Handbook of Food-Drug Interactions

Beverly McCabe-Sellers, Eric H. Frankel, Jonathan J. Wolfe, Beverly McCabe-Sellers, Eric H. Frankel, Jonathan J. Wolfe

• Publisher: CRC Press
• Year: 2003
• ISBN:
  9781135504571
• Edition: 1
• Topic: Medicine
• Subtopic: Clinical Medicine

With contributions from the fields of pharmacy, dietetics, and medicine, Handbook of Food-Drug Interactions serves as an interdisciplinary guide to the prevention and correction of negative food-drug interactions. Rather than simply list potential food-drug interactions, this book provides explanations and gives specific recommendations based on th

CHAPTER 1

Pharmacy: Basic Concepts

Eric H. Frankel

Basic information about pharmaceutics, pharmacology, pharmacokinetics, and pharmacodynamics is discussed in this chapter. The information will allow readers to appreciate the mechanisms that can result in interactions between drugs and nutrients.

BACKGROUND VIEW OF DRUGS

Animals are dependent on food for their very existence. Man is no exception. Man, as hunter and gatherer and later as agronomist, looked to plants and animals for more than just food. Animals and plants provided tools, shelter, clothing, and transportation, as well as labor.

Early man manifested an intelligence that led him to attempt to influence the external world and to change things to his advantage. Inevitable injury and illness were treated by means influenced by logic and intelligence. The means readily available to preliterate mankind included experimentation with plant and animal materials in the immediate environment. The trial and error method, combined with oral traditions and later written record keeping, produced diverse local practices of medicinal arts.

“The desire to take medicine is perhaps the greatest feature which distinguishes man from animals.” William Osler (1849–1919), Canadian writer, lecturer, and physician.

Pharmacognosy, the study of the origin, nature, properties, and effects of natural products on living organisms, grew from such instinctive responses to disease. Pharmacology, the study of the origin, nature, properties, and effects of various substances (naturally occurring and synthetic) on living organisms, grew from roots grounded for centuries in these primitive practices. It is interesting to note that there is a recent resurgence of interest in natural products for medical use.

With this new interest in natural products, keep in mind that efficacy, purity, and active ingredient concentration of substances sold as nutritional supplements are not regulated by any arm of the U.S. federal government. Recently, the U.S. Pharmacopeial (USP) Convention began a voluntary program for the certification of purity and active ingredient concentration of nutritional supplements. The USP is a private, not-for-profit entity founded in 1820 and entirely independent from the government. Except for products certified by this process, a potential for variance still exists between manufacturers, between lots from the same manufacturer, and even within the same lot.

THE PERFECT MEDICATION

Ideally, medications should be extremely specific in their effects, have the same predictable effect for all patients, never be affected by concomitant food or other medications, exhibit linear potency, be totally nontoxic in any dosage, and require only a single dose to effect a permanent cure. Unfortunately, that “perfect” drug has yet to be discovered. The concept has fascinated pharmacists and physicians since Galen of Kos expressed it nearly 18 centuries ago.

In reality, most drugs have multiple effects on the host. Those actions may even vary among hosts, depending upon factors as diverse as genetics and local environments. A drug is usually taken for one desired pharmacological action, but this is often accompanied by other, usually undesired, reactions referred to as side effects. Even drugs genetically engineered and chemically close to an endogenous chemical may fall short of the ideal profile. Exogenous administration of a “normally occurring substance” may disturb or fail to match a particular patient’s internal control mechanisms for homeostasis, the balance of physiology. Part of the interest in natural products is motivated by the wish to produce a desirable effect with fewer side effects. However, on a philosophical level, the reality of pharmacology is that all substances in high amounts, including even oxygen or water, can be toxic. From this viewpoint, drugs can be likened to poisons that may have desirable side effects. If health professionals adopt this viewpoint in using, prescribing, or recommending medications, iatrogenic drug misuse, misadventures, abuse, and nosocomial-medication-related errors could be minimized. In many cases, knowledge of both the indicated use of a product and its reported side-effect profile allow the caregiver to select among similar agents for an individual patient in order to minimize undesired side effects.

DRUG DELIVERY AND ADMINISTRATION

Prior to discussing basic pharmacology and pharmacokinetics, some exposure to pharmaceutics is helpful. This area of pharmacy knowledge focuses on dosage forms and routes of administration. Knowledge of pharmaceutics is required in order to begin to understand how drugs work.

For a medication to be effective, it first needs to reach a target location in the organism. Some type of delivery system is needed for this to occur. This requires use of a specific route of administration. Routes of administration are more numerous than people outside the medical professions would think. Thanks to technological advances, both routes for drug administration and dosage forms (a term describing the specific physical form of the drug’s active and inactive ingredients) exhibit more variety today than ever before.

Three major routes are used for drug delivery: topical, enteral, and parenteral. The topical route (cutaneous) can be used to apply a drug for its local activity at the area of application. Antifungal medications, such as miconazole creams for athlete’s foot, serve as examples. Drugs may also be applied topically (transcutaneous) to a site from which they can be absorbed to exert a systemic effect. Nitroglycerin ointment or patches, used to prevent angina pain, are examples of this route. Vaginal creams and suppositories are examples of topical drugs used in contact with mucous membranes rather than the epidermis. Topical drugs are also used for the eye (ophthalmic), ear (otic), and nose (intranasal). Finally, certain topical drugs can be delivered into the lung (inhalation) for both local and systemic effects.

The most common and convenient route for drug administration is via the gastrointestinal tract. The oral route (per os, PO) is the most common enteral route, but not the sole one. Medication may be administered sublingually (SL), using tablets formulated for SL administration. Nitroglycerin is available as a sublingual tablet. This dosage form is rapidly absorbed into the bloodstream. Medication can also be administered buccally (in contact with the oropharyngeal mucosa), as in the case of nystatin oral suspension; and rectally. When medication is given via the gastrointestinal tract, mechanisms usually involved in the absorption of nutrients are “borrowed” to transport the drug into the body. In effect, the gastrointestinal tract takes on an added function. This is possible because absorbable drugs have some chemical features in common with nutrients. This facilitates the active or passive absorption of the drug. The nasoenteric and percutaneous enteral tubes, familiar to many for delivery of nutrition, may, with appropriate precautions, also be pressed into service for enteral drug delivery.

The most invasive route for drug administration is the parenteral route. Whereas, technically, parenteral means not via the gastrointestinal tract, it is commonly used to refer to routes requiring some form of injection. Once again, a variety of routes come under this umbrella. The routes include injection into the bloodstream, most commonly intravenously (IV), or into a vein. This can be done rapidly (IV push), over a limited time (IV piggyback), or over a longer time (IV infusion). Occasionally, the blood vessel may be an artery instead of a vein. Arteries are sometimes used as the injection site for provision of intrahepatic chemotherapy. This is referred to as intraarterial injection.

Medication can be injected into the subcutaneous tissue (SQ), muscle tissue (intramuscularly, IM), or the skin (intradermal). Medication may also be injected into the spinal canal or into the dura surrounding the spinal cord. This is done mainly for pain control. The techniques here are intrathecal and subdural, respectively. Occasionally, chemotherapy for cancer or infection is given intrathecally in an attempt to decrease systemic side effects while maximizing central nervous system (CNS) effectiveness or to compensate for poor passage of many medications across the blood/brain barrier from the bloodstream into the cerebrospinal fluid. Antiinflammatory steroids, used for severe arthritis, may be injected into the space within a joint. This is called synovial injection. Occasionally medication, particularly hydration fluids, may be given by slow infusion subcutaneously rather than into a vein. This is called hypodermoclysis, and it is no longer commonly used for large volumes. Small volumes are sometimes given this way. An example of this would be insulin delivered by a pump. Medication can also be given directly into the peritoneum (intraperitoneal), directly into the wall of the heart or into one of its chambers (intracardiac), and sprayed into the trachea (intratracheal). The latter two routes may be used during cardiopulmonary resuscitation. Occasionally, drugs can be given via catheter into the ventricles of the brain. This is called intraventricular administration. During gestation, drugs may even be administered to a fetus in utero or into the amniotic fluid, referred to as intrauterine injection. Finally, there is a route of injection called intraosseous, where the injection is done into the bone marrow of long bones such as the tibia. This may be useful in children with poor veins and relatively soft bones.

DOSAGE FORMS

In order to take advantage of this multitude of medication administration routes, a similarly diverse number of dosage forms have been devised. Some, such as urethral bougies, are no longer in common use, while others, such as the transcutaneous patch and metered dose inhalers (MDI), are becoming increasingly popular.

Pills and Powders

When the general public thinks of an oral dosage form, the word pill is commonly used. The pill is actually an archaic dosage form. Pills consist of medication combined with inactive ingredients to form a gelatinous (doughy) mass. This mass is then divided, rolled into cylinders on a pill tile, and then cut into individual pills. The pills are then dried prior to use. Currently, few medications are truly pills. Carter’s Little Liver Pills^® and Lydia Pinkham’s Pills® are among the last of a once popular dosage form for both manufactured and extemporaneously prepared medications. Powder papers (a small, precisely measured quantity of medication and diluent inside a folded piece of paper) were once a popular method of drug delivery. Two over-the-counter (OTC) popular medications are available in this form: BC Powders^® and Goody’s Powders^®.

Tablets, Capsules, and High Tech

The most common dosage form is the tablet. It is prepared from a dry mixture of active and inactive ingredients (excipients). The excipients include binders, lubricants, diluents, and coloring agents. This mixture is mechanically compressed into solid tablets in various shapes. The excipients are considered inert ingredients, but can occasionally cause difficulty in individual patients. Lactose is commonly used as a diluent. The quantity is usually too small to cause adverse effects, even in a lactose intolerant individual. Tartrazine, commonly called FD&C yellow dye No. 5, is a coloring agent. Serious allergic reactions are possible to this agent and to medications colored with it. Capsules are the other most common oral dosing form. Active ingredients, diluents, and lubricants (to improve the flow of the powder through the equipment) are put into preformed, hard gelatin shells that are then mated with a second gelatin shell. Liquid medication can also be sealed into a capsular shell. Several variations on the manufacturing of tablets and capsules can result in delayed or extended medication release into the gastrointestinal tract. The absorption of the drug into the bloodstream and the pharmacological effect of the drug will be affected by this alteration in the release of the medicine. The most advanced oral dosage forms use semipermeable membranes or laser technology to produce dosage forms that release medication into the gastrointestinal tract at a controlled rate.

Some drugs may be absorbed from the capillary beds in the mouth. Nitroglycerin tablets are designed to dissolve under the tongue and will be absorbed sublingually. Recently, rapid dissolving tablets have been developed to deliver medications into the gastrointestinal tract. The medication is released in the oral cavity but is absorbed at numerous locations in the gastrointestinal tract. This results in a quicker onset of action. Rapid disintegration (RD) is frequently associated with this type of dosage form. Other medications may be designed for absorption from the inner aspect of the cheek. These are referred to as buccal dosage forms. Lozenges may be used to deliver medication into the oral cavity for both local and systemic action. Local anesthetics for treating a sore throat can be put into a lozenge. A powerful pain medication, fentanyl, is available in a lozenge on a stick form for transmucosal absorption. Cough suppressants are also available as lozenges.

Liquids

Of course, oral liquids remain a popular dosage form. This category includes solutions such as teas (infusions and decoctions), fluid extracts, syrups, drops, and tinctures, as well as emulsions and powders ready for reconstitution with water. With the popularity of “natural remedies,” the use of teas and homemade preparations has increased. All oral liquids are relatively simple in comparison to oral liquid nutritional supplements. The supplements are generally oil-based solutions emulsified within water-based solutions with some of their ingredients suspended in a colloidal form.

Recently, the introduction of foods having desirable pharmacological properties has further blurred the distinction among drugs, nutritional supplements, and foods. Benecol^® (contains plant stanol esters) and Take Control^® (plant sterol-enriched spread) are the best examples of this, but even the marketing of oatmeal and oat bran ventures into this newly grayed area separating drugs and foods.

Rectal Dosage Forms

Other enteral dosage forms are designed for absorption in the sigmoid colon and may be solid dosage forms (suppositories), liquids (enemas), or aerosols (foams). Again, both local and systemically acting medications may be given via this route. Hemorrhoid treatments, antiemetics, laxatives, and antipyretics (medications used to treat fever) are all commonly given in these forms.

Topical Agents

Topical dosage forms are similarly diverse. Ointments (oil base) may deliver topical medications. Creams (water-soluble base), gels, and mustards (pasty substance spread on a cloth and wrapped around a body part) also do so. Shampoos, soaps, solutions, and topical patches may also deliver medication in a useful manner. Nasal, ophthalmic, and otic (for the ear) solutions and suspensions are available. Aerosols, sprays, nebulized medications, metered dose inhalers, and powders for inhalation are used to deliver medication to the respiratory tract. Intravaginal suppositories (also called vaginal tablets), creams, douches, and sponges are used to deliver medications.

Injections

Parenteral dosage forms are mainly water-based solutions, but a few novel approaches are used. These include solutions in solvents other than water, oil-in-water emulsions, and even drug-impregnated solids used as subdermal implants. Recently, drugs have even been delivered inside liposomes in a parenteral liquid.

Pharmaceutical Elegance: Coats to Disguise, Protect, and Increase Duration

Coatings have been used on tablets to hide bad tastes (e.g., E-Mycin—erythromycin). One liquid suspension (Biaxin^®—clarithromycin) consists of film-coated granules. The coating again hides the taste of the medicine. Interestingly, this is a liquid medication that should not be given via a small-bore feeding tube. The granules can “logjam” at the curves in the tube and occlude it. Other coatings, referred to as enteric coatings, are used to prevent dissolution and inactivation of the drug in the stomach by gastric secretions. Extensive efforts have been made to engineer dosage forms that change the absorption of medications. The goal is usually to extend the duration of action for a drug with a relatively short half-life. Repetabs^® provide an example of tablets designed to provide a quantity of quickly released medication followed by a quantity of drug released slowly over time. Capsules can contain pellets coated with varying thickness of slowly dissolving excipients to achieve a timed-release bioavailability. Since medications are sometimes crushed before administration, one needs to know why the coating was on the tablet, where the drug will enter the gastrointestinal tract, and how removing the coating will affect the bioavailability of the dosage form.

COMPOUNDING: WHAT’S OLD IS NEW AGAIN

As can be seen from the preceding information, the history of pharmacy goes back to production of medication by a pharmacist rather than a commercial manufacturer. Today, many pharmacists are entering a niche market meeting individualized needs with individualized products. Compounding of pharmaceutical products provides such an opportunity. In this area, pharmacists with knowledge of product and patient work as problem solvers to provide a solution to a medical problem not amenable to treatment with off-the-shelf approaches.

Dosage forms, which are prepared by compounding pharmacists, parallel commercial dosage forms. Capsules, topical preparations including transdermal gels with enhanced ability to penetrate the skin, ophthalmic ointments, suppositories, troches, medicinal lollipops, and oral suspensions are among the dosage forms used by compounding pharmacists. Flavoring of liquid oral preparations is another area of expertise used by these practitioners.

Dosage forms containing multiple drugs can also be prepared to increase patient compliance and alleviate problems in patients who have difficulty swallowing capsules, tablets, or liquid medications. Specially prepared lozenges that slowly dissolve and release small volumes of medications into the gastrointestinal tract are useful for this purpose. Preparations that may have a therapeutic advantage but also have limited stability, and hence require short expiration dating, are poorly suited for large-scale manufacturing operations. A compounding pharmacy may be the only source for these types of preparations.

PHARMACOKINETICS

In order to understand drug interactions and drug interactions with nutrients, one needs to have a basic knowledge of pharmacokinetics. Pharmacokinetics is a science that deals with the progressive movement and alteration of chemical substances within the body. Bioavailability is important when reviewing the effects or pharmacology of a drug. In order for a drug to have an effect, it needs to be physically present at the site where it exerts its pharmacological action. First, the drug needs to be absorbed, and then it needs to be distributed or transported to a receptor—the site of action. The drug may then exert its pharmacological effect. Subsequently, the drug may be metabolized and then excreted. The acronym ADME is used to help people remember the pharmacokinetic arenas of absorption, distribution, metabolism, and elimination.

Keep in mind that drugs are usually substances not commonly ingested. All the pharmacokinetic mechanisms for each of the four ADME processes probably did not evolve to handle drugs. Drugs can be likened to a “Trojan Horse.” Most frequently, drugs enter the body via the gastrointestinal tract, a route that clearly serves the purpose of absorbing food. Drugs have to be chemically similar to food substances in order to be absorbed, but dissimilar enough to avoid digestion. For example, the reason that insulin must be injected is that it is a polypeptide. If ingested, insulin would be digested into smaller peptides and amino acids and lack the pharmacological action expected from insulin.

In order to understand drug dosing, one needs to appreciate how the amount of drug in the bloodstream changes after administration of the drug. Pharmacologists will frequently employ a graph of serum concentrations of a drug vs. time in order to describe the drug’s bioa...