Biomedical subjects
Publications and source records attributed to J Sternon.
It is possible to observe in the aging male an hypotestosteronemia below 3 ng/ml. The indications of an androgenic treatment are discussed with their benefits, risks, contra-indications and choices of molecules. Testosterone-gel seems to be now the first choice for this type of patient. In case of normal testosteronemia and erectile dysfunction, the benefits/risks ratio of sildenafil is very favorable, except when contra-indicated.
Thalidomide comes back forty years after the discovery of its teratogenicity. Due to its antiangiogenic and immunomodulating properties, thalidomide is proposed in the treatment of multiple myeloma but also in the management of erythema nodosus leprosis, cutaneous lupus erythematosus and severe aphtosis.
During the last years, treatment of Alzheimer's disease has improved following a better detection of this disease and, more importantly, following a better knowledge of its physiopathogeny. After years of aspecific symptomatic treatments, acetylcholinesterase inhibitors have been recently released and can be considered as a specific symptomatic treatment. In this pharmacologic class, more practical and less toxic drugs are nowadays available. Treatments of behavioral disturbances have also been recently improved. Nowadays we have to find treatments able to modify the clinical evolution and eventually prognosis of this disease, and even to prevent it for the patients at risk. Nevertheless a simplification of the prescriptions is justified, to the detriment of drugs without any proven activity.
The coxibs, specific anti-Cox-2, represent an interesting evolution for the treatment of patients suffering from rheumatic conditions and presenting gastrointestinal ulcer risk. Anti-inflammatory effectiveness is comparable with the other NSAIDs, but the toxicity for the gastrointestinal mucosa is slightly lower. Contra-indications, extradigestive adverse affects and interactions are the same as for any other NSAIDs. Their risks and cost must be taken into account as such as the rheumatic condition of the patient. They may be prescribed to patients presenting a gastrointestinal risk and the relevant cost is reasonable. Pharmacovigilance survey at mid to long term is necessary.
Thanks to the better understanding of the physiopathological mechanisms in action in rheumatoid arthritis (RA), new therapeutic weapons have appeared, which have dramatically modified our approach of the disease. These so-called "biological" therapies antagonize the action of the cytokine at the top of the cascade which maintains the synovial inflammation, and leads to the joint destruction, i.e. the Tissue Necrosis Factor alpha (TNF alpha). Several controlled clinical studies have clearly demonstrated their short and middle term efficacy and safety profile, and they will soon become at the Belgian clinicians disposal. They have a rapid and dramatic effect on the signs and symptoms of RA and they slow down the radiologic progression. Some questions remain unresolved concerning their place in the general therapeutic strategy against RA, due to the uncertainties of their use in the long run, and to their cost.
During the last years, treatment of Alzheimer's disease has improved following a better detection of this disease and, more importantly, following a better knowledge of its physiopathogeny. After years of aspecific symptomatic treatments, acetylcholinesterase inhibitors have been recently released and can be considered as a specific symptomatic treatment. In this pharmacologic class, more practical and less toxic drugs are nowadays available. Treatments of behavioral disturbances have also been recently improved. Nowadays we have to find treatments able to modify the clinical evolution and eventually prognosis of this disease, and even to prevent it for the patients at risk. Nevertheless a simplification of the prescriptions is justified, to the detriment of drugs without any proven activity.
Presentation of six drugs: clopidogrel, raloxifene, mecillinam, natiglinide and repaglinide, pneumococcal conjugate vaccine. For each, positive and negative arguments, questions on hold and rating.
Levofloxacin, levorotatory isomer of ofloxacine, is the only FQ3G on the belgian market since the middle of 2000 and is a little more efficient than the FQ2G against S. pneumoniae. The FQ4G are in vitro active against the common and atypic respiratory pathogenes and significantly more efficient against the Gram positive cocci, principally against S. pneumoniae. Their long duration of action allows one oral administration a day sufficient to obtain bactericidal levels in the serum. Their secondary effects are located principally at the level of digestive tract, neurologic system or cutaneous area. In the U.S.A., several FQ4G (clina-, grepa-, spar-, trova-floxacin) were withdrawn from use after observance of severe toxicity, while there were being administrated on a large scale. Furthermore, two of these "respiratory" FQ4G (gemi- and moxi-floxacin) should reinforced our therapeutic armoury, moxifloxacin as of 2002 and gemifloxacin as of 2004. The position of FQ3G and 4G are in discussion. In the case of pneumonia acquired in the community and confirmed by X-Ray, our recommendation is to administer a new FQ at the first choice if the patient is allergic to penicillin, debilitated or if a penicillin resistant S. pneumoniae suspected (epidemiology, recent antibiotherapy) and at the second choice if it is resistance to penicillin or to macrolide, in case of atypic pneumonia. Today, the majority of the pneumonia acquired outside the hospital is empirically treated with a betalactam (oral or intravenous), with or without macrolide. The new FQ are important drugs. One must avoid overprescription which leads to bacterial resistance (especially S. pneumoniae).
The using of generic forms (GF) is presented as a potential source of budgetary "saving of money" in the field of pharmaceutical expenses. Not frequently prescribed in Belgium, they win a new interest thanks to the recent making use of the "reference repayment". Sale's authorization of GF is controlled by european rules, but some questions about their identity to original medications remain. Do similarities based only upon qualitative and quantitative composition in active molecules, pharmaceutical forms and biodisponibility give us all requested guarantees? Several cases of discordances can appear: the major elements of non conformity are the nature of excipients, notice's contents and the value of biodisponibility studies. However, in term of economy, in the drug market, development of GF appears to constitute an unavoidable phenomenon.
The prevention of osteoporotic fractures in post-menopausal women must be viewed in the framework of the treatment of menopause. SERMs ("Selective Estrogen Receptor Modulators") derivative from steroid hormones have estrogenic and antiestrogenic properties according to the substance and the target tissue. Raloxifene is a second generation SERM. It increases bone mass by 1 to 3% according to the measured site and, after 3 years of therapy at the dose of 60 mg per day, it reduces the incidence of vertebral fractures by 30 to 50% if patients have or do not have vertebral fractures before therapy. This drug is approved for the prevention of vertebral fractures in post-menopausal women at increased risk of fractures. A significant reduction in the incidence of hip fractures has not been demonstrated. Raloxifene exerts favorable effects on cardiovascular risk factors but one has to wait for the results of controlled prospective trials before concluding that raloxifene reduces the risk of atherogeniec disease. Preliminary results indicate a substantial reduction of the risk of invasive breast cancer, still to be confirmed. The incidence of vaginal bleeding does not differ from placebo as raloxifene does not stimulate endometrial proliferation. The most serious adverse event, although infrequent, consists in an increase of the relative risk of thromboembolic disease by 3.1 as compared to placebo. Longer term studies are necessary to compare raloxifene with the estrogen replacement therapy and to determine the extra-bone effects.
Etonorgestrel is provided in an subcutaneous implant to assure a contraception of long duration. This progestogen derived from desogestrel already used in several combined oral contraceptives acts by inhibiting ovulation and modifying the viscosity of the endocervical mucus. The contraceptive effect is rapidly obtained after insertion. After removal of the implant, the serum concentration of etonorgestrel rapidly drops down so that most patients ovulate after 3 weeks. The most important side effect of this contraceptive device is the bleeding irregularity encountered in a minority of patients (frequent or prolonged bleedings).
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By blocking the renin-angiotensin system, angiotensin converting enzyme inhibitors and more recently introduced angiotensin II receptor antagonists are two important classes of antihypertensive drugs. Whether one class is superior to the other is presently unknown. Their antihypertensive efficacy is comparable. Angiotensin II receptor antagonists are particularly well tolerated but the converting enzyme inhibitors have broader indications. The results of the large studies with morbidity and mortality end-points are awaited to better define the place of the angiotensin II antagonists in monotherapy and in combination.
Present and future solutions to the problem of bacterial multiple resistance involve physicians, patients and veterinarians. Their behaviour should evolve to take into account the medical and economical issues of antibiotic prescription. The clinical diagnosis requires a more rigorous assessment, based on bacteriological and rapid antigenic tests. Vaccination in both young people and the elderly, is an essential prophylactic tool, which is too often neglected. When a bacterial infection is suspected or proven, priority should be given to a targeted antimicrobial therapy with a bactericidal activity, in order to quickly eradicate pathogens. Therapies should be shorter and questionable antibio-prophylaxis should also be avoided. A watch laboratory network should provide physicians with an adequate information on local bacterial resistance patterns on a regular basis, in order to allow them adjusting their prescription.
Insulin resistance is the major defect in type 2 diabetes. Troglitazone is the first of a new class of drugs, the thiazolidinediones (TZD) with insulin sensitising actions. The TZD activate PPAR gamma (Peroxisome Proliferator Activated Receptor gamma). In clinical trials, the TZD decrease plasma glucose, plasma insulin and Hb A1C. Moreover they are synergistic with the glucose lowering drugs (biguanides and sulfonylureas) and with insulin therapy. The TZD also decrease triglycerides and increase HDL cholesterol, while reducing LDL oxidation. Few side effects have been reported but concerns persist about their safety. Hepatic dysfunction is seen in about 2% of the patients receiving troglitazone, leading sometimes to liver failure. This potentially lethal side effect appears to be less frequent with the second generation TZD, rosiglitazone and pioglitazone. Drug interactions, fluid retention, induction of colon polyps are other potential unwanted effects. This new class of drugs could play an important role in diabetes therapy, if clinical trials prove their long term efficacy and safety.
After levodopa, dopaminergic agonists are the most powerful agents in idiopathic Parkinson's disease treatment. Used in monotherapy or rather in early combination with levodopa, they allow a dramatic reduction of long-term motor side effects of the latter: onset and peak-dose dyskinesias, early morning dystonias. Their gastro-intestinal (nauseas) and moreover psychiatric (confusion and hallucinations) side effects limit their use, notably in geriatric populations. Superiority of so-called "second generation" agonists (ropinirole, pramipexole) on "first generation" agonists (bromocriptine, pergolide) remains to be proved.
Overprescription of antibiotics is evident in the community as well as in hospital, in veterinary practice or in agriculture. This leads to bacterial multiresistance and treatment failures. The limitation of this overprescription will not be obtained unless diagnostic, therapeutic and preventive guidelines are followed particularly in the management of the upper respiratory tract infections.