Sedation from benzodiazepines

Reducing benzodiazepine use in elderly patients is important for several reasons. Long-term use of benzodiazepines can accelerate cognitive decline in elderly patients (Paterniti et al. 2002). The elderly experience excessive sedation from benzodiazepines compared with younger individuals (Lechin et al. 1996). Benzodiazepine use by elderly patients are not only associated with cognitive side effects... 

Girdler NM, Lyne JP, Fairbrother K, Neave N, Scholey A, Hargaden N, Wesnes KA, Engler J and Rotherham NA (2002). A Study of post-operative cognitive and psychomotor recovery from benzodiazepine sedation Effects of reversal with flumazenil over a prolonged recovery period. British Dental Journal, 192, 335-339. 

As the withdrawal progresses, symptoms can become episodic, ranging unpredictably from mild to severe. Treatment typically focuses on providing support and managing symptoms, such as sedation with benzodiazepines and barbituates. In-patient hospitalization is recommended for detoxification. 

Benzodiazepines are involved in many intentional overdoses. While these overdoses are rarely fatal when a benzodiazepine is the sole ingestant, they often complicate overdoses with other central nervous system depressants (e.g., ethanol and sedatives) due to their synergistic activity. Flumazenil finds its greatest utility in the reversal of benzodiazepine-induced sedation from minor surgical procedures. The initial flumazenil dose is 0.2 mg and should be administered intravenously over 30 s. If no response occurs after an additional 30 s, a second dose is recommended. Additional incremental doses of 0.5 mg may be administered at 1 min intervals until the desired response is noted or until a total of 3 mg has been administered. Flumazenil should not be administered... 

Although rare, benzodiazepine toxicity may occur from an overdose of the drug. Benzodiazepine toxicity causes sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote (antagonist) for benzodiazepine toxicity and acts to reverse die sedation, respiratory depression, and coma within 6 to 10 minutes after intravenous administration. The dosage is individualized based on the patient s response, widi most patients responding to doses of 0.6 to 1 mg. However, die drug s action is short, and additional doses may be needed. Adverse reactions of flumazenil include agitation, confusion, seizures, and in some cases, symptoms of benzodiazepine withdrawal. Adverse reactions of flumazenil related to the symptoms of benzodiazepine withdrawal are relieved by die administration of die benzodiazepine. 

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. 

The clinical consequences of the currently used benzodiazepines range from sedation, muscle relaxation, seizure reduction, anxiolysis, and hypnosis. Clearly, it would be highly desirable to be able to separate some of these effects. In addition, it would be useful to reduce other undesirable consequences such as development of tolerance and dependence, abuse, synergistic interaction with ethanol, and memory impairment (for a comprehensive review see [22]). Animal models for some of the aforementioned conditions, in combination with transgenic mouse technology, have recently led to a deeper understanding of the contribution some of the individual a subunits make to these behaviors. 

Medications for symptomatic relief from vertigo consist of antiemetics, benzodiazepines and antihistamines. They are all mostly aimed at the psychological consequences of dizziness and can all have highly unfavourable side effects, for example, sedation, anticholinergic effects and insomnia. The psychological consequences of dizziness in elderly should rather be treated with information about the condition, supportive help actions and increased social activities, than with drugs. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

Related hypnotics that also act at benzodiazepine receptors are the newer agents zolpidem, a imida-zopyridine, zaleplon a pyrazolopyrimidine and the cyclopyrrolone zopiclone. Zopiclone might have a role for the treatment of benzodiazepine addiction. In patients in whom zopiclone was substituted for a benzodiazepine for 1 month and then itself abmptly terminated, improved sleep was reported during the zopiclone treatment, and withdrawal effects were absent on discontinuation of zopiclone. A series of non-sedating anxiolytic drugs derived from the same structural families as the above mentioned nonbenzodiazepines, have been developed, such as alpi-dem and pagoclone. 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Among ai-, a2- and as-point-mutated mice, only the ai(HlOlR) mutants were resistant to the depression of motor activity by diazepam and zolpidem (Rudolph et al. 1999 Low et al. 2000 Crestani et al. 2000). This effect was specific for ligands of the benzodiazepine site, since pentobarbital or a neurosteroid remained as effective in ai(HlOlR) mice as in wild-type mice in inducing sedation. An ai(HlOlR) mouse line was also generated by McKernan et al. (2000), confirming that sedation is finked to ai GABAa receptors and differs mechanistically from the anxiolytic action of benzodiazepines. 

Benzodiazepines have very few side effects. As you would expect, because benzodiazepines work by enhancing the inhibitory neurotransmitter GABA, the most common complaint from people who use benzodiazepines is that they feel drowsy, sedated, slowed down, or experience slurred speech. It is important to emphasize that people taking benzodiazepines should not drive or operate dangerous machinery until they have determined how the drug will affect them. 

In summary, buspirone is an effective generalized anxiety treatment that differs from conventional antianxiety drugs in speed of symptom reduction and types of symptoms affected. Although buspirone might seem to be the drug of choice for treatment of chronic anxiety, it has not displaced the use of benzodiazepines in the treatment of anxiety, perhaps because of its side-effect profile [dizziness, sedation, nausea], slow onset of action, and the opinion of some clinicians that its anxiolytic efficacy is less robust than that of benzodiazepines. Buspirone is accepted as an anxiolytic treatment much more widely in the United States than in most other countries [Kunovac and Stahl 1995]. 

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