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In This Article
  Introduction
   Historical Overv...
  Types of Spaceflight
   Effects of Micro...
   Extra-vehicular ...
   Medical Emergenc...
   Spacecraft Emerg...
   Space Medicine D...
   Pharmacology in ...
   Physiological Al...
   Future of Person...
  Conclusions
   References

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 Table of Contents    
EDITORIAL
Year : 2023  |  Volume : 55  |  Issue : 5  |  Page : 281-285
 

Space medicine: Hunting for pharmacologist's guide in dealing with drugs in microgravity


1 Department of Pharmacology, Jawaharlal Nehru Medical College, KAHER, Belagavi, Karnataka, India
2 Department of Pharmacology, PGIMER, Chandigarh, India

Date of Submission11-Sep-2023
Date of Decision10-Oct-2023
Date of Acceptance23-Oct-2023
Date of Web Publication02-Nov-2023

Correspondence Address:
Bikash Medhi
Department of Pharmacology, PGIMER, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.ijp_591_23

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How to cite this article:
Mahalmani V, Medhi B. Space medicine: Hunting for pharmacologist's guide in dealing with drugs in microgravity. Indian J Pharmacol 2023;55:281-5

How to cite this URL:
Mahalmani V, Medhi B. Space medicine: Hunting for pharmacologist's guide in dealing with drugs in microgravity. Indian J Pharmacol [serial online] 2023 [cited 2023 Dec 9];55:281-5. Available from: https://www.ijp-online.com/text.asp?2023/55/5/281/389239





  Introduction Top


Space medicine may be defined as: “The practice of all aspects of preventive medicine including screening, health-care delivery, and maintaining human performance in the extreme environment of space and preserving the long-term health of space travellers.”[1] President John F. Kennedy in 1961 committed the United States to land a man on the Moon and return him securely to the Earth. The effects of space-flight on human physiology were not very well known. The variations due to acceleration, cabin pressure, vibration, CO2 concentration, and micro-gravity were not very well known. Moreover, external threats such as radiation exposure, meteorites, and extreme temperatures were also to be taken into consideration.[2]


  Historical Overview of Space Medicine Top


Dogs were the first to fly into space. Initial short-term human spaceflights proved to be safe. Nevertheless, the detrimental effects of zero gravity began as the flight duration increased. The efforts of scientists, technologists, and doctors are commendable in formulating the technical and medical standards to ensure the safety of crew members. Knowledge of human physiology is of utmost importance to study the effects of zero gravity under the confined conditions of spacecraft.[3]

In 1961, Yuri Gagarin a cosmonaut was the first man to fly for about 1 h and 48 min in space and orbit around the earth. On May 5, 1961, Alan B. Shepard, a National Aeronautics and Space Administration (NASA) astronaut became the first to fly in space. These breath taking expeditions began a modern era of human space expeditions. Neil Armstrong and Buzz Aldrin were the first humans to step on the Moon in the year 1969.[4]


  Types of Spaceflight Top


“Spaceflight” involves missions that occur more than 100 km beyond the sea level. This internationally identified altitude boundary is referred to as the “Karman line” beyond which lies space. Human spaceflight is categorized into suborbital, low earth orbit (LEO), and exploration class missions. Suborbital missions are short, lasting for a couple of hours, out of which few minutes are spent encountering the weightlessness of microgravity. LEO refers to flights at an altitude of 200–400 km orbit around the earth. Exploration class missions are the ones beyond LEO. These include missions to the moon, mars, and other celestial objects.[5]


  Effects of Microgravity Top


Microgravity is a condition where one appears to be weightless in a spacecraft. There occurs extreme transition in the human body in response to microgravity. Sensory disturbances involving the vestibular system are the most immediately evident effect.

Around, 60%–80% of astronauts experience nausea, vomiting, and pallor in the initial few days known as “space adaptation syndrome.”[6] The effects of microgravity include widespread redistribution of body fluids from the lower to the upper parts of the body, the most evident physiological change that results due to the abolition of the gravity experienced on the earth. This leads to a “puffy face” appearance because of facial edema.[7] At the same time, there is a reduction in leg volume leading to a “chicken legs” appearance.[7]

Two important considerations to be kept in mind are radiation exposure and physiologic alterations, particularly in the case of long-duration spaceflights. Cosmic radiation can pose a threat to cancers as they damage cellular DNA. Strategies to reduce radiation exposure are to schedule missions when there is minimum solar activity, using low atomic mass materials to upgrade shielding, high hydrogen content, and chemo-preventive therapy.[8],[9] Increased calcium excretion occurs leading to bone demineralization that can predispose to the risk of calcified stone in the renal tract or a fracture.[10],[11] Spaceflight also causes immune dysregulation giving rise to increased granulocytes, B-cells, and a reduction in lymphocytes and natural-killer cells.[12],[13] Hemopoiesis might be affected because of a decrease in the red cell mass giving rise to “space anemia.”[14] Sleep disruption may also be observed due to disruptions in light dark cycles.[15] Soon after landing, astronauts might encounter generalized weakness, neurosensory disturbances, and orthostatic intolerance affecting one's ability to walk.[16] In order to boost both musculoskeletal and cardiovascular systems, astronauts undergo physical re-conditioning persistently.[17]


  Extra-vehicular Activity Top


Spacewalk, also known as “extra vehicular activity,” indicates human activities taking place outside the spacecraft while in space. These spacewalks are quite challenging as they generate tremendous heat which is unbearable. Therefore, space suits protect astronauts from environmental threats such as thermal stress, radiation hazards, and micrometeoroids.[5]


  Medical Emergencies in Space Top


According to the NASA, the possibility of an illness or injury increases with exploration beyond LEO.[18] Maintaining crew health becomes very important for the smooth conduct of the missions. There are numerous challenges associated with even storage of medications. They should have an adequate shelf life, be chemically stable, and be thermally robust.[19] Radiation exposure in space may cause faster degradation of the medications compared to the earth.[20]

In addition, restricted space, power, and equipment are some of the difficulties encountered in the conduct of anesthesia.[21] Response to anesthetic agents might also vary because of alterations in human physiology in the space environment.

In case of acute loss of cardiac output, cardiopulmonary resuscitation (CPR) is the mainstay to keep up blood circulation and oxygenation. There are numerous techniques of CPR that have been tailored to microgravity.[22],[23],[24] However, following a cardiac arrest, CPR is just a temporary life-saving measure. Therefore, complex supportive critical care is of utmost importance and is difficult to make available in the space environment.


  Spacecraft Emergencies Top


As per the International Space Station, the three important spacecraft emergencies include;

  1. Loss of pressurization: Because of a leak in the spacecraft or spacesuit
  2. Fire
  3. Toxic leak such as ammonia.


An emergency return from LEO can be achieved in a few hours even though options might be restricted due to various factors such as the type of evacuation vehicle and its availability, the physical state of the patient and the medical assistance needed. Moreover, not much is known regarding the impact of microgravity or +Gx acceleration on an injured or ill person at the time of re-entry into the Earth's atmosphere. Evacuation time depends on the type of space mission.


  Space Medicine Doctor Top


The space medicine doctor is also referred to as a “flight surgeon.” His role differs from that of normal medical practice. They need to work in circumstances where intense environments, engineering, medicine, and flight intersect with each other. NASA clearly states that a physician must be an integral part of the team for planetary expeditions lasting more than 210 days.[19]


  Pharmacology in Space Top


Medications are necessary in space to treat illnesses that are quite common to human beings on the Earth and also due to physiological alterations as a result of the space environment. Drugs have been used in space missions involving human beings since the very beginning, yet our knowledge pertaining to the effects of space expeditions on drug pharmacodynamics and pharmacokinetics is limited. With experience from previous human spaceflights and the escalation in flight duration, there has been a consistent growth in the number of drugs contained in these kits. The initial spaceflights like Gemini 7 and Apollo 11 had 10 and 13 pharmacologically active compounds in their medical kits, respectively.[25] These numbers kept on rising, counting to 107 items as per the 2017 evidence report sent by the NASA.[19] During space missions, drugs are used often for nonlife-threatening conditions such as pain, sleep disturbances, motion sickness, congestion, or allergy.[15],[26],[27] In addition, NASA reported using antibiotics[26],[25] vitamins[25],[28] Alendronate[29] drugs for digestive disorders,[25] and oral contraceptives.[30]

Earlier, most of the space expeditions remained in LEO and were of shorter duration.[31] Till date, only four people have been a part of expeditions lasting for a year or more.[28] The upcoming human space expeditions to the Moon and Mars are going to be quite challenging due to various factors such as considerable radiation exposure, restricted communication, and failure to immediately evacuate severely ill crew members back to the Earth.[19],[32]

Every phase of space mission is associated with challenges because of physiological changes leading to alterations in pharmacokinetics and pharmacodynamics. In addition, changes in bacterial virulence and chemical disposition of drugs make the treatment more complicated in space.[33],[34],[35]


  Physiological Alterations in Space and their Significance on Drug Pharmacokinetics Top


Drug absorption

Gastrointestinal transit time is altered by drugs used for space motion sickness mainly with scopolamine and promethazine.[36],[37] Antimuscarinic drugs will slow down drug absorption or cause degradation of drugs in the stomach (acidic environment) because of delayed gastric emptying. Altered nutritional intake, decreased or limited calorie intake along with stressors related to space missions can cause alteration in gut microbiota.[38]

Caco-2 cell lines, an in vitro model to assess drug permeability have shown notable variations in the expression of various proteins under microgravity conditions, thereby indicating changes in drug absorption through the intestinal wall.[39] Variations in gut microflora, alteration in velocity of hepatic blood flow, and first-pass metabolism play a vital role in drug absorption and its bioavailability.

Drug distribution

The decline in total body water by 3% has been noted after a prolonged spaceflight. There is also a decline in total body mass attributed to a decrease in lean body mass. Therefore, for a given dosage, the plasma concentration of a drug is anticipated to be greater.[40] The apparent volume of drug distribution (Vd) is slightly lower as the overall blood volume is a bit lesser. Thus, effective drug concentrations are expected to be higher in space compared to the Earth.[41] Alterations in cardiovascular parameters can have an influence on the pharmacokinetics of drugs, having an effect on their safety and efficacy. Nevertheless, the human body seems to adapt to these variations.[42]

Drug metabolism

Cytochrome variations can result in either an increase or decrease in drug metabolism that in turn can lead to adverse effects or therapeutic failure. An 8-day space mission involving rats revealed a reduction in the levels of liver enzymes with antioxidant activity such as catalase glutathione reductase (GSH) and GSH sulfur-transferase.[43]

Simulated high-altitude hypoxic conditions revealed a decline in the transcription of organic cation transporter 2 and uridine diphosphate glucuronosyltransferase 1A1 leading to changes in the pharmacokinetics of metformin and acetaminophen.[44] Additional evidence is required about identified genes and enzymes, particularly the ones involved in metabolizing common drugs used in spaceflight. In addition, one has to focus on drug-drug and drug-diet interactions in spaceflight.

Drug excretion

According to a study by Norsk et al., a simulated microgravity model showed an increase in glomerular filtration rate (GFR) and diuresis.[45] However, Drummer et al. revealed that renal plasma flow, GFR, and urine output remained unchanged in space.[46],[47] Sudden arrest in the activity of large muscle groups may lead to a decline in plasma volume.[48] This would probably lead to a reduction in renal blood flow and excretion of drugs. A compensatory rise in anti-diuretic hormone and plasma renin activity was noted in spaceflights of short duration.[49],[50] Physiological changes occurring during spaceflights affect drug pharmacokinetics. A study evaluating the pharmacokinetics of Acetaminophen in flight, using saliva samples revealed higher variability when compared on the earth.[51] However, few studies have been performed and there is a lack of enough literature pertaining to the drug pharmacokinetics comparing their effect in the microgravity and Earth.


  Future of Personalized Medicine in Space Top


As mentioned earlier, space flight uncovers humans to intense conditions. Pharmacogenetic screening is to be performed for astronauts as a part of personalized medicine that helps to minimize risk, keep up astronaut health, and also for effective diagnosis and treatment of emergent medical problems arising during space missions.

Biomarkers have been an important tool in personalized medicine to speculate the result of any therapy. In the era of “omics” and high throughput technologies, enormous data can be gathered from individuals. In support of this, NASA conducted a study on monozygotic twins to evaluate various parameters such as physiological, transcriptomic, proteomic, metabolomic, microbiomic, telomeric, epigenetic, cognitive, and vision-related data to compare the effect of a long space mission of 340 days on a twin and concurrent effects of the same parameters in another twin of the terrestrial environment. They observed several multisystem variations during human space missions some of which returned back to normal whereas some persisted beyond the study duration.[28] However, the new approaches are quite complex which can raise ethical issues as well. Hence, there is still a lot more to explore about space medicine. Therefore, this field can act as a new approach to figuring out the impact of space missions on the crew.


  Conclusions Top


The current data suggest that physiological variations occurring during space missions might probably alter drug potency, efficacy, and safety which in turn depends on the drug, formulation, duration of space travel, and environmental factors. Therefore, the current evidence cannot be generalized to longer missions, for example, mars. A better understanding of space pharmacology is essential for such long missions.



 
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