Biomedical subjects

K L Goa

Publications and source records attributed to K L Goa.

At least 73 records · Page 4Linked to original sources

PubMed1998

Raloxifene.

Raloxifene is a selective estrogen receptor modulator which mimics the effects of estrogens on bone and blood lipid levels without stimulatory effects on the breast or uterus. Raloxifene inhibits estrogen-dependent proliferation of human breast cancer cells in vitro and development of induced mammary tumours in rats in vivo. Raloxifene inhibits bone resorption induced by estrogen deficiency in murine and human studies and lowers serum cholesterol levels. In clinical studies in postmenopausal women, raloxifene 60 mg/day for 2 years significantly increased bone mineral density compared with placebo. In comparative clinical studies, raloxifene 60 mg/day had more modest effects than conjugated estrogens 0.625 mg/day on bone resorption and formation parameters and appeared to be less effective in increasing bone mineral density. In older postmenopausal women with existing bone fractures, raloxifene 60 or 120 mg/day for 1 year produced modest increases in bone mineral density. The most common treatment-related adverse events in raloxifene recipients were hot flushes and leg cramps. The risk of venous thromboembolic events is increased during raloxifene therapy. In contrast with conjugated estrogens 0.625 mg/day, raloxifene 200 or 600 mg/day for 8 weeks or 150 mg/day for 1 year did not produce endometrial proliferation.

Animals↗

PubMed1998

Bicalutamide in advanced prostate cancer. A review.

UNLABELLED: Bicalutamide is a nonsteroidal antiandrogen with a long elimination half-life (t1/2) that permits once-daily administration. When combined with a gonadorelin (gonadotrophin releasing hormone; GnRH) agonist in maximum androgen blockade (MAB) regimens, bicalutamide 50 mg once daily is at least as effective as flutamide 250 mg 3 times daily, as shown in a large randomised trial. Rate of treatment failure, the primary end-point, was significantly lower at 49 weeks with bicalutamide in this study, mainly because of a lower rate of withdrawal due to adverse events. Final results at a median follow-up of 160 weeks revealed longer median times to progression and death with bicalutamide than flutamide, but between-group differences were not significant overall. Although early trials demonstrated clinical benefits with bicalutamide 50 mg/day as monotherapy, the drug in this dosage is less effective than castration. Increasing the dosage to 150 mg/day has improved its efficacy in patients with non-metastatic disease: combined data from 2 trials demonstrate similar survival with bicalutamide in this dosage compared with castration. Accumulating evidence from these and other studies indicates that sexual interest appears to be better preserved with bicalutamide than with castration. The tolerability profile of bicalutamide is characteristic of antiandrogens, with breast pain and gynaecomastia occurring most often. Bicalutamide has not been causally associated with problems such as interstitial pneumonitis and difficulty with light/dark adaptation seen with nilutamide, and in a 50 mg/day dosage causes a lower incidence of diarrhoea than flutamide 750 mg/day. Changes in hepatic function are generally transient and resolve or improve during therapy or after bicalutamide treatment is withdrawn. CONCLUSIONS: Bicalutamide, with its once-daily regimen and good tolerability, is an attractive option when combined with a GnRH agonist in patients with advanced prostate cancer who are suitable to receive MAB regimens. The role of bicalutamide as monotherapy in the management of this common malignancy is currently being assessed.

Androgen Antagonists↗

PubMed1998

Risedronate.

Risedronate is a pyridinyl bisphosphonate that can be administered orally in lower dosages than other antiresorptive bisphosphonates. Like others of its class risedronate inhibits osteoclast-mediated bone resorption. In experimental models of osteoporosis, risedronate inhibited bone loss and improved trabecular architecture. In patients with Paget's disease, pain diminished or disappeared and serum alkaline phosphatase levels decreased after treatment with oral risedronate 30 mg/day for < or = 3 months. Risedronate 30 mg/day orally for 2 months significantly reduced pain, whereas etidronate 400 mg/day orally for 6 months tended to reduce pain, in a randomised double-blind trial of patients with Paget's disease. Oral risedronate 5 mg/day for < or = 2 years increased bone mass in postmenopausal women with low or normal bone mass. Risedronate 2.5 mg/day prevented bone loss in postmenopausal women treated with glucocorticoids for rheumatoid arthritis. The incidence of gastrointestinal or other adverse events was similar in patients treated with risedronate or placebo in clinical trials.

Animals↗

PubMed1998

Transdermal testosterone.

Nightly application of testosterone transdermal (TTD) system to nonscrotal sites in men with hypogonadism results in a 24-hour serum testosterone concentration profile which mimics the circadian pattern observed in healthy young men. The system also normalises dihydrotestosterone/testosterone and estradiol/testosterone ratios and reduces luteinising hormone levels towards the normal range. A multicentre, open-label study demonstrated that nocturnal erectile response and overall sexual function improved during 12 months' treatment with the TTD system (5 mg/day) in men with hypogonadism. Individual variables of sexual desire, arousal, frequency of sexual activity, orgasm and satisfaction also improved. The TTD system is well tolerated, with application site reactions such as pruritus, burn-like blisters and erythema being the most commonly reported events. Prostate-specific antigen levels and prostate volume remain in the normal range during long term treatment.

Administration, Cutaneous↗

PubMed1998

Zanamivir.

Zanamivir is the first of a new class of selective influenza virus neuraminidase inhibitors. It inhibits both influenza A and influenza B virus replication in vitro. In the ferret model of influenza, zanamivir reduced viral replication and diminished pyrexia associated with the infection. Repeated passage of influenza virus in the presence of zanamivir could produce resistance in vitro. However, there have been no changes in sensitivity to zanamivir in any influenza virus isolates from patients receiving zanamivir in clinical trials. In experimental infection in humans, in which the virus replicates only in the nasal passages, intranasal zanamivir (3.6 to 16 mg) prevented infection with influenza virus. A combination of inhaled (10 mg) and intranasal (6.4 mg) zanamivir for 14 days was effective in preventing influenza in a nursing home setting during an influenza A virus outbreak. Inhaled zanamivir (10 mg) with or without intranasal zanamivir (6.4 mg) reduced the time to alleviation of influenza symptoms compared with placebo in patients with confirmed infection.

Animals↗

PubMed1998

Triflusal.

Triflusal is an antiplatelet agent structurally related to the salicylate group of compounds, but it is not derived from aspirin (acetylsalicylic acid). Platelet antiaggregant properties of triflusal and its active 3-hydroxy-4-trifluoro-methylbenzoic acid metabolite are primarily mediated by specific inhibition of platelet arachidonic acid metabolism. Triflusal, compared with placebo for 6 months, significantly reduced the incidence of nonfatal myocardial infarction in patients with unstable angina. In patients with peripheral arteriopathy, total and pain free walking distances were markedly improved in triflusal compared with placebo recipients. The cumulative event rate for stroke, ischemic cardiopathy and vascular death was lower, but not significantly different, in patients with atherothrombotic stroke who received triflusal than in aspirin recipients. Differences were significant, and favoured triflusal, in a subgroup of patients with > 70% carotid stenosis. Prophylaxis with triflusal for 6 months after aortocoronary vein grafting reduced the number of new distal anastomosis occlusions and the graft attrition rate more than aspirin or placebo. The incidence of deep vein thrombosis or pulmonary embolism in more than 500 patients undergoing hip surgery was similar for these 3 treatments. The amount of blood transfused was significantly reduced in triflusal compared with aspirin recipients who underwent hip surgery. Risk of haemorrhage was also reduced in ischemic stroke patients receiving triflusal versus aspirin.

Adult↗

PubMed1998

Amphotericin-B colloidal dispersion. A review of its use against systemic fungal infections and visceral leishmaniasis.

UNLABELLED: Formulation of amphotericin B with sodium cholesteryl sulphate alters the pharmacokinetic properties of the drug, particularly reducing its distribution to the kidneys. The antifungal activity in vitro of amphotericin B colloidal dispersion (ABCD) is similar to that of conventional amphotericin B (C-AmB) against true pathogenic organisms including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides species and the opportunistic organisms such as Candida and Cryptococcus species. In animal models, ABCD was generally less effective than an identical dose of C-AmB, but overall was more effective because of its improved therapeutic index. Although ABCD appeared to be more effective than C-AmB in resolving infection and improving survival in patients with proven or probable invasive aspergillosis, the retrospective design of the study and the greater prevalence of neutropenia in patients treated with the conventional formulation necessitate cautious interpretation of the results. ABCD has been effective and seldom caused nephrotoxicity in patients with fungal infection who had previously failed to adequately respond or had developed renal toxicity with C-AmB. Similarly, ABCD was effective in patients with proven or suspected fungal infection after bone marrow transplantation. Preliminary results from a pilot study comparing ABCD and C-AmB in patients with neutropenia and persistent fever reported similar response rates with both formulations. ABCD is an effective treatment for visceral leishmaniasis in immunocompetent patients. In 1 study, about 12% of ABCD recipients discontinued the drug because of adverse events; infusion-related events were the most common cause of discontinuation. The renal tolerability of ABCD is better than that of C-AmB. ABCD appears to be an effective alternative to conventional amphotericin B in patients with invasive aspergillosis or visceral leishmaniasis and in those with proven or suspected systemic fungal infection who are intolerant of the conventional formulation or have pre-existing renal impairment. Preliminary data also suggest that ABCD is an alternative to C-AmB when used empirically in patients with neutropenia and fever. Nevertheless, the efficacy of ABCD compared with that of the conventional formulation has yet to be adequately demonstrated and the role of ABCD relative to that of liposomal and other lipid-based formulations has not been determined. CONCLUSIONS: ABCD, like other lipid-based and liposomal formulations of amphotericin B, has been designed to deliver the active drug to the target site, while reducing renal toxicity. The aim of increasing the therapeutic index compared with C-AmB has been achieved.

Amphotericin B↗

PubMed1998

5-Methoxypsoralen. A review of its effects in psoriasis and vitiligo.

UNLABELLED: 5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo. In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity. However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen. In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment. Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally. Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas. Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study. The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials. Adverse hepatic events after oral administration of the drug were uncommon. Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis. CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients. The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established. Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.

5-Methoxypsoralen↗

PubMed1998

Fixed combination verapamil SR/trandolapril.

Verapamil sustained-release (SR)/trandolapril is a combination of a phenylalkylamine calcium antagonist and an angiotensin converting enzyme inhibitor for the management of essential hypertension. Verapamil SR/trandolapril does not adversely influence glucose, insulin or lipid parameters in patients with mild to moderate essential hypertension and type 2 (non-insulin-dependent) diabetes mellitus with or without elevated cholesterol and/or triglyceride levels. Verapamil SR/trandolapril reduces proteinuria to a greater extent than the individual components in patients with diabetic or non-diabetic proteinuria. The antihypertensive efficacy of once daily verapamil SR/trandolapril (180/1 or 180/2 mg) for 8 weeks or 6 months is similar to that of atenolol/chlorthalidone (100/25 mg) and lisinopril/hydrochlorothiazide (20/12.5 mg), and was at least as good as that of metoprolol/hydrochlorothiazide (100/12.5 mg) in a small trial. The reduction in sitting or supine diastolic and systolic blood pressure is greater after verapamil SR/trandolapril (180/2 to 240/4 mg) than after monotherapy with verapamil SR (180 and 240 mg/day) or trandolapril (2 to 8 mg/day). Fewer cardiac events occurred after verapamil SR/trandolapril (240/1 to 360/2 mg/day) than after trandolapril (1 to 2 mg/day) in postmyocardial infarction patients with congestive heart failure. The incidence of adverse events after verapamil SR/trandolapril is similar to that of comparator drugs and the individual components of the combination.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Candesartan cilexetil. A review of its use in essential hypertension.

UNLABELLED: Candesartan cilexetil is completely converted to the nonpeptide angiotensin II receptor blocker candesartan during absorption from the gastrointestinal tract. Candesartan selectively blocks and dissociates slowly from the angiotensin II subtype 1 (AT1) receptor which mediates most of the known activities of angiotensin II. When administered once daily, oral candesartan cilexetil 8 to 32 mg dose-dependently and effectively reduces blood pressure in patients with mild to moderate essential hypertension. In comparative studies, candesartan cilexetil 8 mg/day was as effective as usual therapeutic dosages of enalapril, losartan potassium, hydrochlorothiazide and amlodipine. One study showed candesartan cilexetil 16 mg/day to be more effective than losartan potassium 50 mg/day. Furthermore, the combination of candesartan cilexetil with either hydrochlorothiazide or amlodipine resulted in additive antihypertensive effects. Preliminary evidence suggests that the blood pressure-lowering effects of candesartan cilexetil are associated with the prevention or improvement of end-organ damage in patients with hypertension. However, this requires further confirmation in clinical studies. Candesartan cilexetil improves insulin sensitivity in patients with hypertension and does not affect glucose homeostasis or the serum lipid profile in those with coexisting type 2 (non-insulin-dependent) diabetes mellitus. Candesartan cilexetil is well tolerated in patients with hypertension. Pooled data indicate that the tolerability profile of the drug is not significantly different from that of placebo, with headache being the most commonly reported event. Adverse events are not dose related and are mostly mild to moderate in severity. Candesartan cilexetil is better tolerated than enalapril, primarily because of a reduced incidence of cough, and was not associated with the hypokalaemia or hyperuricaemia seen with hydrochlorothiazide in a study in patients aged > or = 75 years. The drug has an adverse events profile similar to that of losartan potassium in patients with mild to moderate hypertension. CONCLUSIONS: once daily candesartan cilexetil is effective and well tolerated when used once daily (as monotherapy or in combination with other antihypertensive agents) in patients with mild, moderate or severe hypertension. Initially, however, the drug is likely to be used as an alternative to other agents in patients not responding to or intolerant of their current drug therapy.

Aged↗

PubMed1998

Urapidil. A reappraisal of its use in the management of hypertension.

UNLABELLED: Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. CONCLUSIONS: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.

Antihypertensive Agents↗

PubMed1998

Tirofiban. A review of its use in acute coronary syndromes.

UNLABELLED: Tirofiban is an intravenously administered nonpeptide glycoprotein IIb/IIIa receptor antagonist which specifically inhibits fibrinogen-dependent platelet aggregation and prolongs bleeding times in patients with acute coronary syndromes. Adenosine diphosphate (ADP)-induced platelet aggregation returns to near-baseline levels within 4 to 8 hours after cessation of a tirofiban infusion, a finding consistent with the drug's elimination half-life of approximately 2 hours. Three large clinical trials have shown that, when administered with a standard heparin and aspirin regimen, tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction (MI) and in patients undergoing percutaneous revascularisation. In PRISM-PLUS, a study involving 1915 patients with unstable angina/non-Q-wave MI, administration of intravenous tirofiban (0.4 microgram/kg/min loading dose for 30 minutes followed by a 0.10 microgram/kg/min infusion) with heparin for at least 48 (mean 71.3) hours reduced the 7-day risk of the composite end-point of MI, death and refractory ischaemia by 32% compared with heparin alone. The between-group risk reduction remained significant at 30 days (22%) and 6 months (19%). Similarly, in high-risk patients undergoing coronary angioplasty in RESTORE, the addition of tirofiban (10 micrograms/kg bolus in the 3 minutes prior to intervention followed by 0.15 microgram/kg/min for 36 hours) to a standard heparin regimen significantly reduced the risk of ischaemic complications by 38% on day 2 and 27% on day 7 compared with heparin alone. Although interim analysis in PRISM-PLUS showed that the use of tirofiban without heparin increased the 7-day risk of death compared with heparin alone, this finding was inconsistent with the effects of tirofiban on the risk of death in PRISM, a study involving 3232 patients with unstable angina/non-Q-wave MI. Tirofiban is generally well tolerated. Bleeding complications were the most commonly reported events associated with tirofiban in clinical trials, but the rate of major bleeding in tirofiban recipients was not significantly different from that reported with heparin. Thrombocytopenia (platelet count < 90,000 cells/microliter) occurred slightly more frequently with tirofiban (with or without heparin) than with heparin alone. CONCLUSIONS: Tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave MI and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin. Furthermore, the drug has an acceptable tolerability profile. Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.

Acute Disease↗

PubMed1998

Sibutramine. A review of its contribution to the management of obesity.

Sibutramine is an orally administered centrally acting weight management agent apparently devoid of amphetamine-like abuse potential. Its primary (M2; BTS 54,505) and secondary (M1; BTS 54,354) amine metabolites are pharmacologically active and are thought to induce the natural processes leading to enhancement of satiety and thermogenesis by inhibiting serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (norepinephrine) reuptake. In clinical trials, once-daily sibutramine was administered at dosages of < or = 30 mg for < or = 24 weeks and 10 or 15 mg for 1 year in conjunction with reduced calorie intake, increased daily exercise and advice on eating behaviour. Dose-related bodyweight loss was greater with sibutramine than with placebo. Clinical effects were most commonly apparent at dosages > or = 10 mg/day. Weight loss of > 1% within the first month of treatment appears indicative of good long term response with sibutramine. Weight loss was maintained during therapy for 1 year; longer term data are lacking. Weight regain occurred after treatment cessation in studies of < or = 24 weeks' duration; data from longer trials are unavailable. Up to 15% of patients in < or = 6-month studies did not respond to treatment irrespective of dose. Obese patients with type 2 (non-insulin-dependent) diabetes or hypertension lost significantly more mean bodyweight with sibutramine than with placebo, although weight loss was less than that in obese patients without comorbidities. The effect of sibutramine on mean fasting blood glucose levels and plasma lipid levels was unclear. Sibutramine, compared with placebo, statistically significantly increased blood pressure and heart rate in obese patients with or without hypertension when given for up to 12 months. However, after 12 weeks' treatment in hypertensive obese patients, diastolic blood pressure was reduced by similar amounts with sibutramine or placebo. Concerns over potential pressor effects with sibutramine are reflected in the manufacturer's dosage and administration recommendations.

Animals↗

PubMed1998

Risperidone. A pharmacoeconomic review of its use in schizophrenia.

UNLABELLED: The availability of new atypical antipsychotics, such as risperidone, that have higher acquisition costs than conventional treatments has promoted pharmacoeconomic evaluation of their costs and benefits. Risperidone is reported to have superior efficacy to haloperidol and similar efficacy to other atypical antipsychotics. At dosages < or = 8 mg/day, risperidone is generally associated with a lower risk of extrapyramidal symptoms than conventional antipsychotics and may have a more favourable effect on cognitive function and quality of life. Overall treatment costs during the first year of risperidone treatment were lower than in the previous year in a number of studies in patients with schizophrenia, reflecting a reduction in hospitalisation, although costs slightly increased after risperidone initiation in 2 studies. Total treatment costs were not significantly different with risperidone or conventional antipsychotics in a large, prospective naturalistic study. The use of risperidone in preference to conventional antipsychotics in patients with chronic schizophrenia has been supported by several modelled studies, including a cost-effectiveness analysis that compared risperidone and haloperidol in chronic schizophrenia and a cost-utility study that compared the drug with oral haloperidol, depot haloperidol decanoate and depot fluphenazine decanoate for 1 year's treatment of an initially hospitalised chronic schizophrenic patient with moderate symptoms. In another study, the cost-utility ratio for risperidone versus haloperidol was 24,250 Canadian dollars per quality-adjusted life year (year of costing not stated), but only drug costs were considered. Risperidone had favourable cost-benefit ratios relative to conventional antipsychotic treatment in a study that investigated a scenario in which all patients hospitalised with newly diagnosed schizophrenia received conventional antipsychotic therapy for 6 months, and then those who did not respond received a 6-month trial of risperidone or clozapine. The results of 2 limited decision-analytical models did not favour risperidone. One study compared risperidone with oral haloperidol or depot haloperidol decanoate for the outpatient treatment of a schizophrenic patient with a history of relapse and rehospitalisation. The other compared risperidone, olanzapine and oral haloperidol for the treatment of schizophrenia. CONCLUSIONS: Despite its high acquisition cost, risperidone does not increase, and may even reduce, overall treatment costs of schizophrenia by reducing hospitalisation compared with standard treatment regimens. While further pharmacoeconomic evaluation of risperidone as a first-line agent is required, pharmacoeconomic data overall support its use in patients with chronic schizophrenia.

Antipsychotic Agents↗

PubMed1997

Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses.

Olanzapine is a thienobenzodiazepine derivative which displays efficacy in patients with schizophrenia and related psychoses. It has structural and pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the classical antipsychotic haloperidol. In several large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine generally 5 to 20 mg/day was at least as effective as haloperidol (5 to 20mg) and more so than placebo, as assessed by overall rating scales for psychoses. Olanzapine improved negative symptoms to a greater extent than haloperidol in 2 of 3 comparative trials, including the largest trial. Efficacy of olanzapine has a rapid onset (within 1 to 2 weeks). Its clinical benefits appear to be maintained for treatment periods of up to 1 year, as shown by analysis of the extension phase of several trials demonstrating decreased probability of hospitalisation over this period compared with haloperidol. Preliminary data suggest the drug may also improve quality of life. Olanzapine was associated with significantly fewer adverse movement disorders (e.g. akathisia, dystonia, hypertonia, extrapyramidal symptoms) than haloperidol. There have been no reports of agranulocytosis (as occurs with clozapine) or any other haemotoxicity attributed to olanzapine, and the drug has shown minimal effect on prolactin levels. Transient increases in levels of hepatic transaminases seem to be clinically important. The only events recorded more frequently during olanzapine than during haloperidol therapy were weight gain, dry mouth and increased appetite. Although the antipsychotic activity of olanzapine has been well demonstrated. Its efficacy in refractory schizophrenia and its place relative to other atypical antipsychotics remain to be determined. Nevertheless, if the long term tolerability profile of olanzapine is confirmed, the drug should provide a valuable therapeutic alternative in the management of schizophrenia and related psychoses.

Animals↗

PubMed1997

Octreotide long-acting release (LAR). A review of its pharmacological properties and therapeutic use in the management of acromegaly.

Octreotide is a somatostatin analogue: a long-acting release (LAR) formulation of octreotide is designed for once-monthly intramuscular administration. As with native somatostatin, octreotide LAR exerts potent inhibitory effects on the secretion of growth hormone and on various peptides of the gastroenteropancreatic endocrine system. When patients with acromegaly who show a positive response to treatment with subcutaneous octreotide 300 to 600 micrograms/day are switched to octreotide LAR 20 or 30 mg, the resulting decrease in growth hormone levels is stable and sustained. Reductions in growth hormone levels to < 5 micrograms/L for about 4 weeks are seen in 86 to 100% of patients, to < 2 to 2.5 micrograms/L in 39 to 75% and to < 1 microgram/L in 24 to 40%. Levels of insulin-like growth factor-1 (IGF-1) decrease in parallel and are often normalised with repeated drug treatment. There is no evidence of tachyphylaxis with long term therapy (up to 34 months). Treatment with octreotide LAR improves facial appearance and soft tissue thickening, and eliminates or reduces the incidence of symptoms such as headache, fatigue, arthralgia and excessive perspiration. Tumour shrinkage has been noted in some, but not all, patients receiving octreotide LAR, although this has not been widely evaluated in clinical studies. Overall, octreotide LAR is well tolerated, and the mild to moderate gastrointestinal events experienced by up to 50% of patients are of short duration and often subside with continued drug administration. The incidence of gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) increases in patients receiving long term therapy with subcutaneous octreotide, although most patients remain asymptomatic. The incidence of gallbladder abnormalities in patients receiving octreotide LAR compares favourably with that during subcutaneous administration. Glycaemic control is not usually altered during octreotide LAR treatment. In summary, octreotide continues to be the principal pharmacological option for most patients with acromegaly. Octreotide LAR offers the convenience of once-monthly administration compared with daily subcutaneous drug administration. In addition, the good efficacy and tolerability profile of octreotide LAR should enhance patient compliance and acceptability of octreotide therapy and contribute to an improvement in patient quality of life.

Acromegaly↗

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

Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus.

Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data supporting an additional place in managing normotensive patients with microalbuminuria and IDDM. These findings, together with some evidence for an effect of lisinopril in delaying progression of retinopathy and in reducing mortality, suggest a broader role for the drug in managing diabetic vascular complications.

Angiotensin-Converting Enzyme Inhibitors↗