Pharmacology in space: pharmacotherapy.

This chapter summarized the information available on the pharmacological kits onboard spacecraft and on the use of drugs in space, while the next chapter is dedicated to the impacts of weightlessness on drug pharmacokinetics. The need of a selected group of drugs for the use of astronauts during short-term and long-term spaceflights has been discussed. Recommendations are made for a Space Pharmacopoeia as well as for the areas of research needed to adapt medication to the weightlessness of the space environment. Although the usefulness of these drugs has been clearly demonstrated, their use also raises several problems. Physiological changes due to weightlessness may induce changes in pharmacokinetic behavior of drugs and influence their dosage regimen. Inflight data obtained by salivary drug monitoring have shown changes in the distribution of scopolamine and a significant change in the disposition of the common pain-relief agent acetaminophen taken inflight, in both drug concentration and time course. The authors of this study emphasize, however, that their data are preliminary and as yet incomplete. Further simulation studies and, if possible, inflight experiments are required. In vitro studies of the antibacterial activity of antibiotics under space conditions have shown an increased resistance of Escherichia Coli to colistin and kanamycin, and a lowered resistance of Staphylococcus Aureus to oxacillin, chloramphenicol, and erythromycin. The possible consequences of these findings for the treatment of infections contracted by astronauts are yet to be elucidated. There is still a lack of pharmacological countermeasures, particularly for preventing the progressive bone demineralization occurring in weightlessness. The treatment of space motion sickness with drugs carries with it the problem of undesirable side-effects on psychomotor performance. In order to arrive at the most appropriate medical kit for a particular mission, the best trade-off of risk versus benefit for the individual and the mission must always be attempted for any pharmacological agent.

Pharmacology in space: pharmacokinetics.

The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.

The use of medicaments in space--therapeutic measures and potential impact of pharmacokinetics due to weightlessness.

In support of the preparatory programme for the European manned space infrastructure, the Long-Term Programme Office (LTPO) within ESA's Space Station and Microgravity Directorate initiated a series of studies aimed at a better understanding of the physiological and psychological aspects of living in space. In this context, in 1991 MEDES (Institut de medecine et physiologie spatiale) was contracted by the Agency to investigate the type and efficacy of drugs available for use by astronauts during space missions to counteract the effects of weightlessness or for medical treatments. This paper summarises the main outcome of this research, in the context of the so-called 'Pharmemsi Study'. The first part is dedicated to the content of the medical kits used by astronauts in flight, while the second describes how weightlessness can modify the action of drugs (i.e. pharmacodynamics and pharmacokinetics parameters) on the human body. Recommendations are given on 'Space Pharmacopoeia' as well as the areas of research needed to adapt medication to the weightless environment.

An attempt to determine the ideal psychological profiles for crews of long term space missions.

NASA: This paper reviews possible psychological criteria for selection at individual level (personality, psychological stability, competence, social skills) as well as at crew level (crew size, gender, compatability, group homeostasis). Once astronauts have been selected an important effort will have to be made pre-flight to prepare the crew to the autonomy necessary for a Mars trip. During the mission psychological support will be important, but probably limited by the mission constraints. At this stage, mission success will probably rely mainly on the capacity of the crew to prevent and manage crises internally. Post-flight psychological support is necessary to help astronauts to readapt to a normal way of life on Earth.^ieng

Habitability constraints/objectives for a Mars manned mission: internal architecture considerations.

It is generally accepted that high quality internal environment shall strongly support crew's adaptation and acceptance to situation of long isolation and confinement. Thus, this paper is an attempt to determine to which extent the resulting stress corresponding to the anticipated duration of a trip to Mars (1 and a half years to 2 and a half years) could be decreased when internal architecture of the spacecraft is properly designed. It is assumed that artificial gravity shall be available on board the Mars spacecraft. This will of course have a strong impact on internal architecture as far as a 1-g oriented design will become mandatory, at least in certain inhabited parts of the spacecraft. The review of usual Habitability functions is performed according to the peculiarities of such an extremely long mission. A particular attention is paid to communications issues and the need for privacy. The second step of the paper addresses internal architecture issues through zoning analyses. Common, Service and Personal zones need to be adapted to the constraints associated with the extremely long duration of the mission. Furthermore, due to the nature of the mission itself (relative autonomy, communication problems, monotony) and the type of selected crew (personalities, group structure) the implementation of a "fourth zone", so-called "recreational" zone, seems to be needed. This zoning analysis is then translated into some internal architecture proposals, which are discussed and illustrated. This paper is concluded by a reflection on habitability and recommendations on volumetric requirements. Some ideas to validate proposed habitability items through simulation are also discussed.