Updated date:

Alcohol's Effect on Drug Metabolism in Active Women and Sedentary Men

Charlotte likes pretty things, and she loves the beach, sushi, coffee and seashells.

It is usually assumed that the same drug works the same exact way for everyone. Of course, this is not true. That's why many similar medications—either slightly or significantly changed—are presented for the same disease state. This gives the patient options since the way that drugs affect an individual may be completely variable and even ineffective.

Most medications, regardless of gender, will work in their intended way in similar effects. With some drugs, women may more slowly metabolize the medications than men. Zolpidem is one example. "Women seem to be more susceptive to this risk because they excrete zolpidem from their bodies more slowly than men." (Center for Drug Evaluation and Research). When a typical drug is administered orally, it is absorbed within 1-3 hours. General factors, such as the environment and culture, and physiological factors, such as height and weight, and other drugs in the system, such as alcohol, can all affect the rate of absorption.

Drug Metabolism and Alcohol in Women Who Are Active and Height/Weight Proportionate

Women have less alcohol dehydrogenase, an enzyme created in the liver that helps break down alcohol. Since women have less, the alcohol metabolizes at a significantly lower rate, and therefore, the female may become intoxicated more quickly. Also, women typically have a higher percentage of body fat, and because of this, women have a smaller volume for distribution for alcohol than men. Women will also have higher peak blood alcohol levels than men when given the same dose of alcohol in g/kg body weight, but no differences occur when given the same dose per liter of body water (Cederbaum, 2012). The first-pass metabolism is an essential component to consider. This is when a drug's efficacy and strength is reduced at a tremendous rate before it even reaches the person's circulatory system. ADH is the antidiuretic hormone. Alcohol sends signals to lower levels of the antidiuretic hormones, and when these levels go down, the kidneys don't reabsorb as much water, and then the person produces more urine. Drugs like those that are H2 blockers (ranitidine, aspirin, or cimetidine) inhibit stomach ADH activity. This then decreases the first pass metabolism mentioned earlier and then increases blood alcohol concentrations in women. Even though women may have more significant fat levels, their bodies are usually smaller in size, meaning they may have a lower lean body mass.

Ethanol elimination per unit lean body mass is more significant in women. With individuals who exercise, some studies have reported that the alcohol elimination rate, due to higher body temperatures, may experience an increased alcohol elimination rate. Certain drugs may decrease the alcohol elimination rate, such as Antabuse (or disulfiram). Typically, a smaller female will absorb a drug quicker than a more substantial-in-size male. Also, alcohol can play a role in the interaction of drugs. Took this drug with alcohol in her system, it might have a pharmacokinetic interaction and increase the level of the drug in her system and amplify the adverse effects (Advokat, Comaty, & Julien, 2014).

How Drug Metabolism May Occur in Sedentary, Overweight Men

On average, men are more substantial in size than women. Body size differences result in larger distribution volumes and faster total clearance of most medications in men compared to women (Schwartz, 2003). There may be a small drop in alcohol elimination with aging, perhaps due to decreased liver mass, or body water content (Cederbaum, 2012). A man's renal processes seem to be faster in man than in women. Filtration rate may have weight and gender as a factor. The age of the subject may prove to affect P450 enzymes, or CYP's, by reducing their functions. Aging may have a significant effect on the individual may have a considerable liver volume reduction. Blood flow also decreases with age and reduces by seventeen to forty-six percent (Kinirons, 2004). At six foot and 235 pounds, this individual is at a 31.9 body mass index, which indicates to obesity. Obesity can affect the drug's metabolism rate. A drug's metabolism is affected by the degree of plasma protein binding and tissue blood flow. In obese individuals, P450 cytochromes activity increases. The elimination half-life (t ((1/2))) of a drug depends on both the V (d) and CL. Since the V (d) and CL are biologically independent entities, changes in the t ((1/2)) of a drug in obese individuals can reflect changes in the V (d), the CL, or both. (Hanley, 2010) In this case, V (d) is the volume of distribution, and the CL is the drug clearance. T ((1/2)) is the elimination of the drug's half-life.

Other Factors That May Affect Drug Metabolism

Drug metabolism may also be affected by cigarette smoking and pregnancy, among other situations. Surprisingly, food interaction (such as with grapefruit) can have an enormous impact on a drug's metabolism within the body. Other factors that could affect a drug's metabolism are gut motility and transit time, gut pH, biliary secretion and gut flora (enterohepatic circulation and impact oral contraceptives) can have a significant influence on specific drug absorption (Soldin, 2009). Both of the subjects presented here drink. The woman appears to drink more frequently than the man. It does not know what volume of alcohol that they are drinking per hour, when they do drink, but a few assumptions can be safely made. Socioeconomic status (SES) indicators (i.e., education, income, and occupation) usually are reliable predictors of health behaviors and outcomes and tend to be positively associated with health. People with higher SES tend to drink more frequently than others. Those who are lower in socioeconomic status seem to drink more copious volumes of alcohol (Sudhinaraset, 2016). Aging involves progressive impairments in the functional reserve of multiple organs, which might also affect drug metabolism and pharmacokinetics. Also, the elderly population will develop various diseases and, consequently, often has to take several drugs (Klotz, 2009). Many changes in a person's body composition happen as someone ages. Drugs that are considered lipophilic can have an increased volume of distribution (or Vd) with a prolonged half-life. Drugs that are considered water soluble have a smaller volume of distribution. Renal activity in older individuals is also decreased, even up to fifty percent. Kidney function may decline with heart disease and even hypertension. Environmental factors and diet can have a significant effect on drug metabolism and half-life. When a medicine's benefits outweigh its known risks, the FDA considers it safe enough to approve (Center for Drug Evaluation and Research). Side effects of medication, age, weight, body fat composition, gender, lifestyle, current medications, drinking habits should be considered.

Pharmacokinetics can be simplified with ADME. ADME is the four-letter acronym for absorption, distribution, metabolism, and excretion that has defined pharmacokinetics for 50 years (Doogue, 2013). The administration has to do with the route of the drug. Bioavailability has to do with first pass metabolism and absorption. Clearance has to do with the excretion of the active drug, and distribution is the steady state of the person's body .which the drug concentration within the person systemic system. All these circumstances need to be considered when administering a patient medication. The therapeutic and side effects should continue to be monitored to ensure adequate dosing is maintained as well. The 4th leading cause of death among hospitalized patients in the US is toxic drug effects (Teft, & Kim, 2013).

References:

Advokat, C. D., Comaty, J. E., & Julien, R. M. (2014). Julien's primer of drug action: A comprehensive guide to the actions, uses, and side effects of psychoactive drugs (13th ed.). New York, NY: Worth Publishers.

Cederbaum, A. I. (2012). ALCOHOL METABOLISM. Clinics in Liver Disease, 16(4), 667–685. http://doi.org/10.1016/j.cld.2012.08.002

Center for Drug Evaluation and Research. (n.d.). Drug Safety and Availability - Questions and Answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). Retrieved March 08, 2018, from https://www.fda.gov/drugs/drugsafety/ucm334041.htm

Hanley, M. (2010) Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010; 49(2):71-87. Doi: 10.2165/11318100

Kinirons, M. T., & O’Mahony, M. S. (2004). Drug metabolism and aging. British Journal of Clinical Pharmacology, 57(5), 540–544. http://doi.org/10.1111/j.1365-2125.2004.02096.x

Klotz, U. (2009) Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009; 41(2):67-76. Doi: 10.1080/03602530902722679.

Schwartz (2003) the influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003; 42(2):107-21.

Soldin, O., & Mattison, D. (2009). Sex Differences in Pharmacokinetics and Pharmacodynamics. Clinical Pharmacokinetics, 48(3), 143–157. http://doi.org/10.2165/00003088-200948030-00001

Sudhinaraset, M., Wigglesworth, C., & Takeuchi, D. T. (2016). Social and Cultural Contexts of Alcohol Use: Influences in a Social–Ecological Framework. Alcohol Research : Current Reviews, 38(1), 35–45.

Teft, W. A., & Kim, R. B. (2013). Sunny outlook for personalized medicine: Tamoxifen and beyond. Pharmacogenomics, 14(13), 1533-6. doi:http://dx.doi.org/10.2217/pgs.13.130

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2018 Charlotte Doyle