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Biomedical subjects

G Tognoni

Publications and source records attributed to G Tognoni.

At least 307 records · Page 17Linked to original sources
PubMedDate not supplied

Clinical pharmacokinetics of diazepam.

Diazepam is still one of the most used of the benzodiazepine group of drugs. Extensive studies over 10 years have defined a fairly complete profile of its kinetics. Minor aspects relating to patterns of its metabolism and excretion in certain age groups and in some disease states remain to be described quantitatively. However, there is more than sufficient kinetic information available for the requirements of good clinical practice. For optimum clinical benefit with minimum side-effects the following kinetic properties should be borne in mind: (a) there is a large interindividual variation (up to 30-fold) in dose/blood level ratios, especially when treatment is short-term; (b) the elimination half-life is prolonged in the elderly and the newborn and in some cases of liver disease; (c) there is accumulation of the active N-desmethylated metabolite during long-term treatment; and (d) administration of diazepam to pregnant women leads to rapid distribution from the maternal to fetal compartment: accumulation of both diazepam and desmethyldiazepam could cause prolonged sedation in the newborn. As there does not appear to be any clear relationship between the concentration of diazepam in the plasma and clinical effect, measurement of blood levels, other than for research purposes, is unnecessary. Based on kinetic data, a single administration of diazepam at night should be adequate for hypnotic and anxiolytic effects in most patients.

Adipose Tissue↗
PubMedDate not supplied

Monitoring plasma concentrations of salicylate.

Measurement of the plasma concentration of salicylate has been made in the majority of clinical settings where salicylates, mostly in the form of acetylsalicylic acid (aspirin), are used extensively to treat chronic rheumatic conditions. At the same time, studies on the kinetics of salicylates have increased in the specialised literature. Analysis of published papers suggests a surprising difference between principles documented in controlled situations and what happens in routine clinical practice. Recommended dosage regimens are based on a rather narrow amount of data, as relevant studies include few patients and have not used readily comparable protocols. The wealth of information available on the kinetics and metabolism of salicylates has not yet produced generally accepted agreement on how to achieve optimum therapeutic results. Plasma concentration monitoring programmes aim mainly at avoiding side effects and checking compliance, but do not deal specifically with overall evaluation of therapeutic outcome. In the longer term, aspirin may possibly become less favoured as the initial drug of choice for the treatment of chronic rheumatic conditions, and the merits of monitoring plasma salicylate levels could be even less favoured. In the meantime, however, as clinical practice still largely involves use of aspirin, prospective collection of more controlled data on larger population groups seems warranted, not only for the benefit of treated patients but also for the purpose of assessing more thoroughly the clinical relevance of therapeutic drug monitoring in this area.

Humans↗
PubMedDate not supplied

Clinical pharmacokinetics of cerebrospinal fluid.

The distribution of drugs into the cerebrospinal fluid has long been considered a challenging field of investigation in 2 major respects: (a) understanding how the physicochemical properties (molecular weight, pKa, plasma protein binding) of various molecules influence their movements across such a specific structure as the blood-brain barrier; and (b) defining the relationship between cerebrospinal fluid concentrations of various drugs and their central (side) effects. An attempt has been made to review the very dispersed information presently available to offer a clinically orientated picture of this area of pharmacokinetics. Drugs acting on the central nervous system (benzodiazepines, tricyclic antidepressants, anticonvulsants, opioids), antibacterial agents, cardiovascular drugs (beta-adrenoceptor blockers and digoxin), antineoplastic drugs (mainly methotrexate), and other miscellaneous agents (corticosteroids, cimetidine, methylxanthines) are reviewed. The available evidence seems to support the conclusion that only for methotrexate and antibacterial agents does knowledge of cerebrospinal fluid pharmacokinetics have direct therapeutic implications, while the mosaic of information available for other drugs does little more than provide a partially satisfactory picture.

Anti-Infective Agents↗
PubMedDate not supplied

Clinical pharmacokinetics of amiodarone.

Amiodarone is an iodinated benzofuran derivative with recognised antiarrhythmic activity in man. As yet, its pharmacokinetic behaviour has not been satisfactorily characterised. Specific and sensitive high-pressure liquid chromatographic methods have become available only recently and this partly explains the scarcity of pharmacokinetic data on the drug. Available evidence suggests that absorption of amiodarone following oral administration is erratic and unpredictable; oral bioavailability ranges from 22 to 86%. The drug is eliminated largely by metabolism; less than 1% of the dose is excreted unchanged in the urine. Biliary excretion may have a role in the overall elimination of the drug. Desethyl-amiodarone is the only metabolite positively identified in the plasma of patients receiving treatment with amiodarone; no data are available on its possible pharmacological activity. Since it is a highly lipophilic drug, amiodarone is extensively distributed into tissues. Adipose tissue and skeletal muscle accumulate large amounts of the drug during long term treatment. Myocardium/plasma ratios of amiodarone are high both in man and in animals; peak concentrations in the myocardium are reached within half an hour after administration of an intravenous bolus to dogs. Placental transfer of amiodarone has been demonstrated in humans, while its blood profile is not modified by dialysis treatment. In vitro protein binding of amiodarone has been reported to be 96.3 +/- 0.6%. The plasma half-life of amiodarone after single-dose administration has been reported to be in the range of 3.2 to 79.7 hours. However, after withdrawal of long term amiodarone treatment the half-life is as long as 100 days. Total body clearance ranges from 0.10 to 0.77 L/min after single-dose intravenous administration, and the apparent volume of distribution ranges between 0.9 and 148 L/kg. Amiodarone disposition kinetics in patients with cardiac arrhythmias are not different from those in healthy volunteers. However, the possible effects of liver and cardiac failure on the drug's kinetics have not been studied. Amiodarone potentiates the anticoagulant effect of warfarin, probably by inhibition of its metabolism. Increases of steady-state concentrations of digoxin, together with the appearance of signs of digitalis toxicity, have been reported when amiodarone was given to patients receiving long term treatment with digoxin. Amiodarone has also been shown to interact with other antiarrhythmic agents such as quinidine and procainamide. The time of onset of action of amiodarone after a single intravenous dose ranges between 1 and 30 minutes and its duration of effect between 1 and 3 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMedDate not supplied

Profile of secondary prophylaxis among children with rheumatic heart disease in Alexandria, Egypt.

A cross-sectional study was conducted in specialist children's hospitals in Alexandria, which aimed to evaluate the current regimen of secondary prophylaxis for children suffering from rheumatic heart disease. Two-thirds of the patients had complied with their prophylactic regimen. Prophylactic failure occurred in one-third of the patients, raising doubts about the efficacy of the brands of penicillin prescribed. Recurrence of rheumatic fever was recorded in 37.3% of the patients, with semiruban or rural residence and non-compliance with secondary prophylaxis the significant risk factors. These unsatisfactory findings suggest the need for a more effective strategy of primary and secondary prophylaxis for controlling rheumatic fever in our community.

Adolescent↗
PubMedDate not supplied

Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.

Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.

Aged↗
PubMedDate not supplied

[Andrea's story].

First-hand accounts of illness experiences provide important insights for other patients and their carers and can be a powerful tool for patient information and professional education. Andrea was ran over by a motor-bike while he was carried by bike and reported a complicated femur fracture. Three different representations of the story are reported and confronted: the bold chronicle of events, that sets the scenery and time sequence; Andrea's mother point of view on what happened after the accident, and during the course of the illness; and Andrea's story, told with his words and drawings. The methodological comments offered as discussion, stress how the collection of relevant patients stories can be a valuable research resource because it can offer a broad perspective which cannot be obtained by other means.

Accidents, Traffic↗
PubMedDate not supplied

[3 years of "new developments" in pharmacotherapy. An update which is also a proposal for participative experimentation].

The analysis of the contents of key national and international drug bulletins provides a comprehensive overview of what has been produced worldwide in the field of pharmacology and therapeutics over the last few years after the last publication in R d 1). The work presented, tries to avoid the risk of being a purely descriptive listing of true and false "new" information, and may be seen as an "experiment of information transfer": the available data are presented and summarised from various complementary points of view, to suggest also a methodology of permanent education, for which instruments are also proposed. Further, the text is tentatively proposed as an experiment of communication between nurses and pharmacists, to stimulate their dialogue and interaction both with respect to the use of drug literature and to the evaluation of daily needs of information in routine hospital practice.

Drug Therapy↗
PubMedDate not supplied

[Somatosensory evoked potentials after stimulation of the posterior tibial nerve in multiple sclerosis: comparative analysis with other modalities of evoked response and magnetic resonance].

Electrophysiological tests have proved to be a valuable method in assessing multiple sclerosis (MS) patients. In the last few years, scalp recorded short latency somatosensory evoked potentials to stimulation of nerves in the "lower extremity" have been more and more extensively employed. Some studies have aimed at comparing the sensitivity of MR imaging and multimodality evoked potentials, with somewhat conflicting results. In the present study posterior tibial nerve somatosensory evoked potentials (ptnSEPs) were performed in 29 MS patients with the aim to investigate the ability in revealing spinal cord conduction abnormalities and the sensitivity towards other evoked potentials and MR in MS. ptnSEPs showed a high percentage of abnormalities which did not significantly differ from that of visual evoked potentials; moreover in conjunction with median nerve SEPs can be used to localize thoracic or lumbar cord demielinating lesions, not evidenced on MR imaging. These results confirm that ptnSEPs, although non specific and crude in terms of precise localization, are a sensitive tool in detecting lesions, even subclinical, in MS patients. Moreover in anatomic regions like spinal cord where MR imaging is not very sensitive because the lower signal-to-noise ratio, they represent the only method available for demonstrating lesions.

Adult↗