Beclomethasone dipropionate. A reappraisal of its pharmacodynamic properties and therapeutic efficacy after a decade of use in asthma and rhinitis

Inhaled beclomethasone dipropionate is now well established in the management of asthma. Studies conducted over the last decade, and since the drug was previously reviewed in the Journal, have confirmed that inhaled beclomethasone dipropionate 400 to 800 micrograms daily can reduce the need for oral maintenance corticosteroids in the majority of asthmatic patients requiring such therapy, and that increasing the dosage to 2000 micrograms daily may provide additional clinical benefit in some patients unresponsive to usual therapeutic dosages. Follow-up over a period of several years has confirmed that the initial response to inhaled beclomethasone can be maintained in most patients. Recent studies indicate that beclomethasone dipropionate 400 micrograms daily is equally effective when administered in 2 or 4 divided doses in patients with stable asthma, but it is likely that the lower frequency of administration will be less effective when the asthma is unstable. Recent studies have established the usefulness and good tolerability of intranasal beclomethasone dipropionate in the treatment of perennial and seasonal rhinitis, where the drug has been shown to be more effective than intranasal sodium cromoglycate and similar in efficacy to flunisolide. Nasal polyps decrease in size during continuous treatment with intranasal beclomethasone dipropionate, but enlarge again during periods of respiratory infection. After a decade of treatment with inhaled and intranasal beclomethasone dipropionate, there is no evidence that the drug damages the tracheobronchial lining or the nasal mucosa. Thus, the initial promise of beclomethasone dipropionate has been fulfilled. It has had an important role in asthma therapy over the past decade, which will continue into the future.     

Zimelidine: a review of its pharmacological properties and therapeutic efficacy in depressive illness

Zimelidine is a new antidepressant, which is structurally unrelated to the tricyclic and tetracyclic antidepressants. The pharmacological profile of zimelidine is different to that of other antidepressants in that it appears to owe the major part of its activity to the inhibition of serotonin uptake within the central nervous system. It appears that the demethylated metabolite, norzimelidine, may be responsible for most of the pharmacological activity. Studies to date suggest that zimelidine has overall efficacy comparable with that of amitriptyline, desipramine, maprotiline and doxepin in depressive illness, but at dosages which have achieved a similar overall clinical improvement zimelidine does not cause sedation, and anticholinergic side effects are mild and occur infrequently. Preliminary evidence suggests that zimelidine is effective against concomitant anxiety in depressed patients, and that it may also be useful in treating phobic anxiety. Zimelidine appears less likely to cause serious cardiotoxicity, in therapeutic dosages or an overdosage, than the tricyclic antidepressants, but it has not been studied in patients with cardiovascular disease. Sleep disturbance has occurred significantly more frequently during zimelidine therapy than during therapy with other sedative antidepressants, but whether this simply reflects the absence of sedation with zimelidine, or an effect on sleep as such, is presently unclear. Zimelidine appears to be effective and well tolerated in elderly patients. Thus, some aspects of the drug's profile (e.g. apparent low incidence of anticholinergic effects or drowsiness) may offer potential advantages in some patients; however, clinical experience with zimelidine to date has been limited, and further well designed studies are required to define the role of the drug more clearly in treating depressive illness compared with other antidepressants, and particularly to define whether some types of depression may respond more readily to zimelidine than to other antidepressants.     

Moxalactam (latamoxef). A review of its antibacterial activity, pharmacokinetic properties and therapeutic use

Moxalactam (latamoxef) is a new synthetic oxa-beta-lactam antibiotic administered intravenously or intramuscularly. It has a broad spectrum of activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria, is particularly active against Enterobacteriaceae and is resistant to hydrolysis by beta-lactamases. Moxalactam has moderate activity against Pseudomonas aeruginosa, but on the basis of present evidence can not be recommended as sole antibiotic treatment of known or suspected pseudomonal infections. Like the related compounds, the cephalosporins, moxalactam is effective in the treatment of complicated urinary tract infections and lower respiratory tract infections caused by Gram-negative bacilli. As moxalactam is also active against Bacteroides fragilis it has considerable potential in the treatment of intra-abdominal infections in patients with normal immunological mechanisms, as well as in immunocompromised patients, when used alone or in combination with other antibiotics. Likewise, its ready penetration into the diseased central nervous system, its high level of activity against Gram-negative bacilli, and the lack of necessity to monitor drug plasma concentrations, indicate its potential value in the treatment of neonatal Gram-negative bacillary meningitis. Further clinical experience is needed before it can be determined whether moxalactam alone can be used in the treatment of conditions for which the aminoglycosides are drugs of choice, but if established as equally effective, moxalactam has the advantage of being devoid of nephrotoxicity. Bleeding is a potentially serious problem, however, particularly in the elderly, malnourished and in the presence of renal impairment.     

Ranitidine: a review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases

Ranitidine is a new histamine H2-receptor antagonist which, unlike cimetidine, does not contain an imidazole group. On a weight basis, ranitidine is 4 to 10 times more potent than cimetidine in inhibiting stimulated gastric acid secretion in humans. Therapeutic trials comparing ranitidine and cimetidine have demonstrated that ranitidine 150 mg twice daily is an effective alternative to cimetidine 1000 mg daily in 4 divided doses in increasing the rate of healing of duodenal and gastric ulcers over a period of 4 to 6 weeks. Ranitidine, given as a single 150 mg dose at night, decreases the incidence of ulcer recurrence. Preliminary studies in the Zollinger-Ellison syndrome and in patients intolerant of, or unresponsive to cimetidine, indicate that ranitidine controls the gastric hyperacidity and heals most ulcers, including those which failed to respond to months of treatment with cimetidine 1 to 1.6 g daily. Ranitidine, unlike cimetidine, has no antiandrogenic effects and does not alter hepatic metabolism of drugs. Ranitidine is well tolerated. Preliminary reports of the resolution of cimetidine-induced adverse effects following substitution of ranitidine, suggest that ranitidine may be of value in patients intolerant of cimetidine. However, wider clinical experience with ranitidine is needed to determine the clinical relevance of these reports.     

Vitamin A acid: a review of its pharmacological properties and therapeutic use in the topical treatment of acne vulgaris.

Vitamin A acid (retinoic acid: tretinoin) is a vitamin A derivative used in the topical treatment of acne. It acts by 'unseating' comedones, improvement developing slowly over a period of 2 to 3 or more months, and is also said to prevent the formation of new lesions. About three-quarters of patients with acne vulgaris benefit from treatment. In controlled studies, results achieved after a 3 to 4 months course of treatment were superior to those with sulphur-resorcinol-salicylic acid. When compared with benzoyl peroxide, results were variable and appear to depend on the length of treatment, the types of formulations used, and the concentrations compared. Application of vitamin A acid should be continued until the patient has been free of new lesions for several months. Further continued application at a less frequent interval or using a less active dosage form may help to prevent exacerbations of acne. A systemic antibacterial agent such as tetracycline can be given as well as in patients with moderate to severe lesions. Vitamin A acid is used in conjunction with gentle washing (to remove surface oil) but should be applied to a dry skin to avoid unnecessary irritation. Patient education and encouragement are crucial during the initial phase of treatment when microcomedones may be converted to pustules prior to desquamation.     

Cefoperazone: A review of its in vitro antimicrobial activity, pharmacological properties and therapeutic efficacy

Cefoperazone is a new 'third generation' semisynthetic injectable cephalosporin. It has a broad spectrum of antibacterial activity which includes Pseudomonas aeruginosa (unlike older cephalosporins), along with the Enterobacteriaceae and other Gram-negative bacteria, Gram-positive bacteria and anaerobic bacteria. Unlike other cephalosporins, cefoperazone is excreted to a considerable extent by extrarenal mechanisms. Given by intravenous or intramuscular injection, cefoperazone is effective against a wide variety of infections caused by Gram-negative or Gram-positive aerobes, including infections of the biliary tract, and in many anaerobic infections. It is generally well tolerated, diarrhoea and skin rashes being the most frequently reported side effects.     

Atenolol: a review of its pharmacological properties and therapeutic efficacy in angina pectoris and hypertension.

Atenolol is a beta-selective (cardioselective) adrenoceptor blocking drug without partial agonist or membrane stabilising activity. Its profile of action most closely resembles that of metoprolol which differs only in that it has some membrane stabilising activity. Atenolol has been well studied and is effective in the treatment of hypertension and in the prophylactic management of angina. Its narrow dose response range obviates the need for highly individualised dose titration. In patients with angina its long duration of beta-blocking activity allows once daily dosage, whereas other beta-blockers, unless in sustained release dosage forms, need to be given in divided doses. Other beta-blockers can be given once daily in hypertension, but at presnt the evidence for effective control with a once daily regimen is more convincing with atenolol. Further studies are need to clarify any important differences in blood pressure control between the various beta-blocking drugs, both in conventional or sustained release dosage forms. As with metoprolol, atenolol is preferable to non-selective beta-blockers in patients with asthma or diabetes mellitus. Atenolol has been well tolerated in most patients, its profile of adverse reactions generally resembling that of other beta-blocking drugs, although its low lipid solubility and limited penetration into the brain results in a lower incidence of central nervous system effects than seen with propranolol. Atenolol is eliminated virtually entirely as unchanged drug in the urine and dosage needs to be reduced in patients with moderate to severely impaired renal function (glomerular filtration rate less than 30 ml/min). There is no need for modification of dosage of atenolol in liver disease.     

Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia

Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and apolipoprotein B concentrations, and increases LDL receptor activity without adverse effects on other products in the cholesterol pathway. In patients with heterozygous familial or polygenic (non-familial) hypercholesterolaemia, oral lovastatin 20 to 40 mg twice daily reduces plasma total cholesterol and LDL-cholesterol concentrations by 25 to 40% over a period of several weeks. Lovastatin also produces decreases in plasma triglyceride and VLDL-cholesterol concentrations, although to a lesser extent. In addition, small though significant increases in HDL-cholesterol concentrations have been observed. Combined administration of lovastatin with other lipid-lowering drugs results in further reductions in plasma total and LDL-cholesterol concentrations beyond those seen with either drug alone. From findings in short term studies, lovastatin appears to be well tolerated with a low incidence of side effects. However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established. As would be expected at this relatively early stage of its clinical 'life,' lovastatin has not yet been studied in a manner that would determine its effect on cardiovascular mortality during long term administration. Nevertheless, if the substantial improvements to patients' lipid and lipoprotein profiles observed in short term studies are maintained during long term administration, then lovastatin will have an important role in the pharmacological management of hyperlipidaemia.