Learning Outcomes
By the end of this section, you should be able to:
- 15.3.1 Describe the pathophysiology of alcohol use disorder.
- 15.3.2 Identify clinical manifestations of alcohol use disorder.
- 15.3.3 Identify the etiology and diagnostic studies related to alcohol use disorder.
- 15.3.4 Identify the characteristics of drugs used to treat alcohol use disorder.
- 15.3.5 Explain the indications, actions, adverse reactions, and interactions of drugs used to treat alcohol use disorder.
- 15.3.6 Describe the nursing implications of drugs used to treat alcohol use disorder.
- 15.3.7 Explain the client education related to drugs used to treat alcohol use disorder.
Alcohol Use
Alcohol, more specifically ethanol, is the byproduct of the fermentation of carbohydrates and is one of the most widely used psychoactive compounds in the world. While alcohol is legal to purchase and seen as a socially acceptable substance for recreational use, it is also a major contributor to significant morbidity and mortality. In the United States alone, alcohol has been causally linked to over 200 different chronic health conditions (e.g., hepatitis, diabetes, heart disease) and contributes to 18.5% of emergency department visits (Rehm et al., 2021). Annually, alcohol contributes to 95,000 deaths, making it one of the leading causes of preventable death in the United States. Despite the known harms of alcohol, it is estimated that there are 29.5 million people over age 12 in the United States with an alcohol use disorder (AUD) (Substance Abuse and Mental Health Services Administration, 2023a).
Alcohol works by increasing the actions of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. When GABA activates GABA-A receptors, it leads to an influx of chloride into the neuron, hyperpolarizing it and making the generation of action potentials more difficult. When enhanced by the actions of alcohol and other sedative drugs, this leads to an overall slowing of neuronal transmission and produces the characteristic effects of alcohol intoxication (e.g., slurred speech, stumbling gait, memory impairment).
Alcohol Intoxication
Alcohol intoxication follows a predictable dose response in clients with low or no routine alcohol consumption. At low doses, alcohol lowers inhibitions and can cause a mild euphoria. At moderate doses, ethanol will cause ataxia (e.g., gait instability), slurred speech, and impaired memory. At higher doses, alcohol can cause total memory loss (i.e., blackouts), CNS depression, and risk for respiratory depression. The risk for respiratory depression and death increases significantly if consumed along with other CNS depressants (e.g., opioids, benzodiazepines). Alcohol intoxication may also lead to nausea and vomiting. If the client is sufficiently CNS depressed and vomits, there is a risk for the client to aspirate their stomach contents, leading to respiratory failure and death. Another concern with alcohol intoxication is the risk for trauma, including fatal head traumas because of falls. Certain clients may be prone to violence under the effects of alcohol, leading to altercations. Impaired decision making can lead clients to operate motor vehicles, leading to motor vehicle accidents.
The degree of alcohol intoxication can be determined objectively by measuring the blood alcohol level directly with a blood sample or indirectly, such as with a device that measures alcohol content in the expired air of the intoxicated client (i.e., a breathalyzer). The legal definition of drunkenness can vary by location but is considered in many places to be a blood alcohol level of 0.08% or 80 mg/dL.
Alcohol Withdrawal
Alcohol withdrawal occurs when the client who chronically uses alcohol has an abrupt discontinuation of the substance. Because of the chronic increase in GABA effects in the CNS, GABA receptors become downregulated. When alcohol is removed, the client will experience a shift toward the actions of glutamate, the major excitatory neurotransmitter in the CNS. This leads to the opposite actions of alcohol where clients may develop anxiety, restlessness, piloerection, hallucinations, and seizures. Severe alcohol withdrawal is commonly referred to as delirium tremens. Withdrawal from alcohol may begin as soon as a few hours after the last consumption of alcohol but may take 2–3 days to fully manifest. As compared to the minimal risk of death seen with opioid withdrawal, alcohol withdrawal can be fatal and should be managed promptly to avoid withdrawal-related delirium and seizures.
Drugs Used to Treat Alcohol Use Disorders
This section covers medications used in the treatment of alcohol use disorders, including agents to treat the potentially life-threatening withdrawal symptoms as well as agents to deter the client from further use of alcohol. Indications for when to use these medications, along with their own precautions, are also given to ensure the safe and appropriate use in clients with alcohol use disorders.
Chlordiazepoxide
Chlordiazepoxide falls into the category of drugs known as benzodiazepines. These drugs, like alcohol, work to enhance the actions of GABA to cause a general CNS depression. Benzodiazepines bind to the benzodiazepine receptor to allow GABA to bind to the receptor more readily, increasing its effects. Benzodiazepines are used for a variety of conditions, including anxiety and seizures, but in the case of AUD, they serve as a replacement for alcohol to treat and/or prevent withdrawal symptoms. Clients with significant AUD should be monitored for seizures with rescue medications, including chlordiazepoxide, available at a moment’s notice. Historically, chlordiazepoxide has been used to treat AUD because of its long half-life. This long half-life means chlordiazepoxide stays in the body longer, thus preventing abrupt withdrawal symptoms from occurring. Chlordiazepoxide is still available commercially but has been replaced with newer benzodiazepines because of their more favorable pharmacokinetics. The downside of chlordiazepoxide’s long half-life is that it tends to accumulate in the client’s body, leading to oversedation, especially when combined with alcohol should the client relapse during treatment.
Disulfiram
Disulfiram is a drug that works by inhibiting the actions of the enzyme acetaldehyde dehydrogenase. In the liver, alcohol is first metabolized by the enzyme alcohol dehydrogenase, which converts it to acetaldehyde. Acetaldehyde is then further metabolized by acetaldehyde dehydrogenase. Acetaldehyde itself is a very irritating substance that in excess will cause facial flushing, nausea, vomiting, and headaches. Interestingly, an inherited deficiency of acetaldehyde dehydrogenase is found in 8% of people in the world overall, and in 36% of Asian people, leading to a familiar flushing reaction upon consuming alcohol (Jeon et al., 2022). Disulfiram is used to intentionally inhibit acetaldehyde dehydrogenase to cause a client to develop this uncomfortable reaction should they relapse and consume alcohol. In this way, it serves as a deterrent to alcohol consumption rather than a means to replace alcohol to manage withdrawal symptoms. As disulfiram is only available as an oral tablet, client compliance with disulfiram therapy may be poor, as they may opt to just not take the medication. To initiate disulfiram therapy, clients should abstain from alcohol for at least 12 hours since their last drink to avoid a flushing reaction. Clients should also be educated that disulfiram reactions can occur up to 2 weeks after drug discontinuation and that they should avoid alcohol consumption during this time to avoid flushing reactions.
Haloperidol
Haloperidol is in the category of medications known as first-generation antipsychotics and is traditionally used to treat the symptoms of schizophrenia. It works by blocking dopamine-2 (D2) receptors that cause hallucinations and agitation. Haloperidol is sedating, and this is thought to help manage the symptoms of alcohol withdrawal in conjunction with benzodiazepine therapy.
Lorazepam
Like chlordiazepoxide, lorazepam is a benzodiazepine used to treat anxiety and seizures and to control the symptoms of alcohol withdrawal. Replacement of alcohol with lorazepam helps prevent and/or minimize withdrawal symptoms, and it is the drug of choice to treat alcohol withdrawal-induced seizures. In the hospital setting, validated scales such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) use a symptoms-based approach to manage the symptoms of alcohol withdrawal as they occur and allow for a more customized approach based on which withdrawal symptoms manifest in the client and their severity. These scores are recorded by the client’s nurse initially every 4 hours and can be checked less frequently as the client’s withdrawal symptoms improve. This allows providers to determine the most appropriate dose of lorazepam needed to manage the client’s current withdrawal symptoms.
Table 15.4 lists common medications used to treat alcohol use disorders and typical routes and dosing for adult clients.
| Drug | Routes and Dosage Ranges |
|---|---|
| Chlordiazepoxide (Librium) |
Management of alcohol withdrawal symptoms: Initial dose 50–100 mg orally followed by repeated doses as needed up to 300 mg/day. |
| Disulfiram (Antabuse) |
125–500 mg orally daily. |
| Haloperidol (Haldol) |
Management of alcohol withdrawal symptoms: Oral: 2–10 mg every 6 hours as needed; maximum dose: 20 mg/day. Intramuscular: 2–10 mg every 6 hours as needed; maximum dose: 20 mg/day. |
| Lorazepam (Ativan) |
Management of alcohol withdrawal symptoms: IV: 1–4 mg every 4–6 hours as needed. |
Adverse Effects and Contraindications
Like alcohol, the main adverse effects of chlordiazepoxide and lorazepam are sedation and memory impairment. Clients should be educated to avoid operating heavy machinery while using these medications. Use of benzodiazepines is contraindicated in pregnancy.
The main adverse reactions seen with disulfiram occur when clients drink alcohol while taking the medication and include nausea, vomiting, skin flushing, and feeling hot.
Haloperidol can lower the seizure threshold, which increases the risk of the client developing alcohol withdrawal-related seizures. Because of this, haloperidol is not routinely recommended for this indication. Other side effects associated with haloperidol include sedation and the rare risk of sudden cardiac death (Dar et al., 2020).
Table 15.5 is a drug prototype table for medications used to treat alcohol use disorders featuring disulfiram. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.
| Drug Class Irreversible acetaldehyde dehydrogenase inhibitor Mechanism of Action Inhibits the enzyme acetaldehyde dehydrogenase, producing a sensitivity to alcohol that results in a highly unpleasant reaction when the client under treatment ingests even small amounts of alcohol |
Drug Dosage 125–500 mg orally daily. |
| Indications Aiding in alcohol cessation (maintaining alcohol abstinence) Therapeutic Effects Helps support alcohol cessation by making its consumption unpleasant |
Drug Interactions Metronidazole Isoniazid Phenytoin Tinidazole Warfarin Food Interactions Ethanol Kombucha |
| Adverse Effects Hepatitis/hepatotoxicity Drowsiness Headache Peripheral neuropathy Allergic dermatitis Metallic taste Heart failure |
Contraindications Recent use of alcohol or metronidazole Hypersensitivity Psychoses Severe myocardial disease Severe pulmonary disease Chronic renal impairment Caution: Diabetes Rubber contact dermatitis Hepatic impairment Seizures |
Nursing Implications
The nurse should do the following for clients who are taking a medication for AUD:
- Advise the client to avoid consuming alcohol with any of these medications due to the risk for adverse reactions. Even small amounts of alcohol may cause a reaction.
- Monitor for seizure activity in clients receiving haloperidol for treatment of alcohol withdrawal.
- Monitor the client’s liver function tests to assess for liver toxicity.
- Use the CIWA-Ar scale to assess alcohol withdrawal symptoms to determine appropriate dosing of lorazepam.
- Advise clients to not take multiple CNS depressants (e.g., alcohol, lorazepam, and chlordiazepoxide) at the same time to avoid excessive CNS and respiratory depression.
- Provide client teaching regarding the drug and when to call the health care provider. See below for additional client teaching guidelines.
Safety Alert
Benzodiazepines
Benzodiazepines such as lorazepam and chlordiazepoxide should generally not be used at the same time as other CNS depressants such as alcohol, muscle relaxants, or opioids, as these effects can synergize and increase the risk of severe CNS and respiratory depression. Concomitant use of any combination of these agents should be done under the direction of a skilled clinician.
Client Teaching Guidelines
The client using a medication to treat AUD should:
- Alert their health care provider about any signs of allergic reactions, including throat swelling, severe itching, rash, or chest tightness.
- Alert other health care providers that they are taking these medications, including the dose and frequency.
- Take the drug with food if it causes an upset stomach.
- Take a missed dose as soon as they remember; however, they should not take double doses.
- Avoid consuming these medications with alcohol.
- Avoid taking other medications that cause sedation.
- Avoid consuming nontraditional sources of alcohol, including mouthwashes, cough syrups, hand sanitizers, and any other product that contains alcohol.
- Seek out community organizations such as Alcoholics Anonymous to aid in the treatment of AUD.
Clinical Tip
Assess for Cognitive Impairment in Older Adults
Older adult clients receiving benzodiazepines such as chlordiazepoxide and lorazepam to treat an AUD should be assessed for cognitive impairment (e.g., memory impairment, executive dysfunction), because this client population is more sensitive to the sedative effects of the medications.
FDA Black Box Warning
Benzodiazepines
The use of benzodiazepines, including chlordiazepoxide and lorazepam, exposes users to risks of abuse, misuse, and addiction (dependence), which can lead to overdose or death.
Disulfiram should never be administered to a client when they are in a state of alcohol intoxication or without their full knowledge. The provider should instruct relatives accordingly.