Biomedical subjects

K L Goa

Publications and source records attributed to K L Goa.

At least 163 records · Page 9Linked to original sources

PubMed1990

Guar gum. A review of its pharmacological properties, and use as a dietary adjunct in hypercholesterolaemia.

Guar gum is a dietary fibre advocated for use in lowering serum total cholesterol levels in patients with hypercholesterolaemia. Its mechanism of action is proposed to be similar to that of the bile-sequestering resins. Although guar gum is also employed as an adjunct in non-insulin-dependent diabetic patients this review is restricted to its efficacy as a hypolipidaemic agent. Clinical trials indicate that, when used alone, guar gum may reduce serum total cholesterol by 10 to 15%, although some studies show no significant response. An attenuation of this effect during longer term treatment has been seen but evidence of this effect is equivocal. As an adjunct to established therapies (bezafibrate, lovastatin or gemfibrozil) guar gum has shown some promise: it may produce a further reduction in total cholesterol of about 10% in patients not responding adequately to these drugs alone. Gastrointestinal effects, notably flatulence, occur relatively frequently and may be considered unacceptable by some patients. Standardization of formulations and methods of administration of guar gum is required to clarify its pharmacological and clinical properties. Thus, on the basis of presently available evidence guar gum as monotherapy may be considered at most modestly effective in reducing serum cholesterol levels. Nonetheless, further investigation of guar gum is warranted, particularly its use as an adjunct to produce additional reductions in serum cholesterol in patients not responding optimally to other lipid-lowering agents.

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

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↗

PubMed1990

Ketotifen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in asthma and allergic disorders.

Ketotifen is an orally active prophylactic agent for the management of bronchial asthma and allergic disorders. Accumulated evidence indicates that after 6 to 12 weeks of administration, ketotifen significantly reduces respiratory symptoms and the need for concomitant antiasthmatic drugs in about 70% and 50%, respectively, of patients with mild to moderate bronchial asthma. However, absolute improvement in lung function is generally slight. Ketotifen also has pronounced antihistaminic and antianaphylactic properties which result in moderate to marked symptom improvement in the majority of patients with atopic dermatitis, seasonal or perennial rhinitis, allergic conjunctivitis, chronic or acute urticaria or food allergy. Comparative trials with established agents--notably sodium cromoglycate (cromolyn sodium) in asthma and histamine H1-antagonists in allergic disorders--indicate that ketotifen has comparable clinical utility. Unlike inhaled sodium cromoglycate, ketotifen ameliorates the symptoms of asthma, rhinitis and dermatitis when present together in atopic patients. Patient acceptance of ketotifen is good, although sedation can be troublesome in older children and adults for the initial 2 weeks of treatment. Weight gain is another notable effect in a small percentage of patients. Thus, ketotifen appears to be a useful agent for the management of allergic disorders and bronchial asthma, particularly in patients for whom oral therapy is preferred. Although a lengthy run-in period is needed in the treatment of asthma, in those patients who respond, continued reduction in the frequency and severity of symptoms and in the use of additional antiasthmatic drugs can be anticipated.

Asthma↗

PubMed1990

Simvastatin. A review of its pharmacological properties and therapeutic potential in hypercholesterolaemia.

Simvastatin (epistatin; synvinolin; MK 733), an HMG-CoA reductase inhibitor, acts by decreasing cholesterol synthesis and by increasing low density lipoprotein (LDL) catabolism via increased LDL receptor activity. In patients with heterozygous familial and nonfamilial hypercholesterolaemia, orally administered simvastatin 10 to 40mg once daily reduces plasma total and LDL-cholesterol concentrations by about 30 to 45%. It also produces a beneficial moderate decrease in plasma triglycerides and a small, although significant, increase in high density lipoprotein (HDL)-cholesterol. Like many other hypocholesterolaemic agents simvastatin does not appear useful in patients with homozygous familial hypercholesterolaemia who lack LDL receptors. The hypocholesterolaemic activity of simvastatin is greater than that of the bile acid sequestrants, probucol and the fibrates. Combined administration of simvastatin with bile acid sequestrants results in further reductions in plasma cholesterol levels beyond those seen with either drug alone. Simvastatin appears well tolerated in the short to medium term, but its long term tolerability needs to be confirmed. No comparisons of simvastatin and other HMG-CoA reductase inhibitors have been reported. As yet there have been few investigations to determine the impact of simvastatin or other HMG-CoA reductase inhibitors on cardiovascular events relative to their hypocholesterolaemic effects, but at least one such trial is ongoing. Simvastatin, like other HMG-CoA reductase inhibitors, has considerable potential advantages over other classes of hypocholesterolaemic agents, i.e. the magnitude of its cholesterol-lowering effect and convenience of administration. If further study confirms long term tolerability and an impact on cardiac mortality and morbidity, then simvastatin and others of its class should offer a significant new approach to the treatment of hypercholesterolaemia.

Animals↗

PubMed1990

Transdermal nitroglycerin (glyceryl trinitrate). A review of its pharmacology and therapeutic use.

Nitroglycerin (glyceryl trinitrate) has been used for many years via the sublingual route for treating acute anginal attacks. In recent years transdermal delivery of nitroglycerin has gained popularity for prophylaxis against angina. However, nitrate tolerance appears to be a therapeutic problem with all long-acting nitrates regardless of delivery mechanism, and it occurs in most patients with stable angina treated with continuous 24-hour application of nitroglycerin patches. Since continuous 24-hour plasma concentrations of nitroglycerin do not appear to be desirable, alternative approaches to therapy are needed. A simple method to minimise tolerance with transdermal nitroglycerin patches is to remove the patch at bedtime and reapply a new patch in the morning. Such intermittent therapy allows a patch-free period during the night, when most patients experience few angina attacks, but optimises nitrate sensitivity during the daytime. However, the place of intermittent nitroglycerin patch therapy in the treatment of stable angina needs clarification with further study, particularly comparisons with other long-acting forms of nitrates. There are insufficient data to recommend the use of transdermal nitroglycerin patches in the treatment of patients with unstable angina or congestive heart failure. In conclusion, transdermal nitroglycerin patches offer a convenient and cosmetically acceptable dosage form which has potential use in stable angina if administered as an intermittent regimen providing a patch-free period each night.

Administration, Cutaneous↗

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

Enalapril. An update of its pharmacological properties and therapeutic use in congestive heart failure.

Enalapril provides significant haemodynamic, symptomatic and clinical improvement when added to maintenance therapy with digitalis and diuretics in patients with congestive heart failure [NYHA (New York Heart Association) classes II to IV]. These effects are not attenuated during long term therapy. More significantly, a clinical study demonstrated that enalapril reduces mortality when added to established therapy in patients with severe congestive heart failure (NYHA class IV) refractory to digitalis, diuretics and other vasodilators. Thus, ACE inhibitors such as enalapril offer a significant advance in the treatment of congestive heart failure. Because these drugs improve symptoms in patients with classes II to IV failure, and reduce mortality in patients with severe heart failure, they should be considered as first choice adjuvant therapy when a vasodilator is needed in addition to conventional treatment with digitalis and diuretics.

Clinical Trials as Topic↗

PubMed1989

Tamoxifen. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic use.

Tamoxifen, a non-steroidal antioestrogen, represents a significant advance in treatment of female breast cancer. In trials of tamoxifen as postsurgical adjuvant treatment of early breast cancer, disease-free survival is consistently prolonged, representing an enhanced quality of life in association with tamoxifen's favourable adverse effect profile. Moreover, overview analysis indicates a survival benefit of approximately 20% at 5 years for all women, most clearly evident in women over 50 years, while a survival benefit independent of menopausal, nodal or oestrogen receptor status has been demonstrated in some individual trials. Thus, for postmenopausal women, tamoxifen is clearly optimal adjuvant treatment, although the relative benefit of adjuvant chemotherapy in node-negative patients requires clarification. A survival benefit for women under 50 has not been clearly demonstrated in overview analysis, but is not precluded by these rather limited data, and adjuvant treatment of premenopausal women with tamoxifen may also warrant serious consideration. Response rates to tamoxifen in advanced breast cancer are around 30 to 35%, increasing with patient selection for oestrogen receptor positivity. Tamoxifen must be regarded as first-line endocrine treatment in postmenopausal women, and may represent an alternative to first-line ovarian ablation in premenopausal women. An emergent role in primary therapy of elderly and frail patients with operable disease is apparent. Tamoxifen is also of benefit following surgery in male breast cancer, and may have a role as first-line endocrine treatment. Tamoxifen also has a potential role in other hormone-sensitive malignancies such as pancreatic carcinoma, and in treatment of benign breast disease. Finally, tamoxifen has a place in treatment of male and female infertility. because of adverse effects is rarely necessary. The most frequent adverse effects are related to the drug's anti-oestrogenic activity, and include hot flushes, nausea and/or vomiting, vaginal bleeding or discharge, and menstrual disturbances in premenopausal patients. Thus, tamoxifen continues to play a major role in management of female breast cancer in both early and advanced stages of disease, with a place also in treatment of male breast cancer and of infertility.

Adult↗

PubMed1989

Sultamicillin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. Sulbactam is a semisynthetic beta-lactamase inhibitor which, in combination with ampicillin, extends the antibacterial activity of the latter to include some beta-lactamase-producing strains of bacteria that would otherwise be resistant. The combination of sulbactam plus ampicillin for parenteral use has previously been shown to be clinically and bacteriologically effective in a variety of infections. The chemical linkage of sulbactam and ampicillin has now produced an orally effective compound, sultamicillin, with antibacterial activity and clinical efficacy which are similar to those of the parenteral formulation. Sultamicillin has been shown to be clinically effective in non-comparative trials in patients with infections of the respiratory tract, ears, nose and throat, urinary tract, skin and soft tissues, as well as in obstetric and gynaecological infections, and in the treatment of gonorrhoea. In a small number of controlled trials, sultamicillin has shown comparable clinical efficacy to phenoxymethyl penicillin (penicillin V) and to amoxycillin (alone and in combination with clavulanic acid) in the treatment of paediatric streptococcal pharyngitis and acute otitis media, respectively; to cefaclor in the treatment of acute otitis media in adults; and to bacampicillin, cloxacillin and flucloxacillin plus ampicillin in skin and soft tissue infections in adults, children and adult diabetic patients, respectively. Sultamicillin was superior in efficacy to bacampicillin in the treatment of chronic respiratory infections, to cefaclor in the treatment of acute otitis media in adults, and to cefadroxil in the treatment of patients with complicated urinary tract infections. However, in single-dose treatment of uncomplicated gonorrhoea, sultamicillin (1500mg plus probenecid 1g) was inferior to a 2g intramuscular dose of spectinomycin. While in several studies the incidence of diarrhoea associated with sultamicillin was greater than that with comparative antibacterials, sultamicillin-associated diarrhoea was generally mild and transitory, although occasionally severe enough to necessitate discontinuation of treatment. Further studies in larger groups of patients are needed to clarify the therapeutic efficacy and safety of sultamicillin in comparison with other antibacterial regimens, and to determine the optimum single dosage for the treatment of gonorrhoea. Nonetheless, sultamicillin appears to provide a similar pharmacodynamic and pharmacokinetic profile to that of parenteral sulbactam plus ampicillin and, as such, will extend the therapeutic efficacy of ampicillin, with the further advantage of allowing treatment of patients with an oral formulation, thus avoiding the potentially adverse clinical and financial effects of prolonged parenteral therapy.

Ampicillin↗

PubMed1989

Labetalol. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in hypertension and ischaemic heart disease.

Since labetalol was first reviewed in the Journal (1978), its scope of therapeutic use has expanded and become better defined. Labetalol is an adrenoceptor blocking drug with combined alpha- and beta-blocking properties. These result in a more favourable haemodynamic profile for labetalol compared with 'pure' beta-blockers or pure alpha-blockers, but also contribute to a wider range, but not an overall increased incidence, of adverse effects. The drug is effective and well-tolerated in patients with all grades of hypertension, but is of particular value in special subgroups such as Black patients, the elderly and patients with renal hypertension. While comparative studies are not extensive, available data show that the drug reduces blood pressure to a similar extent, and in a similar proportion of patients, as 'pure' beta-blockers such as propranolol, pure alpha-blockers such as prazosin, calcium antagonists (nifedipine, verapamil), and centrally acting drugs (clonidine and methyldopa). Labetalol is very effective in hypertensive pregnant women and in hypertensive crises, where it provides good control of blood pressure without serious adverse effects, and where few therapeutic options exist. Few controlled studies have investigated the use of labetalol in deliberate induction of hypotension or prevention of hypertension during anaesthesia, and also in patients with ischaemic heart disease. However, available evidence suggests a role for labetalol in these indications and further studies should aid in clarification of its efficacy in these areas. Thus, with its broad scope of therapeutic use in hypertension labetalol remains an important therapeutic option, and the drug may well find an additional place in the treatment of myocardial ischaemia if further evidence confirms encouraging preliminary findings.

Coronary Disease↗

PubMed1989

Probucol. A reappraisal of its pharmacological properties and therapeutic use in hypercholesterolaemia.

Probucol is a lipid-regulating agent structurally dissimilar to other known agents, with a unique pharmacodynamic and clinical profile. It is effective in the treatment of primary Type IIa and IIb hyperlipoproteinaemias, including polygenic (non-familial) hypercholesterolaemia and both heterozygous and homozygous forms of familial hypercholesterolaemia, with reductions in plasma total cholesterol and low density lipoprotein (LDL)-cholesterol levels of about 10 to 20% being attained. Marked effects on cutaneous and tendinous xanthomas have been observed, with significant regression often apparent after 2 or 3 months' therapy. Preliminary trials also indicate efficacy in hyperlipoproteinaemia secondary to nephrotic syndrome and diabetes mellitus. The mechanism of the reduction in LDL-cholesterol levels is yet to be fully elucidated, but it is thought that the decrease results from enhanced catabolism, and there is preliminary evidence of an independent antioxidant effect. In contrast with all other known lipid-lowering agents, probucol also effects a consistent reduction in serum high density lipoprotein (HDL)-cholesterol levels, of around 20 to 30%; the clinical significance of this observation is unclear, although some preliminary investigations suggest a beneficial effect in enhancing reverse cholesterol transport. The influence of probucol treatment on cardiovascular morbidity and mortality remains to be fully investigated; a large trial quantifying the potential effect of probucol against the development of atherosclerotic lesions is currently in progress. Adverse effects of probucol are generally mild, seldom requiring treatment withdrawal, with gastrointestinal effects such as diarrhoea predominating. However, indications of an increased frequency of ventricular arrhythmias and sudden death in association with QT interval prolongation in some animals have prompted some concern. Although there is evidence of a degree of QT prolongation in a number of trials in humans, the nature and clinical significance of this effect requires clarification, as no increased incidence of cardiac arrhythmias is apparent. Thus, probucol appears to be of benefit in primary and secondary hyperlipoproteinaemia of Types IIa and IIb, and particularly in homozygous familial hypercholesterolaemia, with marked effects on xanthomas, and a generally favourable adverse effect profile. There is no evidence to date causally relating occasional QT interval prolongation in patients to any incidence of arrhythmias or sudden death. Pharmacodynamic investigations are likely to clarify further the place of probucol in therapy, particularly with respect to its distinctive lowering of plasma HDL-cholesterol levels.

Humans↗

PubMed1989

Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent.

Coronary arterial thrombolysis is becoming an established treatment of acute myocardial infarction. If given early enough, it recanalises occluded coronary arteries, salvages myocardial function and reduces mortality. A reduction of mortality in patients with acute myocardial infarction has now been demonstrated for streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase) and recombinant tissue-type plasminogen activator (rt-PA). From the biochemical point of view, rt-PA has several attractive properties. It is similar to or identical with the physiological plasminogen activator in blood, it does not induce an antibody response, and it is more fibrin-specific than most or all other currently known thrombolytic agents. The rate of recanalisation of occluded coronary arteries with rt-PA is about 60 to 80% in non-comparative and placebo-controlled trials. rt-PA was similar in efficacy to urokinase in the only trial to compare the 2 agents. In 2 comparative trials evaluated by meta-analysis, rt-PA appeared more effective than streptokinase for the early recanalisation of occluded arteries. Both agents were comparable in their effects on left ventricular function in 2 comparative trials, but further study is needed to conclusively evaluate this parameter. Moreover, both agents reduce inhospital mortality, but much larger direct comparative trials are required before scientifically valid statements can be made on the relative clinical efficacy of available thrombolytic agents in terms of their effects on both morbidity and mortality. Thus, rt-PA constitutes a notable contribution of recombinant DNA technology to the treatment of thromboembolic disease, the main cause of death and disability in Western societies.

Animals↗

PubMed1989

S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism.

S-Adenosyl-L-methionine (SAMe) is a naturally occurring molecule distributed to virtually all body tissues and fluids. It is of fundamental importance in a number of biochemical reactions involving enzymatic transmethylation, contributing to the synthesis, activation and/or metabolism of such compounds as hormones, neurotransmitters, nucleic acids, proteins, phospholipids and certain drugs. The administration of a stable salt of SAMe, either orally or parenterally, has been shown to restore normal hepatic function in the presence of various chronic liver diseases (including alcoholic and non-alcoholic cirrhosis, oestrogen-induced and other forms of cholestasis), to prevent or reverse hepatotoxicity due to several drugs and chemicals such as alcohol, paracetamol (acetaminophen), steroids and lead, and to have antidepressant properties. In all of these studies SAMe has been very well tolerated, a finding of great potential benefit given the well-known adverse effects of tricyclic antidepressants with which it has been compared in a few trials. Thus, with its novel mechanisms of action and good tolerability, SAMe is an interesting new therapeutic agent in several diverse disease conditions, but its relative value remains to be determined in appropriate comparisons with other treatment modalities in current use.

Animals↗

PubMed1989

Famotidine. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in peptic ulcer disease and other allied diseases.

Famotidine is a highly selective histamine H2-receptor antagonist. In healthy volunteers and patients with acid hypersecretory disease it is approximately 20 to 50 times more potent at inhibiting gastric acid secretion than cimetidine and 8 times more potent than ranitidine on a weight basis. As shown in placebo-controlled trials, famotidine is effective in healing both duodenal and gastric ulcers. Famotidine 20mg twice daily or 40mg at bedtime achieves healing rates and symptom relief similar or superior to those achieved by cimetidine 800mg daily or ranitidine 300mg daily in patients with peptic ulcer disease. Results of 1 placebo-controlled study suggest that famotidine prevents recurrence of duodenal ulcer, but comparative trials are needed to establish its relative efficacy in maintenance therapy. The few non-comparative trials conducted to date also suggest that famotidine 10 to 20mg twice daily may be effective in the treatment of gastritis and reflux gastro-oesophagitis. In comparative trials, famotidine was similar in efficacy to cimetidine in the treatment of upper gastrointestinal bleeding and to ranitidine in the prevention of pulmonary aspiration of acid. In patients with Zollinger-Ellison syndrome, the potency and long duration of action of famotidine may confer an advantage over other H2-receptor antagonists--in individualised doses (mean 0.33 g/day) famotidine successfully controlled acid secretion for up to 72 months in 1 study of such patients. Accumulated clinical evidence confirms that famotidine is very well tolerated and is free of the antiandrogenic effects infrequently reported with cimetidine. Moreover, famotidine is not associated with altered hepatic metabolism of drugs. Thus, famotidine is an effective, well-tolerated alternative to cimetidine and ranitidine. Famotidine is also promising as maintenance therapy for preventing recurrence of duodenal ulcer and as initial or maintenance treatment of gastric hypersecretory disorders, but further clinical experience, particularly in the long term, is needed to define the relative efficacy and tolerability of famotidine in these indications.

Famotidine↗

PubMed1989

Netilmicin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Netilmicin is a semisynthetic aminoglycoside derived from sisomicin. It is active against most Gram-negative and some Gram-positive bacteria, including many gentamicin-resistant strains. Netilmicin has proved to be effective in Gram-negative infections of the urinary tract, skin and skin structure, and lower respiratory tract, as well as in intra-abdominal infections, septicaemia and other miscellaneous infections. In some trials, the more easily implemented once daily administration of netilmicin has been as effective as multiple dosing regimens. However, further investigation is required to confirm that efficacy and safety are not compromised with once daily administration. Comparative studies have generally revealed similar clinical and bacteriological efficacies between netilmicin and gentamicin, amikacin or tobramycin. As with other aminoglycosides, the principal adverse effects of netilmicin are nephrotoxicity and ototoxicity. Although animal studies strongly suggest that these are less common with netilmicin than with related drugs, there appears to be no difference in their incidence in clinical use; in clinical trials the incidence of nephrotoxicity and ototoxicity has been low, with the symptoms in many cases being minor and reversible. Netilmicin is, therefore, an effective antibacterial drug for the parenteral treatment of severe infections, offering theoretical advantages in safety which may indicate its use for patients believed to be at risk of adverse effects.

Animals↗

PubMed1989

Midodrine. A review of its pharmacological properties and therapeutic use in orthostatic hypotension and secondary hypotensive disorders.

Midodrine, a peripheral alpha-adrenergic agonist, finds use in the clinical management of patients with orthostatic hypotension or hypotension secondary to other clinical conditions or drug therapies. Midodrine is almost completely absorbed after oral administration and undergoes enzymatic hydrolysis to form its pharmacologically active metabolite, de-glymidodrine. In patients with refractory orthostatic hypotension oral midodrine increases standing blood pressure and improves symptoms of orthostatism, such as weakness, syncope, blurred vision and fatigue, without any associated cardiac stimulation. Comparative studies have shown midodrine to be clinically at least as effective as other sympathomimetic agents (norfenefrine, etilefrine, dimetofrine and ephedrine) and dihydroergotamine in this regard. Additionally, midodrine appears to cause less frequent and severe adverse effects associated with alpha-receptor agonism such as piloerection and urinary hesitancy. The most commonly experienced adverse effects--piloerector reactions, gastrointestinal disorders, and cardiovascular complaints--are generally mild and can be controlled by reducing the dosage of midodrine. Thus, midodrine is at least as useful as other currently available options in the management of orthostatic or secondary hypotension, and represents a stepping stone towards optimal therapy.

Animals↗

PubMed1988

Clinical pharmacology and pharmacokinetic properties of topically applied corticosteroids. A review.

The development of topical corticosteroids since the 1950s has opened new doors for dermatologists previously faced with treating intractable dermatoses, so that the pharmacology of topically applied corticosteroids is now reasonably well described. Manipulation of the steroid molecule has produced compounds with greater lipophilicity, fewer mineralocorticoid properties and high potency. Potency is determined through various techniques, notably the vasoconstrictor assay as well as the mitotic index suppression method and atrophogenic potential assay. The mechanism of activity of corticosteroids is thought to result, at least in part, from binding of the drug to steroid receptors, with resultant effects on the synthesis of proteins responsible for specific effects. Corticosteroids are proposed to alter the inflammatory response, and thus provide therapeutic benefits, via actions on mediator release and function, inflammatory cell function and release of lysosomal enzymes. Disadvantages of corticosteroid activity include the possibility of adrenal suppression, epidermal and dermal thinning, and local effects such as purpura, striae, and steroid-induced rosacea and perioral dermatitis. The cutaneous pharmacokinetics, particularly of absorption of topical corticosteroids, must be examined in parallel with their pharmacodynamic effects to gain a more complete understanding of activity. Many factors can affect percutaneous steroid absorption: drug lipophilicity and solubility, drug concentration, anatomical site, age of the patient, presence of skin disease and use of occlusive dressings will each influence the degree to which topically applied corticosteroids achieve their intended therapeutic results. Cutaneous metabolism is a poorly understood process at present, but one which is acknowledged to have some impact on the biotransformation of corticosteroids applied topically. Thus, although some gaps still persist in present knowledge of the pharmacology and pharmacokinetics of this important class of drugs, there can be no denying the contribution of topical corticosteroids to the therapy of dermatoses.

Administration, Topical↗