Abstract
The use of alcohol can be traced back in time over thousands of years and remains prevalent in modern society. Alcohol consumption has shown to both improve health and cause health problems. One such health problem is the potential interaction that can occur when alcohol is consumed while taking certain medications. The drug–alcohol interaction can be due to alternations in the drugs absorption, distribution, metabolism, and/or elimination. It can also occur as a result of the additive effect that alcohol can have on an already existing effect of the medication (eg, enhanced sedation). Covered in this article are some of the common drug–alcohol interactions and a brief description about the interaction. The medication classes reviewed include pain relievers, antidepressants, antidiabetic medications, first-generation antihistamines, antipsychotics, sedatives and hypnotics, antibiotics, and warfarin.
The use of alcohol can be traced through history for over 10,000 years. 1 Today, alcohol continues to be a prevalent part of our modern society. In the United States, approximately 50% of adults currently drink alcohol on a regular basis, and another 14% drink alcohol on an infrequent basis. 2 The topic of alcohol is important in lifestyle medicine because it has been shown to both improve health and cause significant health problems. The difference between the two appears to be related to quantity, drinking pattern, gender, age, and genetic factors.1,2
Many prescription and over-the-counter drugs can interact with alcohol to produce unwanted side effects. Drug–alcohol interactions can occur in 2 different ways: pharmacokinetic interactions and pharmacodynamic interactions. Pharmacokinetics is a subspecialty within pharmacology that studies drug absorption, distribution, metabolism, and elimination. Pharmacokinetic drug–alcohol interactions generally occur when alcohol interferes with the normal metabolism or elimination of a medication, or vice versa. Pharmacodynamics is also a subspecialty within pharmacology dealing with the reactions between drugs and living systems. Pharmacodynamic drug–alcohol interactions relate to the additive effect that alcohol can have on an already existing effect of the medication. The most common example is the sedation effect that alcohol can have coupled with the sedation effect that some medications can have, resulting in possible significant and unpredictable levels of sedation.
Many prescription and over-the-counter drugs can interact with alcohol to produce unwanted side effects.
Alcohol is metabolized in the liver by a number of enzymes, most important of which are the alcohol dehydrogenase and cytochrome P2E1 (CYP2E1) enzymes. 3 One of the interesting, and often unknown, facts about drug–alcohol interactions is that the mechanism of the interaction depends on the pattern of drinking behavior. In people who consume alcohol on an occasional basis, the primary metabolizing enzyme is alcohol dehydrogenase with CYP2E1 playing a minimal role. 3 However, chronic alcohol consumption can increase the activity of CYP2E1 by up to 10 times that of occasional drinkers. This results in a much higher proportion of the alcohol being metabolized by CYP2E1 compared with alcohol dehydrogenase. Therefore, drug–alcohol interactions may vary from person to person depending on the chronic or acute nature of the drinking behavior. 3
Several classes of medications have the potential to interact with alcohol. Listed below are some of the most common medications that interact with alcohol along with a brief description of the effect of the interaction.
Pain Relievers (Non-Opioid)
Aspirin, Nonsteroidal Anti-Inflammatory Drugs, Acetaminophen
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen increase the risk for gastrointestinal hemorrhage. The substances and alcohol can independently damage the gastric mucosal barrier and when used in combination, can result in an additive effect. 3 Aspirin and NSAIDs should not be taken on an empty stomach, especially with alcohol. In addition, aspirin should not be taken within 8 hours of heavy alcohol consumption. 3
Acetaminophen use in chronic alcoholics places them at a higher risk for acetaminophen induced hepatotoxicity by enhancing the formation of hepatotoxic metabolites of acetaminophen while lowering serum acetaminophen concentrations. 3 Individuals who consume large amounts of alcohol on a daily basis should avoid large and prolonged doses of acetaminophen. The maximum acetaminophen dose in a 24-hour time period is 4 g. 3
Pain Relievers (Opioids)
Meperidine, Methadone, Propoxyphene
Meperidine and methadone combined with alcohol can cause excessive central nervous system (CNS) depression and impaired psychomotor function leading to respiratory depression. 3 Overdoses of propoxyphene combined with alcohol have been linked to fatal reactions. Alcohol should be completely avoided if with these medications and all other opioid medications. 3
Antidepressants
Tricyclic Antidepressants, Monoamine Oxidase Inhibitors
Alcohol combined with tricyclic antidepressants such as amitriptyline can result in excessive CNS depression and impaired psychomotor performance. 3 This is especially prevalent in the first week of antidepressant therapy and with tricyclics that have more of a sedating effect such as amitriptyline and doxepin. Monoamine oxidase inhibitors (MAOIs) such as phenelzine can interact with alcoholic beverages containing tyramine causing severe hypertension. 3 Tyramines can be found in high levels in red wine and beer, but beverages such as white wine and vodka contain little tyramine. Alcohol significantly inhibits the metabolism of tyramine, which then causes blood pressure to increase. Individuals taking an MAOI should avoid alcohol. 3
Antidiabetic Medications
Sulfonylureas, Insulin, Metformin
Consuming alcohol while taking sulfonylureas such as glipizides may prolong the drugs effect on blood glucose by delaying glipizide absorption and elimination. 3 This has been shown to lead to hypoglycemia. Individuals taking sulfonylureas may have an occasional alcoholic drink but should avoid excess consumption to prevent hypoglycemia. Alcohol should be completely avoided if hypoglycemia symptoms such as flushing or headache occur after drinking. 3
Likewise, alcohol may enhance the glucose lowering action of insulin putting the individual at risk for hypoglycemia. 3 People taking insulin should not drink alcohol in access or on an empty stomach. In addition, alcohol plus metformin may increase risk for lactic acidosis. Individuals taking metformin should limit their consumption of alcohol and monitor for signs and symptoms of lactic acidosis when consuming alcohol. 3
Antihistamines (First Generation)
Diphenhydramine, Chlorpheniramine
Enhanced CNS depression and impaired psychomotor performance is likely to occur with the combination first-generation antihistamines and alcohol. 3 Alcohol consumption should be limited when taking these medications. The effects may be more pronounced in the elderly. It should be noted that nonsedating antihistamines do not seem to adversely interact with alcohol. 3
Antipsychotics
Chlorpromazine, Risperidone
Several antipsychotic medications in the phenothiazine class and also atypical antipsychotics such as risperidone are known to interact with alcohol causing excessive CNS depression and impaired psychomotor performance. 3 In general, alcohol should be avoided if taking an antipsychotic medication. 3
Sedatives and Hypnotics
Medications that are used for the purposes of sedation will naturally have an enhanced affect when combined with alcohol. Examples of medications that are used for sedation include barbiturates, benzodiazepines, non-benzodiazepines, and others. 3 It is recommended to check with a pharmacist or other health care provider regarding the recommendations for each specific medication as some recommend limiting intake and other recommend avoiding alcohol completely.
Other Medications
Several antibiotic medications warn against the use of alcohol and taking the medication at the same time. While some antibiotics show little effect with alcohol, others have reported significant interactions and warn against concomitant use. 3 Individuals are advised to check with a pharmacist or other health care provider before consuming alcohol while taking an antibiotic medication.
Warfarin is noted to have a significant interaction with alcohol. The combination can enhance the anticoagulant effects with acute intoxication and reduce the anticoagulant effects with chronic and excessive consumption. 3 It is recommended to monitor international normalized ratios if the patient consumes more than 3 alcoholic drinks per day or if there has been a significant change in the amount of recent alcohol consumption. 3
Approximately 50% of US adults drink alcohol on a regular basis with another 14% occasionally consuming alcohol. 2 Several different and wide-ranging types of medications are known to interact with alcohol at both small and large quantities. The drug–alcohol interactions presented in this article are just a few of the common interactions that are known. It is prudent to advise all patients to talk with their pharmacist or other health care professionals regarding potential drug–alcohol interactions prior to starting a new medication.