How Drugs Work

Background

The Human Body

The average human body is composed of approximately 50 - 200 trillion cells. ²There are about 5-6 liters of blood pumping through the body at a rate of 5 liters per minute. The body is about 70% water. It is possible to calculate the number of liters of water in your body. Take your weight in pounds and multiply by 0.7 (or 70%). This will give you the weight of the water in your body in pounds. Next divide by 2.2, since there are 2.2 pounds in 1 kilogram. The density of water is 1 kg/L (or 1 g/mL), so you now have the number of liters of water in your body. Here is an equation that describes this calculation: Bodyweight, lbs x 0.7 x kg/2.2lb x 1L/kg = Bodywater,L.

Oxygen, carbon, hydrogen, and nitrogen together make up 96% of the mass of the human body. Oxygen (65%) and hydrogen (10%) are found mostly in water. The table below lists the elements that make up the human body and their percents in terms of body weight. ³

Table 1: Percentage of Elements Found in the Human Body

table 12.05.05.01 is available in print form

There are 200 different types of cells in the human body. Cells are the basic structural and functional unit of the body. All cells are genetically the same but can be different in size, shape, and molecular makeup. Similar cells group together to create tissue. Two or more primary tissues grouped together for a specific function form an organ. Organs then work to form a system and our systems perform the functions we need to survive. ⁴

The body is phenomenally intelligent and complex, however it is not invincible. Dysfunction in the body can lead to disease, illness, aches and pains. Through years of research - as well as trial and error - scientists have discovered many drugs to help treat and prevent diseases, illnesses, aches, and pains.

Principles of Drug Administration

What is worse, bad tasting medicine, swallowing pills, or painful shots? Why are different drugs administered different ways? Bioavailability, the fraction of drug absorbed into the blood stream, is different for each route of administration. There are advantages and disadvantages for the different routes of administration that must be considered. No single method of administration is best for all drugs.

Oral is the most common route of administration. There are numerous drugs available orally such as vitamins, antibiotics, painkillers and more. A drug taken orally is absorbed in the GI tract, which includes the stomach, small intestine, large intestine, rectum and anus. This method is popular because people are able to self-administer their medication. It is also cheaper than other routes and clearly more convenient. However, it doesn't work for every drug. Drugs administered orally have low bioavailability and they don't start working right away. Many drugs can irritate the GI tract and the acid and fluids within the GI tract can also destroy the drugs. It can be difficult to regulate patient compliance and not possible to administer to an unconscious patient. ⁵

Inhalation is when the drug is absorbed through the lungs. Drugs for asthma and allergies are often administered through an inhaler. The metered-dose inhaler or MDI is pressurized and releases a fixed amount of drugs into the lungs. The lungs have a large surface area. There are approximately 300 million alveoli in the lungs. The alveoli are small air sacks with a diameter of about 0.25 millimeters. They give the lungs their huge surface area, almost 150 square feet. This is the size of a tennis court! ⁶The large surface area allows the drug to enter the circulation system and begin working right away. This type of administration has its downfalls because it does not work for all drugs, particularly because many drugs can cause damage to the lungs. ⁷

Intramuscular drugs are injected into the muscle. It is advantageous that the drug does not have to go through the digestive system and it is localized. However it is slow to take effect and can be painful. Vaccines, insulin, and epinephrine are intramuscular drugs. ⁸

Subcutaneous drugs are injected into tissue between the skin and the muscle. They are localized but often are slow to take effect. Usually between 15 and 30 minutes. Anesthetics are administered in this way. ⁹

Intravenous drugs are injected directly into the vein. There are two types of intravenous administrations. In intravenous injection, the drug is injected in the vein all at once. In intravenous infusion, the drug is continually being administered. The intravenous route allows for 100% bioavailability. Large quantities can be given and the effects are usually immediate. High-dose antibiotics, painkillers, and chemotherapy are often given intravenously. ¹⁰

Vitamins

Vitamins are important organic compounds the body needs to grow and develop. The body is unable to produce most of these diverse sets of molecules; therefore it must acquire them through a vitamin rich diet or supplements. The body actually makes some vitamins like D and A, but it needs sunlight and precursors (like beta-carotene) to do so. Vitamins are usually administered orally, however high-doses administered intravenously have been used to treat certain diseases.

Vitamins are classified by their ability to dissolve in liquids. Fat-soluble vitamins such as A, D, and E dissolve in fat and then are absorbed into the bloodstream. These vitamins are stored in fatty tissue and the liver; therefore, they are not needed on a daily basis. Their standard unit of measure is the International Unit (IU), which measures potency. The potency changes from vitamin to vitamin so there is no formula to convert vitamins measured in grams to IU. For this unit we will use an online website that converts grams to IU for each specific vitamin (http://www.robert-forbes.com/resources/vitaminconverter.html). Water-soluble vitamins, like C and B dissolve in water. They are eliminated through urine; consequently they are needed on a daily basis. Milligram (mg) or microgram (mcg) are the units of measure.

Regardless of their classification or form vitamins are crucial to human health and development. Deficiency diseases have become rare in the United States, because of attention to the minimum daily doses of vitamins necessary to avoid deficiency. However, vitamins can help prevent degenerative diseases and slow the aging process, but the optimal dose for that effect is not always known.

Discovery of the Vitamin

In the 1800s chemists began studying the nutritional makeup of the human diet. They realized proteins, fats, starches, and sugars were necessary to provide usable energy. These elements were common in the average diet. However, through research of diseases such as scurvy, beriberi, and pellagra it became clear there were other nutrients in foods necessary for premium health.

Sailors who traveled for long periods of time often contracted Scurvy, a disease that causes weakness, pains in the joints, loose teeth, and death from the bursting of the main artery. However, even extremely sick sailors would recover if they made it to land and were given fresh fruit. It wasn't until 1765 when sailors began drinking lemon juice on long voyages that Scurvy was avoidable. From the 16 ^th to 18 ^th centuries Scurvy killed more sailors than all other diseases and wars combined.

Beriberi is a disease that causes weakness, loss of feeling in the feet and legs, difficulty breathing, and death from heart failure. In 1803, Thomas Christine, a British physician gave patients citrus fruits, hoping to see the same effects as were seen with Scurvy. The citrus fruits had no effect on the disease. Later in the 1890s Dutch military physician Eijkman infected chicks with the disease. He found that the symptoms of the disease were only seen in chicks who ate white rice. The brown rice that was harvested went bad quickly unless the outer grain layer was rubbed off. The white rice lacked the outer bran layer known as the polishings. When Eijkman fed the polishings to the chicks they stopped suffering from the Beriberi symptoms. Interestingly, initially it was believed the disease was caused by a harmful amount of starch in the white rice. He believed the polishings were an antidote to the starch. More evidence for his findings came from Vorderman, a medical inspector at over 100 prisons. He was aware of Eijkman's findings. The disease was present in the prisons, but disproportionately. Upon closer inspection Vorderman found that prisons serving brown rice had less than 1 prisoner in 10,000 with Berberi where prisons serving white rice had 1 in 39.

In 1896 Gerrit Grijns, a doctor from the Netherlands, continued the research on the chicks but instead fed them only meat. Again, the chicks that were given the polishings did not show any Beriberi symptoms. This was important because it proved that the disease was not a result of the starch found in the white rice. Grijns was quoted with what came to be known as the Vitamin Statement, "there occur in various natural foods, substances which cannot be absent without serious injury to the peripheral nervous system. These substances are easily disintegrated. Which shows that they are complex substances and cannot be replaced by simple compounds." ¹¹

The goal was to find and synthesize the material in the polishings. Casimir Funk, a biochemist from Poland thought the material belonged to a chemical class called amines. He referred to these "vital amines" as "vitamine". It was later discovered that they were not "amines", so the word was shortened to vitamin. In 1929, with much debate over who deserved the credit, Eijkman was awarded the Nobel Prize for Physiology or Medicine for the discovery of the vitamin. ¹²

The Roll of Vitamins as Antioxidants

Oxygen, the second most reactive element on earth, reacts with glucose in the body and converts to water and carbon dioxide. However, some oxygen molecules are only partly converted and therefore become free radicals. A free radical is an oxygen atom that has an unpaired electron. The oxygen's unpaired electron looks for a match and takes it from other molecules. It then becomes attached to the molecule and the molecule is oxidized. During this natural process, known as oxidation, free radicals cause damage to molecules, cells, and structures. One of the molecules that is susceptible to attack by free radical oxygen is DNA. In an individual, it is estimated that oxygen free radicals make 100,000 attacks on DNA every day. ¹³

The cellular damage from free radicals leads to aging and degenerative diseases such as heart disease, cancer, arthritis, lung disease, diabetes, and eye diseases. The National Cancer Institute defines antioxidants as the substances that protect cells from the damage caused by free radicals. The antioxidants provide electrons for the free radicals before they do damage to other molecules. The body repairs itself by making a number of its own antioxidants. However, air pollution, cigarette smoking, stress, drugs, excessive exercise, and prolonged time in the sun can increase the level of free radicals in the body. This creates a need for additional antioxidants.

Vitamins A, C, and E have shown powerful antioxidant effects. In fact, 120 out of 130 clinical studies revealed people with high levels of vitamins A, C, and E had a lower risk of cancer.

Vitamin C

Vitamin C is an organic compound with the molecular structure of ascorbic aid. Hungarian biochemist, Albert Szent - Gyogyi isolated vitamin C and Norman Haworth made it available to the public by synthesizing it in 1937. It is the most commonly taken supplement and most important antioxidant.

Vitamin C has numerous functions. It is necessary for the production of collagen, which is the main structural protein found in the flesh and connective tissue. Collagen is vital for healthy teeth, bones, gums, cartilage, skin and blood vessels. Vitamin C is also known to heal cuts, fight infections, avert colds, and prevent scurvy. One of its most valuable rolls is as an antioxidant. Eight human enzymes take electrons from Vitamin C. ¹⁴

Fredrick Klenner, an M.D. from Duke Medical School said, "If in doubt, give vitamin C." ¹⁵ He wrote 27 papers between the 1940s and 1970s describing the importance and uses of high levels of vitamin C. He died in 1984. The papers fell into the hands of Lendon Smith who summarized and published the information in "The Clinical Guide To The Use Of Vitamin C." Klenner felt that the recommendations for vitamin C were much too low. His passion followed the Puerto Rican Legend about the acerola fruit. If there is an acerola tree in the backyard, a cold won't enter the front door. The acerola fruit has 30 times more vitamin C than an orange. ¹⁶

Klenner believed that vitamin C could be used to prevent or heal many serious diseases: polio, pneumonia, hepatitis, herpes, chickenpox, measles, mumps, arthritis, cancer, cavities, ruptured discs, sunburns, lead poisoning, and the list goes on. In some ways Klenner was a vitamin C fanatic. "Vitamin C will work in any problem. The negative results reported are only because an insufficient amount was used." ¹⁷

He claimed enough vitamin C could destroy all virus organisms. For severe illnesses he recommended 350 mg per 1 kg of bodyweight to be given intravenously. In the case of chicken pox he claimed 250 mg per 1 kg would cause the pox to crust in 5 days and eliminate the virus. ¹⁸

Fascinating stories about Klenner and his research are available. I recommend, "Vitamin C Cures" ¹⁹ and "Observations on The Dose and Administration of Ascorbic Acid When Employed Beyond the Range of a Vitamin in Human Pathology" ²⁰. Both articles are entertaining and informative about Klenner's research and use of high doses of vitamin C. This is something students might enjoy reading and comparing to current government recommendations.

Vitamin E

Vitamin E is a fat-soluble compound that comes in both natural (d-alpha-tocopherol) and synthetic (dl-alpha-tocopherol) form. Olives, avocados, oily fish, sunflower seeds, and spinach are all rich in vitamin E. It is used in many creams to increase healing of the skin and minimize the appearance of scars and burns, and is a powerful antioxidant.

The outer layer of every cell in the human body has a protective barrier against free radicals and other damaging molecules. This barrier is made mostly of fat and therefore absorbs the fat-soluble vitamin E. By penetrating through the cell membrane, Vitamin E distributes into the cell and works to protect the cell from free radicals.

High levels (150 IU daily) of vitamin E are necessary in order to experience its benefits. The foods that contain vitamin E are often high in fat and sodium as well. For example, 8 oz. of sunflower seeds would provide the necessary 150 IU along with 1,300 calories! So vitamin E is a great argument in support of supplementation. ²¹

Vitamin A

Vitamin A is a fat-soluble vitamin that benefits the fatty tissue that protects the body. Deficiency in vitamin A can lead to eye damage as well as blindness. It is good for the skin, important for cell growth, and helps maintain the immune system.

Vitamin A can be taken as a supplement or found in animal sources such as turkey, liver and eggs. When ingested as Vitamin A the excess is stored in the liver. It is toxic, so too much vitamin A can be dangerous. However, beta-carotene that is found in plant sources such as carrots, spinach, tomatoes, yellow vegetables, and kale is not toxic. Beta-carotene is known as the pre-cursor to vitamin A. The body is able to convert the beta-carotene into vitamin A on an as needed basis. The rest of the beta-carotene then becomes a powerful antioxidant. ²²

Recommendations

Vitamins are required and beneficial for normal body function. But, there is conflicting information available about necessary dosages. Continued research shows higher vitamin intake can help fight against degenerative diseases, slow the aging process, and improve overall health. When looking at recommended dosages it is important to keep in mind the intention and research behind the recommendation.

Recommended Daily Allowance (RDA) - During World War II the U.S. National Research Council developed the RDA to be used for people on rations. The RDA then became the standard or norm for vitamin and nutrient recommendations. This was never the intention or purpose of the RDA. The recommendations of the RDA are too low to induce high-quality health and prevent diseases like arthritis, cancer, diabetes, and heart disease. The truth is that necessary levels of nutrients are much higher than the RDA for optimal health.

The Reference Daily Intakes (RDI) - The Food and Drug Administration uses the RDI for nutrition labeling. Since the entire population uses nutrition labels the values were taken from the highest RDA for each nutrient in 1968.

Dietary Reference Intake (DRI) - The Food and Nutrition Board of the Institute of Medicine set up the DRI in 1997. They are the most current version of recommendations and are intended to replace the RDAs. The DRI will be the basis for updating the RDIs. The DRI has also led to the development of the Adequate Intake (AI) and the Tolerable Upper Intake Level (UI).

Over the years foods have been enriched with different nutrients. In the 1920's iodine was added to salt, in the 1930s vitamin D was added to milk, in the 1980s calcium was added to various foods, and in 1998 the FDA required folate to be added to grain. Even with nutrient rich foods, some have argued that it is impossible to get the necessary nutrients from food alone. Over processing, long storage periods, and modern growing methods have lowered nutrient levels in many foods. ²³

As research about the benefits of vitamins continues it is clear they are valuable compounds to help maintain optimal health. Nutrient rich foods as well as supplements supply the necessary vitamins and minerals needed to aide the body in fighting disease and staying strong.