Benzodiazepines anesthetics

AHopregnanolone and similar A-ring-reduced pregnanes potentiate GABA effects at these receptors. These steroids mimic the effects of the benzodiazepines, changing chloride ion conductance and producing sedative and hypnotic behavioral effects (276,277). Neuroactive steroids can be therapeutically useful as anticonvulsants, anxiolytics, or anesthetics (qv) (see also Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

Combinations of barbiturates and benzodiazepine tranquilizers or even antihistaminergics having sedative properties are sometimes used. Furthermore, infusion of anesthetics can be used to provide long-term anesthesia for intensive care medicine. The antagonist flumazenil (18) is available to reverse the effects of anesthetics of the benzodiazepine class. 

GABA, and molecules that act at GABA-A receptors, have been classically recognized as hypnotics (i.e. benzodiazepines) and anesthetics (i.e. barbiturates). Benzodiazepine (BZD) receptors, a modulatory site on the GABA-A receptor, were... 

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

Further, the removal of benzodiazepine sensitivity in a selective a subunit in a mouse using the gene knockin technique has established that the al subunit plays a major role in the sedative and amnesiac effects of benzodiazepines, part of the anticonvulsant effect and little of the anxiolytic effect the latter effects are more importantly mediated by the a2 subunit [5, 6], The 0 subunit selectivity for the drugs loreclezole (an anxiolytic) and etomidate (an anesthetic) allowed determination that a single residue in the M2 domain could account for this selectivity (02 = 03 >01). When a mouse knockin selectively removed the etomidate sensitivity of the 02 subunit, the animals showed reduced sensitivity to sedative effects of etomidate but no reduction of the true anesthetic effects. In contrast, mutation of the 03 subunit to negate etomidate sensitivity of that subunit alone resulted in a mouse with no sensitivity to the anesthesia produced by etomidate. This proved that the GABA receptor is the target of at least this one anesthetic (etomidate) and, furthermore, that the specific locations in the brain of 03 subunits are important for anesthetic action, while the... 

Midazolam is a rapidly metabolized benzodiazepine (p. 228) that is used for induction of anesthesia. The longer-acting lorazepam is preferred as adjunct anesthetic in prolonged cardiac surgery with cardiopulmonary bypass its am-nesiogenic effect is pronounced. 

Unlike barbiturates, benzodiazepine derivatives administered orally lack a general anesthetic action cerebral activity is not globally inhibited (respiratory paralysis is virtually impossible) and autonomic functions, such as blood pressure, heart rate, or body temperature, are unimpaired. Thus, benzodiazepines possess a therapeutic margin considerably wider than that of barbiturates. 

Since general anesthetics are related to a variety of classes of chemical compounds, there is no general pattern that exists between their chemical structure and their activity. Particular patterns only exist for different groups of compounds (barbiturates, benzodiazepines, etc.). 

Drugs that may interact with buprenorphine hydrochloride include barbiturate anesthetics, benzodiazepines, CNS depressants, CYP3A4 inducers and inhibitors, and MAOIs. 

Drugs that affect nefazodone include general anesthetics, sibutramine, sumatriptan, buspirone, carbamazepine, and propranolol. Drugs that may be affected by nefazodone include alcohol, benzodiazepines, buspirone, carbamazepine, cisapride, digoxin, haloperidol, HMG-CoA reductase inhibitors, MAOIs, propranolol, St. John s wort, cyclosporine, and tacrolimus. 

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. 

Opioids play an important role in anesthetic practice. Opioid analgesics potentiate the efficacy of anesthetics. They can be given as part of the premedication as well as during the operation. Examples of short acting agents with high potency are fentanyl, sufentanyl, alfentanil and remifentanil. Because of their hemodynamic stability these agents can be used for patients with compromised myocardial function. Respiration must be maintained artificially and may be depressed into the postoperative period. They are usually supplemented with inhalation anesthetic, benzodiazepines or propofol. 

The popularity of the benzodiazepines as an anesthetic supplement in cardiac surgery is related to their amnesic potential. They can ensure unawareness during the initial period, when the anesthetics are being diluted in the fluid of the bypass circuit. Lorazepam is often chosen for this purpose because it is longer acting and more potent than either midazolam or diazepam. Benzodiazepine administration may cause amnesia even when used in doses that do not produce unconsciousness. Antegrade amnesia may occur with the doses that are used to relieve preoperative anxiety. 

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