Are Medications Involved in Vision and Intracranial Pressure Changes Seen in Spaceflight

The Food and Drug Association Adverse Event Reports (FDA AER) from 2009-2011 were used to create a database from millions of known and suspected medication-related adverse events among the general public. Vision changes, sometimes associated with intracranial pressure changes (VIIP), have been noted in some long duration crewmembers. Changes in vision and blood pressure (which can subsequently affect intracranial pressure) are fairly common side effects of medications. The purpose of this study was to explore the possibility of medication involvement in crew VIIP symptoms

Pharmacology During Spaceflight Missions

No abstract availabl

New Pharmacology Studies on the ISS

It is known that medications degrade over time and that extreme storage conditions will hasten their degradation. This is the basis of the HRP Risk of Ineffective or Toxic Medications Due to Long Term Storage. Gaps include questions about the effects of the spaceflight environment and about the potential for safe use of medications beyond their expiration dates. There are also open questions regarding effects of the spaceflight environment on human physiology and subsequent changes in how medications act on the body; these unanswered questions gave rise to the HRP Concern of Clinically Relevant Unpredicted Effects of Medication. Studies designed to address this Risk and Concern are described below

Pharmacology in Spaceflight

No abstract availabl

Changes in Liver Metabolic Gene Expression after Radiation Exposure

The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments

Changes in Liver Metabolic Gene Expression from Radiation Exposure

Radiation exposure is one of the unique physiological challenges of human spaceflight that is not encountered on earth. While radiation exposure is known to impart physiological stresses and alter normal function, it is unclear how it specifically affects drug metabolism. A major concern is that the actions of medications used in spaceflight may deviate from the expectations formed from terrestrial use. This concern was investigated at the molecular level by analyzing how gamma radiation exposure affected gene expression in the livers of mice. Three different doses of radiation were administered and after various intervals of recovery time, gene expression was measured with RT-qPCR screening arrays for drug metabolism and DNA repair. After examining the results of 192 genes total from each of 72 mice, 65 genes were found to be significantly affected by at least one of the doses of radiation. In general, the genes affected are involved in the metabolism of drugs with lipid or steroid hormone-like structures, as well as the maintenance of redox homeostasis and repair of DNA damage

Monitoring Astronaut Health in Space

No abstract availabl

Charge Scan Reveals an Extended Region at the Intracellular End of the GABA Receptor Pore that Can Influence Ion Selectivity

Selective permeability is a fundamental property of ion channels. The Cys-loop receptor superfamily is composed of both excitatory (ACh, 5-HT) and inhibitory (GABA, glycine) neurotransmitter-operated ion channels. In the GABA receptor, it has been previously shown that the charge selectivity of the integral pore can be altered by a single mutation near the intracellular end of the second transmembrane-spanning domain (TM2). We have extended these findings and now show that charge selectivity of the anionic ρ1 GABA receptor can be influenced by the introduction of glutamates, one at a time, over an 8–amino acid stretch (−2′ to 5′) in the proposed intracellular end of TM2 and the TM1–TM2 intracellular linker. Depending on the position, glutamate substitutions in this region produced sodium to chloride permeability ratios (PNa+/Cl−) varying from 0.64 to 3.4 (wild type PNa+/Cl− = 0). In addition to providing insight into the mechanism of ion selectivity, this functional evidence supports a model proposed for the homologous nicotinic acetylcholine receptor in which regions of the protein, in addition to TM2, form the ion pathway

Limitations in Predicting Radiation-Induced Pharmaceutical Instability during Long-Duration Spaceflight

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed towards the rapid development of an effective pharmacy for future spaceflight endeavors.Comment: in press, Nature Microgravit

Space Pharmacology

“Space Pharmacology” is a review of the current knowledge regarding the use of pharmaceuticals during spaceflights. It is a comprehensive review of the literature, addressing each area of pharmacokinetics and each major physiological system in turn. Every section begins with a topic overview, and is followed by a discussion of published data from spaceflight, and from ground experiments meant to model the spaceflight situation. Includes a discussion looking forward to the new medical challenges we are likely to face on longer duration exploration missions. This book is a snapshot of our current knowledge that also highlights areas of unknown