Alcohol, sedative effects

There is an increase in anticholinergic effects when antihistamines are administered with the monamine oxidase inhibitors (MAOIs) and additive sedative effects if administered with central nervous system depressants (eg, narcotic analgesics or alcohol). When cimetidine and loratadine are administered together there is a risk for increased loratadine levels. 

Despite the paucity of systematic studies in humans, the available evidence suggests that, like drugs such as alcohol, sedatives, and stimulants, inhalant drugs (i.e., solvents, general anesthetics, and nitrites) exert reinforcing effects and increase motor activity. Furthermore, with continuous use, these drugs appear to induce both tolerance and symptoms of withdrawal. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Valerian, ginger, goldenseal, and chamomile all interact with sedatives (such as barbiturates and alcohol) to increase sedative effects. 

In psychiatric practice, chlorpromazine is used in various conditions of psychomotor excitement in patients with schizophrenia, chronic paranoid and also manic-depressive conditions, neurosis, alcohol psychosis and neurosis accompanied by excitement, fear, stress, and insomnia, hi comparison with other neuroleptics, chlorpromazine is unique in that it has an expressed sedative effect. It is sometimes used in anesthesiological practice for potentiating narcosis. It also has moderate anticonvulsant action. The most common synonyms are aminazine, megaphen, largactil, thorazine, prompar, and others. 

Do not administer until the patient has abstained from alcohol for at least 12 hours. Initial dosage schedule Administer a maximum of 500 mg/day in a single dose for 1 to 2 weeks. If a sedative effect is experienced, take at bedtime or decrease dosage. Maintenance regimen The average maintenance dose is 250 mg/day (range, 125 to 500 mg), not to exceed 500 mg/day. Maintenance therapy may be required for months or even years. 

It does not cause cognitive impairment and has a low potential for abuse. It does not show withdrawal reactions and has no anticonvulsive, hypnotic, muscle relaxant and sedative effects. The anxiolytic effect gradually evolves over 1-3 weeks, it does not potentiate the sedative effects of alcohol and is indicated for the short-term management of generalized anxiety disorder. 

GABA is formed by the decarboxylation of glutamate, and is the major inhibitory neurotransmitter, hi recent years the GABAa receptor has been identified as the mediator of the anxiolytic and sedative effects of drugs such as alcohol and the benzodiazepines. Abnormahties of this receptor have been identified in humans with anxiety disorders (Nutt and Mahzia 2001). 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

Mirtazapine has been found to have synergistic depressant effects on motor and cognitive performance when used in conjunction with benzodiazepines or alcohol (Kuitunen, 1994). Somnolence and increased appetite accompanied by weight gain are common adverse effects. Lower doses are clearly associated with more sedative effects than those with higher doses. It is unclear if a similar pattern is noted for appetite and weight gain. 

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. 

Taken with alcohol they potentiate the sedative effects and impairment of psychomotor performance. Hepatic enzyme induction by barbiturates or nicotine may reduce plasma levels. Cimetidine may increase levels by enzyme inhi bition. Some antipsychotic drugs may compete for similar metabolic pathways. 

They found that a strain of mice that lacks the gene for NPY—NPY knockout mice—consume more ethanol than control mice and are less sensitive to ethanol s sedative effects. As would be expected if increased concentrations of NPY in the brain make mice more sensitive to ethanol, a strain of mice that overexpresses NPY drinks less alcohol than the controls even though their total consumption of food and liquid is normal. Work with other transgenic knockout mice support the central role in ethanol responses of signaling molecules that have long been believed to be involved (eg, GABA A, glutamate, dopamine, opioid, and serotonin receptors) and has helped build the case for newer candidates such as NPY and cannabinoid receptors, ion channels, and protein kinase C. 

Drug(s) Alcohol Classification/ Action Sedative-hypnotic Route/Method of Administration Oral, from various beverages [wine, beer, other alcoholic drinks] Effect Desired by User Euphoria relaxed inhibitions decreased anxiety sense of escape Principal Adverse Effects Physical dependence impaired motor skills chronic degenerative changes in the brain, liver, and other organs Additional Information See Chapter 6... 

PCP has a sedative effect on certain systems in the body and interactions with other central nervous system depressants such as alcohol and benzodiazepines may lead to coma or accidental overdose. 

Walsh JK, Humm T, Muehlbach MJ, Sugerman JL, Schweitzer PK. Sedative effects of ethanol at night. J Stud Alcohol 1991 52 597-600. 

Zaleplon possesses several of the clinical characteristics of traditional benzodiazepines, including the potential for additive CNS depression when administered with alcohol or other CNS depressants, a low potential for abuse, and relative safety in overdose. Zaleplon exhibited sedative effects similar to those of the benzodiazepines, with a lower likelihood of such undesirable side effects as memory loss, interaction with alcohol, and abuse potential [22],... 

As these drugs are usually taken orally and the tablets or capsules are consistent in drug content, inadvertent fatal overdoses of single agents are rare. Tolerance may develop to the sedative effect but not to the respiratory depressant effect. Thus, if these drugs are used with other respiratory depressants, eg, large amounts of alcohol or opioids, fatalities can occur. 

THC has a variety of pharmacologic effects that resemble those of amphetamines, LSD, alcohol, sedatives, atropine, and morphine. Important opioid interactions include reduction in opioid dependence in CB1 knockout mice lacking the CB1 receptor. 

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