Introduction
Here’s an important fact many people do not know—there are many medications out there that can deplete vital nutrients from your body. Not only do few people know that—many physicians don’t always know that or take it into account when they are talking to patients on how and when to take prescription medications. The one group of professionals you can always ask—and nearly always get an answer from—are pharmacists. These are the professionals whose business it is to know (or be able to check) for medication-induced nutrient depletions or, in acronym form, MINDs.
Pharmacology—the study of how, where, and when drugs work – has its own set of acronyms. One of the first acronyms a student in pharmacology learns is ADME—which means absorption, distribution, metabolism, and excretion. These are also known as the “Four Steps” of pharmacokinetics, or the study of the time drugs pass through the body to do what the drug is meant to do and what happens during that time. Another branch of pharmacology is pharmacodynamics—this is the study of what the drug DOES to the cells, tissues, and organs of the body.
In this “Part 1”, we will talk more in an “overview” kind of way—Part 2 will get into specifics, telling you which drugs deplete which nutrients—and if you can replace those nutrients WHILE you are taking the medications or if you should wait until a short course of medication is completed. For example, if you are taking antibiotics, most physicians will now recommend taking probiotics during the 7- or 10- day (or however long) course. On the other hand, some nutrients depleted during antibiotic treatment (e.g. Magnesium) can wait until you are done with the antibiotics—one reason being is that some antibiotics cause diarrhea, and taking magnesium during that time may: 1) make the diarrhea worse (!!) and/or 2) reduce the effectiveness of the antibiotic and/or 3) be a waste of time and money because the digestive processes necessary for absorption are disrupted by the antibiotic.
The Basics of ADME
Absorption
Absorption is the process by which a drug (or any substance) gets into the body—there are 4 main “delivery systems” or routes by which this can happen:
- Oral via the digestive tract
- Inhaled via the lungs
- Topical application to the eyes, skin, or mucus tissue of the nose, mouth, vulval or vaginal areas or rectum
- Direct injection intramuscularly (im) or intravenously (iv).
In the first 3 methods, the drug must first cross a cell membrane (or more than one) to pass into the blood to be circulated throughout the body. In #4, iv delivery gets the drug directly into circulation. In im injections, the drug diffuses into the circulation around cells.
Crossing a cell membrane can be done in 4 different ways—3 of which are forms of diffusion.
- Diffusion can be active (requiring energy), passive (requiring no energy), or facilitated (using a carrier protein).
- Endocytosis where the drug is absorbed into a cell using a pocket which forms in the cell membrane—that pocket becomes enveloped in membrane and enters the cell as a spheroid “micelle”.
How a drug is absorbed can affect its “bioavailability”—how much of the drug is absorbed without a change in form (without being metabolized). Only iv delivery systems are 100% bioavailable. Inhalation also provides high bioavailability. For the other delivery systems, bioavailability depends on several different factors, including if the drug is water- or fat-soluble, whether it has to undergo “first pass metabolism”, and other chemical and physical properties.
Distribution
After absorption, the drug may be distributed around the body, usually in the blood. Topical (skin) applications tend to have the lowest distribution—sometimes by design, but this is also inherent in the delivery method—if you are giving a medication for an area of muscle pain, you would want it to just be applied to that area and not diluted (and therefore less effective) by distribution throughout the body. Distribution throughout the body occurs via blood circulations and is dependent on the delivery method as well as the chemical and physical properties of the drug.
Metabolism
Metabolism covers a whole lot of processes, but in pharmacology, it is essentially the conversion of a drug by cells (primarily in the liver cells) to one or more products—called metabolites. Some metabolites may still have drug activity, and some may have increased toxicity and cause adverse effects, but the point of this metabolism is to change the drug into a form that can be easily excreted—because that is part of what the liver does! Metabolism, in this sense, generally means making a drug more water-soluble so it can be excreted in the urine or stool.
First Pass Metabolism
First Pass Metabolism is the phrase used to describe what occurs when medications are taken by mouth, though it can occur with other delivery systems.
When a medication is taken by mouth, it is absorbed into the blood vessels around the digestive system. It then passes through the liver, where most first pass metabolism occurs. This process decreases the total amount of medication that can then be delivered to the rest of the body. The liver converts a fraction of the medication into various metabolites, leaving the rest to distribute through the rest of the body.
There is a large family of enzymes involved in first pass metabolism—the Cytochrome P450 (CytP450 or simply P450) family. Every individual has a slightly different pattern of P450 enzymes, and each medication has a unique set of P450 enzymes that are active on that medication. Some medications induce (increase the activity of) some enzymes and decrease others, while others induce or inhibit a whole different set of enzymes. This produces different complex patterns of increased or decreased sets of P450 enzymes. Yes—it is VERY complex, and we are just now beginning to get a better understanding or these.
But why is first-pass metabolism important? Because it can affect how much medication is bioavailable in each individual—AND can make a very big difference if someone is taking more than one medication. But that is not the only reason—it is also important because it can affect decisions about dose, delivery system (via mouth, iv or im, topical), and because of potential drug-drug interactions.
But that is not all—because first pass metabolism can also be affected by herbs, supplements along with vitamins and minerals! And these effects can interfere with actions of medications, herbs, supplements, vitamins, and minerals. This is particularly important in seniors where polypharmacy—the use of several different drugs, some of which can interact to produce adverse effects—AND nutrient depletions, is very, very common. One of the most common adverse effects of drugs in seniors is to increase the risk of falling.
Excretion
Finally, the drug is excreted—usually in the urine or the stool. Some drugs are excreted by the skin as sweat or by exhaling from the lungs. However, this is the case for water-soluble drugs. Fat-soluble substances like some drugs, some drug metabolites, and fat-soluble vitamins (e.g. Vitamins D, E, A, and K) can get stored in fat tissues—and cause adverse effects over time.
What’s Next in Part 2?
In part 2, we will talk about different medications and how (if we know) they deplete nutrients. We will also look at if they induce or inhibit any of the P450 enzymes to determine if THAT can end up depleting nutrients as well. We will also look at what part of the process of ADME may be disrupted and lead to nutrient depletions.
Why read Part 2? Because if your medication may be depleting nutrients you need—that is an important thing to know! It is also important to know how to avoid depletion or how to replenish that nutrient. And THAT is what Part 2 can help you determine.