Drugs and adverse reactions: an economic view of a medical problem.

This monograph attempts to show how patient, physician and drug producer should assess the value and risks of a drug from the economic point of view. The value of a drug lies in its efficacy against disease and pain; the risks are the various side effects. A hypothetical example illustrates the evaluation from the point of view of an individual patient. A distinction must be made here between diseases which may prove fatal and those of a less serious nature. This means that a distinction must also be made in evaluating the risks attached to a drug and the individual attitude to side effects. For the physician, the task of recognizing an adverse drug reaction (ADR) is an extremely complex one. A 11-step flow chart for decision making is presented as a benchmark procedure. Several empirical studies on the incidence of ADRs in ambulatory and hospitalized patients are shown to use shortcuts, which are entirely justified in daily medical practice, but questionable in a scientific analysis. For various reasons the drug manufacturer too is anxious to recognize ADRs at an early stage and to avoid them whenever possible. Prolonged clinical trials, however, produce a steep rise in costs and delay the launching of the product, while the additional information obtained is not always comprehensive and exhaustive. Moreover, the mere fact of recognizing an ADR does not mean that it can be prevented. The producer is therefore forced to consider the risks and costs involved in speeding up or delaying the introduction of a product. The fact that the drug has been approved for sale does not automatically release introduction of a product. The fact that the drug has been approved for sale does not automatically release him from the obligation to carry out further intensive monitoring for the entire period that it is on the market.

[Diagnostic and therapeutic trends in the use of on an easily executed method of blood volume determination]. / Orientamenti diagnostici e terapeutici sulla guida di una metodica di determinazione della volemia de facile esecuzione clinica.

In 59 subjects with varying pathology--mainly hepatic, cardiac and digestive diseases--the plasmatic, corpuscular and total blood volume was calculated by means of a colorimetric method: BSP clearance. The normal values compared with those obtained by other colorimetric methods give a slight overestimation. On the basis of the Ht the subjects are divided into three groups. In each group, subgroups are recognised with reference to total and fractional blood volume changes. The analysis evidences that a normal Ht is often present in pathological states, with variations in the two consensual blood volume components. In other situations in which the Ht is impaired, the degree of variation may be over or underestimated through inverse variation of the two components.

[Blocked suprahepatic pressure and the portohepatic gradient in evaluation of the portal circulation (author's transl)]. / La pressione sovraepatica bloccata e il gradiente porto-epatico nella valutazione del circolo portale.

Blocked suprahepatic pressure and the portohepatic gradient were studied in correlation with the circulation parameters and expressed by graphical representation allowing approximate quantitative evaluation of their variation. It is a complete analysis of the possible variations produced in the hepatic and portal circulation by extrahepatic and especially intrahepatic shunts resulting from morphological changes due to the active and passive fibrous septa that are established during cirrhosis. This leads to a hemodynamic classification of the condition of the portal and hepatic circulation, evidencing the importance of determination of the blocked suprahepatic pressure and portohepatic pressure gradient for correct interpretation of the clinical picture and for medical or surgical therapeutic guidance.

[Changes in circulatory indices in hepatopathic patients (author's transl)]. / Modificazioni degli indici circolatori negli epatopatici.

In more than 70% of subjects suffering from chronic liver disease of varying gravity without presenting signs of renal failure, a haemodynamic situation of hyperkinetic type was evidenced. The increase in flow is linked to the reduction of vascular resistances. A hemodynamic classification is proposed in order to evidence relationships between physical and mechanical adaptation and the mechanisms of regulation and counter-regulation, and within which the test case may find a possible interpretation.

[Stenosis of hepatic artery associated with portal vein anomaly and splenomegaly: a haemodynamic evaluation (author's transl)]. / Associazione di stenosi dell'arteria epatica e di anomalie della vena porta con splenomegalia: studio della situazione emodinamica.

The authors describe one case of stenosis of the common hepatic artery associated with splenomegaly. After commenting on the rarity and peculiarity of such an occurrence, they explain the decisive role of selective celiac tripod arteriography not only for precise diagnostic definition of the case but also in terms of formulating an appropriate therapeutic program. The study of this case includes a detailed exploration of the hemodynomic situation created by the anomaly in the hepatosplenic district, and an equally detailed study of the associated blood picture changes.

[Variations of hematic and plasmatic viscosity as a function of flow velocity, analyzed by means of an experimental model]. / Variazioni della viscosita' ematica e plasmatica in funzione della velocita' di flusso, analizzate mediante modello sperimentale.

The authors have determined the hematic and plasmatic viscosity in 60 sound subjects, 30 men and 30 women respectively, at different values of cut drop, corresponding to the values that can be found at different levels of circulatory system. These subjects had value of Ht, total protidemy, cholesterolemy and trigliceryds, included in normal limits. For these determinations, made at constant temperature, they have used Well-Brookfield with a divergent angle of 0,8 degrees. In this way they could determinate the normality limits of hematic and plasmatic viscosity, in men and women, in connection with the physiologic modifications of flux speed. It has been confirmed the tixotropo behaviour of blood, whose viscosity increases exponentially for lessenings of cut drop and we have put this fact in touch with genesis of thrombosis. They haven't shown any expressive difference in the behaviour of the curves of two undergroups; the curve of middle values is higher for men, and it seems that this difference is owing to Ht. esclusively. In the end they have considered the curves of subjects that had values of viscosity different from normality; in this way they have found three different curves, in pathologic conditions.

[Exploration of possible associations of antineoplastic chemotherapeutic agents in view of their mechanisms of action (author's transl)]. / Studio delle possibilita' di associazione dei farmaci chemioterapici in riferimento al loro meccanismo d'azione.

A careful study of the principal multidrug regimes wil reveal in each case the criteria upon which the drug association was based. In this paper the authors emphasize the importance of correlating the parameter, point of attack of the drug, with the parameter, metabolism of the malignant cell, the latter being differentiated into different functions according to thermodynamic criteria and to the particular organization of enzyme systems in the cells. Thus a multidrug association will be the more rational, the greater the number of parameters taken into consideration in its engineering; in these terms the authors outline a method of drug association affording more and more complex combinations and also the replacement of one or more component drugs in the case of resistance phenomena.