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Biomedical subjects

D Faulds

Publications and source records attributed to D Faulds.

At least 109 records · Page 6Linked to original sources

Moxonidine. A review of its pharmacology, and therapeutic use in essential hypertension.

Interest in centrally acting antihypertensive agents has recently been renewed with the development of drugs that are associated with fewer central adverse effects (e.g. sedation, dry mouth) than the older drugs in this class. Moxonidine reduces sympathetic outflow and hence lowers blood pressure through stimulation of central imidazoline receptors. Blood pressure is decreased by 10 to 20% during moxonidine treatment, with about 70% of patients with mild to moderate hypertension achieving a diastolic pressure of < 90mm Hg. The relatively few published comparative studies demonstrate that moxonidine has efficacy comparable with that of clonidine, prazosin, atenolol, nifedipine, captopril and hydrochlorothiazide. It is at least as well tolerated as these agents in trials and, importantly, appears to cause less sedation and dry mouth than clonidine. Compliance may be aided by the once- or twice-daily administration schedule with moxonidine, and dosage adjustment is only necessary in patients with moderate renal impairment. While its published clinical data base needs further expanding, moxonidine thus appears to be a more attractive option than oral clonidine, and may be considered along with the other classes of drug used to treat patients with mild to moderate hypertension.

Animals↗

Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders.

Hydroxyethylrutosides is a standardised mixture of semisynthetic flavonoids, mainly mono-, di-, tri-, and tetrahydroxyethylrutosides, which acts primarily on the microvascular endothelium to reduce hyperpermeability and oedema. In patients with chronic venous insufficiency or diabetes, hydroxyethylrutosides improves microvascular perfusion and microcirculation, and reduces erythrocyte aggregation. The preparation also has a possible protective effect on the vascular endothelium. In short to medium term placebo-controlled studies (up to 6 months) hydroxyethylrutosides therapy improved signs and symptoms of chronic venous insufficiency, including venous insufficiency associated with pregnancy and lymphoedema, and was well tolerated. However, the long term effects of hydroxyethylrutosides administration have yet to be demonstrated. The preparation also alleviated symptoms in patients with severe haemorrhoids, although there were no corresponding objective improvements. Hydroxyethylrutosides administration has been associated with reductions in retinal vascular permeability in patients with diabetic retinopathy but has no apparent effect on signs of retinal haemorrhage, although a reduction in oedema and haemorrhage has been reported in other patients receiving oral hydroxyethylrutosides in the acute phase of central retinal vein occlusion. There are only limited effective pharmacological treatment options for patients with chronic venous insufficiency or lymphoedema, and hydroxyethylrutosides clearly improves signs and symptoms of these disorders. While its role in diabetic retinopathy and haemorrhoids requires some clarification, hydroxyethylrutosides therapy shows promise as a useful additional option for the management of oedema and other symptoms of chronic venous insufficiency.

Animals↗

Recombinant granulocyte colony-stimulating factor (rG-CSF): pharmacoeconomic considerations in chemotherapy-induced neutropenia.

Recombinant granulocyte colony-stimulating factor (rG-CSF) therapy is associated with a dose-proportional reduction in the frequency, duration and severity of neutropenia associated with cytotoxic chemotherapy. This is associated with a decrease in the incidence of infection, with subsequent reductions in the number of hospitalisations, days of hospitalisation and antibiotic requirements. These effects produce marked reductions in costs, and could contribute substantially towards offsetting the costs of rG-CSF, although the magnitude of the savings will vary between institutions and with the chemotherapy regimen used. Other benefits include a reduction in the frequency and severity of mucositis, and an improved patient quality of life. However, further research is required to evaluate other potentially important considerations including the targeting of specific patient populations (e.g. those receiving regimens with a curative intent), and additional improvements in patient quality of life and, perhaps, mortality. Thus, although specific pharmacoeconomic analyses are limited, preliminary evidence indicates that rG-CSF, administered prior to the onset of neutropenia in patients receiving cytotoxic chemotherapy, can provide cost reductions both from an institutional and a payor perspective, with even greater potential savings from a societal viewpoint.

Cost-Benefit Analysis↗

Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer.

Mitoxantrone is a dihydroxyanthracenedione derivative which as intravenous mono- and combination therapy has demonstrated therapeutic efficacy similar to that of standard induction and salvage treatment regimens in advanced breast cancer, non-Hodgkin's lymphoma, acute nonlymphoblastic leukaemia and chronic myelogenous leukaemia in blast crisis; it appears to be an effective alternative to the anthracycline component of standard treatment regimens in these indications. Mitoxantrone is also effective as a component of predominantly palliative treatment regimens for hepatic and advanced ovarian carcinoma. Limited studies suggest useful therapeutic activity in multiple myeloma and acute lymphoblastic leukaemia. Regional therapy of malignant effusions, hepatic and ovarian carcinomas has also been very effective, with a reduction in systemic adverse effects. Mitoxantrone inhibits DNA synthesis by intercalating DNA, inducing DNA strand breaks, and causing DNA aggregation and compaction, and delays cell cycle progression, particularly in late S phase. In vitro antitumour activity is concentration- and exposure time-proportional, and synergy with other antineoplastic drugs has been demonstrated in murine tumour models. Leucopenia may be dose-limiting in patients with solid tumours, whereas stomatitis may be dose-limiting in patients with leukaemia. Other adverse effects are usually of mild or moderate severity although cardiac effects, particularly congestive heart failure, may be of concern, especially in patients with a history of anthracycline therapy, mediastinal irradiation or cardiovascular disease. Mitoxantrone displays an improved tolerability profile compared with doxorubicin and other anthracyclines, although myelosuppression may occur more frequently. Thus, mitoxantrone is an effective and better tolerated alternative to the anthracyclines in most haematological malignancies, in breast cancer and in advanced hepatic or ovarian carcinoma. Further studies may consolidate its role in the treatment of these and other malignancies.

Animals↗

Adenosine. An evaluation of its use in cardiac diagnostic procedures, and in the treatment of paroxysmal supraventricular tachycardia.

Adenosine (adenine riboside), administered either as the free base or as the 5'-triphosphate (ATP) by rapid intravenous bolus, depresses atrioventricular (AV) nodal conduction, resulting in transient AV block. Adenosine is the active agent and ATP is rapidly converted to adenosine after exogenous administration. By blocking the anterograde AV nodal limb of a re-entrant circuit, adenosine 6 to 12 mg (or ATP 10 to 20 mg) converts almost all episodes of paroxysmal supraventricular tachycardia (PSVT) involving the AV node within 30 seconds of administration. This is at least equivalent in efficacy to verapamil in adults, and superior to lanatoside C in children, with a considerably more rapid onset of action. Furthermore, if a dose of adenosine is ineffective, the exceptionally short plasma half-life of the adenyl nucleosides (less than 10 sec) allows rapid upward dosage titration until PSVT is terminated. Because the induced conduction block primarily affects the AV node, adenosine is a useful diagnostic tool in patients with broad or narrow QRS complex tachycardia; it terminates arrhythmias dependent on the AV node, unmasks other supraventricular mechanisms during transient AV block, but almost always has no effect on ventricular tachycardia. Noncardiac adverse effects, i.e. flushing, dyspnoea and chest pain, may occur during acute arrhythmia termination or diagnosis with adenosine, and arrhythmias may develop; however, these effects are usually transient (lasting less than 1 minute). Adenosine has also been used to induce coronary vasodilation in patients undergoing thallium-201 single photon emission computed tomography (201Tl SPECT), 2-dimensional echocardiography or positron emission tomography to evaluate suspected coronary artery disease. Intravenous infusion of adenosine 140 micrograms/kg/min for 6 minutes was generally associated with only mild adverse effects. These usually resolved within 1 to 2 minutes of discontinuing adenosine, although occasionally patients required aminophylline and/or nitroglycerin (glyceryl trinitrate). Diagnoses based on the results of scintigraphy were of a sensitivity, specificity and predictive accuracy comparable to those achieved with exercise- or dipyridamole-201Tl SPECT. Adenosine is therefore particularly suitable for the diagnosis of tachycardias and the acute management of PSVT involving the AV node in all age groups, without the risks of cardiac arrest and hypotension associated with verapamil. Furthermore, intravenous adenosine infusion may be used to induce coronary vasodilation in patients unable to perform exercise stress tests for 201Tl scintigraphy, and is well tolerated.

Adenosine↗

Formoterol. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease.

Formoterol, a long-acting beta 2-selective adrenoceptor agonist, produces dose-proportional bronchodilation in patients with obstructive airways disease with a reversible component. A significant effect occurs within minutes of inhalation of a therapeutic formoterol dose and persists for approximately 12 hours. Oral formoterol has a slower onset of action than the inhaled formulations, but also produces prolonged bronchodilatory effects. Inhaled formoterol has shown a therapeutic efficacy equivalent to or better than comparable dosages of the conventional beta 2-agonists salbutamol, fenoterol and terbutaline in short and long term trials, in both adults and children with asthma. Its prolonged duration of action permits a twice-daily dosage regimen and results in improved control of nocturnal symptoms by reducing the 'morning dip'. Formoterol also compares well with oral slow release theophylline. In addition, significantly more patients with chronic obstructive airways disease (COAD) had an improvement in symptoms when treated with formoterol compared with salbutamol or fenoterol. Noncomparative studies indicate formoterol also provides effective prophylaxis of exercise-induced asthma. Development of tachyphylaxis has not been observed. Formoterol is generally well tolerated. Adverse effects observed represent predictable extensions of its pharmacology. Tremor and palpitations are most frequently reported. The incidence of adverse events is dose-proportional and therefore related to the route of administration, being more frequent following oral than inhalation therapy. The long-acting beta 2-agonists, including formoterol, represent a significant advance over current maintenance or prophylactic bronchodilator therapy with intermediate-acting beta 2-agonists such as salbutamol, fenoterol and terbutaline, predominantly because of the twice daily administration regimen. However, comparisons with other long-acting beta 2-agonists, such as salmeterol, evaluation of its role in improving symptom control in patients failing to respond to prophylactic therapy, and clarification of the optimal role of beta 2-agonists in asthma maintenance therapy are required to fully determine the value of formoterol in the management of obstructive airways disease.

Airway Obstruction↗

Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer.

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.

Drug Evaluation↗

Doxacurium. A review of its pharmacology and clinical potential in anaesthesia.

Doxacurium, a benzylisoquinolinium diester, provides nondepolarising neuromuscular blockade (and thus surgical relaxation), without vagolytic or sympathomimetic effects. At equipotent doses, the duration of action of doxacurium is similar to that of the long-acting neuromuscular blocker pancuronium. Supplemental doses of doxacurium administered at approximately 25% recovery reliably increase the depth and duration of neuromuscular blockade without accumulation. Although patients will recover spontaneously from doxacurium neuromuscular blockade, pharmacological reversal with neostigmine is recommended in line with accepted clinical practice, and permits acceleration of recovery when necessary. Doxacurium may also be used to facilitate endotracheal intubation. However, even with large doses onset of action is delayed, suggesting more rapidly acting neuromuscular blocking agents will be preferred when rapid sequence induction and intubation is required. Doxacurium has been successfully used in children, the elderly, and in patients with renal failure, hepatic failure, or cardiovascular disease. The absence of clinically significant effects on cardiovascular parameters and relative lack of histamine release observed in clinical trials indicates that doxacurium is suitable for use in high-risk patient groups. Thus, while there are only a limited number of studies comparing doxacurium with other nondepolarising neuromuscular blockers, particularly other 'cardiostable' agents, its ability to produce sustained effective muscle relaxation without significantly affecting the cardiovascular system or inducing histamine release would seem to make it a preferred agent for surgery of longer duration, particularly in high-risk patient groups.

Anesthesia↗

Idarubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer.

Idarubicin is a 4-demethoxy-anthracycline analogue of daunorubicin which, when administered intravenously in combination with cytarabine, has therapeutic efficacy superior to that of standard induction and salvage treatment regimens in acute myelogenous leukaemia. Idarubicin alone or in combination regimens has also been effective in limited studies in patients with other acute leukaemias, advanced breast cancer, multiple myeloma and non-Hodgkin's lymphoma. Idarubicin is more lipophilic than its parent drug daunorubicin. It intercalates DNA, induces DNA strand breaks and delays cell cycle progression. Leucopenia is often dose-limiting in patients with solid tumours treated with idarubicin, and most other adverse effects are similar in incidence and severity to those experienced with other anthracycline cytotoxic agents, except for alopecia which appears to occur with a reduced incidence and severity. Cardiotoxic effects have been reported with idarubicin as with other anthracyclines, but animal data and preliminary clinical findings suggest the possibility of reduced cardiotoxicity with idarubicin--a potentially important advantage if confirmed on further study. A maximum cumulative dose of idarubicin beyond which the incidence of cardiotoxicity rapidly increases has not been determined. Thus, intravenous idarubicin is a useful alternative to other anthracyclines (particularly in combination with cytarabine) in the treatment of acute myelogenous leukaemia, and there is some evidence that it is less cardiotoxic than other anthracycline drugs. Further studies are required to establish the use of intravenous idarubicin as a replacement for other intravenous anthracyclines, especially its effect on response duration and survival, and to confirm the evidence of reduced cardiotoxic effects. The role of idarubicin as consolidation and maintenance therapy for various malignancies requires further investigation, as does the potential use of oral idarubicin which is currently under development.

Animals↗

Ofloxacin. A reappraisal of its antimicrobial activity, pharmacology and therapeutic use.

Ofloxacin is a fluoroquinolone whose primary mechanism of action is inhibition of bacterial DNA gyrase. In vitro it has a broad spectrum of activity against aerobic Gram-negative and Gram-positive bacteria, although it is poorly active against anaerobes. Ofloxacin, unlike most other broad spectrum antibacterial drugs, can be administered orally as well as intravenously. Penetration into body tissues and fluids is highly efficient. Clinical trials with orally and intravenously administered ofloxacin have confirmed its potential for use in a wide range of infections, where it has generally proved as effective as standard treatments. Ofloxacin in well tolerated, and in comparison with other available fluoroquinolones is less likely to cause clinically relevant drug interactions. Ofloxacin thus offers a valuable oral treatment (with an option for intravenous administration if necessary) for use in a wide range of clinical infections, but with a particular advantage in more severe or chronic infections when recourse to parenteral broad spectrum agents would normally be required, thereby providing cost savings and additionally allowing outpatient treatment.

Bacterial Infections↗

Colfosceril palmitate. A review of the therapeutic efficacy and clinical tolerability of a synthetic surfactant preparation (Exosurf Neonatal) in neonatal respiratory distress syndrome.

Colfosceril palmitate (dipalmitoylphosphatidylcholine) is the primary surface-active agent of natural lung surfactant and the major constituent of exogenous surface replacement preparations. Exogenous surfactants derived from either natural (i.e. animal and human) or synthetic sources are indicated for the prophylaxis and treatment of neonatal respiratory distress syndrome. One of the synthetic surfactants, Exosurf Neonatal, is the focus of this review. This preparation is composed of colfosceril palmitate plus cetyl alcohol and tyloxapol, which facilitate rapid spreading and adsorption of the surface-active agent at the air-alveolar interface. For review purposes, this preparation is referred to only as colfosceril palmitate. Comparative trials with air placebo have shown that colfosceril palmitate improves clinical outcome in infants weighing greater than 700g at birth by reducing mortality and increasing the number of infants who survive without bronchopulmonary dysplasia. It also reduces the number of deaths from respiratory distress syndrome and decreases the incidence of air leak events such as pulmonary interstitial emphysema and pneumothorax. Although colfosceril palmitate itself is very well tolerated and does not increase the incidence of most complications of prematurity or of respiratory distress syndrome, its use is associated with a higher incidence of apnoea of prematurity and pulmonary haemorrhage compared with air placebo, possibly because of earlier extubation of surfactant-treated infants following an improved clinical course and decreased pulmonary vascular resistance secondary to improved ventilation, respectively. Colfosceril palmitate thus has an established efficacy in the prophylaxis and treatment of premature infants with respiratory distress syndrome. Ongoing trials may identify whether prophylactic or rescue administration of the surfactant preparation is the preferred approach and whether different dosage regimens or different administration techniques impart greater therapeutic efficacy. Importantly, it also remains to be determined whether any of the available surfactant preparations, including Exosurf Neonatal, will provide distinct therapeutic advantages over the others.

1,2-Dipalmitoylphosphatidylcholine↗

Salmeterol xinafoate. A review of its pharmacological properties and therapeutic potential in reversible obstructive airways disease.

Salmeterol xinafoate, like salbutamol (albuterol), is a saligenin derivative, and a selective beta 2-adrenoceptor agonist. It produces bronchodilation for at least 12 hours following inhalation of a single 50 micrograms dose. Salmeterol is intended for regular twice-daily treatment of reversible airways obstruction and not for immediate symptomatic relief, and when used in this manner, 50 micrograms twice daily is more effective than salbutamol 200 micrograms or terbutaline 500 micrograms administered 4 times daily, or individually titrated oral doses of theophylline in improving objective and subjective criteria of efficacy in patients with mild to moderate asthma. Salmeterol 100 micrograms inhaled twice daily may provide better control than the lower dose in patients with severe asthma. The long duration of effect of salmeterol makes it particularly suitable for treating patients with nocturnal asthma in whom it improves sleep quality. The place of salmeterol, like that of other beta 2-adrenoceptor agonists used regularly in the treatment of asthma, is being debated. Patients in need of regular beta 2-agonist therapy should also be regarded as candidates for inhaled corticosteroids to counteract underlying inflammation. Thus, salmeterol may be particularly useful in patients requiring regular treatment with beta 2-agonists for nocturnal asthma and results of trials in progress involving large numbers of patients are awaited with interest.

Administration, Inhalation↗

Break-join recombination in phage lambda.

In phage lambda, when DNA replication is blocked, recombination mediated by the Red pathway occurs only near the double-chain break site, cos, that defines the termini of the virion chromosome. The recombinants initiated by cos contain newly synthesized DNA near cos, in amount corresponding to a few percent of the length of lambda. A restriction enzyme cut delivered to one parent far from cos results in elevated recombination near the restriction site. Recombinants induced by this cut have a similarly small amount of DNA synthesis in these replication-blocked crosses. When restriction cuts are introduced in the presence of normal amounts of all of the DNA replication enzymes, many of the resulting recombinants still enjoy, at most, a small amount of DNA synthesis associated with the exchange event. Thus, these experiments fail to support the previously considered possibility that Red-mediated recombination in lambda proceeds largely through a break-copy pathway.

Bacteriophage lambda↗

Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections.

Ganciclovir is a nucleoside analogue with antiviral activity in vitro against members of the herpes group and some other DNA viruses. It has demonstrated efficacy against human cytomegalovirus infections and should be considered a first-line therapy in the treatment of life- or sight-threatening cytomegalovirus infection in immunocompromised patients. Clinical efficacy varies with the underlying aetiology of immunocompromise and the site of disease, and prompt diagnosis and early treatment initiation appear to improve the response. In patients with cytomegalovirus pneumonia, particularly bone marrow transplant recipients, concomitant administration of cytomegalovirus immune globulin may significantly improve clinical outcome. Maintenance therapy to prevent recurrence is usually required by bone marrow transplant recipients until the recovery of adequate immune function, whereas AIDS patients may require indefinite ganciclovir maintenance therapy to prevent disease progression, as ganciclovir (like other antivirals) does not eradicate latent viral infection. Haematological effects occur relatively frequently during ganciclovir administration but are usually reversible. Ganciclovir has not been directly compared with other antiviral drugs because of the absence until recently of other effective treatments. However, comparative studies with foscarnet, particularly in cytomegalovirus retinitis, will be of considerable interest. Thus, ganciclovir represents a major advance in the therapy of severe cytomegalovirus infections in immunocompromised patients. Comparative studies, and investigation of ways of reducing toxicity (intravitreal administration; concomitant use of stimulants of haematopoiesis; use in conjunction with other antivirals with differing mechanisms of action), may further expand its eventual role.

Animals↗

Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders.

Ticlopidine inhibits platelet aggregation induced by adenosine diphosphate (ADP) and most other platelet agonists in ex vivo studies of human platelets. The drug also improves other abnormalities of platelet function seen in patients with cerebrovascular disease, peripheral arterial disease, ischaemic heart disease or other conditions involving platelet hyperaggregation. Abnormal platelet activity has been implicated in a variety of clinical conditions in which patients are at high risk of thromboembolic events, and thus the effectiveness of ticlopidine has been investigated in such patients. Since the initial review of the drug appeared in the Journal, data from several large multicentre studies have shown that ticlopidine has a substantial benefit to offer patients who have experienced transient ischaemic attacks or stroke, and in those with peripheral arterial disease or ischaemic heart disease. Ticlopidine reduces the incidence of further stroke, myocardial infarction or vascular death, and is superior to placebo and aspirin in this regard in studies of patients with recent stroke or transient ischaemic attacks, or intermittent claudication. Ticlopidine is equally effective in both men and women and also improves symptoms of claudication in patients with peripheral arterial disease, and appears to reduce anginal pain. Patients with subarachnoid haemorrhage and sickle cell disease have shown some improvement with ticlopidine administration. The drug reduces thromboembolic events and re-stenosis in patients undergoing haemodialysis and cardiac surgery, and appears to prevent the progression of nonproliferative diabetic retinopathy. Ticlopidine in large clinical trials is associated with a higher incidence of adverse effects than placebo and an overall incidence similar to aspirin. Most adverse effects do not require withdrawal of treatment. Gastrointestinal symptoms (particularly diarrhoea) are most common, occurring almost twice as frequently with ticlopidine as with aspirin. Other adverse effects associated with ticlopidine include skin rash, haemorrhagic disorders, and haematological effects; these latter effects require careful monitoring of patients during the initial weeks of therapy. In conclusion, ticlopidine is a valuable addition to the prophylactic treatments available for the management of patients with cerebrovascular disease, peripheral arterial disease or ischaemic heart disease, who present a high risk of thromboembolic events. Although tolerability may be a problem for some patients, the overall benefit conferred by the drug would appear to outweigh this potential disadvantage. Because of its antiplatelet activity, ticlopidine has a promising role in other disorders mediated by platelet dysfunction. However, the precise role of the drug in these additional therapeutic indications awaits clarification with wider clinical experience.

Adult↗

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

Teicoplanin is a glycopeptide antibiotic with a molecular structure which is related to that of vancomycin. Gram-positive bacteria such as staphylococci (including methicillin-resistant strains), streptococci, enterococci and many anaerobic Gram-positive bacteria are susceptible to teicoplanin in vitro. Teicoplanin has an exceptionally long half-life, allowing once-daily intramuscular or intravenous administration. Teicoplanin is clinically and bacteriologically effective against a wide variety of Gram-positive infections such as septicaemia, endocarditis, skin and soft tissue infections and infections associated with venous catheters. The drug is equally efficacious against methicillin-resistant and -susceptible staphylococci. Adverse effects with teicoplanin are generally limited to local effects or hypersensitivity reactions. While teicoplanin has the potential for ototoxicity and nephrotoxicity, the incidence appears to be quite low when recommended serum concentrations are maintained. Teicoplanin is a valuable alternative to vancomycin, and providing controlled comparative studies prove equivalent safety and efficacy between the 2 glycopeptides the more easily administered teicoplanin should become the preferred antibacterial agent.

Anti-Bacterial Agents↗

Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis.

Epoetin (recombinant human erythropoietin) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The therapeutic efficacy of epoetin in the treatment of anaemia associated with chronic renal failure has been established, with almost all patients responding with increases in haematocrit and haemoglobin levels, and improvements in quality of life. Some patients demonstrate relative epoetin resistance and require a higher dosage to achieve target haemoglobin and haematocrit levels. Maintenance of an adequate iron supply is essential and iron supplementation is recommended if serum ferritin is below 100 to 150 micrograms/L or transferrin saturation is less than 20%. The incidence of serious adverse effects may be reduced by maintaining a moderate rate of increase in the haematocrit with close monitoring of blood pressure and dialysis efficacy. Individual titration of epoetin dosage is recommended, with increases made in small increments to achieve haematocrit and haemoglobin levels of 30 to 33% and 10 to 12 g/dl, respectively, although the optimal haematocrit for each patient should be individually determined. Some patients will also require a modest increase in heparin dosage because of a possible increase in clotting tendency. Hypertension is the most common adverse effect in patients with chronic renal failure, occurring partially as a result of increasing blood viscosity and peripheral vascular resistance with the correction of anaemia. Maintenance epoetin therapy has been given for more than 2 years without a decrease in responsiveness and does not appear to adversely affect the outcome of renal transplantation. Thus, epoetin represents a significant therapeutic advance in the treatment of anaemia associated with chronic renal failure and should be considered a first option for these patients. Its potential value in the treatment of anaemia associated with other disorders and in facilitating autologous blood donation remains to be fully determined.

Anemia↗