertension and oedematous conditions which require diuretic therapy. Further studies are now required to confirm the long term efficacy and tolerability of torasemide, and to investigate the place of the drug in therapy relative to cardiovascular agents other than furosemide and the thiazide diuretics.

Age Factors↗

PubMed1995

Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria.

Rifaximin is a derivative of rifamycin which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration; thus it is used primarily to treat local conditions within the gastrointestinal tract. In vitro data indicate rifaximin possesses good activity against species of Staphylococcus, Streptococcus and Enterococcus but lesser activity against species of Enterobacteriaceae. Bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. Results of comparative trials demonstrate that rifaximin is similar in efficacy to neomycin and lactulose in patients with hepatic encephalopathy and appears to be better tolerated. In 1 study, cyclical administration of rifaximin for 15 days per month was associated with progressive improvement over a 3-month period. In patients with infectious diarrhoea, rifaximin induces more rapid improvement in stool consistency and decreased frequency of faecal evacuations when compared with placebo, and is similar in efficacy to neomycin. Available data suggest rifaximin may be of some use in acute diverticulitis, but its use for the prevention of inflammatory complications or for control of common symptoms of diverticulosis requires further study. Preoperative treatment with rifaximin as antibacterial prophylaxis in colorectal surgery shows some potential but should be further investigated. Overall, rifaximin may be useful as an alternative therapy in hepatic encephalopathy but more data are needed to better define its clinical potential in infectious diarrhoea, diverticular disease and as antibacterial prophylaxis prior to colorectal surgery.

Diarrhea↗

PubMed1995

Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension.

Since the earlier review in Drugs substantial additional data have accumulated regarding the antihypertensive efficacy of isradipine in various clinical situations, as well as data on its clinical effects in atherosclerosis. Recent therapeutic trials confirm that the efficacy of isradipine in the treatment of patients with mainly mild to moderate hypertension, when administered orally as a conventional or modified release preparation, is similar to that of titrated dosages of amlodipine, felodipine, nifedipine, diltiazem, captopril, methyldopa, metoprolol, prazosin and hydrochlorothiazide. A further decrease in blood pressure can be expected when isradipine is combined with another antihypertensive drug in patients who have not responded adequately to monotherapy. Initial studies have shown that intravenous isradipine is effective in controlling hypertension following coronary artery bypass graft surgery and that it appears useful in the treatment of intraoperative hypertension and hypertensive crisis, and in hypertensive disorders in pregnancy, when administered orally or intravenously. A large study, the Multicentre Isradipine Diuretic Atherosclerosis Study (MIDAS), was designed to compare the efficacy of isradipine and hydrochlorothiazide in reducing the rate of progression of carotid artery wall thickness, measured by B-mode ultrasound, as a surrogate for early atherosclerosis. Results indicated that wall thickness increased significantly less with isradipine than hydrochlorothiazide after 6 months of therapy. Thereafter the rate of progression remained parallel for the remainder of the 3-year trial. The confirmation of its antihypertensive efficacy, along with its favourable haemodynamic profile and reversal of left ventricular hypertrophy, minimal effect on glucose and lipid metabolism, preservation of quality of life and good tolerability, makes isradipine a suitable drug for the treatment of most patients with mild to moderate hypertension.

Cardiac Surgical Procedures↗

PubMed1995

Cefixime. A review of its therapeutic efficacy in lower respiratory tract infections.

Cefixime is an orally active third generation cephalosporin with in vitro antibacterial activity against most important lower respiratory pathogens. The drug is active against Haemophilus influenzae, Moraxella catarrhalis and penicillin-susceptible Streptococcus pneumoniae but not Staphylococcus aureus. Cefixime has a long elimination half-life (3 hours compared with 0.5 hours for cefaclor and 1.5 hours for cefalexin), which allows once daily administration. Several trials have established the clinical efficacy of the drug in patients with lower respiratory tract infection (LRTI). In comparative studies cefixime had similar efficacy to amoxicillin +/- clavulanic acid, cefaclor, cefalexin, cefuroxime axetil and clarithromycin. Trials evaluating the efficacy of cefixime as the oral component of intravenous to oral switch therapy have produced promising preliminary results although further carefully designed trials are needed in this area. As with certain other drugs of its class, gastrointestinal disturbances are the most frequently reported adverse events in patients taking cefixime and cases of pseudomembranous colitis have been reported. Thus, cefixime is an effective treatment for mild to moderate LRTI and may have a role as the oral component of intravenous to oral switch therapy although further well designed studies are needed to confirm initial favourable results in this important emerging area of antibacterial therapy.

Anti-Bacterial Agents↗

PubMed1995

Meropenem. A review of its antibacterial activity, pharmacokinetic properties and clinical efficacy.

The parenteral carbapenem meropenem is relatively stable to inactivation by human renal dehydropeptidase (DHP-1) and does not require concomitant administration of a DHP-1 inhibitor such as cilastatin. It has a broad spectrum of antibacterial activity in vitro, the majority of Gram-negative, Gram-positive and anaerobic pathogens being highly susceptible to the drug. Meropenem has shown clinical and bacteriological efficacy in the treatment of a wide range of serious infections in adults and children which is at least comparable with that of currently available treatment options. Its clinical and bacteriological efficacy is similar to that of imipenem/cilastatin, clindamycin plus tobramycin and cefotaxime plus metronidazole in the treatment of intraabdominal infections; cefotaxime or ceftriaxone in the treatment of meningitis; imipenem/cilastatin, and ceftazidime with or without an aminoglycoside, in lower respiratory tract infections; and imipenem/cilastatin or ceftazidime in the treatment of urinary tract infections. Satisfactory clinical and bacteriological response rates have also been achieved in patients with skin and skin structure infections, obstetric and gynaecological infections or septicaemia, and in immunocompromised patients with febrile episodes. Preliminary findings also indicate efficacy in the treatment of respiratory tract infections in patients with cystic fibrosis. The tolerability profile of meropenem is generally similar to that of comparator agents, although it is associated with a lower incidence of adverse gastrointestinal effects (nausea and vomiting) than imipenem/cilastatin. Importantly, the incidence of seizures in patients with meningitis is not increased following administration of meropenem. Thus, meropenem is an effective broad spectrum antibacterial drug for the treatment of a wide range of infections including polymicrobial infections in both adults and children, with comparable efficacy to imipenem/cilastatin and various other treatment regimens. Meropenem is likely to be of greatest value as empiric monotherapy in the treatment of serious infections for those caused by multiply-resistant pathogens. Further clinical experience is necessary, however, to ultimately define its place in therapy.

Absorption↗

PubMed1995

Nifedipine gastrointestinal therapeutic system (GITS). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in hypertension and angina pectoris.

Nifedipine 'gastrointestinal therapeutic system' (GITS) is a recently developed formulation that slowly releases the drug into the intestinal tract over a 24-hour period. When administered once daily, it is of similar efficacy to sustained release formulations of felodipine, verapamil, and diltiazem and at least as effective as standard formulations of lisinopril and enalapril, and long-acting propranolol and atenolol in the treatment of patients with mild to moderate essential hypertension. Substitution of nifedipine GITS for conventional formulations of nifedipine, diltiazem or verapamil, maintained adequate control of anginal symptoms in patients with stable angina pectoris. Nifedipine GITS appears to maintain quality of life and is apparently better tolerated than those formulations of nifedipine which require 2 or 3 times daily administration in both elderly and younger patients. In addition, it has minimal effect on lipid and glucose metabolism and reverses left ventricular hypertrophy, and is thus suitable for treatment of the majority of patients with mild to moderate hypertension or angina pectoris.

Administration, Oral↗

PubMed1994

Pimobendan. A review of its pharmacology and therapeutic potential in congestive heart failure.

Pimobendan is a novel cardiotonic vasodilator (inodilator) which derives its inotropic activity from a combination of phosphodiesterase III inhibition and sensitisation of myocardial contractile proteins to calcium. The acute haemodynamic benefits of pimobendan (2.5 to 10mg orally; 5 to 10mg intravenously) seen in patients maintained on conventional diuretic, digitalis and vasodilator therapy for chronic heart failure (increases in cardiac output and stroke volume, and reductions in left ventricular preload and afterload) persisted on short term (1 month) therapy, and showed only limited evidence of attenuation on longer term (6 months) oral therapy with pimobendan 2.5 or 5mg twice daily. Adjunctive therapy with pimobendan 1.25 to 5mg twice daily for periods of 3 to 6 months improved exercise tolerance on symptom-limited exercise testing, New York Heart Association (NYHA) functional class, and quality of life, and additionally reduced the need for hospitalisation in patients with moderate to severe chronic heart failure. Pimobendan appears to be well tolerated at therapeutic doses (1.25 to 5mg twice daily) in patients with chronic heart failure, and preliminary indications suggest that it is largely devoid of the proarrhythmic effects of classical phosphodiesterase III inhibitors. Although information regarding the long term effects of pimobendan on mortality is currently lacking, the drug nevertheless shows potential benefit as an adjunctive therapy in patients with chronic heart failure.

Administration, Oral↗

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

Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.

Combining tazobactam, a beta-lactamase inhibitor, with the ureidopenicillin, piperacillin, successfully restores the activity of piperacillin against beta-lactamase-producing bacteria. Tazobactam has inhibitory activity, and therefore protects piperacillin against Richmond and Sykes types II, III, IV and V beta-lactamases, staphylococcal penicillinase and extended-spectrum beta-lactamases. However, tazobactam has only species-specific activity against class I chromosomally-mediated enzymes. Resistant organisms include some Citrobacter spp., Enterobacter spp., Serratia spp., Xanthomonas maltophilia and Enterococcus faecium. Consistent with its in vitro activity, preliminary clinical data indicate that the fixed combination of piperacillin/tazobactam (dose ratio 8:1) is effective in the treatment of moderate to severe polymicrobial infections, including intra-abdominal, skin and soft-tissue and lower respiratory tract infections. In limited comparative trials, piperacillin/tazobactam demonstrated equivalent or better efficacy than standard comparator regimens in these infections. Piperacillin/tazobactam in combination with an aminoglycoside was effective in the empirical treatment of fever in patients with neutropenia and compared favourably with ceftazidime in combination with an aminoglycoside, although second-line therapy with a glycopeptide antibiotic may be indicated in unresponsive episodes. Data from phase III trials indicate that piperacillin/tazobactam has a tolerability profile typical of a penicillin agent. Piperacillin/tazobactam provides a broad spectrum of antibacterial activity in a convenient single formulation suitable for use in the treatment of polymicrobial infections. Possible limitations concern its restricted activity against class I beta-lactamases, enzymes that are becoming increasingly important in the nosocomial environment. Combined therapy with an aminoglycoside may be necessary in more serious infections.

Animals↗

PubMed1994

Anagrelide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of thrombocythaemia.

Anagrelide, an orally active quinazolin, induces thrombocytopenia in humans and has therefore been evaluated for use in conditions associated with thrombocythaemia. In patients with essential or myeloproliferative thrombocythaemia, anagrelide (usually 1 to 4 mg/day) produced sustained reductions in platelet counts for 1 to more than 28 months and also reduced the incidence of disease-related symptoms. 60 to 93% of patients responded to anagrelide therapy with clinically significant reductions in platelet count. Anagrelide has a tolerability profile different from that of most other agents used in the treatment of thrombocythaemia; most adverse effects are related to its vasodilatory or positive inotropic properties. Anagrelide has a high specificity towards megakaryocytes (and thus decreases platelet levels), although haematocrit is also reduced in some patients. If longer term trials confirm the lack of leukaemogenic and mutagenic potential with this drug, anagrelide may become the agent of choice for the treatment of thrombocythaemia, especially in younger patients in whom the risk of leukaemogenic transformation with some alternative drugs is of particular concern.

Adolescent↗

PubMed1994

Teicoplanin. A reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy.

Since an earlier review in the Journal substantial additional data have accumulated, further clarifying the in vitro activity, pharmacokinetic profile, clinical efficacy and tolerability of teicoplanin. Recent therapeutic trials confirm the efficacy of teicoplanin in the treatment of microbiologically confirmed Gram-positive infections, including septicaemia, endocarditis, and infections of skin and soft tissue, bone and joints, and the lower respiratory tract. As teicoplanin can be administered once daily intramuscularly as well as intravenously, it has potential for outpatient treatment of severe Gram-positive infections. Teicoplanin is appropriate as treatment of patients with fever and neutropenia, but there is still controversy over the timing for introduction of glycopeptide antibiotics into therapeutic regimens. Teicoplanin is generally reserved for secondary therapy of patients with documented bacteraemia who fail to respond to initial empirical antibiotic regimens, but probably should be part of the initial empirical regimen in the setting of a high incidence of methicillin-resistant staphylococci. Teicoplanin has a lower propensity than vancomycin to impair renal function when either drug is combined with an aminoglycoside, causes fewer anaphylactoid reactions, and appears to be of comparable efficacy. Thus, teicoplanin may be preferred to vancomycin in the treatment of Gram-positive infections, and where a glycopeptide antibiotic is deemed a necessary inclusion in a regimen for empirical treatment in patients with fever and neutropenia.

Animals↗

PubMed1994

Rifabutin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy.

Rifabutin is a derivative of rifamycin S with activity against mycobacteria including atypical organisms such as Mycobacterium avium and M. intracellulare, also referred to as Mycobacterium avium-intracellulare complex (MAC). To date, rifabutin is the only drug to have been studied in large prospective placebo-controlled trials that has been shown to significantly reduce the incidence of disseminated MAC infection when administered prophylactically as a single agent to patients with acquired immune deficiency syndrome (AIDS). Initial studies also indicate that rifabutin may be a useful component of multiple drug regimens for the treatment of MAC infection, although further studies combining rifabutin with other recently available antimycobacterial drugs are required to determine the most effective regimens. When rifabutin is combined with at least two other antimycobacterial drugs, the combination appears to be of similar efficacy to rifampicin (rifampin)-containing regimens in patients with newly diagnosed pulmonary tuberculosis. Since available therapy for MAC infection in patients with AIDS is still suboptimal, rifabutin, at present the only first-line agent for prophylaxis against disseminated MAC infection in patients with advanced human immunodeficiency virus (HIV) infection, has the potential to make a valuable contribution to the continuing attempts to preserve the quality of life of patients with AIDS.

AIDS-Related Opportunistic Infections↗