Biomedical subjects

H M Bryson

Publications and source records attributed to H M Bryson.

At least 19 recordsLinked to original sources

PubMed1997

Donepezil.

Donepezil is a specific and potent acetylcholinesterase inhibitor according to in vitro data. It displays primarily noncompetitive inhibitory activity. In vivo, donepezil inhibited acetylcholinesterase activity in human erythrocytes and increased extracellular acetylcholine levels in the cerebral cortex and hippocampus of the rat. Donepezil demonstrated efficacy in tests of reference memory in animals, but had less consistent activity in tests of working memory. Donepezil 5 or 10 mg/day was associated with significant improvements in cognitive function [assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)] after 14 and 30 weeks and patient global function (Clinician's Interview-based Impression of Change incorporating caregiver input score) after 30 weeks, compared with placebo, in patients with mild to moderate Alzheimer's disease. After 2 years, donepezil 5 or 10 mg/day was associated with an ADAS-cog score approximately 4 points better than would be expected in untreated patients with mild to moderate Alzheimer's disease. The most common adverse events reported in association with donepezil 5 mg/day were gastrointestinal events (nausea/vomiting, diarrhoea, gastric upset and constipation) and dizziness. No hepatotoxicity was reported after 12 weeks' treatment.

Aged↗

PubMed1997

Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders.

The central alpha 2 adrenoceptor agonist tizanidine is a myotonolytic agent used in the treatment of spasticity in patients with cerebral or spinal injury. Wide interpatient variability in the effective plasma concentrations of tizanidine means that the optimal dosage must be titrated over 2 to 4 weeks for each patient (dosages of 2 to 36 mg/day have been used in clinical trials). Maximum effects occur within 2 hours of administration. Antispastic efficacy has been demonstrated for tizanidine in placebo-controlled trials, with reduction in mean muscle tone scores of 21 to 37% versus 4 to 9% for patients receiving placebo. Improvement in muscle tone occurred in 60 to 82% of tizanidine recipients, compared with 60 to 65% of baclofen and 60 to 83% of diazepam recipients. Spasm frequency and clonus are also reduced by tizanidine. The most common adverse effects associated with tizanidine are dry mouth and somnolence/drowsiness. Muscle strength, as assessed by objective means, appears not to be adversely affected by tizanidine and subjective muscle weakness is reported less often by tizanidine recipients than by those receiving baclofen or diazepam. Global tolerability was assessed as good to excellent in 44 to 100% of patients receiving tizanidine, compared with 38 to 90% of baclofen and 20 to 54% of diazepam recipients. In conclusion, tizanidine is an antispastic agent with similar efficacy to that of baclofen and a more favourable tolerability profile. While drowsiness is a frequently reported adverse effect with both agents, subjective muscle weakness appears to be less of a problem with tizanidine than with baclofen. Tizanidine, therefore, appears to be an attractive therapeutic alternative for patients with spasticity associated with cerebral or spinal damage.

Adrenergic alpha-Agonists↗

PubMed1997

Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression.

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.

Animals↗

PubMed1997

Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections.

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with in vitro activity against most urinary tract pathogens. It is particularly active against Escherichia coli, and Citrobacter, Enterobacter, Klebsiella, Serratia and Enterococcus spp. There appears to be little cross-resistance between fosfomycin and other antibacterial agents, possibly because it differs from other agents in its general chemical structure and site of action. In its new formulation as the oral tromethamine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean elimination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentrations occur within 4 hours and remain high (> 128 mg/L) for 24 to 48 hours, which is sufficient to inhibit most urinary tract pathogens. In clinical trials in patients with acute uncomplicated lower urinary tract infection, single-dose fosfomycin tromethamine therapy was effective, and comparable with several other antibacterial agents given either as single-dose or multiple-dose treatments [e.g. beta-lactam and fluoroquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitrofurantoin and pipemidic acid]. Bacteriological eradication rates of 75 to 90% were achieved 5 to 11 days after therapy, with eradication rates of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind comparisons with ciprofloxacin, cotrimoxazole and nitrofurantoin, 99% of fosfomycin tromethamine recipients and 100% of patients receiving comparator agents were considered clinically cured or improved after therapy. Fosfomycin tromethamine is well tolerated, with a low incidence of adverse events. These comprise mainly gastrointestinal symptoms that are transient, mild and self-limiting. Thus, fosfomycin tromethamine achieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerated. The single-dose administration regimen and favourable US pregnancy category rating of fosfomycin tromethamine should also encourage its use in this indication.

Acute Disease↗

PubMed1997

Sparfloxacin. A review of its antibacterial activity, pharmacokinetic properties, clinical efficacy and tolerability in lower respiratory tract infections.

Sparfloxacin is a fluoroquinolone antibacterial agent with activity against a broad range of Gram-negative and Gram-positive organisms including Streptococcus pneumoniae, one of the main pathogens in community-acquired pneumonia. In this infection, sparfloxacin has shown efficacy similar to that of amoxicillin, erythromycin, roxithromycin, amoxicillin/clavulanic acid and amoxicillin plus ofloxacin, producing clinical cure rates of 80 to 84% assessed by intention-to-treat analyses in European or multinational trials. US studies showed similar results for sparfloxacin to those for erythromycin and cefaclor. Sparfloxacin was also as effective as all other comparator drugs in patients with other lower respiratory tract infections, usually acute exacerbations of chronic obstructive pulmonary disease (COPD). The profile of adverse effects for sparfloxacin is generally similar to that of other quinolones: gastrointestinal discomfort and CNS effects are the most common in clinical trials. Sparfloxacin causes fewer gastrointestinal disturbances than agents such as amoxicillin and erythromycin and doses not interact with theophylline, an important consideration when treating patients with respiratory disease. Its long elimination half-life permits once-daily dosage regimens. On the other hand, there are infrequent reports of prolonged QTc interval (3% increase) during sparfloxacin therapy. Photosensitivity occurs more frequently than with the other fluoroquinolones (2% of patients in an ongoing postmarketing study and 7.9% of those in US trials), and requires ongoing surveillance. In summary, the good activity of sparfloxacin against S. pneumoniae and other respiratory pathogens supports its use in lower respiratory tract infections, particularly community-acquired pneumonia. Its profile of good efficacy, once-daily dosage, good gastrointestinal tolerability and lack of interaction with theophylline are advantageous, but clinicians and patients must be alert to the possibility of photosensitivity reactions. On this basis, sparfloxacin, when appropriately prescribed, can provide the clinician with a useful alternative treatment option for these common infections.

Animals↗

PubMed1997

Cisatracurium besilate. A review of its pharmacology and clinical potential in anaesthetic practice.

Cisatracurium besilate (besylate) is a nondepolarising neuromuscular blocking agent with an intermediate duration of action. It is the R-cis, R'-cis isomer of atracurium besilate and is approximately 3-fold more potent than the mixture of isomers that constitute the parent drug. The ED95 for cisatracurium besilate (dose required to produce 95% suppression of twitch response to nerve stimulation) in adults is 0.05 mg/kg during N2O/O2 opioid anaesthesia. As for atracurium besilate, the primary route of elimination of cisatracurium besilate is by spontaneous degradation. Cisatracurium besilate is not associated with dose-related histamine release (at bolus doses of < or = 8 x ED95) and, consistent with this, has demonstrated cardiovascular stability in both healthy patients (< or = 8 x ED95) and those with coronary artery disease (< or = 6 x ED95). In clinical trials, cisatracurium besilate has been used successfully to facilitate intubation (at 2 to 4 x ED95) and as a muscle relaxant during surgery and in intensive care. Compared with vecuronium, cisatracurium besilate was associated with a significantly faster recovery after continuous infusion in patients in intensive care. Relative to atracurium besilate, cisatracurium besilate has a lower propensity to cause histamine release is more potent but has a slightly longer onset time at equipotent doses. It also offers a more predictable recovery profile than vecuronium after prolonged use in patients in intensive care. Thus, comparative data provide some indication of the potential of cisatracurium besilate as an intermediate-duration neuromuscular blocking agent but further comparisons with other like agents are required to define precisely its relative merits.

Adult↗

PubMed1996

Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction.

Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the diameter of cavernous arteries; this leads to erection. Following intracavernous administration, alprostadil is either locally metabolised or rapidly cleared from the penis into the systemic circulation where it is extensively metabolised by the lungs. Studies suggest that long term use of intracavernous alprostadil may increase penile blood flow, although the clinical relevance of this is not currently known. In men with erectile dysfunction (ED), short term trials have shown that intracavernous alprostadil is superior or equal, in inducing erections, to other intracavernous agents such as papaverine, the combination of papaverine plus phentolamine, linsidomine and topical nitroglycerin (glyceryl trinitrate). Intracavernous alprostadil induced erections in around 70% of patients with ED of various origins in short term studies. 49 to 84% of patients accept the offer of joining self-injection programmes and 13 to 60% of these patients withdraw from such programmes for a variety of reasons. At therapeutic doses, intracavernous alprostadil is well tolerated. The most common adverse event of transient penile pain occurred in around one-third of patients and in 11% of injections, causing 3 to 5% of patients to withdraw from self-injection programmes. Potentially serious adverse events such as priapism and fibrosis occurred in 4 and 8% of patients. Overall, available data suggest that the efficacy of intracavernous alprostadil is superior or equal to that of other erectogenic agents which are in use. Furthermore, the drug is well tolerated especially with regard to serious adverse events. Thus, although further research is necessary to confirm its use in combination with other agents, alprostadil appears likely to become the intracavernous agent of choice for the management of erectile dysfunction.

Alprostadil↗

PubMed1996

Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states.

Amitriptyline is a tricyclic antidepressant agent which also has analgesic properties. Whether its analgesic effects are linked to its mood-altering activity or attributable to a discrete pharmacological action (or a combination of both) is unknown. Clinical trials demonstrate that oral amitriptyline achieves at least a good or moderate response in up to two-thirds of patients with post-herpetic neuralgia and three-quarters of patients with painful diabetic neuropathy, neurogenic pain syndromes that are often unresponsive to narcotic analgesics. Amitriptyline has also demonstrated efficacy in heterogeneous groups of patients with chronic non-malignant pain. Other possible areas of use for amitriptyline are in patients with fibromyalgia or as an adjuvant for uncontrolled cancer pain, although evidence for the latter application is limited. Adverse events resulting from the antimuscarinic activity of amitriptyline (primarily dry mouth and sedation) are commonly reported, even at the low dosages used for the control of pain. Low starting doses and careful dosage titration may help to minimise these effects. Orthostatic hypotension and tachycardia, sometimes associated with tricyclic antidepressant agents, may also pose a problem in the elderly. In summary, amitriptyline has a valuable place in the treatment of chronic pain conditions that affect the elderly provided that the drug is used judiciously to minimise adverse effects. Importantly, amitriptyline remains the best studied of the antidepressant agents in post-herpetic neuralgia and diabetic neuropathy and is an important and effective treatment option in these syndromes.

Aged↗

PubMed1996

Liarozole.

Liarozole prevents the catabolism of retinoic acid via inhibition of 4-hydroxylase and exhibits retinoid-sparing and retinoid-mimetic effects in vivo. Liarozole is also a potent inhibitor of estrogen (via inhibition of aromatase) and testicular androgen synthesis (inhibition of 17, 20-lyase). Although testosterone levels decrease in vivo after single dose administration of liarozole, testosterone levels normalise as a result of pituitary feedback after multiple doses. Liarozole reduced the tumour size of androgen-dependent and -independent prostatic carcinomas in animal models. Liarozole also demonstrated chemopreventive activity in vivo. In phase I and II trials in patients with relapsed prostate cancer, liarozole achieved a complete response (assessed using prostate specific antigen levels) in 4% and a partial response in 26% of patients. Cutaneous adverse events, similar to those associated with excess levels of retinoic acid, were the most frequently reported events associated with liarozole.

Animals↗

PubMed1996

Imipenem/cilastatin: an update of its antibacterial activity, pharmacokinetics and therapeutic efficacy in the treatment of serious infections.

The prototype carbapenem antibacterial agent imipenem has a very broad spectrum of antibacterial activity, encompassing most Gram-negative and Gram-positive aerobes and anaerobes, including most beta-lactamase-producing species. It is coadministered with a renal dehydropeptidase inhibitor, cilastatin, in order to prevent its renal metabolism in clinical use. Extensive clinical experience gained with imipenem/cilastatin has shown it to provide effective monotherapy for septicaemia, neutropenic fever, and intra-abdominal, lower respiratory tract, genitourinary, gynaecological, skin and soft tissues, and bone and joint infections. In these indications, imipenem/cilastatin generally exhibits similar efficacy to broad-spectrum cephalosporins and other carbapenems and is at least equivalent to standard aminoglycoside-based and other combination regimens. Imipenem/cilastatin is generally well tolerated by adults and children, with local injection site events, gastrointestinal disturbances and dermatological reactions being the most common adverse events. Seizures have also been reported, occurring mostly in patients with impaired renal function or CNS pathology, or with excessive dosage. Although it is no longer a unique compound, as newer carbapenems such as meropenem are becoming available, imipenem/cilastatin nevertheless remains an important agent with established efficacy as monotherapy for moderate to severe bacterial infections. Its particular niche is in treating infections known or suspected to be caused by multiresistant pathogens.

Bacteria↗

PubMed1996

Itraconazole. A reappraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections.

Itraconazole is an orally administered triazole antifungal agent. Its spectrum of activity includes dermatophyte, dimorphic and dematiaceous fungi, yeasts, and some moulds. In clinical trials, mycological cure was attained in approximately 70 to 80, > or = 70 and > or = 80% of patients with, respectively, fingernail and toenail onychomycosis (200 mg/day for 3 months), dermatophytosis (100 mg/day for 2 to 4 weeks) and vaginal candidiasis (400 mg/day for 1 day or 200 mg/day for 3 days). Approximately 20 to 30% of patients with onychomycosis may relapse after completion of therapy; relapse rate data are limited for the other indications. Recently developed intermittent regimens of itraconazole (400 mg/day for 1 week per month for 3 to 4 months) appear to have similar efficacy to standard regimens in the treatment of onychomycosis. Shorter, higher dosage itraconazole treatment regimens (200 or 400 mg/day for 1 week) are also beneficial in dermatomycoses. Discrepancies and limitations of study design hamper conclusions about efficacy relative to other antifungal drugs. Newer intermittent and short course higher dosage itraconazole regimens have also not been evaluated in comparative studies. Available studies show that the efficacy of itraconazole appears to be greater than that of griseofulvin, but similar to or lower than that of terbinafine in patients with dermatophyte onychomycosis or cutaneous fungal infections. Moreover, the efficacy of itraconazole may be similar to or lower than that of fluconazole in the treatment of cutaneous mycoses. Comparative data from patients with acute vaginal candidiasis suggest that itraconazole is at least as effective as intravaginal clotrimazole and oral fluconazole, and superior to intravaginal econazole. These results require confirmation. Prescription-event monitoring data indicate that itraconazole is generally well tolerated. Gastrointestinal disturbances, dizziness and headache occur most commonly; liver toxicity has been rarely described. Its usefulness in some clinical situations may be limited because of its ability to interact with various therapeutic agents. In conclusion, itraconazole along with other established agents should be considered a first-line treatment for patients with extensive or recalcitrant cutaneous fungal infections, mixed dermatophyte and Candida onychomycosis or vaginal candidiasis. It is currently considered a second-line drug for dermatophyte onychomycosis; the use of newer intermittent itraconazole treatment regimens may, however, extend its role in the management of this condition. Although itraconazole offers greater benefit than conventional therapies (griseofulvin and ketoconazole) in terms of efficacy and tolerability, wider clinical experience is required to determine its merits relative to the newer agents, terbinafine and fluconazole.

Absorption↗

PubMed1996

Cidofovir.

Cidofovir is a nucleotide analogue which inhibits viral DNA polymerase and is effective against human cytomegalovirus (CMV) infection. It is phosphorylated to its active form by cellular enzymes. With the long intracellular half-life of its metabolites, cidofovir can be administered weekly during induction and every other week during maintenance therapy. Viral resistance has not been documented in patients treated with cidofovir to date, but has developed in vitro. Immediate cidofovir therapy delayed progression of CMV retinitis compared with deferred treatment in patients with AIDS. Cidofovir also delayed the progression of CMV retinitis relapsing after previous treatment. To avoid nephrotoxicity, probenecid and intravenous saline hydration must be administered with each dose of cidofovir.

Animals↗

PubMed1996

Quinupristin-dalfopristin.

Quinupristin-dalfopristin (RP 59500) is an injectable streptogramin antibiotic. It possesses a wide spectrum of activity against Gram-positive bacteria including methicillin-resistant staphylococci, glycopeptide-resistant. Enterococcus faecium and penicillin-resistant pneumococci. Quinupristin-dalfopristin has activity against some anaerobes and selected Gram-negative pathogens. Quinupristin-dalfopristin, by way synergism of between its 2 components, is unaffected by most forms of bacterial resistance. Rare forms of macrolide-lincosamide-streptogramin group B resistance may affect its activity; however, at present the incidence of strains with this type of resistance remains low. Quinupristin-dalfopristin is bactericidal against streptococci and staphylococci but has weak or no bactericidal activity against enterococci. In a compassionate use programme, 67% of 95 evaluable patients with vancomycin-resistant Gram-positive infections or intolerant of vancomycin showed improvement with eradication of infection.

Animals↗

PubMed1996

Riluzole. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis.

Riluzole, a benzothiazole, affects neurons by 3 mechanisms: by inhibiting excitatory amino acid release, inhibiting events following stimulation of excitatory amino acid receptors and stabilising the inactivated state of voltage-dependent sodium channels. It has demonstrated neuroprotective activity in vivo and in vitro. Results from 2 randomised double-blind placebo-controlled trials in patients with amyotrophic lateral sclerosis (ALS; motor neuron disease) have demonstrated that riluzole can extend survival and/or time to tracheostomy. After 18 months, the relative risk of death or tracheostomy with riluzole 100 mg/day was reduced by 21%. Although riluzole slowed the rate of deterioration in muscle strength in the first trial, this was not confirmed in the second, larger trial. Riluzole had no effect on any other functional or secondary variable. Gastrointestinal effects, anorexia, asthenia, circumoral paraesthesia and dizziness were reported more frequently with riluzole than placebo. Elevated alanine aminotransferase levels were observed in 10.6 versus 3.8% of patients treated with riluzole 100 mg/day versus placebo, leading to treatment withdrawal in 3.8 versus 2.1% of patients. In conclusion, riluzole is the first drug that has been shown to have an effect on survival in patients with ALS. Although the effect of riluzole was modest, it has allowed some insight into the pathogenesis of ALS from which future gains may be made.

Administration, Oral↗

PubMed1995

Topical capsaicin. A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy and osteoarthritis.

Capsaicin, the active principle of hot chili pepper, is thought to selectively stimulate unmyelinated C fibre afferent neurons and cause the release of substance P. Prolonged application of capsaicin reversibly depletes stores of substance P, and possibly other neurotransmitters, from sensory nerve endings. This reduces or abolishes the transmission of painful stimuli from the peripheral nerve fibres to the higher centres. In clinical studies of patients with post-hepatic neuralgia, diabetic neuropathy or osteoarthritis, adjunctive therapy with topical capsaicin achieved better relief than its vehicle in most studies. In a single trial, topical capsaicin in demonstrated similar efficacy to oral amitriptyline in patients with diabetic neuropathy. Topical capsaicin is not associated with any severe systemic adverse effects. However, stinging and burning, particularly during the first week of therapy, is reported by many patients. Topical capsaicin merits consideration as adjuvant therapy in conditions such as post-herpetic neuralgia, diabetic neuropathy and osteoarthritis, where the pain can be chronic and difficult to treat.

Administration, Topical↗

PubMed1995

Amorolfine. A review of its pharmacological properties and therapeutic potential in the treatment of onychomycosis and other superficial fungal infections.

Amorolfine is a structurally unique, topically active antifungal agent, which possesses both fungistatic and fungicidal activity in vitro. Its spectrum of in vitro activity includes dermatophyte, dimorphic, some dematiaceous and filamentous fungi, and some yeasts. In clinical trials, application of amorolfine 5% nail lacquer once or twice weekly for up to 6 months produced mycological and clinical cure in approximately 40 to 55% of patients with mild onychomycosis 3 months after cessation of therapy. Overall cure and improvement was observed in approximately 85 to 90% of patients with superficial dermatomycoses following treatment with amorolfine 0.25% cream for up to 6 weeks. However, few controlled, comparative trials are available for these different mycoses, and only small numbers of patients have been evaluated to date. Both preparations appear to be well tolerated; only minor localised adverse events have been reported in clinical trials. At present, the major potential indication for topical amorolfine appears to be onychomycosis. Within this clinical setting, amorolfine should be reserved for patients with mild infection without nail matrix involvement. Systemic therapy, however, remains essential for patients with severe intractable onychomycosis involving the nail bed. Evidence to date does not clarify whether the use of adjuvant topical amorolfine reduces the need for systemic therapy in patients with severely infected nails, or whether amorolfine is beneficial in individuals unresponsive to other treatment options.

Animals↗

PubMed1995

Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications.

Epoetin alfa is a recombinant form of the principal hormone responsible for erythrogenesis, erythropoietin. Already an established treatment for anaemia associated with renal failure, epoetin alfa may also be used to correct anaemia in other patient groups. The drug increases the capacity for autologous blood donation in patients scheduled to undergo surgery and attenuates the decrease in haematocrit often seen in untreated autologous donors. However, transfusion requirements did not significantly decrease in many trials. Epoetin alfa also accelerates red blood cell recovery after allogeneic--but not autologous--bone marrow transplant. Limited data in patients with adult rheumatoid arthritis suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall clinical rheumatological status may not improve. However, the drug did improve quality of life in a small cohort of children with juvenile rheumatoid arthritis in addition to correcting anaemia. Response rates to treatment with epoetin alfa in patients with anaemia associated with cancer range between 32 and 85%. Anaemia associated with cancer chemotherapy also responds well to treatment with the drug as does anaemia associated with zidovudine therapy in patients with acquired immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as treatment for anaemia of prematurity have used different methodologies and dosages, making overall analysis difficult. Nevertheless, it appears that high dosages are necessary for response. Results from 1 study suggest that treatment with epoetin alfa appears to be more costly than transfusional support in this application; the relevance of this finding is questionable, however, given that the aim of treatment with epoetin alfa is elimination of transfusion requirements. The incidence of many adverse events associated with epoetin alfa treatment in patients with renal failure (hypertension, seizures and thromboembolic events) has been minimal in patients without renal failure. Adverse events occurred at a similar rate in placebo and epoetin alfa recipients in placebo-controlled trials evaluating the use of the drug as treatment for anaemia in patients with cancer receiving chemotherapy or patients with AIDS receiving zidovudine. In summary, epoetin alfa is an effective alternative to blood transfusion, reducing anaemia and producing consequent improvements in quality of life in many nonrenal applications. It was more effective than placebo in a number of double-blind trials and may be particularly useful as treatment for anaemia associated with other drugs such as cisplatin and zidovudine.

Absorption↗

PubMed1995

Cabergoline. A review of its pharmacological properties and therapeutic potential in the treatment of hyperprolactinaemia and inhibition of lactation.

Cabergoline is a synthetic ergoline which shows high specificity and affinity for the dopamine D2 receptor. It is a potent and very long-acting inhibitor of prolactin secretion. Prolactin-lowering effects occur rapidly and, after a single dose, were evident at the end of follow up (21 days) in puerperal women, and up to 14 days in patients with hyperprolactinaemia. In the only comparative study to date, cabergoline 0.5 to 1.0 mg twice weekly was more effective than bromocriptine 2.5 to 5.0 mg twice daily in the treatment of hyperprolactinaemic amenorrhoea, restoring ovulatory cycles in 72% of women and normalising plasma prolactin levels in 83%, compared with 52 and 58%, respectively, for bromocriptine. In the prevention of puerperal lactation, a single dose of cabergoline 1.0mg was as effective as bromocriptine 2.5mg twice daily for 14 days. A significantly lower incidence of rebound lactation in the third postpartum week was seen with cabergoline. Unpublished data suggest cabergoline 0.25mg twice daily for 2 days is effective in suppressing established puerperal lactation in about 85% of women. Nausea, vomiting, headache and dizziness are characteristic adverse events of the dopaminergic ergot derivatives. Cabergoline appears to be better tolerated than bromocriptine in both patients with hyperprolactinaemia and postpartum women. Most patients intolerant of other ergot derivatives can tolerate cabergoline. Bromocriptine use in the puerperium has been associated with an increased risk of serious thromboembolic events. However, there are no such reports with cabergoline and whether these events will become associated with other dopaminergic agents is unknown. The teratogenic potential of cabergoline has not been extensively investigated in humans. Ten congenital abnormalities have been reported in 199 cabergoline-associated pregnancies. Although there is no pattern to these abnormalities, the limited experience with cabergoline in pregnancy means the drug cannot be considered as a first-line therapy for the treatment of infertility associated with hyperprolactinaemia. At this stage of its development, cabergoline will prove useful in patients with hyperprolactinaemia who have failed treatment with, or are intolerant of, other dopamine agonists such as bromocriptine. If drug treatment is required for the prevention or suppression of puerperal lactation, cabergoline offers significant advantages over bromocriptine and should become the drug treatment of first choice for this indication.

Administration, Oral↗