Biomedical subjects

S P Clissold

Publications and source records attributed to S P Clissold.

At least 19 recordsLinked to original sources

PubMed1992

Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease.

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.

Biological Availability↗

PubMed1992

Calcipotriol. A review of its pharmacological properties and therapeutic use in psoriasis vulgaris.

Calcipotriol (calcipotriene) is a vitamin D3 analogue which inhibits epidermal cell proliferation and enhances cell differentiation. In patients with chronic plaque psoriasis involved in short term studies of 6 to 8 weeks' duration, calcipotriol ointment applied twice daily was significantly more effective than betamethasone valerate and dithranol (anthralin). Pooled data from clinical trials show that calcipotriol is well tolerated, with the majority of adverse events being mild and transient local reactions. Topically applied calcipotriol has low hypercalcaemic potential and, in contrast to topical corticosteroids, oral retinoids and orally administered calcitriol, methotrexate and cyclosporin, calcipotriol does not appear to be associated with a risk of serious adverse events. Thus, at this early stage in its clinical development, calcipotriol appears to be an effective and well tolerated topical therapy for the management of psoriasis; if promising preliminary clinical findings are confirmed, calcipotriol will represent a major advance in this difficult area of therapeutics.

Anthralin↗

PubMed1992

Sumatriptan. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache.

Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the acute treatment of migraine headache. Its antimigraine activity is believed to derive from selective vasoconstriction of cranial blood vessels which are dilated and distended during migraine headache and/or from inhibition of neurogenically mediated inflammation in the dura mater. In placebo-controlled comparative studies, sumatriptan reduced migraine headache from 'moderate or severe' to 'mild or none' within 2 hours in 50 to 73% of patients following oral administration of 100 or 200 mg, and within 1 hour in 70 to 80% of patients following subcutaneous doses of 6 to 8 mg or intranasal doses 20 mg into each nostril. In addition, sumatriptan alleviated the accompanying symptoms of nausea, vomiting, and photophobia/phonophobia more effectively than placebo, and permitted higher percentages of patients to resume normal daily activities. Sumatriptan 100 mg orally was more effective in the acute treatment of migraine than oral combination therapy consisting of ergotamine 2 mg plus caffeine 200 mg or aspirin 900 mg plus metoclopramide 10 mg. Pooled data from nearly 5000 patients treated with either oral or subcutaneous sumatriptan in clinical trials indicate that it is well tolerated. However, migraine recurrence within 24 or 48 hours of initial symptom resolution developed in approximately 40% of patients treated with sumatriptan, irrespective of route of administration. It is likely that migraine recurrence is related to the short half-life of the drug (approximately 2 hours). Future studies should attempt to ascertain whether additional doses of sumatriptan will help prevent migraine recurrence in patients with attacks of long duration and if so, should determine the optimum interval between dosages. In conclusion, sumatriptan is an important addition to the range of drugs currently available for acute treatment of migraine. It provides rapid relief from debilitating symptoms in a high percentage of patients, particularly after subcutaneous administration. At this stage in its development a number of questions remain to be answered - most notably whether repeat doses will help prevent recurrent attacks and which patients are most likely to respond to therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and tolerability that is unique in this particular clinical setting.

Acute Disease↗

PubMed1992

Clarithromycin. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic potential.

Clarithromycin is an acid-stable orally administered macrolide antimicrobial drug, structurally related to erythromycin. It has a broad spectrum of antimicrobial activity, similar to that of erythromycin and inhibits a range of Gram-positive and Gram-negative organisms, atypical pathogens and some anaerobes. Significantly, clarithromycin demonstrates greater in vitro activity than erythromycin against certain pathogens including Bacteroides melaninogenicus, Chlamydia pneumoniae, Chlamydia trachomatis, Mycobacterium chelonae subspecies--chelonae and--abscessus, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium avium complex, Legionella spp. and, when combined with its 14-hydroxy metabolite, against Haemophilus influenzae. However, bacterial strains resistant to erythromycin are also generally resistant to clarithromycin. The antimicrobial activity of clarithromycin appears to be enhanced by the formation in vivo of the microbiologically active 14-hydroxy metabolite. In combination, additive or synergistic activity against a variety of pathogens including Haemophilus influenzae, Moraxella catarrhalis, Legionella species (principally Legionella pneumophila) and various staphylococci and streptococci has been demonstrated. Clarithromycin has a superior pharmacokinetic profile to that of erythromycin, allowing the benefits of twice daily administration with the potential for increased compliance among outpatients where a more frequent regimen for erythromycin might otherwise be indicated. The clinical efficacy of clarithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (including those associated with atypical pathogens), skin/soft tissues, and in paediatrics. Clarithromycin was as effective as erythromycin and other appropriate drugs including beta-lactams (penicillins and cephalosporins) in some of the above infections. A most promising indication for clarithromycin appears to be in the treatment of immunocompromised patients infected with M. avium complex, M. chelonae sp. and Toxoplasma sp. Small initial trials in this setting reveal clarithromycin alone or in combination with other antimicrobials to be effective in the eradication or amelioration of these infections. Noncomparative studies have provided preliminary evidence for the effectiveness of clarithromycin in the treatment of infections of the urogenital tract, oromaxillofacial and ophthalmic areas. However, the promising in vitro and preliminary in vivo activity of clarithromycin against Mycobacterium leprae and Helicobacter pylori warrant further clinical trials to assess its efficacy in patients with these infections. Despite the improved pharmacokinetic profile and in vitro antimicrobial activity of clarithromycin over erythromycin, comparative studies of patients with community-acquired infections reveal the 2 drugs to be of equivalent efficacy. However, clarithromycin demonstrates greater tolerability, principally by inducing fewer gastrointestinal disturbances.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1991

Foscarnet. A review of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with cytomegalovirus retinitis.

The pyrophosphate analogue, foscarnet, selectively inhibits the DNA polymerase of human herpes viruses, including cytomegalovirus, and the reverse transcriptase of HIV. Viral replication is therefore prevented, but resumes when the drug is cleared from infected cells. In vitro, the combination of foscarnet and zidovudine (azidothymidine) has an additive effect against cytomegalovirus and acts synergistically against HIV. An improvement in cytomegalovirus retinitis is obtained in over 85% of affected AIDS patients during foscarnet induction therapy, but relapse usually occurs within a month of ceasing treatment. There is a similar duration of remission during maintenance therapy given for 5 days each week, but this can be extended 4- to 5-fold with daily administration of higher doses. In allograft recipients, progression of retinitis can be halted by foscarnet until immune function recovers and eradicates the virus. The incidence of acute renal failure, which is common during foscarnet therapy, may be reduced by dosage adjustment and adequate prehydration. Anaemia, phlebitis, nausea and vomiting, and disturbances in serum calcium and phosphate levels, perhaps resulting from uptake of foscarnet into bone or chelation with ionised calcium, have also been associated with administration of the drug. Cytomegalovirus retinitis is difficult to treat, with few therapeutic options available. Although treatment with foscarnet produces some severe adverse effects, with care these can be minimised, and the drug produces clinical improvement in a large proportion of patients; this is a highly encouraging finding at this stage in its development. Preliminary comparative data indicate that foscarnet and ganciclovir are similarly effective, but foscarnet may have some theoretical advantages in AIDS patients since it can be used in combination with zidovudine without potentiating myelosuppression.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness.

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin, thereby facilitating serotoninergic transmission; this action appears to account for the antidepressant activity observed with this drug. A mean terminal elimination half-life of approximately 24 hours permits once daily administration. Results of short term clinical trials have shown paroxetine to be significantly superior to placebo, and comparable to amitriptyline, clomipramine, imipramine, dothiepin and mianserin in relieving symptoms associated with major depressive disorders. Paroxetine has shown some preliminary promise in the treatment of depressive illness resistant to tricyclic antidepressant therapy but further studies are required before any conclusions can be drawn. Paroxetine in therapeutic doses has been very well tolerated, and the favourable tolerability profile of this agent appears to be its primary advantage over traditional antidepressant agents. Paroxetine causes minimal anticholinergic-type adverse effects, and unlike tricyclic antidepressants, it does not precipitate cardiovascular effects or provoke cardiac conduction disturbances. Nausea has been the most frequently reported adverse event during short term use of paroxetine, but it is generally mild and transient and subsides with continued use. With longer term use headache, sweating and constipation were the most frequently reported side effects but the incidence rate was not significantly different from that noted for comparator antidepressants. Furthermore, the frequency of withdrawal due to adverse effects is less with paroxetine than with tricyclic antidepressant agents. Overall, available data appear to indicate that while the efficacy of paroxetine is similar to that of traditional antidepressant drugs, the newer agent possesses much improved tolerability. In addition, the wide therapeutic index of paroxetine may be beneficial when treating patients with an increased risk of suicide. Thus, paroxetine clearly looks to become a valuable addition to the range of drugs currently available to treat depressive illness. Future research may help to further define the relative place of this newer agent in antidepressant therapy and determine how its overall therapeutic efficacy compares with that of other related antidepressant agents such as fluoxetine.

Amitriptyline↗

PubMed1991

Tenoxicam. An update of its pharmacology and therapeutic efficacy in rheumatic diseases.

Tenoxicam administered orally, rectally or parenterally is an effective analgesic and anti-inflammatory agent for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and various rheumatic conditions such as tendinitis, bursitis, sciatica, back pain and gouty arthritis. In clinical trials its efficacy is at least equivalent to that of other NSAIDs and it is at least as well tolerated as piroxicam and probably better tolerated than diclofenac, indomethacin and ketoprofen. Compared with many other NSAIDs, tenoxicam offers certain advantages in that it is conveniently administered once daily and dosage adjustment is not required in the elderly or in patients with renal or hepatic impairment.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1991

Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis.

Ivermectin, a derivative of avermectin B, is an orally effective microfilaricidal agent. It is the current drug of choice for treating patients infected with the nematode Onchocerca volvulus, which is a major cause of blindness in inhabitants of some tropical areas. Ivermectin is administered orally as a single dose of 150 micrograms/kg given annually. Skin and ocular microfilarial counts are dramatically reduced after the first dose, with some evidence for a resulting decrease in transmission of infection by the blackfly vector. With the exception of rare serious reactions such as severe systemic postural hypotension, ivermectin is generally well tolerated. The drug has the clear advantages of ease of administration and better tolerability compared with diethylcarbamazine and suramin, agents previously used to treat onchocerciasis. Thus, ivermectin is suitable for inclusion in mass treatment programmes and is the best therapeutic option presently available to combat onchocerciasis. As such it provides hope for many thousands of people at risk of becoming blind, and represents a major contribution to tropical medicine.

Animals↗

PubMed1991

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↗

PubMed1990

Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease.

When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options.

Animals↗

PubMed1990

Bendazac lysine. A review of its pharmacological properties and therapeutic potential in the management of cataracts.

Bendazac is an oxyacetic acid with anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties, but its principal effect is to inhibit the denaturation of proteins. The lysine salt, which is better absorbed than the parent compound after oral administration, has been evaluated as a treatment for cataract, a condition which appears to result mainly from the denaturation, aggregation and precipitation of proteins within the lens. Results from a very small number of preliminary studies using objective photographic and densitometric methods have suggested that oral bendazac lysine, usually at a dosage of 500 mg 3 times daily, can stabilise the progression of lens opacification in patients with cataract. Significant improvements in individual and mean visual acuities in treated patients have been reported by several studies, but this parameter is not universally accepted as a reliable index of lens status. Preliminary studies evaluating bendazac lysine 0.5% eyedrops have reported comparable results to those obtained with oral treatment. Overall, tolerability of the drug has been good in studies to date. A dose-related laxative effect and other gastrointestinal disturbances are the most common adverse effects associated with oral therapy, and a transient burning sensation is the most commonly reported symptom occurring with eyedrop application. Bendazac lysine is one of a number of agents which have been introduced for the management of cataract. Although the results of preliminary studies have suggested that the drug may be useful for delaying the progression of cataract, further clinical studies using proven objective methods are required to fully establish its value in the management of this condition and its long term tolerability.

Animals↗

PubMed1990

Intravenous streptokinase. A reappraisal of its therapeutic use in acute myocardial infarction.

Streptokinase, the first of the thrombolytic agents to be used in acute myocardial infarction, has now been administered to many thousands of patients with this condition. Since early intervention and accessibility of care is paramount in these patients, intravenous infusion of streptokinase has largely replaced intracoronary use. Results of major trials (GISSI, ISIS-2 and ISAM) comparing streptokinase with standard treatment in more than 30,000 patients prove convincingly that intravenous streptokinase increases patient survival after myocardial infarction. The largest trial, ISIS-2, demonstrated a 23% reduction in 5-week vascular mortality after streptokinase use. The greatest benefits occur where streptokinase infusion is initiated early after symptom onset, although late benefit has been observed in patients treated up to 24 hours after pain onset. Importantly, mortality is further decreased by combining streptokinase with aspirin, as shown by a 53% reduction in mortality using the combination in the ISIS-2 trial. Mortality has also been reduced in trials investigating the use of the thrombolytic agents rt-PA and anistreplase. Streptokinase and rt-PA produced similar reductions in mortality in the recent GISSI-2 and International t-PA/Streptokinase Mortality trials, findings which may be further clarified by ongoing comparative trials such as ISIS-3. Reperfusion of about 50 to 60% of occluded coronary arteries occurs with intravenous streptokinase, and left ventricular function is improved. Direct comparisons with rt-PA show a superior effect for the newer agent on early reperfusion, but a similar ability to salvage myocardial function. The complexities of the relationship between reperfusion, left ventricular function and mortality constitute an area of considerable clinical interest requiring further study to clearly differentiate between the drugs available to the physician. The most common adverse events observed during intravenous streptokinase infusion are bleeding complications. An incidence of 3.6% for minor bleeding and 0.4% for major haemorrhage (requiring transfusion) is derived from the combined results of the GISSI and ISIS-2 studies. Bleeding does not appear to be more frequent or severe with intravenous streptokinase than with the more fibrin-selective agent, rt-PA. While the risk to benefit ratio of sequential heparin following streptokinase therapy remains equivocal, the adjuvant use of aspirin confers a clinical advantage over streptokinase alone. In conclusion, streptokinase has now been proven to reduce mortality in patients with acute myocardial infarction, with an acceptable risk of bleeding complications. Given the substantial data that have now accumulated with extensive clinical experience, intravenous streptokinase should be considered a first-line agent in suitable patients.

Fibrinolysis↗

PubMed1990

Fluconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses.

Fluconazole is a bis-triazole antifungal drug with novel pharmacokinetic properties (metabolic stability, relatively high water solubility) which contribute to its therapeutic activity. Clinical experience is limited to a relatively small number of mycoses and, as might be expected at this early stage of development, optimal dosage and duration of treatment for some serious mycoses is not yet established. Further study to evaluate higher dosages and to establish the efficacy of fluconazole relative to more established antifungal agents is required. In patients with oropharyngeal or oesophageal candidiasis, fluconazole produces rapid relief and eradicates the yeast in 50 to 90% of patients. Relapse of oral infection is common in chronically immunocompromised patients regardless of the antifungal used, and adequate primary therapy plus long term prophylaxis appears necessary in patients with AIDS. A single oral dose of fluconazole was comparable to standard topical azole therapy in women with acute vaginal candidiasis. Preliminary reports of success against deep-seated candidiasis are encouraging; moreover, experience in noncomparative clinical trials suggests that fluconazole 200 to 400mg once daily resolves infection in the majority of seriously ill patients. Clinical improvement has been reported in a few cases of pulmonary Aspergillus infection but the overall efficacy of conventional dosages of fluconazole in this mycosis has not been as impressive. Early experience in coccidioidosis, predominantly meningitis, suggests a beneficial clinical effect with oral fluconazole in this difficult to treat mycosis but relapse remains a problem. Fluconazole is a promising treatment of cryptococcal meningitis. The rate of clinical resolution and eradication of Cryptococcus neoformans from cerebrospinal fluid has been similar between fluconazole and amphotericin B treatment groups in comparative trials. Comparative trials of maintenance therapy indicate a similar low rate of relapse among patients given oral fluconazole once daily and intravenous amphotericin B once weekly. However, these results are preliminary and further study is required. Fluconazole has been well tolerated to date but wider clinical experience is needed, especially with regard to the rate occurrence of hepatotoxicity and exfoliative skin reactions. The promising clinical response of patients with various forms of candidiasis or cryptococcosis--together with convenient administration regimens--recommends fluconazole as a useful addition to currently available systemic antifungal therapies, in particular for the treatment of mycoses in patients with AIDS.

Animals↗

PubMed1990

Ocular betaxolol. A review of its pharmacological properties, and therapeutic efficacy in glaucoma and ocular hypertension.

Betaxolol is a lipophilic beta-adrenoceptor antagonist relatively selective for beta 1-adrenoceptors with only weak beta 2-blocking activity. Used topically in glaucoma and ocular hypertension, betaxolol 0.5% solution produces a reduction in intraocular pressure of between 13 and 30%, an effect comparable with that of ocular timolol. It may usefully be combined with other types of anti-glaucoma agents. The most notable feature of its adverse effect profile is transient local stinging or irritation, occurring in 25 to 40% of patients. Following ocular administration, betaxolol appears to be largely devoid of adverse bronchopulmonary or cardiac effects, in comparison with nonselective ocular beta-adrenoceptor antagonists, which may be more likely to exert systemic effects. Betaxolol has negligible local anaesthetic activity, so that corneal desensitisation does not occur with its use. Thus, betaxolol is an alternative therapeutic option available to the physician for the management of chronic open-angle glaucoma and ocular hypertension. Its apparently lower propensity to affect the cardiopulmonary system represents a significant advantage over other ocular beta-adrenoceptor antagonists.

Betaxolol↗

PubMed1990

Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states.

Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states.

Animals↗

PubMed1990

Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension.

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.

Antihypertensive Agents↗

PubMed1989

Loratadine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy.

Loratadine is a long acting antihistamine which has a high selectivity for peripheral histamine H1-receptors and lacks the central nervous system depressant effects often associated with some of the older antihistamines. Results from controlled clinical trials have shown that loratadine (usually 10mg once daily) is a well-tolerated and effective antihistamine which will be beneficial in patients with allergic rhinitis and chronic urticaria. It was found to be significantly superior to placebo, faster acting than astemizole and as effective as usual dosages of terfenadine, clemastine, mequitazine and azatadine in eliciting relief of symptoms. Importantly, loratadine is associated with a lower incidence of sedation than azatadine, clemastine, chlorpheniramine and mequitazine. Thus, loratadine, with its convenience of once daily administration, will be a useful addition to those drugs currently available for the treatment of patients with allergic diseases in whom a histamine H1-receptor antagonist is indicated. Indeed, it is likely to find a place as one of the newer 'agents of choice' in this setting.

Animals↗

PubMed1989

Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses.

Itraconazole is an orally active triazole antifungal drug which has demonstrated a broad spectrum of activity and a favourable pharmacokinetic profile. It is a potent inhibitor of most human fungal pathogens including Aspergillus sp. In non-comparative clinical trials itraconazole was shown to be extremely effective in a wide range of superficial and more serious 'deep' fungal infections when administered once or twice daily. Generally, greater than 80% of patients with superficial dermatophyte or yeast infections are cured by itraconazole. Similarly, good to excellent response rates (clinical cure or marked improvement) are achieved in paracoccidioidomycosis, histoplasmosis, sporotrichosis, blastomycosis, systemic candidiasis, coccidioidomycosis, chromomycosis, aspergillosis and cryptococcosis. Understandably, given the rare nature of some of these diseases, clinical experience is relatively limited and further evaluation, preferably controlled trials with amphotericin B and ketoconazole, would help clarify the ultimate role itraconazole will have in their management. Preliminary findings also indicate that itraconazole may hold promise for the prophylaxis of opportunistic fungal infections in patients at risk, for example women with chronic recurrent vaginal candidiasis, immunodeficient patients with chronic mucocutaneous candidiasis, AIDS patients and patients receiving immunosuppressant drugs. In studies to date itraconazole has been very well tolerated. Transient changes in indices of liver function occurred in 1 to 2% of patients; however, symptomatic liver dysfunction (as occurs infrequently with ketoconazole) has not been reported. Wider clinical experience is needed to permit clear conclusions as to whether liver dysfunction can result from itraconazole administration. Thus, while several aspects of the drug's profile require further investigation, itraconazole is a promising new oral treatment of fungal disease. The extent to which itraconazole will be employed in preference to ketoconazole will be clarified by wider clinical experience.

Animals↗