Lorazepam Alcohol

Soo-Ampon S, WonqwitdechaN, Plasen S, Hindmarchl, Boyle J. Effects of word frequency on recall memory following lorazepam, alcohol, and lorazepam alcohol interaction in healthy volunteers. Psychopharmacology (Berl) (2004) 176, 420-5. 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Malcolm R, Myrick H, Roberts J, et al The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. J Gen Intern Med 17 349—355, 2002... 

Seppala T, Aranko K, Mattila MJ, et al Effects of alcohol on buspirone and lorazepam actions. Clin Pharmacol Ther 32 201—207, 1982... 

Volkow ND, Wang GJ, Begleiter H, et al Regional brain metabolic response to lorazepam in subjects at risk for alcoholism. Alcohol Clin Exp Res 19 510-316, 1995... 

Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,10 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.10 Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines. 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

In contrast to chlordiazepoxide and diazepam, lorazepam and oxazepam are not metabolized into active compounds in the liver. Instead, they are excreted by the kidneys following glucuronidation. This is important because many alcohol-dependent patients have compromised liver function. Therefore, when treatment is initiated before the results of blood tests for liver function are known, as is often the case in outpatient clinics, lorazepam and oxazepam may be preferred. Patients with liver disease may still be treated with diazepam and chlordiazepoxide, but at lower doses. This can be accommodated with the loading technique, although hourly dosing with 5 mg of diazepam or 25 mg of chlordiazepoxide may be sufficient. 

High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. 

With symptom-triggered therapy, medication is given only if symptoms emerge, resulting in shorter treatment duration, and avoidance of over sedation. A typical regimen would be lorazepam 2 mg administered every hour as needed when a structured assessment scale (e.g., Clinical Institute Withdrawal Assessment-Alcohol, Revised) indicates that symptoms are moderate to severe. Current guidelines recommend such individualized therapy over fixed-schedule therapy. 

Lorazepam Ativan Oral, IV, IM Intermediate 1-10 Anxiety disorders, alcohol withdrawal, insomnia... 

Benzodiazepines. Like the barbiturates, benzodiazepines bind to the GABA receptor and are therefore cross-tolerant with alcohol. As a result, they also make suitable replacement medications for alcohol and are widely used for alcohol detoxification. Theoretically, any benzodiazepine can be used to treat alcohol withdrawal. However, short-acting benzodiazepines such as alprazolam (Xanax) are often avoided because breakthrough withdrawal may occur between doses. Intermediate to long-acting benzodiazepines including chlordiazepoxide (Librium), diazepam (Valium), oxazepam (Serax), lorazepam (Ativan), and clonazepam (Klonopin) are more commonly utilized. 

All benzodiazepines are indicated in obsessive compulsive disorders. Diazepam and lorazepam are effective in status epilepticus, whereas chlordiazepoxide is indicated in alcohol withdrawal. 

Avoid smoking, drinking alcoholic beverages, and taking other CNS depressants smoking reduces the effectiveness of lorazepam, and alcohol and CNS depressants increase sedation... 

Most sedative drugs, including narcotics and alcohol, potentiate the sedative effects of benzodiazepines. In addition, medications that inhibit hepatic cytochrome P450 (CYP) 3A3/4 increase blood levels and hence side effects of clonazepam, alprazolam, midazolam, and triazolam. Lorazepam, oxazepam, and temazepam are not dependent on hepatic enzymes for metabolism. Therefore, they are not affected by hepatic disease or the inhibition of hepatic enzymes. 

Case Example A 44-year-old chronic alcoholic man presented in the emergency room with disorientation and combativeness after 2 days of abstinence. He complained of visual and tactile hallucinations and was found to have elevated heart rate, blood pressure, and temperature. Lorazepam was slowly administered intravenously, and after 15 minutes, the patient was mildly sedated. He was then transferred to an inpatient unit. During this 30-minute interval, he received no additional lorazepam, and when he arrived on the floor, his symptoms had returned. He became agitated, struck one of the nursing staff, and had to be physically restrained. 

Knowing the differential pharmacokinetics for a class of drugs allows the clinician to choose specific members to either achieve a faster onset or a delayed offset of action (13, 14, 17, 18). For example, lorazepam is rapidly absorbed from the gastrointestinal tract into the systemic circulation and from there distributed into the brain. In contrast, oxazepam, the most polar BZD, is slowly absorbed from the gastrointestinal tract. Even after oxazepam is in the systemic circulation, it slowly enters tissue compartments, including the brain, during the distribution phase. Unlike lorazepam, oxazepam is not available in either the intramuscular or intravenous formulations. Thus, lorazepam would be preferable to achieve acute control of alcohol withdrawal (e.g., delirium tremens), whereas oxazepam would better stabilize a dependency-prone patient on sedative-hypnotics, because it does not cause the euphoria seen with the more rapidly absorbed members of this class. 

Similarly, BZDs are used for insomnia but are best reserved for short-term use. They are also used to assist withdrawal from alcohol, where a long elimination half-life drug is best. In acute psychotic states short-term use of a high-potency drug, such as lorazepam, can be helpful in managing acute agitation or aggression. 

Phenols and aliphatic alcohols abacavir, APAP, almokalant, carvedilol, chloramphenicol, epirubicin, l -OH-estragole, 5-OH-rofecoxib, lorazepam, menthol, 4-methylumbelliferone, 1-naphthol (low), 4-nitrophenol, octyl-gallate, R-oxazepam, propranolol, temazepam, ZDV... 

The correct answer = B. It is important to treat the seizures associated with alcohol withdrawal. Benzodiazepines, such as chlordiazepoxide, diazepam or or the shorter-acting lorazepam, are effective in controlling this problem. They are less sedating than pentobarbital or phenytoin. 

This fivefold clinical activity is possessed, to a greater or lesser extent, by all benzodiazepines in current clinical use. The properties of benzodiazepines make them ideally useful for managing anxiety (e.g. diazepam, chlordiazepoxide, lorazepam) insomnia (e.g. diazepam, temazepam, nitrazepam, loprazolam, flurazepam, lormetazepam) epilepsy (e.g. clobazam, diazepam, lorazepam) sports injuries where muscle relaxation is required (e.g. diazepam) and as premedications prior to surgery (e.g. midazolam, lorazepam). The benzodiazepines have a number of other uses, including management of alcohol withdrawal syndrome (chlordiazepoxide, diazepam) and restless legs (clonazepam). Short... 

In a double-blind, placebo-controlled study of sex differences in the effects of lorazepam in trained social drinkers, lorazepam substituted for alcohol equally in both sexes and increased associated scores for light-headedness (14). The women had much greater performance impairment in a digital symbol substitution test after lorazepam than the men. These results suggest that the stimulus and cognitive effects of benzodiazepine receptor agonists are modulated by different brain mechanisms. 

Benzodiazepine (BZ) intoxication is manifested as slurred speech, poor coordination, swaying, drowsiness, hypotension, nystagmus, and confusion. Signs and symptoms of BZ withdrawal are similar to those of alcohol withdrawal, including muscle pain, anxiety, restlessness, confusion, irritability, haJlucinations, delirium, seizures, and cardiovascular collapse. Withdrawal from short-acting BZs (e.g., oxazepam, lorazepam, alprazolam) has an onset within 12 to 24 hours of the last dose. Diazepam, chlordiazep-oxide, and clorazepate have elimination half-lives (or active metabolites with elimination half-lives) of 24 to greater than 100 hours. So, withdrawal may be delayed for several days after their discontinuation. Sedative-hypnotic dependence is summarized in Table 73-2. 

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