Pharmacological Effects of Benzodiazepines in the Management of Alcohol Withdrawal

From a medical standpoint, hangover or alcohol withdrawal symptoms are not a headache after violently held parties, but severe condition. Alcohol withdrawal can be viewed as a pathological hangover that occurs in an alcohol addicted person. It is accompanied by a whole bunch of symptoms, including functioning disorders of the internal organs, nervous system, and mental disorders. The clear understanding of how alcohol influences human brains, causing dependence and withdrawal, is crucial. The main symptoms of alcohol intoxication are euphoria, anesthesia, amnesia, respiratory depression, and coma, along with exacerbating intoxication. There are various mechanisms of these effects, developing at the level of cells and cell membranes; therefore, a single-drug treatment of alcoholism is almost impossible. In modern medicine, professionals often prefer using benzodiazepines for alcohol withdrawal syndrome. Considerable attention is paid to type and dosage of benzodiazepines. Moreover, the CIWA protocol modernization is studied for the future accurate use by medical stuff.

Pharmacological Effects of Benzodiazepines in the Management of Alcohol Withdrawal Syndrome and Nursing Implications

The high level of substance abuse is a crucial social and medical problem of modern society. Out of an extensive list of neurotropic substances with addictive characteristics, ethyl alcohol addiction deserves maximum attention. The frequency of alcoholism exceeds other forms of pharmacological addictions. Alcohol withdrawal syndrome is a potentially life-threatening consequence of alcoholism. The signs of the syndrome range from common symptoms, such as insomnia, headache, and tremor to serious complications, such as delirium tremens, for example (Yost, 1996). Alcohol withdrawal syndrome reflects previous intensity and duration of alcohol consumption, in other words, the duration of alcohol dependence (Bayard, McIntyre, Hill, & Woodside, 2004; Booth & Blow, 1993; Koehnke et al., 2002).


Clinical manifestations of alcohol withdrawal syndrome include psychiatric symptoms, such as anxiety, depression, dysphoria, irritability, sleep disorders, and autonomic symptoms that are associated with the termination of alcohol consumption (Trevisan, Boutros, Petrakis, & Krystal, 1998). Neurobiological mechanisms of alcohol withdrawal syndrome were studied in various experimental models (Becker, 1999). It is known that convulsive readiness, neurotoxic effects, as well as some other manifestations of alcohol withdrawal syndrome, are the result of an imbalance between excitatory and inhibitory neurotransmitter systems. They, however, are partly mediated by glutamatergic neurotransmitter system.

The list of pharmacological agents that are used in the alcohol withdrawal syndrome treatment is extremely broad and heterogeneous. Hypnotics, medicaments, tranquilizers, antipsychotics, anticonvulsants blockers, a-2 adrenoceptor agonists, calcium, vitamins, and vitamin-like compound are among those agents.

Above all, the basic principle of the alcohol withdrawal syndrome treatment is mitigation of the alcohol effects by sedated drugs, such as benzodiazepines tranquilizers and barbiturates. (Myrick & Anton, 2000) Although, “it is not possible to draw definite conclusions about the relative effectiveness and safety of benzodiazepines against other drugs in alcohol withdrawal”. (Ntais, Pakos, Kyzas, & Ioannidis, 2005). These medicaments have their own addictive potential that limits their use in the drug practice. Ethyl alcohol and benzodiazepines enhance activation of GABA -A receptors. Prolonged use of high doses of ethanol, barbiturates, or benzodiazepines causes a decrease in the sensitivity of GABA-A receptors (the mechanism of resistance and dependence). In case of a sudden stop in receiving ethanol, GABAergic transmission decreases. Gamma-aminobutyric acid (GABA) is the main inhibitory CNS neurotransmitter. Therefore, this condition is characterized by anxiety, insomnia, and seizures. Increasing the sensitivity of the GABA-A receptors for GABA, benzodiazepines restore normal inhibitory processes in the CNS. Detoxification by benzodiazepine drugs is presumably based on this mechanism and allows the normal activity of the GABA restoring process. Various pharmacological means for alcohol withdrawal syndrome are often used in combination; the choice is the maid for the rational, most effective, affordable, and safe drugs that can be used to treat this complicated condition. In addition, there is evidence that repeated detoxifications with benzodiazepine tranquilizers may cause long-term cognitive impairment; therefore, the disease becomes more severe (Malcolm et al., 2002).

The task of the neural mechanisms, mitigating the effects of ethanol, is a reduction of the glutamatergic neurotransmission (Martin, Cohen, Morrisett, Wilson, & Swartzwelder, 1991). Alcohol acts as an antagonist of N- methyl D- aspartate (NMDA) receptors, a subtype of the ionotropic glutamate receptors that play a crucial role in the mechanisms resisting the development of alcoholic intoxication and alcohol withdrawal syndrome (Simson, Criswell, Johnson, Hicks, & Breese, 1991). “Chronic alcohol exposure results in an increase in NMDA receptor number and function”, as well as an increase in the density of receptors in different areas of the brain (Lovinger, 2008). Alcohol withdrawal syndrome, as a result of ethanol withdrawal, in particular, is accompanied by convulsions caused by the increased glutamatergic transmission, increasing the release of glutamate (Dahchour & De Witte, 2000). In animal experiments, the NMDA receptor antagonists have demonstrated the ability to block seizures in case of alcohol withdrawal syndrome (Grant, Valverius, Hundspith, & Tabakoff, 1990). Therefore, it can be assumed that drugs that block the NMDA receptors (memantine) or suppress glutamatergic neurotransmission by reducing the release of glutamate (lamotrigine) can effectively prevent the alcohol withdrawal syndrome. Therefore, polypharmacy of different drugs that are used in the alcohol withdrawal syndrome treatment, the presence of the drugs’ choice (benzodiazepine tranquilizers) with addictive action, as well as the absence of specific therapy make the development of new effective alcohol withdrawal syndrome methods of treatment extremely important and urgent. The methods are supposed to affect the pathogenetic mechanisms of the syndrome development.

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In the treatment of alcohol withdrawal syndrome, benzodiazepines help eliminate anxiety, agitation, insomnia, autonomic symptoms, and prevent the development of seizures. In addition, patients, taking benzodiazepines, become calmer; therefore, successful detoxification is more likely. Adequate benzodiazepine therapy may prevent the development of such potentially life-threatening conditions as delirium tremens. Therefore, the use of benzodiazepines is particularly important in patients with high risk of delirium tremens, including patients with somatic complications, malnutrition, dehydration, or delirium tremens. With the development of delirium, benzodiazepines act as sedatives.

Care for the patient, who was confronted with alcohol withdrawal syndrome is assistance in the form of pharmacological treatment phases to ease the difficult withdrawal and detoxification (Doyle et al., 2010). It is believed that the entire series of benzodiazepines, in principle, is used in medicine to prevent the symptoms of alcohol withdrawal. Yet, preference is given to the drug within this category, which outstands by its pharmacokinetic and economic properties. Accordingly, the long-acting benzodiazepines are widely used. Clorazepate, Chlodiazepoxide and Diazepam are those medicaments, having a short-time concise with inherently convergent effect (Katzung et al., 2009). Administrating benzodiazepines makes withdrawal process flow smoothly enough (Bayard et al., 2004). However, patients who have liver problems should minimize their use, by virtue of further accumulating of these drugs in the organism (Katzung et al., 2009). For such patients, medical workers apply drugs with at least a lasting effect. These include lorazepam (Ativan) and oxazepam (Serax) (Katzung et al., 2009). A feature of these drugs is the property of the immediate transformation into inactive water-soluble metabolites, thus, respectively, these drugs do not accumulate (Katzung et al. , 2009).

Typically, providers do practice two dosing regimens when using benzodiazepines. Their difference lies in that the first one is a stable mode, and the second is characterized by the use of drugs for the symptomatic character, in other words, on-demand situation (Bayard et al . 2004). “With a fixed- schedule regimen, doses of a benzodiazepine are administered at specific intervals, and additional doses of the medication are given as needed based on the severity of the withdrawal symptoms” (Bayard et al., 2004). Overdose with expiring further entails is possible both in these two modes (Doyle, Kio, and Lynch, 2010). In the practice of the second mode benzodiazepines are used on the basis of the need for their application, which leads to less long-term care with a minimum amount of medicine. (Bayard et al. 2004). Also, this mode is more accurately emphasizes individual drugs needs of each patient (Doyle, Kio, and Lynch, 2010).

Today, CIWA-Ar protocol, an upgraded SIWA protocol, is widely used in alcohol withdrawal syndrome, since, counting certain symptoms; it offers a more appropriate dosage of medication (Bayard et al., 2004). SIWA-Ar protocol’s scale is divided into ten points, each of which contains information about the symptoms and possible ways to eliminate those (Bayard et al., 2004). The health condition of each patient is analyzed on these ten points; the nurse determines the patient’s condition from zero to seven using a Likert scale (Donnelly et al., 2012). Paragraphs of the protocol are presented with complications such as a headache, agitation, auditory disorders, anxiety, nausea, or vomiting, blurred sensorium, tactile disorders, sweating, tremor, visual disturbances (Donnelly et al., 2012). When using this protocol score of eight or less indicates a soft withdrawal, estimates more than eight to fifteen indicate moderate withdrawal. Patient encountered severe withdrawal in case the score is above fifteen. Such patients may be affected by the development of delirium tremens (Bayard et al., 2004).

In general, the SIWA-Ar protocol helps determine and prescribe actual treatment for the patient. Appealing to this protocol with an interval of 4-8 hours during the day is necessary if the patient’s assessment is below eight. (Bayard et al. 2004). If the patient has no evident symptoms, the nurse applies a treatment by SIWA-Ar protocol hourly for optimal drug balance (Bayard et al., 2004). If the evaluation has a range from eight to ten, patients use 10 – 20mg of Valium and 50 – 100 mg Librium until his/her condition will be assessed less than eight (Bayard et al., 2004). The fixed mode has a stable range of Librium, Valium or Ativan application, which is six hours (Bayard et al., 2004). More detailed it looks that way – Librium four doses of 50 mg, the dose then reduced by half and is applied eight times (Bayard et al . 2004). In parallel, four doses of Valium are used in an amount 10 mg dose thereafter similarly halved and applied eight times (Bayard et al., 2004). The dosage of Ativan also halved from 2 mg to 1 mg (Bayard et al., 2004).


Benzodiazepines have a number of side effects, as they have a depressing effect on the central nervous system (Duxbury & Baker, 2004). A list of these side effects is quite substantial – from respiratory depression to muscle weakness to high dis-braking and confusion (Duxbury & Baker, 2004). These medications also can provoke the appearance of insomnia and anxiety (Duxbury & Baker, 2004). “Without care, long-term use of benzodiazepines can lead to problems of tolerance and in some instances the development of addiction” (Duxbury & Baker, 2004). The nurse should also be aware that the withdrawal of the patient can be quite ambiguous in the application of benzodiazepines in less long period of time (Duxbury & Baker, 2004). Different drugs in this group are metabolized differently – from five hours (e.g., Librium) and one hundred hours for blisters (Duxbury & Baker, 2004). The speed of metabolism, here, has a prominent role, as people, who often use alcohol will metabolize these drugs more slowly (Duxbury & Baker, 2004). Other patients should probably be treated with benzodiazepines with a long half-life, such as chlordiazepoxide or diazepam; because of the drugs resumption, the possibility of symptoms recession is minimal. In addition, sustained release medications are usually easier to cancel than short-acting medications. Benzodiazepines dosage should preferably be adjusted in accordance with the dynamics of the clinical condition as the dose inducing sedation varies greatly for each individual.

Differential diagnosis should be made for thyrotoxicosis, poisoning with anticholinergics, amphetamines, or cocaine. These conditions are followed by increased sympathetic activity and mental disorders. Moreover, the differentiation is carried out with hypoglycemia, CNS infections and withdrawal of hypnotics. Treatment and care that a nurse undertakes must be efficient and facilitated despite everything. The major duty of a nurse is to help the patient not only from the medical point of view but purely on the subjective ground of the patient-client relationships. Therefore, without the use of benzodiazepines (diazepam, for example) the patient is not likely to feel him/herself satisfied after the procedure. Moreover, using the same diazepam may cause additive effects if combined with alcohol or pills are taken previously, as well as multi-day insomnia due to binge. As a result, the inexperienced medical officer for its treatment failure can cause the patient depression or breathe stop. There are other ways of fault treatment, which are not associated with the use of sedative drugs that can ease the patient’s conditions in an alcohol withdrawal sending him/her to another world. It is crucial to measure the pressure, since “blood pressure, pulse and temperature were often measured as part of the overall assessment” in the case for the diagnosis of the patient (Williams, 2001). It is difficult to detect a number of abnormalities that may threaten the life of the patient in the treatment without taking them into account. The main conclusion is that nurses need to be especially careful, as mild abstinence syndrome symptoms may be severe withdrawal symptoms. Patients and his/her family have to understand that the treatment of binge is not an ordinary everyday procedure but a serious event. Therefore, any attempts to self-treatment, as well as a doctor’s intentional or accidental misleading, are fraught with dangerous consequences.

Conclusion

Due to its effectiveness and safety, benzodiazepines are considered as drugs of choice in the treatment of alcohol withdrawal. The effect is based on the competitive blocking of the benzodiazepine receptors. Withdrawal symptoms are demonstrative enough for a diagnosis on the basis of examination of the patient and his/her information. Sometimes, though, it is necessary to differentiate abstinence from other pathological conditions. Abstinence requires immutable treatment, so as not to get even more serious disorders or exacerbate the existing ones. Moderate withdrawal symptoms can be treated as outpatients. Stationary conditions are required by patients with severe withdrawal symptoms: brightened delirium tremens, convulsions and active co-occurring psychiatric, and somatic diseases. The constituent elements of the treatment of the alcohol withdrawal are to fill the gap in the fluid and electrolyte balance in the normalization of blood plasma and debugging diet. A question of output to normal levels of electrolytes is to be solved by the infusion therapy that simultaneously cleans out toxins. To prevent seizures and delirium tremens, current medicine use sedation with benzodiazepines (diazepam, lorazepam). The drug is selected depending on its technical and tactical pharmacological characteristics. Nurses’ activities are important for successful treatment in many withdrawal cases with the use of drugs providing a calm, safe, and supportive environment. The activity also means help applying with councils, beliefs, and social support of the medical staff, helping to cope with the syndrome.

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