Recent Pharmacology Studies on the International Space Station

The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during longduration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series

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

Menstrual Cycle Control in Female Astronauts and the Associated Risk of Venous Thromboembolism

Venous thromboembolism (VTE) is a common and serious condition affecting approximately 12 per 1000 people in the USA every year. There have been no documented case reports of VTE in female astronauts during spaceflight in the published literature. Some female astronauts use hormonal contraception to control their menstrual cycles and it is currently unknown how this affects their risk of VTE. Current terrestrial risk prediction models do not account for the spaceflight environment and the physiological changes associated with it. We therefore aim to estimate a specific risk score for female astronauts who are taking hormonal contraception for menstrual cycle control, to deduce whether they are at an elevated risk of VTE. A systematic review of the literature was conducted in order to identify and quantify known terrestrial risk factors for VTE. Studies involving analogues for the female astronaut population were also reviewed, for example, military personnel who use the oral contraceptive pill for menstrual suppression. Well known terrestrial risk factors, for example, obesity or smoking would not be applicable to our study population as these candidates would have been excluded during astronaut selection processes. Other risk factors for VTE include hormonal therapy, lower limb paralysis, physical inactivity, hyperhomocysteinemia, low methylfolate levels and minor injuries, all of which potentially apply to crew members LSAH data will be assessed to identify which of these risk factors are applicable to our astronaut population. Using known terrestrial risk data, an overall estimated risk of VTE for female astronauts using menstrual cycle control methods will therefore be calculated. We predict this will be higher than the general population but not significantly higher requiring thromboprophylaxis. This study attempts to delineate what is assumed to be true of our astronaut population, for example, they are known to be a healthy fit cohort of individuals, and combine physiological impacts of spaceflight (cephalic fluid shifts, lower limb inactivity) to understand specific risks associated with hormonal contraception

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

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

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

Menstrual Cycle Control and Venous Thromboembolism Risk in Female Astronauts

No abstract availabl

Dose Tracker Application for Monitoring Crew Medication Usage, Symptoms, and Adverse Effects During Missions

Medication usage records can be used as a relatively nonintrusive means of monitoring health. This has been attempted previously through crew medical records, but these records are incomplete from the perspective of a research pharmacologist. During the shuttle era, NASA operations did not include routine questioning of crewmembers about their medication use until after missions were complete. The (long!) questionnaire was on paper. Asking crewmembers to recall medication use from weeks before questioning made getting complete and accurate information virtually impossible. This study will document medication usage of crewmembers before and during their missions. It will capture previously unrecorded data regarding medication use during spaceflight, including side effect qualities, frequencies and severities. The research-oriented data will be collected for research purposes, separate from medical records. Dose Tracker employs an iOS application (app) for fast & easy collection of medication usage data from crewmember participants during their missions

Hormone Therapy and Venous Thromboembolism Risk During Space Travel

No abstract availabl