Biomedical subjects

D McTavish

Publications and source records attributed to D McTavish.

At least 55 records · Page 3Linked to original sources

PubMed1993

Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.

Carvedilol is a beta-adrenoceptor antagonist which also causes peripheral vasodilation primarily via alpha 1-adrenergic blockade. Carvedilol produces its antihypertensive effect partly by reducing total peripheral resistance by blocking alpha 1-adrenoceptors and by preventing beta-adrenoceptor-mediated compensatory mechanisms. This combined action avoids many of the unwanted effects associated with traditional beta-blocker or vasodilator therapy. In clinical trials published to date, most of which enrolled small numbers of patients, the antihypertensive efficacy of carvedilol administered once daily was similar to that of atenolol, labetalol, pindolol, propranolol, metoprolol, nitrendipine (in elderly patients), slow release nifedipine or captopril in patients with mild-to-moderate essential hypertension. Combined therapy with carvedilol 25 mg and hydrochlorothiazide 25 mg, nicardipine 60 mg or slow release nifedipine 20 mg has an additive antihypertensive effect. Carvedilol and atenolol at similar doses were equally effective at reducing blood pressure in patients who had previously not responded adequately to hydrochlorothiazide monotherapy. As a result of its multiple mechanisms of action, carvedilol is suited for the management of specific groups of hypertensive patients, such as those with renal impairment. In patients with non-insulin-dependent or insulin-dependent diabetes mellitus carvedilol does not appear to affect glucose tolerance or carbohydrate metabolism. Initial studies have demonstrated that carvedilol and slow release nifedipine have similar efficacy in patients with stable angina pectoris and there is evidence that carvedilol has a beneficial haemodynamic effect in patients with congestive heart failure (NYHA class II or III) secondary to ischaemic heart disease. A postmarketing surveillance study has shown that carvedilol is generally well tolerated with only 7% (164/2226) of patients (83% of the total number received 25mg daily for 12 weeks) withdrawing from treatment because of adverse events. Vertigo, headache, bronchospasm, fatigue and skin reactions were the most common events causing withdrawal. Thus, clinical experience to date suggests that carvedilol is likely to be a valuable addition to the options currently available for treating patients with mild-to-moderate essential hypertension, and may offer particular benefit in specific populations of hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed1993

Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia.

Alfuzosin, a new quinazoline derivative, acts as a selective and competitive antagonist of alpha 1-adrenoceptor-mediated contraction of prostatic, prostatic capsule, bladder base and proximal urethral smooth muscle, thereby reducing the tone of these structures. Consequently, urethral pressure and resistance, bladder outlet resistance, bladder instability and symptoms associated with benign prostatic hyperplasia are reduced. A limited range of clinical studies have shown oral alfuzosin to be more effective than placebo (in studies of < or = 6 months duration), to have sustained effects on long term administration (< or = 30 months), and to be comparable with the alpha 1-adrenoceptor antagonist prazosin, in the symptomatic treatment of benign prostatic hyperplasia. This is reflected in increases in urinary flow rate and decreases in symptom score and residual urinary volume. The most marked improvements occur in patients with severe pretreatment urinary flow abnormalities. Furthermore, preliminary results suggest a beneficial effect of alfuzosin on quality of life in patients with benign prostatic hyperplasia. The overall incidence of adverse effects appears similar to that with placebo, and the incidence of vasodilatory-related adverse effects appears lower than that with prazosin. The relative selectivity of alfuzosin for alpha 1-adrenoceptors in the genitourinary tract compared with receptors in the vasculature is a potential advantage over other alpha-adrenoceptor antagonists, including prazosin, as the symptoms of benign prostatic hyperplasia may be reduced by alfuzosin at doses that have minimal vasodilatory effects, thereby minimising postural hypotension and syncope. However, vasodilatory-related adverse effects are the most common adverse effects that occur with alfuzosin, and dose and first-dose hypotensive relationships, especially in the elderly, cannot be excluded at this stage in the clinical use of alfuzosin. The full potential of alfuzosin in the symptomatic treatment of benign prostatic hyperplasia will be clarified by further long term comparative studies (with large patient numbers) against placebo and other alpha 1-adrenoceptor antagonists. Nevertheless, oral alfuzosin 7.5 to 10 mg/day in divided doses appears to be a promising first-line agent for symptomatic treatment of noncomplicated mild to moderate benign prostatic hyperplasia in patients with a high dynamic component to their obstruction. In addition, alfuzosin offers an alternative to prostatectomy (the current 'gold standard') in patients who require surgery but are unfit for this treatment, and in patients requiring symptomatic relief while awaiting surgery.

Adrenergic alpha-Antagonists↗

PubMed1993

Histrelin. A review of its pharmacological properties and therapeutic role in central precocious puberty.

Histrelin is a synthetic gonadotrophin-releasing hormone (GnRH) agonist which, when administered over a prolonged period, suppresses the release of gonadotrophins from the anterior pituitary. Data from clinical trials undertaken in small numbers of patients with idiopathic central precocious puberty have demonstrated that histrelin 8 to 10 micrograms/kg/day administered subcutaneously desensitises the anterior pituitary to gonadotrophin secretion within 3 months, ablating the pubertal gonadotrophin response to GnRH stimulation and reducing circulating gonadal sex steroid levels. When histrelin is administered to treat central precocious puberty, the rate of secondary sexual maturation is slowed and in some cases there is a reversal of maturation which occurs before initiation of treatment. Of equal importance, histrelin therapy appears to have decelerating effects on skeletal maturation, allowing more statural growth; an increase in final adult height is predicted from available data, but will need to be confirmed in long term follow-up studies currently being undertaken. The most common adverse event reported during histrelin therapy was a skin reaction at the site of subcutaneous injection. Few patients have discontinued therapy because of any adverse event. Although experience with histrelin is limited, the absence of effective clinically available alternatives and the demonstrated efficacy of histrelin justifies its place as a first-line therapy for patients with central precocious puberty.

Amino Acid Sequence↗

PubMed1993

Loracarbef. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy.

Loracarbef is an orally administered member of a new synthetic class of beta-lactam antibiotics, the carbacephems, which is characterised by enhanced chemical stability. At low concentrations (< 2 mg/L) in vitro, it inhibits Streptococcus pneumoniae, S. pyogenes, beta-haemolytic streptococci groups B, C and G. Proteus mirabilis and Moraxella catarrhalis, including beta-lactamase-producing strains. At therapeutic plasma concentrations it is also active in vitro against most strains of Staphylococcus aureus, S. saprophyticus, Escherichia coli and beta-lactamase-positive and -negative strains of Haemophilus influenzae. Like other beta-lactams, loracarbef is inactive against methicillin-resistant strains of S. aureus. When administered at dosages of 200 to 400 mg twice daily, the clinical and bacteriological efficacy of loracarbef is comparable with that of amoxicillin and amoxicillin/clavulanic acid in patients with upper or lower respiratory tract infections, and comparable with that of cefaclor in treating infections of the lower respiratory tract, skin and skin structures and urinary tract. Loracarbef and phenoxymethylpenicillin (penicillin V) were equally effective in treating streptococcal pharyngitis and tonsillitis. Loracarbef is generally well tolerated by all age groups and causes less diarrhoea than amoxicillin/clavulanic acid. It is administered twice daily. It offers a suitable alternative to other orally administered antibiotics for the treatment of mild to moderate infections caused by susceptible organisms.

Adolescent↗

PubMed1993

Fludarabine. A review of its pharmacological properties and therapeutic potential in malignancy.

Fludarabine is a fluorinated purine analogue with antineoplastic activity in lymphoproliferative malignancies. Noncomparative studies have shown response rates in patients with chronic lymphocytic leukaemia (CLL) that appear to be at least equivalent to those achieved with conventional therapy. Prolymphocytic leukaemia, a form of CLL which is often resistant to conventional chemotherapy, has also responded to treatment with fludarabine. Fludarabine combined with prednisone has also induced good response rates in patients with CLL but the limited data suggest that this does not offer an advantage over fludarabine alone. Several clinical trials have demonstrated a good cytoreductive response in patients with advanced, low grade non-Hodgkin's lymphoma, particularly that of follicular histology. Preliminary evidence indicates fludarabine in combination with cytarabine has therapeutic activity as salvage therapy in patients with acute leukaemia. Myelosuppression has been the major dose-limiting adverse effect reported in clinical trials of fludarabine. A reduction in CD4+ cell count may be associated with the increased incidence of fever and opportunistic infections in fludarabine recipients. Nausea and vomiting have also been commonly reported, but these are generally mild to moderate in severity. Reversible neurotoxicity has also been occasionally reported. Thus, fludarabine appears to offer a viable alternative to currently used treatments in CLL and low grade non-Hodgkin's lymphoma. Other potential areas of use for fludarabine include acute leukaemias. Waldenstrom's macroglobulinaemia and mycosis fungoides. However, trials of fludarabine in comparison with currently used therapies and also in combination with other antineoplastic agents are required to fully define its role in the treatment of lymphoid malignancies. In addition, because relapse in these diseases is common, long term trials assessing improvement in survival duration and quality of life would be of value.

Animals↗

PubMed1993

Clarithromycin. A review of its pharmacological properties and therapeutic use in Mycobacterium avium-intracellulare complex infection in patients with acquired immune deficiency syndrome.

Results from noncomparative and placebo-controlled studies demonstrate the efficacy of clarithromycin in the treatment of disseminated Mycobacterium avium-intracellulare complex (MAC) infection in patients with acquired immune deficiency syndrome (AIDS). Whether given alone or in combination with other antimycobacterial treatments, doses of 500 to 2000mg (typically 1000mg) administered twice daily are effective in controlling bacteraemia in these patients. Clarithromycin has also been shown to improve clinical symptoms of infection and may improve quality of life in AIDS patients with MAC infection. Clarithromycin is generally well tolerated when used in the doses typically required for the treatment of MAC infection (1000 or 2000 mg/day). Gastrointestinal disturbances are the most commonly occurring adverse events and occur most frequently at dosages of 4000 mg/day. Thus, clarithromycin, as monotherapy or in combination with other antimycobacterial agents, is well tolerated and effectively eradicates MAC from the blood in the short term in patients with AIDS: however, short term monotherapy may lead to bacterial resistance, underscoring the importance of long term treatment with a combination of antimycobacterial agents. While the optimal combination regimen to prevent the development of resistance to antimycobacterial agents. While the optimal combination regimen to prevent the development of resistance to antimycobacterial agents by MAC remains to be determined, clarithromycin will almost certainly be a valuable agent in any such combination.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states.

Tramadol is a centrally acting analgesic which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. It may be administered orally, rectally, intravenously or intramuscularly. In patients with moderate to severe postoperative pain, intravenous or intramuscular tramadol has generally proved to be of equivalent potency to pethidine (meperidine) and one-fifth as potent as nalbuphine. Intravenous tramadol 50 to 150mg was equivalent in analgesic efficacy to morphine 5 to 15mg in patients with moderate pain following surgery; however, when administered epidurally tramadol was one-thirtieth as potent as morphine. Tramadol has demonstrated efficacy in a few studies in the short term treatment of chronic pain of various origins. Orally administered tramadol was found to be an effective analgesic in step 2 of the World Health Organization's guidelines for the treatment of patients with cancer pain. Tramadol is well tolerated in short term use with dizziness, nausea, sedation, dry mouth and sweating being the principal adverse effects. Respiratory depression has been observed in only a few patients after tramadol infusion anaesthesia. When used for pain relief during childbirth, intravenously administered tramadol did not cause respiratory depression in neonates. The tolerance and dependence potential of tramadol during treatment for up to 6 months appears to be low, although the possibility of dependence with long term use cannot be entirely excluded. Thus, evidence to date of the analgesic effectiveness of tramadol combined with a low respiratory depressant effect and low dependence potential in short term use, suggests that the drug may become a useful alternative to the opioid analgesics currently available for the treatment of patients with moderately severe acute or chronic pain.

Acute Disease↗

PubMed1993

Tropisetron. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as an antiemetic.

Tropisetron is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of receptors both at peripheral sites and in the central nervous system. When compared with antiemetic regimens containing high-dose metoclopramide in a small number of studies, tropisetron was generally as effective at preventing acute and delayed vomiting induced by high-dose cisplatin (> or = 50 mg/m2). In these studies tropisetron completely prevented vomiting occurring in the first 24 hours after chemotherapy in 35 to 76% of patients. Tropisetron was superior to alizapride in preventing emesis induced by high-dose alkylating agents. The effectiveness of tropisetron in patients who had previously had partial control of emesis was improved by the addition of dexamethasone. Tropisetron appears to be well tolerated with the most frequently reported adverse effect being headache. Extrapyramidal effects, which can occur in 5 to 10% of patients receiving high-dose metoclopramide and which may limit its use, have been reported in only isolated cases with tropisetron. Thus, tropisetron is an effective, apparently well tolerated agent which can be administered once daily for the prevention of chemotherapy-induced nausea and vomiting. However, further clinical experience is needed to clarify the optimum role of tropisetron as an antiemetic agent, particularly with regard to other drugs in its class. Nonetheless, preliminary results indicate that tropisetron will be a useful alternative for use in controlling emesis induced by cytotoxic therapy.

Animals↗

PubMed1993

Acarbose. An update of its pharmacology and therapeutic use in diabetes mellitus.

Acarbose delays digestion of complex carbohydrates and disaccharides to absorbable monosaccharides, by reversibly inhibiting alpha-glucosidases within the intestinal brush border, thereby attenuating postprandial blood glucose peaks. Clinical trials have demonstrated that acarbose generally improves glycaemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM) managed with diet alone, or with other antidiabetic therapy, as evidenced by decreased postprandial plasma glucose and glycosylated haemoglobin levels. It does not appear to directly alter insulin resistance, but may lower postprandial plasma insulin levels. Fasting plasma glucose, triglyceride and/or cholesterol levels may also be decreased. Acarbose also improved metabolic control in patients with insulin-dependent diabetes mellitus (IDDM), frequently decreasing insulin requirements, although further studies are required in this indication. Improved metabolic control appears to delay or prevent long term vascular complications of diabetes, and indeed, acarbose appeared to inhibit development of such complications in preliminary animal studies, but this finding requires confirmation in clinical studies. While acarbose seldom causes systemic adverse effects, it is associated with a high incidence of gastrointestinal disturbances such as flatulence, abdominal distension, borborygmus and diarrhoea, caused by fermentation of unabsorbed carbohydrates. However, these symptoms tend to subside with continued treatment and adherence to an appropriate diet. Thus, acarbose appears to be a worthwhile adjunctive therapeutic option for patients with NIDDM inadequately managed by diet alone, or with pharmacological therapy, and possibly also for patients with IDDM. However, further long term efficacy and tolerability data are required, particularly in the latter indication.

Acarbose↗

PubMed1993

Omeprazole: a pharmacoeconomic evaluation of its use in duodenal ulcer and reflux oesophagitis.

Omeprazole regulates gastric acid secretion and is an effective treatment of acute duodenal ulcer and reflux oesophagitis, achieving more rapid healing and symptomatic relief than histamine H 2-receptor antagonists. When administered as maintenance therapy, omeprazole reduces the incidence of relapse. The drug is also highly effective in patients poorly responsive to histamine H 2-receptor antagonists. The daily acquisition cost of omeprazole is higher than that of histamine H 2-receptor antagonists in many countries, and thus it is important to evaluate the pharmacoeconomic impact of omeprazole in the short and long term treatment of duodenal ulcer and reflux oesophagitis. Pharmacoeconomic analyses have been performed in several clinical settings using pooled data from clinical trials or simulated models of clinical practice. In a single analysis using Finnish cost data, omeprazole was more cost effective than ranitidine in the treatment of duodenal ulcer disease over a 6-month period. The cost effectiveness of omeprazole was comparable to that of sucralfate-containing regimens, with patients receiving omeprazole being healed more quickly and experiencing a greater number of healthy days. Using a computer-model simulation and Swedish cost data, omeprazole was more cost effective than ranitidine when administered as intermittent treatment of duodenal ulcer over 5 years. Preliminary reports indicate that regimens which eradicate Helicobacter pylori are more cost effective than those which do not. As short term treatment of reflux oesophagitis, omeprazole 20 to 40 mg/day was the dominating treatment strategy, being less costly and more effective than ranitidine 300 to 1200 mg/day. Omeprazole 20 mg/day produced symptom-free days more cost effectively than either cimetidine 1.6 g/day or ranitidine 300 mg/day. More importantly, as long term (maintenance or intermittent) treatment of reflux oesophagitis, omeprazole 20 mg/day was more cost effective than both ranitidine 150 mg twice daily and 'phase 1' therapy (diet and antacids) over 6 and 12 months. Thus, based on analyses evaluated, omeprazole appears to be more cost effective than ranitidine in the short term treatment of duodenal ulcer. Results for long term treatment are less clear cut, but full details from some studies are not yet available. For the short term treatment of reflux oesophagitis omeprazole is more cost effective than ranitidine or cimetidine and for long term treatment omeprazole is more cost effective than ranitidine. As treatment for reflux oesophagitis, omeprazole is considered to be the dominating treatment strategy.

Cost-Benefit Analysis↗

PubMed1992

Fosinopril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in essential hypertension.

Fosinopril is a phosphinic acid prodrug which, after oral administration, undergoes rapid hydrolysis to its active diacid, the angiotensin converting enzyme (ACE) inhibitor fosinoprilat. Unlike other ACE inhibitors, fosinoprilat has a compensatory dual route of elimination and is cleared by the liver and kidneys. Thus, in patients with diminished renal function increased hepatic clearance of fosinoprilat is noted and, similarly, in patients with diminished hepatic function increased renal clearance seems to occur. Because of this compensatory elimination, fosinopril therapy for all patients can begin with the same recommended dosage. Fosinopril 10 to 40mg administered once daily is an effective antihypertensive regimen that has shown efficacy similar to that of enalapril 5 to 10 mg/day, propranolol 80 to 160 mg/day, hydrochlorothiazide 25 to 50 mg/day and sustained release nifedipine 40 mg/day in preliminary clinical trials. Generally, fosinopril is well tolerated and adverse events associated with the drug are usually mild and similar to those associated with other ACE inhibitors. Thus, fosinopril appears to be a useful alternative to certain 'established' agents used for treating patients with essential hypertension.

Animals↗

PubMed1992

Dexfenfluramine. A review of its pharmacological properties and therapeutic potential in obesity.

Dexfenfluramine stimulates serotoninergic activity by inhibiting serotonin reuptake into presynaptic neurons and by enhancing its release into brain synapses. Based on the serotonin hypothesis of appetite control these effects would be expected to reduce food intake and thus body-weight. Studies in animal models and severely overweight patients have confirmed the effectiveness of dexfenfluramine as a weight-reducing agent which appears to be well tolerated. Permanent weight loss is the goal of weight-reducing strategies and, based on current clinical evidence, dexfenfluramine appears to exert a weight reducing effect over periods of up to 12 months without development of tolerance, a problem that has limited the long term use of other pharmacological agents used in the treatment of this disorder. Dexfenfluramine facilitated weight loss in patients who had not responded satisfactorily to other weight-reducing strategies, prevented relapse in those patients who had achieved weight reduction by other methods, and corrected disturbed eating patterns (and therefore reduced weight gain) in small studies involving patients with premenstrual syndrome, seasonal affective disorder and nicotine withdrawal syndrome. Follow-up of the longest study reported with dexfenfluramine suggests that continued therapy is required in severely overweight patients if weight loss is to be maintained. Dexfenfluramine has not been directly compared with nonpharmacological measures of weight control such as behaviour modification or exercise programmes. The decision that pharmacological means are indicated in overweight patients must be highly individualised, and must consider the many complex factors that often contribute to overweight states, as well as the anticipated magnitude of drug effect. Despite such a cautionary note, and the expected need (at this stage of its development) for an expanded clinical study programme in certain areas, dexfenfluramine is a clear advance in the pharmacological approach to improved management of overweight individuals.

Animals↗

PubMed1992

Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders.

Lansoprazole is an effective acid pump inhibitor acting at the final enzymatic step of the acid secretory pathway of the parietal cell, decreasing gastric acid secretion regardless of the primary stimulus. Results of short term (less than 8 weeks) clinical trials have shown lansoprazole to be significantly superior to placebo and ranitidine in the treatment of duodenal ulcer, both in the rate of healing and in overall healing at 4 weeks. Lansoprazole appears to heal duodenal ulcer more quickly than famotidine, and demonstrates slightly greater efficacy at 4 weeks, although both drugs appear to have equivalent efficacy overall. Gastric ulcers and reflux oesophagitis are also healed by lansoprazole 30 mg/day for 4 to 8 weeks, with healing rates after 8 weeks of approximately 85 to 95% for both indications. Lansoprazole appears to be superior to ranitidine and comparable to omeprazole in treating reflux oesophagitis. Furthermore, lansoprazole has relieved reflux symptoms more quickly than either ranitidine or omeprazole. Preliminary data also indicate that lansoprazole may be effective in the treatment of peptic ulcer disease and reflux oesophagitis refractory to H2-receptor antagonists, and in patients with Zollinger-Ellison syndrome. While direct comparisons with omeprazole are limited, results suggest that lansoprazole, used for short term treatment, is at least as effective as omeprazole in the treatment of peptic ulcer and reflux oesphagitis. Lansoprazole has been well tolerated in short term clinical trials, with an incidence of adverse effects comparable with that of other agents in its therapeutic class. Trials assessing long term tolerability data are ongoing and will be required as part of the assessment of the safety profile, if lansoprazole is to be used prophylactically to prevent ulcer recurrence. Thus, by virtue of its ability to heal ulcers and rapidly relieve associated symptomatology, lansoprazole represents a useful alternative for the treatment of acid related disorders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1992

Budesonide. An updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis.

Inhaled budesonide is now well established in the management of adult and childhood asthma, and when nebulised, shows considerable promise in recurrent wheezing and in severe asthma in infants. Studies conducted since the drug was previously reviewed in the Journal in 1984 have confirmed the comparable efficacy of equal doses of budesonide and beclomethasone dipropionate, the ability of budesonide to reduce oral maintenance corticosteroid requirements, and demonstrated its potential as first-line treatment of mild to moderate asthma. Recent studies have established the usefulness and good tolerability of intranasal budesonide in the treatment of seasonal allergic and perennial rhinitis where the drug is more effective than disodium cromoglycate and at least as effective as beclomethasone dipropionate. After up to 10 years of treatment with inhaled budesonide there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Inhaled corticosteroids continue to play an important role in the treatment of asthma with an increasing focus on their role as first-line therapy, and widespread clinical experience has shown budesonide is an effective and well tolerated member of this class which should be considered where inhaled or intranasal administration of a corticosteroid is indicated.

Aerosols↗

PubMed1992

Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder.

Sertraline is a selective inhibitor of central serotonin reuptake. Thus, it enhances serotoninergic transmission--a property which appears to explain its antidepressant activity. Its elimination half-life (approximately 26 hours) makes it suitable for once daily administration. Although clinical experience with sertraline is limited, it appears to possess antidepressant efficacy similar to that of amitriptyline and dothiepin, marginally better than imipramine, and significantly better than placebo. Additionally, sertraline is the only antidepressant licensed in the UK for the prevention of recurrence of depression, and preliminary findings suggest that the drug may also be effective in the treatment of obsessive-compulsive disorder. Sertraline and other serotonin reuptake inhibitors possess tolerability advantages over tricyclic antidepressants. Sertraline has minimal anticholinergic activity, is essentially devoid of cardiovascular effects, has a wide therapeutic index and may be administered to elderly patients or those with underlying cardiovascular disorders. However, as with other serotonin reuptake inhibitors, sertraline has been associated with gastrointestinal disturbances (nausea, diarrhoea/loose stools) and male sexual dysfunction (primarily ejaculatory disturbance), although each of these effects is usually mild and transient, decreasing in frequency with continued treatment. As a drug class, serotonin reuptake inhibitors such as sertraline appear to provide significant advantages compared with the more established antidepressant agents, particularly in terms of tolerability. Although much broader clinical experience is required before sertraline's full therapeutic potential can be realised, if future studies confirm the encouraging initial findings, sertraline will undoubtedly become an important option in the treatment of depression.

1-Naphthylamine↗

PubMed1992

Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy.

Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease.

Pamidronate [aminohydroxypropylidene diphosphonate disodium (APD), disodium pamidronate] is an orally and intravenously active amino-substituted bisphosphonate which produces potent and specific inhibition of bone resorption at doses devoid of any significant detrimental effect on bone growth and mineralisation. Clinical trials indicate that pamidronate is effective in a variety of conditions characterised by pathologically enhanced bone turnover, including Paget's disease, hypercalcaemia of malignancy, osteolytic bone metastasis, steroid-induced osteoporosis and idiopathic osteoporosis. Pamidronate is highly effective in restoring normocalcaemia in patients with hypercalcaemia of malignancy associated with bone metastases but, in common with other bisphosphonates, is marginally less effective against humoral hypercalcaemia of malignancy. Comparative studies in this area have suggested that, at therapeutic doses, pamidronate has a more pronounced calcium-lowering action than etidronate (etidronic acid) and clodronate (clodronic acid) and provides a longer period of normocalcaemic remission. In Paget's disease arrest and, in some patients, reversal of the progression of osteolytic lesions by pamidronate is associated with a sustained reduction in bone pain, improved mobility and a possible reduced risk of bone fracture. In patients with osteolytic bone metastasis pamidronate reduces skeletal morbidity and slows the progression of metastatic bone destruction. Long term use of low-dose pamidronate in conjunction with conventional antiosteoporotic therapy may halt bone loss in steroid-induced and idiopathic osteoporosis. Pamidronate appears to represent a valuable addition to the drugs currently available for the treatment of symptomatic Paget's disease and cancer-associated hypercalcaemia, and shows promise in the treatment of osteolytic bone metastasis and osteoporosis.

Animals↗

PubMed1991

Acrivastine. A review of its pharmacological properties and therapeutic efficacy in allergic rhinitis, urticaria and related disorders.

Acrivastine is a short acting histamine H1-receptor antagonist with a rapid onset of action. Double-blind clinical trials have shown acrivastine (usually 8mg three times daily) to be an effective and well tolerated antihistamine in the treatment of chronic urticaria and allergic rhinitis. Acrivastine was more effective than placebo and similar in efficacy to clemastine or terfenadine in the treatment of seasonal allergic rhinitis. In the treatment of dermatoses in which histamine has a pathogenetic role, the efficacy of acrivastine was superior to that of placebo and similar to that of usual dosages of clemastine, hydroxyzine, chlorpheniramine, cyproheptadine or terfenadine. Acrivastine caused less drowsiness than clemastine, the incidence of adverse effects being indistinguishable from that with placebo or terfenadine. Thus, acrivastine is an effective addition to drugs currently available for the treatment of patients with allergic diseases in whom a histamine H1-receptor antagonist is indicated. Because of its rapid onset of action acrivastine will be particularly useful for 'on demand' therapy in patients with intermittent symptoms.

Dermatitis, Atopic↗