No abstract

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.

Pefloxacin is a fluorinated quinolone that is structurally related to nalidixic acid. It can be administered both orally and intravenously, and has a broad spectrum of in vitro activity against Gram-negative organisms and staphylococci. The pharmacokinetic profile of pefloxacin is characterised by high bioavailability after oral administration, a long half-life and good penetration of tissue and body fluids. Data from mainly non-comparative studies suggest that pefloxacin has the potential for use in a variety of serious or difficult-to-treat and nosocomially acquired infections in hospitalised and immunocompromised patients. Such infections have included respiratory tract, urogenital tract, and bone and joint infections, septicaemia and surgical infections, in addition to severe Gram-negative infections in neutropenic cancer patients. Pefloxacin demonstrates comparable efficacy with ampicillin combined with gentamicin in upper gynaecological tract infections, ceftazidime in nosocomially acquired Gram-negative infections and co-trimoxazole (trimethoprim + sulphamethoxazole) in uncomplicated urinary tract infections and typhoid fever. Although the place of pefloxacin in this new and expanding class of 4-quinolone antibacterial drugs has yet to be defined and it appears to be a well-tolerated and useful drug for the treatment of serious infections in hospitalised patients, further studies are awaited with interest for confirmation of these preliminary results.

Enoxacin is a new addition to the class of 4-quinolone antibacterial drugs. It has a broad spectrum of in vitro antibacterial activity, and is particularly potent against Gram-negative organisms and staphylococci. The pharmacokinetic profile of enoxacin is similar to that of ofloxacin, achieving higher plasma and tissue concentrations and possessing a longer half-life than norfloxacin or ciprofloxacin. In comparative studies, clinical and/or bacteriological efficacy was comparable or (in studies which statistically analysed the results) not significantly different between enoxacin and amoxycillin in acute cystitis, acute Gram-negative exacerbations of chronic bronchitis and acute or chronic otitis media, between enoxacin and cephalexin in skin, skin structure and soft tissue infections, between enoxacin and trimethoprim in acute cystitis, between enoxacin and co-trimoxazole in complicated urinary tract infection and between enoxacin and pipemidic acid in suppurative otitis media. Significantly (p less than 0.01) more clinical and/or bacteriological cures were effected by enoxacin than pipemidic acid in acute cystitis and complicated urinary tract infection. In uncomplicated gonococcal infections single oral doses of enoxacin were effective in over 90% of patients. Enoxacin is a well-tolerated, orally active broad spectrum antibacterial drug which should prove a worthwhile alternative to currently available antibacterial therapy.

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.