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.

In our previous issue we briefly mentioned that the date fruit facilitates delivery and can be eaten to help prevent infertility. This article will continue to examine their manyfold health benefits with a specific focus on their protective features against many diseases.

All essential amino acids

Dates contain 18 of the 20 amino acids found in living creatures. We may sort the quantity of amino acids found in dates from highest to lowest as: Glutamic acid, Aspartic acid, Leucine, Proline, Arginine, Phenylalanine, Valine, Alanine, Serine, Glycine, Iso-leucine (800 times more than an apple), Lisin (2000 times more than an apple and banana), Threonine, Histidine, Tyrosine, Methionine, Cysteine and Tryptophan.

Dates contain all of the 8 essential amino acids that should never be neglected in nutrition and are not made in the body. Additionally, the fact that dates offer 10 non-essential substances that can be made in the body means that all the necessary materials for the synthesis of these proteins, which serve as the basic building blocks of the human body, are present in dates. In this sense, date is a very unique fruit, and this is why a human being could survive on only dates and water for years. V. H. W. Dowson, one of the renowned experts on this subject, says that a date and a glass of milk will be enough to meet a person’s daily nutritional needs.

Other fruits are generally poor in protein while dates provide protection of the body against diseases and infections by providing amino acids, proteins, a renewal of cells, and a balance of body fluid. Meat is also useful for the body, but it may not be as useful as dates, especially during pregnancy. As a matter of fact, excessive consumption of meat in such a period may cause poisoning in the body. A diet consisting of light vegetables and fruits, such as dates, is more suitable.

A store of elements and amino acids

Dates contain more than 10 elements that are vital for keeping the human body healthy and fit. A hundred grams of dates contains 65 mg calcium, 521 mg potassium, 20 mg magnesium, 72 mg phosphorus, 2.69 mg iron, 0.06 mg sodium, 0.05 mg copper, 0.06 mg zinc, 0.07 mg manganese, sulfur, chlorine, and selenium as well as other elements that are very important for metabolic processes in the human body. Some studies have reported that the amount of minerals found in dates is three to five times higher than those found in apples, bananas, oranges, and grapes. Sodium and chlorine are effective in the activity of the muscular and nervous systems, in adjusting appetite, and protecting the body from gaining weight. They also take part in regulating the pH level in our blood and the water in the body. Sulfur is part of the amino acids cystine and methionine and is involved in the synthesis of many proteins.

In addition, potassium helps transport oxygen to the brain as a result of which we have clarity of thought. Moreover, it provides alkaline (basic) features that are suitable for body fluids. It stimulates the kidneys to remove toxic body waste, and additionally helps to lower high blood pressure and ensure the formation of healthy skin. Calcium and phosphate are essential minerals for muscles and healthy bone development, whereas magnesium is required for the kidneys and energy metabolism. Iron is necessary for the production of hemoglobin in the red blood cells. A person can meet the need for magnesium by eating 2-3 dates a day, and iron by eating 15 dates a day. These amounts will also prevent anemia.

Having been wisely created as a host of so many substances, dates surely have healing features. Numerous studies have been carried out on its feature of terminating harmful “free radical” molecules as well as its antioxidant, antimutagenic, anti-microbial, anti-inflammatory, antihyperlipidemic (anti-greasing) effects. Many studies have been done on the protective immune stimulating effects of dates against the stomach, liver, kidney diseases, and cancer. There are also other studies on the benefits of the seeds, pollen, leaves, and syrups of dates.

Antioxidant activity

In studies of its antioxidant effects, the date fruit has been shown to reduce oxidative stress that damages cells. The protective effect of high levels of vitamin C, A, E, and phenolic substances acts as a powerful antioxidant by accelerating the activity of enzymes such as catalase, glutathione reductase and glutathione S-transferase [1].

Anticancer effect

The components of a date have been found to initiate an antitumor activity. Research found that date juice stops the melanoma cell that causes epithelial colorectal adenocarcinoma, which is a type of intestinal cancer and a type of skin cancer [2].

Effects on diabetes, raising of glucose and fat in blood

The glycemic indices of the sugars in dates are as follows: Maltose (105), Glucose (100), Sucrose (68), Lactose (46), and Fructose (23). Their absorption rate by the body is also different. Glucose is absorbed fastest while fructose is absorbed later. These absorption and glycemic index differences show that dates do not raise blood sugar fast and provide an increased feeling of fullness and are a food that can be used easily for diabetics. They do not raise blood sugar rapidly thanks to the fact that the total glycemic index of a date is 39. This may be due to its minerals, phenolic, and phytoestrogen components. Magnesium plays an important role in regulating and secreting the effect of insulin. Zinc, on the other hand, stimulates the production and release of insulin while strengthening the effect of chromium insulin. Selenium has also been shown to promote glucose uptake.

Phenolic compounds delay the absorption of carbohydrates, preventing the rapid rise of sugar in blood. In scientific literature, the antidiabetic effect of dates have been proven. Lab studies have shown that a-glucosidase and a-amylase were suppressed, thereby delaying digestion and absorption of carbohydrates and normalizing glucose levels in plasma. The effect of date leaves, hydro-alcoholic extract and aqueous solution of seeds are also shown. In another study,[3] scientists treated diabetic rats by giving each rat 10 ml of reconstituted date seed powder per day. It was then observed that the serum glucose, cholesterol and triacylglycerol levels of rats returned to normal values.

Anti-inflammatory activity

There is a great deal of research on the anti-inflammatory effects of dates, expediting wound healing processes, and protecting the heart. Al-Qarawi et al. found that the juice obtained from dates is effective in improving the severity of gastric ulceration and reducing histamine and gastrin concentrations. According to the authors, the anti-inflammatory properties of date extract can be explained by its antioxidant effect [4]. In another study conducted on dates grown in Algeria, it was shown that the extract given orally produced a significant reduction in wound edema in Swiss albino mice. Presumably, this effect is due to the suppression of inflammatory cytokine enzymes that can interfere with prostaglandin synthesis of some active substances in date sap.

Antimicrobial activity

There are a lot of studies about cold pressed date juice. A study found that the juice decreased the reproduction of Streptococcus causing febrile disease by 88.5%. Another study found that sap extracts dissolved in water and ethanol have a strong antibacterial activity against Escherichia coli, Salmonella enterica, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella abec and Enterococ. This germicidal effect is thought to be caused by tannic acid, gallic acid, itaconic acid and ferulic acids that are present in dates [5]. In another study, different degrees of influence were observed between different types of dates. It has been reported to be more efficient against Gram-negative bacteria due to the presence of an outer membrane in Gram-positive bacteria. This effect against microbes is due to phenolic compounds that enable the production of hydrogen peroxide, which stops the growth of bacteria.

Antitoxic activities

There are many studies about the protective effects of dates on the liver, kidney, and nervous system in neutralizing the oxidative stress and poisonous compounds that are obtained from food. It has been shown that p-Sitosterol, a bioactive compound often found in dates, is beneficial for liver injury when date seed powder is added to drinking water [6]. Another study showed the anti-damage effect of the succulent extract of dates on damaged liver cells related to oxidative stress [7].

Kidney-protective role

It is known that toxic substances that enter our body from the environment in various ways can cause great damage to us, especially to our kidneys. An extract prepared from date seeds has been shown to provide significant protection in the kidneys and remove harmful free radicals. This is thought to be due to the proanthocyanidin it contains. Another study showed improvements in mice with impaired renal function.

Scientists concluded that dates show significant improvements in the damage done to the kidneys by aflatoxin, a dangerous fungus that reproduces in foods, which can also be attributed to its antioxidant properties. Scientists believe that the effect here is due to the common effect of melatonin, vitamin E, and ascorbic acid in the extract [8].

Its influence against nerve poisoning

Free radicals have been extensively proven to cause aging and a multitude of age-associated diseases such as Alzheimer’s, Parkinson’s and dementia due to circulatory system failure [9]. Antioxidants obtained from plants have long been used to help prevent neurons from weakening and dying [10]. Studies are concentrated on the effectiveness of joint protection by polyphenolic compounds (resembling flavonoids and plant sterols) and the ascorbic acid that is found in date extract.

Its effect on the cardiovascular system

Dates have been used against high blood pressure for centuries. In one study, an enzyme in dates has been shown to suppress a specific blood pressure hormone called angiotensin [11]. High sodium and low potassium intakes increase blood pressure, whereas dates help maintain electrolyte balances and keep blood pressure in control. Magnesium and calcium in dates play a key role in this control [12]. It has been reported that cholesterol absorption and metabolism can be regulated by the suppression of cholesterol production in the liver due to the fermentation of phytoestrogens in dates [13].

In another study, a Pakistani date variety has been shown to be very effective in lowering compounds such as preprandial blood sugar, cholesterol, triacylglycerol, LDL, and VLDL. In another study, some chemical components such as P-sitosterol, proanthocyanidin, catechin, quercetin, anthocyanins, and selenium have been shown to both protect the heart and lower blood fats [14].

Each and every day, scientific studies are teaching us more about dates and how they have been equipped with more features than any other fruit as we strive to unveil the wisdom and mercy among the bounties offered to us in the shape of food.

References

1. Biglari, F., Al Karkhi A.F.M., Easa, A.M. (2008): Antioxidant activity and phenolic content of various date palm (Phoenix dactylifera) fruits from Iran. Food Chem 2008; 107(4): 1636-41.
2. Eid, N., Enani, S., Walton G., Corona G., Costabile, A., Gibson, G., Rowland, I., Spencer, J.P.E. (2014): The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation. J Nutr Sci 3: e46.
3. Hasan, M., Mohieldein, A. (2016): In Vivo Evaluation of anti-diabetic, hypolipidemic, antioxidative activities of saudi date seed extract on streptozotocin induced diabetic rats. J. Clin. Diagn Res. 10(3): FF06-12.
4. Al-Qarawi A.A., Abdel-Rahman H., Ali B.H., Mousa H.M., El-Mougy S.A. (2005): The ameliorative effect of dates (Phoenix dactylifera L.) on ethanol-induced gastric ulcer in rats. J Ethnopharmacol. 98(3): 313-7.
5. El Sohaimy S., Abdelwahab A., Brennan C., Aboul-enein A. (2015): Phenolic content, antioxidant and antimicrobial activities of Egyptian date palm (Phoenix dactylifera L.) fruits. Aust. J. Basic Appl. Sci. 9(1): 141-7.T
6. Al-Qarawi A.A., Mousa H.M., Ali B.H., Abdel-Rahman H., El-Mougy S.A.(2004): Protective effect of extracts from dates (Phoenix dactylifera L.) on carbon tetrachloride-induced hepatotoxicity in rats. Int. J. Appl. Res. Vet. Med. 2(3): 176-80.
7. Saafi E.B., Louedi M., Elfeki A., Zakhama A., Najjar M.F., Hammami M., Achour L. (2011): Protective effect of date palm fruit extract (Phoenix dactylifera L.) on dimethoate induced-oxidative stress in rat liver. Exp. Toxicol. Pathol. 63(5): 433-41.
8. Al-Qarawi A.A., Abdel-Rahman H., Mousa H.M., Ali B.H., El-Mougy S.A.(2008): Nephroprotective Action of Phoenix dactylifera. in Gentamicin-Induced Nephrotoxicity. Pharm. Biol. 46(4): 22730.
9. Uttara, B.; Singh, A.; Zamboni, P.; Mahajan, R.(2009): Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr. Neuropharmacol. 7(1): 65-74.
10. Pujari R.R., Vyawahare N.S., Kagathara V.G. (2011): Evaluation of antioxidant and neuroprotective effect of date palm (Phoenix dactylifera L.) against bilateral common carotid artery occlusion in rats. Indian J. Exp. Biol. 49(8): 627-33.
11. Braga F.C., Serra C.P., Junior N.S.V., Oliveira A.B., Cortes S.F., Lombardi J.A.(2007): Angiotensin-converting enzyme inhibition by Brazilian plants. Fitoterapia 78(5): 353-8.
12. Tang Z-X, Shi L-E, Aleid S.M. (2013): Date fruit: chemical composition, nutritional and medicinal values, products. J. Sci. Food Agric. 93(10): 2351-61.
13. Alsaif M.A., Khan L.K., Alhamdan A.A.H., Alorf S.M., Harfi S.H., Al- Othman A.M., Arif Z.(2007): Effect of dates and gahwa (Arabian coffee) supplementation on lipids in hypercholesterolemic hamsters. Int. J. Pharmacol. 3(2): 123-9.
14. Auger C., Teissedre P.-L,. Gerain P., Lequeux N., Bornet A., Serisier S., Besancon P., Caporiccio B., Cristol J.-P., Rouanet J.-M.(2005): Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J. Agric. Food Chem. 53(6): 2015-21.

There are two types of pain. One is called sharp or acute pain, which for example might be caused by the prick of a needle, an injury from broken glass or a sharp object like a knife, or contact of skin with a hot object like an element. Such sharp pain is especially important to protect the body through reflex. Similarly, sharp pain in internal organs such as the stomach or intestines may result from a puncture or blockage that prevents the transport of oxygen, or leakage of toxic material such as the stomach acid.

Another type of pain is continuous or chronic pain, of which one obvious example is rheumatic pain. Cancer pain is mostly chronic, although cancer may also cause sharp pain. Whether chronic or sharp, cancer pain can be unbearable, and only endurable with morphine.

What can we do about pain?

Medication should be our last resort when dealing with pain. We should remember that every drug is potentially a poison, and drugs, especially when used for a long time and in high doses, can have numerous adverse effects. Thus no drug, including aspirin, is fully innocent.

The cause of pain must first be diagnosed by a physician. A pain in the chest may simply be a muscle pain, or conversely may be as deadly as a heart attack.

After diagnosis comes the required treatment or operation. Intense pain from appendicitis, for example, is easily treated with an operation. Pain from a heart attack, which causes pain in the left part of the chest, left shoulder and left arm, must be dealt with very seriously under the supervision of a cardiologist.

The first measure to be taken in case of a headache, backache, or neck ache is to avoid the position or movement that causes the pain. Consider the following analogy: the wheels of your car are not properly aligned. One side of the tire is worn due to friction, and thus blows out or loses traction. This result is inevitable, unless one corrects the misalignment leading to friction and wear. The damage cannot be prevented by putting on ear plugs and pretending it doesn’t exist.

If your neck has an ache, you should consult a physician to diagnose the cause. The pain may be related to how you use your pillow; so you can get rid of the pain by simply adjusting the pillow based on your preferred sleeping position, or you may need to buy a new pillow. The pain may also be caused by keeping the head in the same direction for prolonged periods to watch TV or looking into the monitor, we may just need to do some simple physical exercise and sit up right. Desk jobs and extended cell phone use are primary causes of neck aches. Resorting to painkillers immediately is not the right thing to do in such cases. A drug may ease the pain temporarily, but as in the car analogy, we may end up with a flat tire. Painkillers do not resolve the injury to the neck and what is worse, despite the intensifying pain you may not be aware of the body’s warnings, and finally have a serious case of hernia that may require an operation that runs the risk for death or paralysis.

The most important cause of backache is a vicious circle of inactivity and obesity. If a person does not exercise, they will put on weight and as one puts on weight they cannot exercise. Carelessness when picking up something is one of the most common causes of backaches. Obesity is one of the most common causes of herniated disc. Obesity prevents doing exercise; back muscles weaken as one does not exercise, and this leads to a herniated disc. If we do not take necessary care about these and look to drugs for treatment, we may not feel the pain, but the injury and hernia continue to exist. The risk is much lower among those who observe meditation and other religious practices that include physical activity like bowing, prostrating, sitting and standing upright. Eating little and leaving the table before being full are among many prophetic advices that are useful for our health.

The same is true for knee injuries such as meniscus tears and ligament sprains. Our knees are some of our most precious assets. We should be careful about our knees when standing up from a squat or getting on or off a car so that they will not slip sideways. Dangerous, rigorous exercises or movements that may harm the bones and cartilage in the knees, such as lifting heavy weights and jumping off a height, should be avoided, especially after a certain age. Sitting crossed-legged or squatting for long periods may stretch cruciate ligaments too much, and a slight move may cause their rupture.

One of the most common types of headaches is stress-related headaches. In these headaches the muscles in the head become tense, causing the vessels to contract and leaving tissues without oxygen. If we learn how to deal with stress, we can ease the headache and become happier. We should fight stress consciously and actively. We can overcome headaches not by sitting idly but by mental preparation and activity targeting stress.

Cupping and other complementary treatments can be tried before medication. Performing regular prayers may help relieve the aches in the head, neck, and knees, because these prayers reduce stress and are a form of exercise. Washing yourself as a part of prayers includes exercise, cleaning, and getting rid of the stress-related static electricity through water. Cleaning the top of the head, massaging the ears inside out, and washing the face and feet are known to reduce stress and discharge static electricity.

Endorphins, a group of hormones secreted within the brain, are in fact given the task of acting as painkillers in our body. They are thousands of times more powerful than morphine and help us fight headaches. Most of the ache, especially in chronic pains, is eliminated by the “pain-control systems” which were installed in our brains; what we feel as pain is in fact whatever remains after this elimination. Were it not for this mechanism, which is a sign of great compassion, life would be insufferable because of pains.

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

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.