Drug Interactions with Alcohol

by eMedExpert staff
Medical references reviewed: March, 2019

1 How is Alcohol Metabilized in the Body?

Alcohol (ethanol) is metabolized by alcohol dehydrogenase and the cytochrome P450 2E1 hepatic enzyme. This CYP2E1 enzyme is also responsible for the biotransformation of xenobiotics and fatty acids.

2 Types of Alcohol-Drug Interactions

Two types of alcohol - medication interactions exist:

1. PharmacoKinetic Interactions occur when alcohol causes an increase or decrease in the blood levels of drugs by interfering with metabolism, absorption, distribution, or elimination of the drug.
2. PharmacoDynamic Interactions occur when alcohol alters the effects of the medication without changing blood levels of the medication.

3 Liver Toxicity

Acetaminophen (Paracetamol)
Chronic alcohol use can increase blood levels of hepatotoxic acetaminophen metabolites, and reduce blood levels of acetaminophen. Drinking large amounts of alcohol with acetaminophen may increase the risk of liver damage similar to chronic alcohol use.

Isoniazid
Daily alcohol consumption increases the risk of isoniazid-related liver damage and also increases elimination of isoniazid. Also, there is evidence for possible central synergistic effect when isoniazid is used concomitantly with alcohol3.

4 Bleeding

NSAIDs
Alcohol can increase the risk of ulcers and GI bleeding by enhancing the abilityof NSAIDs to damage the stomach mucosa.

Concomitant use of alcohol and NSAIDs produces synergistic effect on gastric mucosal damage. This increases the risk of ulcers and GI bleeding.

Warfarin
Acute alcohol consumption may increase anticoagulant activity of warfarin and the risk of hemorrhages by decreasing warfarin metabolism.

Chronic alcohol consumption can result in insufficient anticoagulant activity of warfarin by increasing warfarin metabolism.

5 Hypoglycemia (Abnormally Low Blood Sugar)

Sulfonylureas
Concomitant use of high amounts of alcohol with long-acting sulfonylureas (chlorpropamide, tolbutamide) can result in hypoglycemia.

Insulins
Patients on insulin therapy should avoid heavy alcohol drinking and avoid alcohol consumption on an empty stomach.

6 High Blood Pressure

MAO Ihibitors
MAOIs may provoke toxicity and severe hypertension if taken with wines or beers rich in tyramine.

6 Disulfiram-like Reactions

Some medications, when combined with alcohol, can inhibit aldehyde dehydrogenase (ALDH) enzyme and can induce disulfiram-like effects such as facial flushing, nausea, vomiting, and hypotension.

List of medications that cause disulfiram-like reactions:

Cefamandole
Cefotetan
Chloramphenicol
Chlorpropamide
Griseofulvin
Ketoconazole
Nitrofurantoin
Nitroglycerin
Sulfamethoxazole

7 Additive Sedative and CNS Effects

Alcohol potentiates the following central nervous system (CNS) effects of medications:

Sedation
Dizziness
Impaired motor skills
Impaired mental performance

Antihistamines
Alcohol enhances the effects of antihistamines on the central nervous system (CNS), such as drowsiness, sedation, and decreased motor skills.

Barbiturates
Alcohol synergistically enhances the sedative effects of barbiturates. In rare cases the interaction can lead to coma or fatal respiratory depression.

Benzodiazepines
Concurrent consumption of benzodiazepines and alcohol causes synergistic sedative effects, leading to strong CNS impairment. Also, the combination of benzodiazepines with alcohol may intensify memory-impairing effect.

Opioid analgesics
Alcohol exacerbates the sedating and respiratory depressant effects of opioid analgesics.

Tricyclic antidepressants
Alcohol increases the sedative and CNS depressant effects of tricyclic antidepressants through pharmacodynamic interactions. The result is excessive sedation, impaired coordination and ability to drive.

8 Risk of Fatal Overdose

Opioid analgesics
Concurrent use of high doses of alcohol and opioids is potentially lethal because they can reduce the cough reflex and breathing function.

Analgesics containing opioid with acetaminophen can be particularly dangerouse when combined with alcohol.

9Minimal Risk of Interactions with Alcohol

Antibiotics
Contrary to common belief, only a few antibiotics (mentioned above) appear to interact with alcohol.
Antidepressants SSRIs, SNRIs
No serious interactions appear to occur when SSRIs or SNRIs antidepressants are consumed with moderate alcohol doses.
Herpes antiviral medications
Antifungal drugs

10Risk Factors

The following categories are especially at risk:

The elderly are more susceptible to adverse events from drug interactions due to physiological changes that affect drug absorption and utilization.
Chronic and multiple medication users.
Drug abusers are especially at risk.

Sources & References

1. Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health. 1999;23(1):40-54. Available at NIAAA
2 Kupari M, Heikkilä J, Ylikahri R. Does alcohol intensify the hemodynamic effects of nitroglycerin? Clin Cardiol. 1984 Jul;7(7):382-6.
3. Karamanakos PN, Pappas P, Boumba V, Vougiouklakis T, Marselos M. The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition. Pharmacology. 2016;98(5-6):267-271.
4. Holton AE, Gallagher PJ, Ryan C, Fahey T, Cousins G. Consensus validation of the POSAMINO (POtentially Serious Alcohol-Medication INteractions in Older adults) criteria. BMJ Open. 2017 Nov 8;7(11):e017453.

Published: March 10, 2019
Last updated: March 10, 2019