We all focused on one topic throughout 2020: Covid-19. No single day passed without news on the pandemic as we counted numbers of positive cases and the death toll while anticipating for a vaccine. In the meantime, we got more familiar with some of the medical processes, like phases, clinical trials, mutations, etc. for all this had to deal with the most precious gift we are given: life.

In our last issue, we touched upon the history of pharmacology and how modern-day drugs are made in an article titled “Pharmacology: The Journey of a Chemical Compound into a Drug.” Now, we will explore the multiple, lengthy phases of clinical trials that drugs must undergo and why they are imperative in order for new medicines to get approved for the marketplace.

Clinical trials are a way to test new methods of diagnosing, treating, or preventing health conditions. The goal is to determine whether a substance is both safe and effective. A clinical trial is only done when there is strong reason to believe that a new test or treatment may improve the care of patients.

A variety of treatment methods such as medications, medication combinations, new uses for existing medications, and medical devices are evaluated through clinical trials. In the United States, all new treatments must go through these trials before being approved for public sale by the Food and Drug Administration (FDA).

At the discovery and development stages, thousands of compounds may be potential candidates for development into a “drug”. After early testing, however, only a small number of compounds look promising and call for further study. The entire process of developing a drug from its pre-clinical research stage to its final marketing phase can take approximately 12 to 18 years and often costs well over $1 billion [3, 4].

Clinical trials show us what works and what does not in the realm of healthcare and are designed to answer some important questions such as:

• Does the new treatment work in people? If it does, how effective is it?
• Is it better than currently used treatments?
• If it is not better, is it just as good and cause fewer side effects?
• Does it work in some people who do not benefit from current treatments?
• Is the new treatment relatively safe? There is virtually no treatment or procedure that is without risk, but do the benefits of the new treatment outweigh the risks?

Answering these questions, while giving as few people as possible an unknown treatment, often requires several clinical trials in different phases. Each phase is designed to answer certain questions while keeping trial participants as safe as possible.

Preclinical phase

Before clinical trials can begin in humans, tests and treatments are assessed in pre-clinical research, which can involve extensive laboratory research over several years of testing on animals and human cells. This research may aim to learn the chemical compound of a drug [1]. If the initial laboratory research is successful, researchers send the data to health authorities for approval in order to begin research and testing on humans.

Once pre-clinical research results are approved, human testing of experimental drugs can begin and is typically conducted in four phases that are denoted by Roman numerals (Phase I, II, III and IV). Each phase is considered a separate trial and, after completion of a phase over many years, researchers are required to submit their data to, and then wait for approval from their local health agency (the FDA in the US) before continuing onto the next phase. If the drug successfully passes through Phases I, II, and III then it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are “post-marketing” or “surveillance” studies that are conducted to monitor how safe the product is over several years [2].

Phase I

This is the first clinical phase that involves humans. Phase I trials most often include healthy volunteers, however there are some circumstances when clinical patients are used, such as patients who have terminal cancer or HIV. These treatments possess a much higher risk for healthy individuals and could cause to become ill and contract serious adverse side effects.

In a Phase I clinical trial, doctors collect information on:

• The dose or treatment
• When it should be taken, and how often
• Any side effects or complications
• How the treatment affects patients and their preexisting conditions

One of the primary goals of Phase I studies is to find the highest dose of a new treatment that can be given safely without causing severe side effects. Although the treatment has been tested in laboratory and most likely been used in animal studies, the side effects in people cannot be known for sure. During Phase I of a clinical trial, researchers spend several months to evaluate safety, side effects, optimal dosage amounts, and formulation method for the drug on about 20 to 80 people who have no underlying health conditions.

In addition to evaluating safety and ideal dosage, specialists also look at the best way to administer the drug such as orally, intravenously, or topically. These trials are often conducted in a clinical trial clinic where the subject can be observed by full-time staff. Safety always remains the foremost concern in Phase I. The research team keeps a close eye on the people and watches for any severe side effects.

Researchers start by giving very low doses of the drug to a few patients while higher doses are given to other patients until side effects become too severe or desired effects are seen. The drug may help patients, but Phase I trials are to test a drug’s safety. If a drug is found to be safe enough, it can be tested in a Phase II clinical trial. According to the FDA, approximately 70 percent of medications move on to Phase II.

Phase 2

Phase II of a clinical trial usually involves anywhere from 50 to several hundred who are living with the condition that the new medication is meant to treat. They are usually given the same dose that was found to be safe in the previous phase. Investigators monitor participants for several months, or years, to see how effective the medication is and to gather more information about any side effects it might cause.

Most phase II studies are randomized trials where one group of patients receives the experimental drug, while a second “control” group receives a standard treatment or placebo. These studies are mostly “blinded” which means that neither the patients nor the researchers know who has received the experimental drug in order to avoid from bias. Doctors use a computer program to randomly sort volunteers into these two separate groups. Each volunteer has an equal chance of ending up in any of the groups and are randomly put in any group.

This allows investigators to provide the pharmaceutical company and the health authority with comparative information about the relative safety and effectiveness of the new drug. When the development process for a new drug fails, this usually occurs during Phase II trials when the drug is discovered to not to work as planned or to have toxic effects. The FDA estimates that roughly one-third of experimental drugs successfully complete both Phase I and Phase II studies.

Phase II clinical programs historically have experienced the lowest success rate of the four development phases. In 2010, the percentage of Phase II trials that proceeded to Phase III was 18% [5] and only 31% of developmental candidates advanced from Phase II to Phase III in a large study of clinical trials conducted during the period of 2006 – 2015 [6].

Phase III

Phase III of a clinical trial usually involves up to 3,000 participants who have the condition that the new medication is meant to treat. These participants must include men, women, and people of different ages and ethnic groups in many places across the country (or even around the world) at the same time. This helps doctors learn how treatment works in different people with different genetic backgrounds, races, and ethnicity. These studies tend to last longer – up to several years – than Phase I and II studies.

One of the additional purposes of Phase III is to evaluate how the new medication works in comparison to existing medications for the same condition. To move forward with the trial, investigators need to demonstrate that the medication is at least as safe and effective as existing treatment options. Due to the larger number of participants and longer duration of Phase III, rare and long-term side effects are more likely to show up during this phase.

There can be more than two treatment groups in Phase III trials. The control group may receive the current standard-of-care treatment for their illness while other groups receive the new treatment on trial. Phase III trials are usually double blinded to eliminate bias when interpreting results.

Placebos may be used in some Phase III studies, but they are never used alone if there is a treatment available that works. Sometimes, a patient who is randomly assigned to the placebo for part of the study will at some point be offered the standard treatment as well. As with other trials, patients in Phase III clinical trials are watched closely for side effects, and treatment is stopped if they become too hard to manage.

Every patient in a Phase III study is watched closely, and the study will be stopped early if the side effects of the new drug are too severe or if one group has significantly better results. Phase III clinical trials are often needed before the FDA will approve the use of a new drug for the general public. If researchers demonstrate that the medication is at least as safe and effective as others already on the market, then the FDA will usually approve the medication.

In the United States, when Phase III clinical trials (or sometimes Phase II trials) show a new drug is more effective or safer than the current treatment, a new drug application (NDA) is submitted to the FDA for approval. The FDA reviews the results from the clinical trials and other relevant information.

Based upon the review, the FDA then decides whether to approve the treatment for use in patients with the illness the drug was tested on. If approved, the new treatment often becomes a standard of care and newer drugs may be tested against it before they can be approved. If the FDA feels that more evidence is needed to show that the new treatment’s benefits outweigh its risks, it may ask for more information or even require that more studies be done. Once Phase III is complete, a pharmaceutical company can request FDA approval to begin marketing the drug. Roughly 25 to 30 percent of medications move on to Phase IV.

Phase IV

Phase IV trials test new drugs that are approved by health authorities and often are called Post Marketing Surveillance Trials. The drugs are available for doctors to prescribe to patients, but Phase IV studies might still be needed to answer important questions. In previous clinical phases the drug may not have been tested for interactions with other drugs, or on certain population groups, such as pregnant women, who are unlikely to subject themselves to trials. This phase involves thousands of participants and can last for many years. Investigators use this phase to get more information about the medication’s long-term safety, effectiveness, and any other benefits.

This is often the safest type of clinical trial because the treatment has already been studied a lot and has likely been given to many people. Phase IV studies look at safety over time. These studies may also look at other aspects of the treatment, such as quality of life or cost effectiveness.

Phase IV studies can result in a drug or device being taken off the market or restricted depending on the findings in the study. Unless an adverse effect of the approved drug is shown or the drug is accepted as safe, it will stay on the market and also in Phase IV forever.

This clinical trial algorithm has come out after many scientific studies. Every point of the clinical trials, and possible problems, have been clarified by policies which may differ from country to country. At the end, clinical trials are a very safe and cautious method of finding out the safest and most effective treatment, or diagnostic method, for people. During clinical trials, scientists are very careful about ethical issues and try not to harm any living organisms, be them animals or humans. There is an ongoing public debate over pharmaceutical companies. While some think they play a major role in the emergence of many methods and scientific developments to benefit human health, others doubt their motivations and questions their contribution to the public good. This debate will surely continue for a long time, but under the current circumstances, pharmaceutical companies are found in the center of all these clinical trials described in this article. Regardless of the truth behind these doubts, it is important to be always aware of the priceless value of life, that it has been given to us and all living things as an inalienable right and a precious gift, and that it is a major responsibility take care of it well and seek healing when needed.

• https://www.nccn.org/patients/resources/clinical_trials/phases.aspx
• “The drug development process”. US Food and Drug Administration. 4 January 2018. Retrieved 17 August 2020
• Holland J (2013). “Fixing a broken drug development process”. Journal of Commercial Biotechnology. 19. doi:10.5912/jcb588.
• Adams CP, Brantner VV (2006). “Estimating the cost of new drug development: is it really 802 million dollars?”. Health Affairs. 25 (2): 420–8. doi:10.1377/hlthaff.25.2.420. PMID 16522582.
• “New drugs failing Phase II and III clinical trials”. MedCity News. 2011-06-02.
• “Clinical Development Success Rates 2006-2015” (PDF). bio.org. Retrieved 2018-02-11.

It is uncommon that we observe the background details of a well-produced film or notice the subtle masterpieces behind a state-of-the-art play. Aside from those that are very observant, these elements usually only come into view when production experiences a horrible mishap, perhaps if an actor’s costume is ruined or they forget their lines. The same can be said for the quiet mechanisms and systems, which our lives are dependent on, on a daily basis, namely our organs and their exceptionally complex makeup that we often take for granted. This issue aims to take a deep look at some of the processes that affect us every day that we usually do not think about.

Modern medicine is perhaps one of the greatest blessings of our time, as synthetic drugs are able to cure complex diseases in previously unknown ways. These medicines undergo intense research, testing, and scrutiny before being released to the general public. We quickly rush to the doctor’s office and pop a few pills when we feel ill, yet we rarely ponder over highly exhausting and costly process of developing these drugs.

Our hearts never rest from the moment we are born to the day we die. This organ we don’t usually think about pumps onwards multiple times per minute and allows us to perform our daily functions. In her piece in this issue, Ceyda Sablak reminds us how delicate the anatomy of this organ is and why we should maintain a healthy, balanced life of physical and spiritual activity, as many spiritual masters have seen a connection between our biological heart and our spiritual well-being.

Stem cell research has been a common point of discussion, debate, and controversy in the past few decades. Researchers argue that they possess an almost endless number of possibilities while advocates argue that they are derived in an unethical manner. The science behind them is fascinating, and the potential that they possess is undoubtedly inspiring.

Lastly, it turns out that our tears are integral to keeping our eyes healthy and itch-free. A lack of tears can result in a multitude of annoying and harmful disorders that can severely affect a person’s life. Searches have been underway to find the perfect “alternative tear” for those that suffer from tear related disorders. Who would have thought that something so simple contributes so much to our normal happiness and peace?

Most of us have taken, or at least interacted with, medicine at some point or another in our lives. This can range from more “simple” over-the-counter drugs to more complex medicines specifically designed for exact illnesses. Considering the Covid-19 era we are going through and as search for a vaccine is at the highest possible speed, it is important to have at least a general idea on how medicines are developed for our use. This article aims to explore how a complicated mix of chemical compounds in a laboratory end up as pills on a shelf in your local pharmacy. We will also explore a brief history of pharmacology, where drugs get their names, how drugs come into fruition, the various affects that drugs can have on our bodies, along with the discrepancies that exist between them in regard to when, how, and why they should be taken.

Pharmacology is the study of the interactions that occur between a living organism and the chemicals that affect normal or abnormal biochemical functions. It includes the study of how a drugs can affect our biological systems, such as individual organs or an entire part of the body, and how the body overall responds to the drug. The discipline encompasses the sources, chemical properties, biological effects and, therapeutic uses of drugs. Substances with medicinal properties are considered pharmaceuticals, whereas drugs given for therapeutic purposes are usually called medications. Drug therapy, which is also called pharmacotherapy, is the use of drugs to prevent, diagnose, and treat signs, symptoms, and disease processes. When prevention or cure is not a reasonable goal, relief of symptoms can greatly improve quality of life and the ability to function properly on a day-to-day basis. Developing an understanding of this craft can allow us to better appreciate how molecules interact to form the drugs and medicines that can change our lives, and perhaps even allow us to contemplate their complex creation and existence.

In its most simplistic definition, a medication is a substance that is ingested or placed onto the body in order to cure a disease or condition (antibiotics are given to cure an infection), treat a medical condition (anti-depressants are given to treat depression), relieve symptoms of an illness (pain relievers are given to reduce pain), given to prevent diseases (flu vaccine helps to prevent the person from complications of having the flu).

Source of drugs

Historically, drugs were mainly derived from plants, animals, and minerals. Morphine, insulin, and iron are all commonly used examples of their respective sources. Belief in the curative powers of plants and certain substances rested exclusively upon traditional knowledge. But empirical information was not subjected to critical examination. Until the end of the 19th century, medicines were made by natural organic or inorganic products including mostly dried or fresh plants and their parts. These compounds might contain substances that possess healing properties or reactions that exert a toxic effect. It is important to remember that many fruits, vegetables, and plants still possess great power despite not having a “modern” origin.

Most drugs used nowadays are synthetic chemical compounds manufactured in laboratories which are synthesized by altering the chemical structure of an existing drug. The first drug of a particular group of drugs are called prototypes. For example, morphine is the prototype of opioid analgesics, and penicillin is the prototype of antibacterial drugs. Drug classifications and prototypes are defined and most new drugs can be assigned to a group. We must be hopeful and continue to search far and wide for cures for all  diseases, whether they be organic or synthetic, since our world is full of an infinite amount of possibilities and discoveries.

Drug names

The systematic naming of pharmaceutical drugs is called “drug nomenclature.” Drugs primarily have three types of names: chemical names, generic names, and trade names. The chemical names are the scientific names that often sound complex and are based upon the molecular structure of a drug. During development, the company will apply for regulatory approval of the drug by the relevant national regulatory agency, such as the U.S. Food and Drug Administration (FDA), and will be granted a generic name for it. Generic names usually indicate, via their stems, what drug class the drug belongs to. For example, oseltamivir is an antiviral drug because its name ends in the -vir suffix.

After development, testing, and regulatory acceptance of a drug, the pharmaceutical company gives the drug a trade name, which is a standard term in the pharmaceutical industry for a brand name or trademark name. Many drugs have multiple trade names which can reflect separate marketing strategies in different countries, manufactured by different companies, or both.

Drug investigation

A new drug investigation is the beginning of the journey of a chemical compound to a drug that will be used in clinics. The testing process of a chemical compound begins with animal studies to determine potential beneficial uses and also potential toxic side effects of the candidate compound.  The results from these animal studies are reviewed, and if the results are satisfactory, the compound then undergoes clinical trials in humans that people can voluntarily sign up for. Most clinical trials use a randomized, controlled experimental design that involves selection of subjects according to established criteria, random assignment of subjects to experimental groups, and administration of the test drug to one group and a control substance to another group.

Patent protection

New drugs that are developed by pharmaceutical companies will be covered under patent protection. This means that only the pharmaceutical company that holds the patent is allowed to manufacture, market, and eventually profit from the drug. This is seen as a return on the company’s investment that it took to develop the drug, which may require years of work and millions of dollars, along with an incentive for developing other drugs. Other pharmaceutical companies cannot manufacture and market the drug during the patent period.

Usually, the drug patent is awarded for around twenty years in the United States, however the number of years varies across countries and drugs. Pharmaceutical companies apply for a patent long before the clinical trial period even begins. The effective patent period after the drug has finally received approval is often around seven to twelve years. After the patented period expires the drug can be manufactured and sold by other companies. The drug is referred to as a generic drug at this point, and they are required to be therapeutically equivalent and much less expensive than trade name drugs.

Pharmacoeconomics

Pharmacoeconomics involves all of the costs that are accrued due to drug therapy and experimentation including those related to purchasing supplies, dispensing the drug, storing it, administrative fees, laboratory and other tests that are used to monitor patient responses, and losses from expiration. The length of a patient’s illness or hospitalization is also considered. While the most important factor is the health of the patient the costs for treatment are increasingly being considered as a major factor when choosing medications, and research projects that compare costs have greatly increased in recent years. The goal is to make it easier for patients to choose the most cost-effective drugs that combine high quality treatment at an affordable price. For drugs or regimens of similar efficacy and toxicity, there is considerable pressure upon doctors and pharmacies to prescribe less costly drugs for shorter duration.

Prescription and non-prescription drugs

In many countries, consumers have two legal routes of access to therapeutic drugs. One route involves a prescription or order from a licensed health care provider, such as a physician, dentist, or nurse practitioner. The other route is by over-the-counter (OTC) purchase of drugs that do not require a prescription. Both of these routes are regulated by various drug laws that change from country to country. Acquiring and using prescription drugs for non-therapeutic purposes, by persons who are not authorized to have the drugs or for whom they are not prescribed, is illegal.

The rejection of drugs in modern society

Nowadays, there are some people who deny various kinds of treatments because of their religious beliefs. This category of people is only a minority, as the majority of religions advocate for people to be healthy and to take care of their health as much as they can. In almost all belief traditions, the human body is believed to be a trust, and in case of any disease, the most appropriate and fastest treatment methods should be used. Even substances that are not normally permitted are allowed by scholars to be used if the person’s safety is concerned. For believers, the most important goal in life is to worship God, and for this to be possible the body must be healthy.

One day, people asked Prophet Muhammad, peace be upon him:

“Should we make use of medical treatment?”

He replied: “Make use of medical treatment, for God has not made a disease without appointing a remedy for it, with the exception of one disease, namely old age.”

People are encouraged to seek out those remedies and to use them with skill and kindness. Let us also remember that Jesus, peace be upon him, too, was very active in his ministry of healing. He showed by God’s permission miracles like curing the blind and the deaf, and bringing the dead back to life. Thus, religions do not refuse treatment with any available methods, and they even strongly encourage treatment and prevention of diseases.

Religions are also well known to treat stress, which wreaks havoc on the mind and body. It is still not known exactly how stress harms our health, but researchers have found that chronic psychological stress is associated with body’s losing its ability to regulate the inflammatory response. It has been shown that the effects of psychological stress on the body’s ability to regulate inflammation can promote the development and progression of disease. We know that religions and beliefs give people hope and significantly decrease the stress.

Human beings are the most precious creation, and health is necessary for us to achieve the purpose of our existence. Using scientific medicine together with faith and religion can help people to protect their health. Being the science of drugs and by investigating new drug therapies, pharmacology helps us exactly with that.

History of Pharmacology

Claudius Galen (129–200 A.D.) was the first person who attempted to consider the theoretical background of pharmacology.

Ali al-Tabari (838 A.D.) Medieval Islamic physicians used natural substances such as Papaver somniferum Linnaeus, poppy, and Cannabis sativa Linnaeus, hemp as a source of medicinal drugs. Although poppy had medicinal benefits, Ali al-Tabari explained that the extract of poppy leaves was lethal, and the extracts and opium should be considered poisons (4).

Theophrastus von Hohenheim (1493–1541), also known as “Paracelsus”, began to question doctrines from antiquity. He prescribed chemically defined substances with such success that professional enemies had him prosecuted as a poisoner. Against such accusations, he defended himself with the thesis that has become an axiom of pharmacology:

“If you want to explain any poison properly, what then isn‘t a poison? All things are poison, nothing is without poison; the dose alone causes a thing not to be poison.”

Johann Jakob Wepfer (1620–1695) was the first to use animal experimentation for pharmacological or toxicological actions.

Rudolf Buchheim (1820–1879) founded the first institute of pharmacology at the University of Dorpat (Tartu, Estonia) in 1847, which firstly made pharmacology as an independent scientific discipline. In addition to a description of effects, he strove to explain the chemical properties of drugs.

Oswald Schmiedeberg (1838–1921), together with his many disciples, helped to establish the high  reputation of pharmacology. He partnered with pathologist Bernhard Naunyn (1839–1925) to found the first journal of pharmacology, which has since been published without interruption.

After 1920, the pharmacological industry had their own pharmacology laboratories outside established university institutes. After 1960, departments of clinical pharmacology were set up at many universities and in industry.

References

1. Clinical Drug Therapy: Rationales for Nursing Practice – Seventh 7th Edition, Lippincott Williams &Wilkins.
2. Basic&Clinical Pharmacology, 12^th Edition, McGrawHill Lange.
3. Modern Pharmacology with Clinical Applications, Sixth Edition, Charles R. Craig and Robert E. Stitzel, Lippincott Williams &Wilkins.

We are all aware of the fact that there is certain rhythm and order in the movement of the sun and the earth, as well as other planets along their pre-assigned orbits. This order has ongoing without a glitch for possibly billions of years. The day and the night become longer and shorter on a schedule, and this is how we can develop calendars by calculating seasons, months, and days.

The movements of celestial bodies impact in multiple ways the biosphere in which we live. Trees shed leaves or bloom, some animals hibernate, and others enter reproduction season.

Time advances not linearly but in cycles. The internal systems by which the metabolisms of living things are organized are made to work according to numerous biological clocks that depend on the cyclical nature of time. These biological clocks are sometimes based on the length of a day and sometimes on long cyclical patterns that may span years. Periods of sunspots followed by explosions on the surface of the sun, for example, cause the reproduction cycles of populations of lynx and hare to peak every 11 years. This cycle is also tied to an increase in the production of wheat and certain species of fish breeding in abundance. The internal clock of the human metabolism is likewise organized during the day.

Scientists have long since noticed and started to research the different reactions of the human body to different time intervals throughout the day. It was realized that pains eased during certain times of day and intensified during others. There are also rising and falling cycles for hormones and the nervous system. These coincided with periods of hunger, meals, and sleep.

It has been found that certain changes occur in the physical and mental makeup of humans during the year, seasons, month and day. Researchers agree that every human has a unique physical and mental clock, but there are generally broad similarities. The scientific field researching these is called chronobiology. Researchers in chronobiology have demonstrated that certain changes occur, according to time periods, in the endocrine and autonomic nervous system as well as the body’s water and salt balance.

Other studies have focused on biological changes with respect to space. The regulation of the body’s biological rhythm is found to be influenced by the movements and positions of the earth on its own axis, the moon around the earth, and the earth around the sun. As the atmospheric environment changes, so do living things.

Towards the end of the 1960s, scientists found that a synthetic corticosteroid drug called methylprednisolone was more reliable for treatment of arthritis and asthma when taken in the morning rather than at other times. “These rhythms might affect responses to cancer treatment,” says Eric Holland, a neurosurgeon at Fred Hutchinson Cancer Research Center, adding that there are optimal times for administrating radiation in mice.

A forty-three-year-old patient with 27 tumors in her liver whose drug treatment for colon cancer did not work volunteered for a trial and recovered from cancer after rescheduling the administration of her drugs. Oncologist Francis Lévi was so amazed by this effect on the patient that he became a supporter of chronotherapy, or time-cycled treatment. To Lévi, who works at Warwick Medical School in the United Kingdom, timing can prove even more important than dose. In the trial, the patient was first wired up to a device like a clock so that metabolic rhythms could be better monitored. The patient had extremely regular sleep-wake cycles, which Dr. Lévi believed was likely to have contributed to the success of the treatment. This novel understanding did not spread before because researchers could not explain molecular foundations of daily rhythms, or circadian cycles, until 10 years ago, and clinical data was inconsistent.

Lévi and his team randomly divided 186 chemotherapy patients into two groups. They administered medicine to one group in accordance with the participants’ biological clocks and to the other group according to the standard procedure. More than 50% of the former responded well, whereas the rate remained at only 29% for the latter. Another study found that 298 patients who had heart operations in the morning were twice as likely to have unsuccessful operations and develop complications as compared to 298 patients who had operations in the afternoon. To prevent the effects of the surgeon’s selection of patients, the same surgeons operated both in the morning and in the afternoon.

The 2017 Nobel Prize for the field of physiology was awarded to three American biologists, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young, for their study into biological rhythms. Their research presents remarkable insights into the reasons why the biological rhythms of plants, animals and humans are created in coordination with the movements of the earth. The researchers used the fruit fly, an exemplary organism, and found the genes that controlled its daily biological rhythm. Discovering that these genes initiate the secretion of a protein that accumulated overnight and dwindled during the day, the researchers revealed that these proteins caused a mechanism made to work in a certain rhythm when the time was right. It was like a watch had been set inside the fruit flies’ cell.

It is estimated that approximately 80% of our genes follow night and day rhythms (and also possibly seasonal rhythms). Indeed, it has been identified that fits of asthma and epileptic seizures develop according to certain daily rhythms. The products expressed by the genes that are active in most tissues peak early in the day and in the afternoon and reach lows after dinner and before bedtime. All these activities are carried out by the “molecular biological watches” written in our genes. If we can better understand our internal clocks, researchers believe they could discover breakthroughs in the treatment of up to 150 diseases, including cancer.

The time machine

Many tissues in the body have their own time schedules arranged by regular cycles in which numerous innate “clock genes” envelop the body like a net. The timing of all these clocks can have a powerful impact on metabolic activity, the increase in the number of immune cells, and many other things. “The best advice I can offer is don’t mess with your body clock,” says Professor Derk-Jan Dijk, director of the Surrey Sleep Research Center in the city of Guildford, England. [1]

The biological clock is an extraordinary system. A group of neurons in the hypothalamus in the brain, called the suprachiasmatic nucleus, are assigned as the central clock for all these activities in the body. The signals from this region play a role in initiating and finalizing the activities of the genes, which channel drugs to their molecular targets and help produce enzymes that destroy drugs. “Clock” genes are found virtually in every organ and tissue, and they are particularly important during cancer treatments, because interventions performed during such critical processes as the cycle of cellular division and growth and repair of DNA damage become significant for killing cancerous cells.

Cisplatin, an effective drug used for almost 50% of solid tissue cancers, kills malignant cells by binding to their certain parts, yet because the drug is toxic to the kidneys, lungs, and nervous system, efforts have been made to develop less toxic versions. Just as a cell develops cancer due to DNA damage, so is the destruction of the cancerous cell started by damaging the cell’s DNA. For this reason, some drug trials focus on blocking the DNA repair of the cancerous cell.

Observations made on the appearance and repair of DNA damage showed, as expected, that DNA damage was repaired more easily during certain periods of the day, leading to the hope that cancer can be treated through DNA repair if drugs are administered in tandem with this cycle. If optimal periods could be established for numerous normal cells to repair their DNA damage, administration of drugs can both optimize the useful effects of drugs and minimize toxicity of drugs with toxic properties.

The human organism and cells are not static, but dynamic. The behavior of our cells changes dramatically before and after a meal. Similarly, the movement and frequency of numerous materials circulated in our body when we are sleeping are different from when we are awake. Therefore, if the amount of a material doubles after lunch followed by a cup of coffee and if the material negates a drug taken by a patient, then that drug can be administered when this material is at its lowest in the body. For example, if the material is at a minimum at two in the morning, the drug can be given at that time, ensuring that the effect is maximized.

The studies into “man, the unknown” are bound to lead to many more discoveries about both treatments of diseases and the knowledge, power, and wisdom waiting to be found in the creation.

Note

1. https://woolcock.org.au/new-2/why-you-shouldnt-mess-with-your-body-clock-expert

References

• Leder, K., Pitter, K., LaPlant, Q. (2014). Mathematical Modeling of PDGF-Driven Glioblastoma Reveals Optimized Radiation Dosing Schedules. Cell. Cilt 156, Sayı 3, s. 603-616.
• Lévi, F., Zidani, R. & Misset, J.-L. (1997): Randomized multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. Lancet 350, 681–686.
• Peeples , L. (2018). Medicine’s secret ingredient — it’s in the timing. Synchronizing drug delivery with a patient’s body clock can yield clear benefits. But will the data be enough to overcome long-standing hurdles? Nature 556, 290-292 (2018).
• “Why You Shouldn’t Mess with Your Body Clock: Expert,” woolcock.org.au. August 7, 2018.

Before anasthesia, even routine surgeries were painful and dangerous. Its advent has allowed for amazing advances in public health and patient safety.

Humanity has faced various kinds of health problems throughout history, and will be facing them until the end of time. Even someone who has not yet suffered from an illness, will almost certainly suffer from one in the future. Let’s take a moment to reflect on all the people who are currently undergoing treatment at hospitals in the hopes of curing an illness.

From time to time we visit close friends and relatives who have undergone such operations. We wish them health and talk with them a little. We ask them how the operation felt, how many stitches they have. They usually say, “They injected me with something and I don’t remember the rest.” Then they may show us their gall bladder, wrapped in gauze, or their kidney stone, which was removed. Have you ever pondered how it is possible not to feel any pain during these kinds of operations, or how it is possible not to remember anything?

Surgical practices have advanced so much in present times. Heart, liver, and kidney transplants are now commonplace, as are finger and arm reattachments. Anesthesia, which makes all of these operations possible and painless, is a great blessing. Even the small and simple surgeries performed just 150 years ago were very difficult for surgeons – not to mention very painful for patients.

In his famous book on physiology and treatment, The Canon of Medicine the renowned 10th and 11th century scholar, Avicenna (Ibn-i Sina) (980-1037), defines anesthesia as, “a numbing and a cooling remedy.” He gives pathophysiological commentary on the influences of anesthetics and analgesics, and summarized painkilling methods as following:

1. A mixture prepared from linseed and dill should be applied to the area of pain.
2. Decreasing the sensitivity of the area of pain by increasing the moisture of the area, or providing narcotics for sleep.
3. Providing cooling and analgesic and anesthetic medicine.

Biruni, another Islamic scholar from the 11th century, documented his work with analgesic and anesthetic medicine. One of his writings recommends boiling the root tubers of henbane, Mandragora, horned poppy (Glaucium flavum), and Iris, together with the attar of roses and vinegar.

In his pharmacological works of the 12th and 13th centuries, Samarqandi recorded the analgesic, sedative (calming), anesthetic, and hypnotic effects of opium, mandragora, henbane, lettuce, beaver testicles, aloe vera, and coriander.

During the end of the 17th century, in Italy, anasthesia was performed by preventing the patients from breathing until they lost consciousness, and then immediately performing surgery on the patient who had fainted. This was called the asphyxia technique. The surgeries performed were relatively easy, such as the cutting of an arm or leg. The surgeon who was fast was considered the best, because patients could wake up during the surgery – that is, if they survived the procedure.

Another interesting anesthetic technique was making the patient lose consciousness by hitting them on the head. The hitting had to be done, “Hard enough to break the shell of an almond but gentle enough not to destroy its seed.” However, a bitter truth is that many patients were killed during this process.

Many have suffered the consequences of the absence of anesthesia in the past. Dr. Warren, a professor at Boston’s Massachusetts General Hospital in 1846, had placed his operating room on the very top floor of the hospital in order to avoid disturbing others with the screams of the suffering patients. One day, while examining one of patient’s tongues with pliers and a scalpel, he pulled the tongue of the patient without warning, and cut off his tongue with the scalpel. Afterwards, without hesitation, he cauterized his patient’s tongue with a hot iron. Dr. Warren observed the screaming, moaning, and suffering of the patients with no sign of emotion. He did not seem disturbed, and this was the exact attitude he needed in order to perform his duty. However, years later when enough advancement was done in the area of anesthesia, he couldn’t hold back his tears during the first operation that was performed with anesthesia.

Surgeries performed without anesthesia were hard on surgeon and patient alike. During his studies, the English gynecologist, Doctor James Young Simpson, fainted while cutting off a breast and considered quitting being a surgeon. Prof. Dr. Robert Liston was a famous surgeon at London University College. Dr. Liston had a reputation for being rude, arrogant, and strong. But he had no choice: he was forced to cut off a leg in 28 seconds, as anesthesia was not yet developed.

As can be seen from these examples, the absence of anesthesia, and the incredible suffering of the patients, pushed surgeons to be incredibly fast and emotionally insensitive. This period of time defined surgeons as strict, insensitive, and despotic. This went on until 1846, when William Thomas Morton performed the first surgery with anesthesia.

Since then, anesthesia has made surgeries much easier for all involved. Today, the definition of general anesthesia is total or partial loss of sensation in a human or animal body before surgical intervention.

Usually, anesthesia is performed by injecting medicine into the blood, or by making a patient breath an anesthetic gas. First, the patient loses consciousness, and then, with the help of muscle relaxants, the patient is put in a state of paralysis. Artificial respiration is performed until the end of the operation with the help of breathing machines called ventilators. For this purpose, an endotracheal tube is inserted in the windpipe of the patient and they are hooked to an anesthesia machine. This feeds oxygen, air, and the anesthetic gas to the patient. The anesthesia doctor controls the patient’s breathing, blood pressure, and heart rhythm, as well as other various, vital parameters, and the fluids that will be fed to the patient throughout the surgery. By doing this, the continuity of the anesthesia is made possible. When the surgery is over, the anesthetic drugs are no longer fed to the patient. When the muscle relaxants lose their effect and breathing returns to normal, the endotracheal tube is taken out and the patient is taken to another room to wake up. This is where the patient opens their eyes; it’s almost like a re-birth.

The chemicals in cannabis, opium, and coca were the essence of the first drugs used for general anesthesia; they are still being used, partially, in modern times. These chemicals, and some synthetic chemicals like them, are used for anesthesia and can be used after surgery in order to soothe pain. Most of our contemporary drugs are mostly synthetic, and they require many years of difficult education to be properly handled. It takes four years of additional education, after medical school, for a surgeon to become proficient with anesthetics.

Medical research done in the last two centuries about the dosage and quantity of these chemicals has advanced the practice of anesthesia incredibly. All this research provides a very good answer to why drugs have been created. While surgeons use the chemicals extracted from cannabis, opium, and coca, and from the synthetic chemicals like them, as a service to humanity, it is really hard to understand why some ill intentioned people use them for the detriment of human health.

Brown and red algae are salt water organisms. These plants grow on rocky shores or in oceans with a rocky bottom. In quiet areas free of excessive waves they can live for up to 15 years. These can be utilized for the special polysaccharides in their bodies. That’s why they are commercially significant. For example, alginic acid and alginates obtained from brown algae can be used in many fields, from the food industry to the medical field, from cosmetics to paper and textiles. An algae species (Macrocystis Pyrifera) that can be found both in North and South America, New Zealand, Australia, and off the African coast is the primary source for the world’s production of alginic acid and alginate. In 2009, 26500 tons of alginate was produced, primarily by the countries of Scotland, Norway, China, and the USA.

Alginic acid is a macro molecule synthesized from mannuronic and gluronic acid molecules. Because of its hydrophilic property, the Na and K salts of alginic acid are used in providing homogeneity to frozen food during defrosting, preventing food decay related to instant temperature spikes, increasing viscosity, preparing jelly like deserts, and stabilizing fruit juices and ice cream. For similar reasons, Alginates are utilized in paper quality enhancement, and the advanced application of ink in glues and in pressed textile products, where they improve the flow of dye. Alginates are also used in cosmetic products, in production of waterproof or fireproof textiles, and in some synthetic dyes because they improve viscosity..

One of the most important uses of alginates is in the medical field. Many people suffer from stomach burn and acid reflux disease. In these treating these symptoms, the percentage of a prescribed medicine containing alginic acid content is 100 %, because in the case of acid reflux, alginic acid contains a preventive property, and antacids. This antacid neutralizes stomach acid. Alginic acid, however, reacts with saliva and Na Bicarbonate ion to produce foam in the upper stomach. In the case of a reflux, this foam barrier prevents the escape of acidic stomach content into esophagus.

According to a study conducted in England in 2010 about obesity treatments, alginic acid added natural fiber and was found to reduce lipid intake 75% in the intestines.

The absorption and removal of drugs in the stomach and intestines plays an important role in ensuring drugs act as intended. For instance a blood clog in a pulmonary vein can be transported to the lungs and may have fatal consequences (a pulmonary emboli). In order to prevent that, low molecular weight, heparin containing, drugs are used. The polymeric alginate beads in these drugs have been found to improve drug efficiency up to 80-90 %. In this kind of controlled release of drugs and enzymes, the use of polymeric alginate additives provides high efficiency.

A new kind of antimicrobial textile that does not stick to wounds is made from the silver coated fibers of an Alginate-carboxymethyl cellulose mixture. This fabric not only provides protection against infections but also, with its non-stick property, prevents traumas; and its high hydrophillic feature allows open wounds to heal faster.

Everything in the universe is beautiful, either directly, by itself, or indirectly, by its consequences. Algae, which many of us dislike, is in fact a great work of art as it is a source of food, a decoration of the seas, and is used to cure various diseases.

The fascinating aspect of these materials stems from the fact that when certain particles or devices are manufactured on the nanometer size region by means of special chemical and physical methods, they start showing distinct properties dependent on size, shape, and elemental compositions (such as huge amount of light absorption/emission, plasmonic resonance, high surface area, ability to convert light into heat, desirable magnetic properties, etc). Each of these features have found many applications in technology and they provide superior properties when compared to conventional materials. This article will not cover each technology based on nanomaterials but rather focus on the medical aspects and applications of nanotechnology and the direction it is heading.

Nano-medicine is a novel branch of nanotechnology seeking to deliver medically relevant drugs and imaging agents to the desired sites of the body. Biomedical imaging and drug delivery fields are benefitting from nanotechnology to a greater extent because not only do nanomaterials provide unprecedented results in diagnosis and therapies, considerable amounts of incentives in the form of governmental and private funding also drive topnotch institutions and scientists to study these materials around globe. For instance, iron oxide—when designed and manufactured on the nanometer order—can compete with, if not replace, most of the commercial magnetic resonance imaging (MRI) contrast agents due to some of its attributes, (i.e., being much more sensitive) requiring a less amount compared to other contrast agents, non-toxic to humans, and easy to manipulate in terms of its chemistry (1). Nanometer-sized spherical and rod-shaped Cadmium/Tellerium/Lead sulfides and selenides, also known as “Quantum Dots,” can absorb and emit light from ultra-violet (UV) to infrared region (IR) and this phenomenon could be utilized to construct biomedical sensors capable of detecting biologically relevant species (such as blood glucose, tumor markers, hormones, and etc.) with great accuracy and speed (2). Even by using multiple colors emitting “Quantum Dots,” one can, in principle, detect more than one biological entity simultaneously. Furthermore, their superior emissive properties could be harnessed to develop sensitive and selective fluorescence imaging techniques and assays which can lead to simple and early diagnosis of diseases. Gold nanorods, if irradiated with IR lasers, can generate extreme local temperatures in the surrounding medium owing to “plasmonic resonance of surface electrons,” and this feature could be directed to killing of localized tumor tissues known as “Photothermal Theraphy” (3).

Another class of nanomaterial called liposomes (4) can actually mimic lipid bilayer of the cell membrane which gives rise to a protective layer around organelles and nucleus, and maintains the transport of ions and molecules in and out of the cell. Synthetic liposomes, strikingly, can accommodate various cargoes extending from drugs to imaging agents in their inner cavity and render controlled release of its cargo as it circulates in the body, thereby providing longer bio-availability.

One of the most alluring uses of nanoparticle formulations in cancer therapy is their dimension. Certain sizes of nanoparticles can permeate into tumoral sites and be retained in that region longer than small particles or molecules. This extraordinary feature of nanoparticles, called “enhanced permeability and retention effect” (5), was utilized with liposomes to deliver chemotherapeutics to cancerous tissues effectively in a slow and controlled manner. In addition, chemical malleability of nanoparticles give rise to smart formulations which could respond to external stimuli in drug delivery applications. For example, the fact that cancer cells have lower pH values as compared to normal cells has been used to trigger release and delivery of drugs on site (6).

An alternative approach to conventional treatments is gene therapy in which the malfunctioning or mutant gene has been reintroduced into cells with a properly functioning one in order to restore the malady (7). Nanoparticles, especially polymeric counterparts, have shown promising results in encapsulating, carrying and delivering the gene of interest into desired cells.

Apart from synthetic nanoparticles, naturally occurring nanoparticles, have lately received great attention due to their unique structures and properties such as biocompatibility, uniform size, as well as suitability to chemical and genetic engineering. Plant and bacterial viruses, known as viral nanoparticles (8), have been tested for imaging and drug delivery applications, and because they infect only plants and bacteria, they are considered to be benign towards mammalians. Their inner and outer amino acids could be chemically modified with drugs and imaging modalities and cleverly engineered drug release mechanism could be invoked to operate upon external or internal stimulus.

Nanomaterials are, furthermore, suitable candidates for vaccine development. The immune system normally recognizes certain chemical groups on the surface of antigens (pathogens) and develops its defense mechanism based on this recognition. Multiple copies of these chemical groups could be chemically tailored around the surface of nanomaterial, and thereby could trigger the same immune response more efficiently (9).

The future of medicine will be shaped and enhanced through a targeted delivery of drugs and imaging contrasts into desired sites. Promisingly, nanoparticles will be able to assist in this regard to a considerable extent. Today’s cancer chemotherapy rely mostly on administering a variety of cancer drugs via intravenous (injecting through the vein) or oral means which delivers drugs to cancer cells as well as a considerable amount to healthy tissues which causes major side effects. In order to accumulate higher doses of drugs in tumor cells selectively and minimize nonspecific delivery, nanoparticles loaded with drugs and chemically decorated with “smart molecules” which have the ability to recognize cancer cells and specifically bind to them have been designed and tested successfully (10). These smart groups (organic molecules, antibodies, peptides and small molecules), surprisingly, have higher binding affinities toward some receptors over-expressed in cancer cells. Furthermore, encapsulation of drugs by nanomaterials provides a protective shell which prevents leakage of drugs to other sites.

An important drawback of cancer therapy is drug resistance in which cancer cells develop mechanisms to pump chemotherapeutics out of cells and decreases the efficacy of drugs. Nanoparticles, however, invalidate these resistance mechanisms by encapsulating drugs and should therefore not be exposed directly to surrounding cell environment. When nanoparticles reach the desired destination in the cell, an engineered mechanism or stimulus augment the release and drugs are expected to show their activity without any compromise (11).

It is fascinating to see how these small nanoparticles behave cleverly and orderly even though they look like inanimate and unconscious clusters of atoms. The extraordinary art, design and engineering witnessed in macro dimensions can also be seen in nano dimensions which means that a conscious and purposeful Hand of Power is present and visible in this nanoworld.

To sum up, nanomaterials could be ideal platforms for drug delivery and imaging applications and could complement the deficiencies in conventional therapies. Loading multiple copies of these entities into nanoparticles and devising clever mechanisms to target and deliver them into desired sites would be key elements in the nanomedicine of the future. We are living in a world where each of us has someone in our families or among our friends who are going through painful cancer treatments, which is a heart-rending and traumatic experience. Hopefully, nanomaterial-based therapies would give rise to solutions and success in battling against cancer. For in one prophetic tradition the Prophet Muhammad, peace be upon him, says: “O servants of God! Search for ways for treatment of illnesses. If God gives you ailments, for sure He bestows upon you cures for those.”

And why can’t this bestowal be in the nano form?

References

• Qiao RR, Yang CH, Gao MY. “Superparamagnetic iron oxide nanoparticles: from preparations to in vivo MRI applications” (vol 19, pg 6274, 2009). J Mater Chem 2009;19:9286-9286.
• Raymo FM, Yildiz I. “Luminescent chemosensors based on semiconductor quantum dots.” Phys Chem Chem Phys 2007;9:2036-2043.
• Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA. “Gold Nanoparticles for Biology and Medicine.” Angew Chem Int Edit 2010;49:3280-3294.
• Jesorka A, Orwar O. “Liposomes: Technologies and Analytical Applications.” Annu Rev Anal Chem 2008;1:801-832.
• Sancey L, Barbier E, Hirsjarvi S et al. “Enhanced Permeability and Retention (EPR) effect in tumors: characterization by MRI and fluorescence imaging.” B Cancer 2011;98:S67-S67.
• Hruby M, Konak C, Ulbrich K. “Polymeric micellar pH-sensitive drug delivery system for doxorubicin.” J Control Release 2005;103:137-148.
• Waehler R, Russell SJ, Curiel DT. “Engineering targeted viral vectors for gene therapy.” Nat Rev Genet 2007;8:573-587.
• Yildiz I, Shukla S, Steinmetz NF. “Applications of viral nanoparticles in medicine.” Curr Opin Biotech 2011;22:901-908.
• Peek LJ, Middaugh CR, Berkland C. “Nanotechnology in vaccine delivery.” Adv Drug Deliver Rev 2008;60:915-928.
• Ruoslahti E, Bhatia SN, Sailor MJ. “Targeting of drugs and nanoparticles to tumors.” J Cell Biol 2010;188:759-768.
• Liang XJ, Chen C, Zhao Y, Wang PC. “Circumventing tumor resistance to chemotherapy by nanotechnology.” Methods Mol Biol 2010;596:467-88.

Some medications are effective directly over the area they are applied to. Some however are transported to distant regions via blood flow and that is where they are most effective. Medication is either taken orally or through injection. When medicine passes into the blood stream from the place of administration, it is considered to be absorbed. A good example is the transportation of medicine into the blood stream of capillary vessels between the muscle cells when injected into muscle tissue. A drug taken orally however is absorbed through the blood vessels in the gastro-intestinal system.

For orally-taken medication to be absorbed, it should be able to dissolve in gastro-intestinal fluids. First, it is broken into smaller units due to the corroding effects of stomach acid and various enzymes are secreted, then chemicals in the drug composition pass into the gastro-intestinal fluid in a molecular form. This event resembles the dissolving of a sugar cube inside a glass of hot tea. First, the sugar cube gets broken into pieces and then dissolves. A mix with a tea spoon makes this event happen a little faster. In a similar fashion gastro-intestinal movements help with the absorption of medicine. Liquid drugs like syrups dissolve in the gastro-intestinal fluid faster since they are already in smaller units; therefore they get absorbed faster.

Drugs mostly get absorbed through the small intestine. The most important task of this organ is to enable the absorption of nutrients. It is approximately 10 meters long and 4 centimeters wide. The inner lining of the small intestine has finger-like projections called villus and even smaller projections that are located on these villi are called microvillus. One of the reasons, maybe the most important reason, why the our intestines are created in this way is that as a result, the inner surface area of intestines increases multifold. Such that the inner surface area of a human beings small intestine can increase up to 200 m2 and this greatly facilitates the absorption. These projections are made of intestinal cells.

The molecules carrying the medication reach the capillary vessels by passing through these cells and then join the blood stream by crossing through capillary vessel cells. Furthermore, intestinal cell membranes host a special protein that filters unwanted substances for the cell and returns them back to intestinal lumen. Thus these unwanted substances are excreted out of the body along with other unabsorbed matter. In the same way, some drugs are held by this protein and released back into the lumen thus decreasing absorption rate for drugs experiencing this reaction.

Liver: The organ responsible for eliminating the harmful effects of medication

As soon as medication joins the bloodstream after absorption, it is first transported to the liver. This is because pulmonary veins that collect blood from the intestines are connected primarily to the liver. One of the many functions of the liver is the elimination of harmful substances entering the body. For this reason, absorbed substances are directly sent to the liver. The liver is employed with the task of chemical conversion with these substances that are transported to it. One of the wisdoms behind liver metabolism is to reduce the effects of these harmful substances via these events and to convert them into an excretal material. In the same way, drugs are metabolized in the liver, lose their efficacy and prepare for excretion.

Many drugs interfere with each other’s metabolism. If one drug’s metabolism is inhibited, blood concentration of such chemicals increase and adverse effects of drugs become more frequent. Irresponsible drug use must be avoided for this reason. Drug interactions may lead to major damage in addition to the drug’s individual adverse effects. Moreover different nutrients also affect drug metabolism. For instance, grapefruit inhibits metabolism of certain medicines, as a result blood concentration of these medicines increase and adverse effects can be observed. On the other hand, some nutrients like broccoli, cabbage, and charcoal roasted meat speed up the metabolism of certain medicines. In this case, the blood concentration of the affected drug drops and may lead to reduced benefits from intended use. Because of this reason, patients on long-term medicine treatment should not consume these types of food.

The rest of the drug molecules that escape these metabolisms is directed towards blood vessels feeding other organs. Some drug metabolisms in the liver present individual differences as metabolic levels change from person to person. Thus, a drug with the same dosage develops desired blood concentrations for some people, fails to meet this level for others or can even cause high blood concentrations enough to generate adverse effects in other individuals. That is why a medicine that has benefited a patient should never be used by somebody else without consulting a doctor.

The function of bile

Bile secretion originating from the liver and gall bladder has critical importance in the digestion and absorption of fats. Bile breaks apart fats into small pieces so that digestive enzymes can affect them. As a result of this, absorption is provided for fats and vitamins like A, D, E, K that are soluble in fats. In a similar fashion bile improves solubility and absorption of some drugs that does not dissolve in gastro-intestinal fluid. Another task of bile secretion is the removal of certain substances from the body. Waste materials in the bile that is dumped into duodenum are excreted through the digestive track. Some drugs are excreted in this way.

Drug intake before or after meals

It is a well known practice that medications are advised either to be taken after or before meals. When medications are taken after a meal, they cause less of the possible unwanted disturbances such as stomach sickness, aches or indigestion.

On the other hand, nutrients may reduce intake of certain drugs, therefore they need to be taken before meals. However medications taken right before a meal does not apply in this case since the food will still mix with the medication in the stomach. When taking these medicines, it should at least be an hour before meals. Generally consumption of a medicine before or after a meal does not really change its absorption level. But medications taken before meals pass the stomach into the intestines without delay and therefore get absorbed faster. This practice is important in cases where an immediate effect is desired such as pain relief. Plentiful water intake also helps with faster and improved absorption of drugs.

Some medications are packed into capsules made of gelatin-like substances. Medicines with undesirable taste and smell can be offered in this form for consumption. Moreover, if a drug is harmful to the stomach or gets degraded in stomach acid, then this drug can be prepared in capsules that are durable to stomach acid but soluble in the intestines. That is why consumption of medication without its intended capsule should be avoided. In a similar fashion, some medicinal tablets are designed to deliver its molecular contents particularly to the intestines. These types of medication must be taken as a whole unit. Otherwise it can be ineffective or may lead to harmful reactions.

Delivery of drugs to targeted regions

The molecules carrying medication that join the blood via absorption get dispersed by blood circulation throughout the body. These molecules reach various parts of the system via blood vessels, and then diffuse into organs via capillary vessels. However, their entry to the brain is difficult because this vital organ of the body has a special protection to guard itself from possible harmful effects of various substances that enter the body from the outside. Capillary vessels in the brain are different from other capillary structures in the rest of the body as they are created without an intercellular space in between vessel cells. Furthermore, these cells are bound to each other with their tight connective regions.

These capillaries are surrounded by a thicker membrane compared to other capillary vessels. This membrane is also host to various cells that wrap around the vessel. Therefore, because of these factors and other similar ones, some medications can enter the brain in very limited amounts. Drug molecules can display their targeted effects when they bind to target proteins, called receptors, in the organs. These proteins, which are very unique to each drug, exist on the cell membrane or in the cell. In addition, drug molecules also bind to other receptors that are not specific for them, and this causes adverse effects as a result.

Excretion of drugs from the body

Drugs are excreted from the body via the liver and kidneys. One function of these organs is to filter the blood from foreign substances. It was previously mentioned that absorbed substances from intestines are transported to the liver first where some amount gets metabolized and the remaining amount rejoins blood circulation that feeds other organs. Drug molecules that pass through the liver return back to it repeatedly many times because of continual blood circulation. In each of these arrivals, some amount is again metabolized. Molecules of metabolized drugs are excreted out of the body via the kidneys and through the bile at a limited level.

Only some portion of drug molecules get excreted via the kidneys without being metabolized. This ratio is higher with some medications. These types of medications are considered to be removed only by the kidneys, whereas some other drug types cannot be excreted without getting metabolized through the liver. As previously mentioned, the purpose of drug metabolism is to convert drugs into easily removable forms. If these types of drugs are not metabolized, they are rejoined to the blood circulation after filtration by the kidneys without joining the urine. It is impossible for the liver to sense these happening within the kidneys if it was not that the liver and every cell in it were employed by one authority who created them in the first place. Drug molecules concentrate in the liver and kidneys since these organs are employed with drug removal. As a result harmful effects of drugs are often experienced in these organs. Therefore unnecessary drug use should be avoided, otherwise the health of these organs deteriorate and eventually fail to carry out their basic functions.

As noted above, events that are taking place within many of our organs, stomach and elsewhere like kidneys impact on the journey of drugs in our body, therefore changing its effect. The harmonious creation of our organs that are home to many miraculous events is the major component of the entire process in which causations have their due role only as much as they are allowed by their Creator. As a test for humankind, both illness and the cure is provided by God, the All-Healer. Therefore it is the duty of a patient to see a doctor, take the medication properly and never forget that cure is only provided by the Almighty, without obsessing over causational chains.

References

• Guyton, Arthur C., John E. Hall. 1991. Textbook of Medical Physiology, Saunders.
• Patton, Kevin T., Gary A. Thibodeau. 1993. Anatomy & Physiology, Mosby.
• Rang, Humphrey P., Maureen B. Dale, James M. Ritter. 1999. Pharmacology, Churchill Livingstone.
• Brunton, Laurence, John Lazo, Keith Parker. 2006. The Pharmacological Basis of Therapeutics. McGraw-Hill Professional

Fred (not his real name) is 21 years old, living in a university community. Last year, he did a project to “stretch into infinity”, i.e. he attempted suicide. Fortunately, his project failed. After his return to the normal life, he found an alternative way to infinity. I wanted to interview him as soon as I learned about his story, which he accepted.

“I am doing a double major in mathematics and biology. Unlike the regular biology students who are educated to think traditionally and memorize constantly, my way of thinking is rather mathematical and rational.”

I wanted to punch a hole in this super confident young boy’s claims about himself. “So, you never fell in love, but instead, rationally proved some girl to be the one meant for you?”

He chuckled. “I guess, I did fall in love, but suppressed my feelings since they were irrational.”

“Then you must have a strong will. How do you rationally explain the human will? I mean, we are talking about a young man whose hormones are keeping him at the verge of love. And how do you think your will fights against these molecules that pervade your body?”

“My thoughts on this are different now, but at the time, I was trying to express everything in terms of testable, concrete concepts. There is so much research on the effects of genes and the environmental conditions on human behavior. So, my will had to be some proteins synthesized from my DNA.”

“So do you think, or did you think that one day people could use love pills for keeping up their love for their partners, and to have compassion for their children?”

“Why not? Actually, it is not just that. I had many thoughts that engulfed my mind and motivated my actions, including my attempt to suicide. I couldn’t receive rationally satisfactory alternatives to my conclusions.”

Then Fred took me on a tour d’horizon of his view of life and people. There were many elements in his views that you could hear from other people, but this one was unique and noteworthy:

“This is a bit irrelevant, but I can tell you a funny one too. If the speeding tickets are issued not due to an actual harm but due to the increased risk of harm, then people who drink more than a minimal amount should be given drinking tickets. Statistically speaking, the number of crimes linked to speeding is nowhere close to the number of crimes linked to drinking. So, if I am getting a ticket for speeding, although I haven’t harmed anyone, then why isn’t my friend for whom I am the designated driver, getting a ticket for his increased potential to harm someone?”

Speechless, I tried to steer him back to his conclusions that led him to what he did.

“You know, I was never hospitalized for depression. Nobody thought that I was in deep trouble, including me. I was considered to be an intellectual, an extraordinary friend. I don’t know how it goes with other people, but when the idea came, it wasn’t like a freaky idea to entertain myself for a minute. It came as an irrefutable theory. It only made sense. Really.”

The idea of suicide making sense? That didn’t make sense to me! Seeing my blurred gaze at him, he picked up again.

“If motivation is essential to accomplish your ideals, how come things that bring motivation are considered harmful?”

He was talking about drugs.

“If success is all about hard work, then why is it forbidden to pave your way to success rather than leave it to luck?”

That is fortifying hard work through taking drugs.

“If my mental activity is nothing but complex dynamics of molecules in my brain, then shouldn’t I take drugs that are the embodiment of rejuvenating and exhilarating inspirations leading to innovations?”

After a second of pause, he concluded:

“If happiness is all about certain molecules in my body, then what is wrong about getting it directly rather than mining it through the thorny relationships with people?”

How would you answer these questions, knowing that they are asked by an individual in the making who is trying to make sense of life but who is bewildered by the discrepancies of the mature people?

“My line of thought and other people’s line of thought in this matter are similar to the graph of 1/x. We are both aiming for the same point, i.e. zero. But our distinct approaches take us to opposite directions. The two couldn’t be more divergent than this.”

In mathematical elegance, Fred was describing the state that nurtured his suicidal thoughts. He could not establish ties with the rest of us. With an intention to never come back, Fred used drugs to become a zero in our world, and to stretch into unknown infinity. Did he succeed?

“But you know, like a sad love story, 1/x never converges to zero. I failed, too, in that sense. The way I conceived it, death was going to be a culmination of motivation, success, and happiness. I aimed for it head on. According to my conviction, I was supposed to have achieved all of those. When I opened my eyes in the hospital, I realized that I had neither success nor happiness.”

You don’t have to be a sage in order to understand that suicide is not a key to success or happiness. But a brief journey to death made Fred a sage.

“It is possible in this life that one receives death while perfectly healthy. It is also possible that one can survive despite a miserable health. In other words, just like being healthy doesn’t necessarily mean you can’t die, there isn’t a mechanic relationship between being unhealthy and arriving at death. My own failure to die despite what happened to me is a living proof of this.”

I noted in my mind that this was a good example of learning from your failures.

“The moment I realized that death is given, just like life is, my suicide attempt transformed from being a story of failure to a story of success, because that’s when I started believing in the unseen.”

Believing in the unseen was a quality that Fred did not have before, but why and how had it been the elixir that changed his failure into success?

“It is so ironic and controversial. In the beginning, what I was missing was my acceptance of self-deficiency in grasping the existence. In the end, by admitting to be incomplete, I was becoming complete; being completed by God.”

Suicide is one of the most severe sins one can commit according to the monotheistic religions. Yet, this young man found God in the very sin that could throw him light years away from God.

“I don’t define myself anymore as an outstanding, perfect intellectual as my friends used to call me. Instead, I am a story in progress. No matter how severe the calamities or how satisfying the joys are, I don’t come to an end unless my author ends the story.”

A wanted child brings happiness to a family; it is a gift from God. And, of course, every woman who wants to give birth wants to bring up a healthy and beautiful child. Unfortunately, the health index of the modern generation of women at child-bearing age is not very high (there are many chronic diseases, spiritual poverty, with a high vulnerability to different infections due to a variety of reasons). Due to this reason, medical interference in what is a natural process has become more frequent recently. Statistics show that more than 92% of women use different drugs at different stages of pregnancy. The question is to what extent this medication is safe for the future baby. This is a fundamentally important matter to investigate because a pregnant woman taking any chemicals is in essence applying a kind of experiment on her as well as the baby’s health which can have a variety of different consequences.

The problem of medical effects on the development of a fetus has recently become very acute. This is because there are many different medications that are common and easily available nowadays, and they are very often taken without a doctor’s prescription. Unfortunately, the consequences of this fact are not pleasant. Prenatal development is one of the most important and difficult stages in a person’s life. Just in 9 months an ovicell (an egg cell) and a sperm cell form an extremely complex living organism that consists of millions and billions of cells! Moreover, all these cells are combined into tissues, organs and systems that are always interacting. The fetus has a fascinating rate of growth to become a structure with an ever-increasing complexity. In addition, all these processes do not happen chaotically but in a strict order. This order is supplied by two factors: the first is a sound genetic program. It is obtained by the fetus from its parents and the decoding of the genome vividly denotes the existence of Divine Power. The second factor is the state of a maternal organism which supplies everything necessary for the realization of the genetic program and protects the fetus from the negative influence of the environment. In this way the failure of one of the mentioned factors can lead to different deviations and to the disturbance of the development, including the formation of congenital malformations of the fetus and even prenatal death.

The history of medicine shows that medications can be the most harmful etiological factor in relation to the fetus. Today, there are many examples proving this fact. One of the best-known is the thalidomide tragedy which happened in Europe in the 1950-60s. As a result of taking a poorly studied medicine (a light tranquilizer) the children of hundreds (!) of women were born with serious physical defects. Unfortunately, the list of drugs that causes fetal malformation is not short. Nowadays doctors are aware of syndromes caused by hydantoin, warfarin, aminopterin, and many other medications. Each of these has a specific effect on the fetus (mostly leading to serious abnormalities) when taken by a pregnant woman. In the past, people believed that such children were marked by Satan. But nowadays we say that it is the unpredictable effect of the medicine on the realization of the Creator’s program. Medical interference can lead to a disruption in the rate of development and affect the order of differentiation in the tissues and organs of fetus. Moreover, drugs can interrupt the blood circulation in the placenta, change the metabolic process between the fetus and the mother, causing a retardation of intrauterine growth or premature labor, or they can be the reason for a falloff in the health of the child in the first years of life.

The influence of drugs on the fetus depends on different factors, such as the term of gestation at which the drug is administered, the dosage, and the length of time that the medicine is taken, as well as the ways that the drug is excreted, the health of the mother and her inherited sensitivity to medicine, and, of course, the properties of the medicine itself. There are many drugs whose influence on the fetus have not yet been examined, as such research is very difficult, expensive, or in many cases simply impossible. If we understand this, we can see that the outlook for scientific interference in God’s creation of human beings is not good.

You may wonder why the wide-spread usage of medication by pregnant women throughout the whole world has not lead to a continuous increase in congenital malformations if it is really this dangerous. Thanks to a happy concourse of circumstances, this process has not become too wide-spread, as there are many factors that allow the fetus to “escape” medical danger. For example, there may be an inherited insensitivity on the part of the fetus to the influence of different medications, the placenta has its own inherent protective function, the medication may be taken in a small dosage, the developmental stage of the fetus may be at a “non-critical” period, plus many other factors. Doubtless, although this has not been proven, is the fact that the mother has a sincere faith in God and believes in God’s protection of her and her child, which has a positive influence on the development of the fetus.

The initial clustering of embryonic cells and the formation of all the fetus’ organs and systems occur in the first trimester of pregnancy. It is particularly in this period that the fetus is very sensitive to the influence of different factors, including different drugs.

It is quite common that the results of the use of some teratogens¹ by pregnant women, which can have fatal effects, can simply go unnoticed in some cases, resulting in the death of the fetus during the first two weeks of development. In this case, the woman does not even know that she is pregnant. Such cases are not rare (according to some researchers, up to 70% of all pregnancies finish in the early death of the fetus).

What should a pregnant woman do if she is ill or feeling unwell? How can she effectively help herself and minimize the risk of any medications on her baby at the same time? It is never a good idea to self-medicate if you are pregnant, particularly in the case of little-known or untested medications. In any case, it is better to consult an experienced doctor or pharmacist. If for some reason this is impossible, please read the prospectus which is to be found with the medicine carefully. Which dangers the medicine can cause are probably mentioned on the prospectus, and it may be written that the drug should not be used if pregnant. If a drug has been used while being unaware of pregnancy (for example, during the first 2 weeks) then immediately consult a specialist about any possible negative effects there might be for the fetus as soon as you found out that your are pregnant. Going to see your doctor early will allow you the necessary time to avoid any dangers and allow you to arrive at a decision about this pregnancy. If the medicine has been prescribed by a doctor then be sure to ask about possible unwanted side effects for the fetus. Don’t hesitate to ask such questions. If it seems to you that your doctor’s attitude to this question is not serious enough (unfortunately, this happens quite often) then consult a competent specialist (a geneticist or a clinical pharmacist).

If you are just planning your pregnancy, then try to predict all the negative factors beforehand. If you have some chronic diseases which may become acute during the pregnancy, or if you have an allergic predisposition or high sensitivity to acute respiratory diseases, then you should consult a doctor. Preventive methods which have been worked out especially for you minimize the risk of the illness and the risk of using drugs that are potentially harmful to the fetus.

During early stages of ontogenesis the fetus has almost no adaptation mechanisms or specific reactions in its response to the influence of pathogenic agents. Only with time will the fetus’ main organs and systems become mature and the functions of the placenta fully form the morphological and functional backgrounds of the response characteristics peculiar to a new-born baby. We usually say that everything happens according to God’s Will but He has created us for a full, vivid, and creative life. And He wants us to understand and be attentive to the miracle that happens during pregnancy.

Note

1. Agents such as drugs, chemicals and infections that can cause birth defects when a mother is exposed to them during pregnancy.