Benzodiazepines anesthesia

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. 

The most important fluorinated benzodiazepine, flurazepam (21) has found considerable use (and abuse) as a hypnotic [I4 Flumazenil (22) is a fast-acting antidote in the treatment of benzodiazepine intoxication and m the reversal of the CNS effects of benzodiazepines dunng anesthesia [f<5,19]... 

Midazolam (Versed), a short-acting benzodiazepine CNS depressant, is used as a preanesthetic drug to relieve anxiety for induction of anesthesia for conscious sedation before minor procedures, such as endoscopic procedures and to supplement nitrous oxide and oxygen for short surgical procedures. When the drug is used for induction anesthesia, the patient gradually loses consciousness during a period of 1 to 2 minutes. 

The answer is e. (Ka.tzu.ng, pp 373-3743 Flumazenil is a competitive benzodiazepine receptor antagonist. The drug reverses the CNS sedative effects of benzodiazepines and is indicated where general anesthesia has... 

The answer is a. (Hardman, p 373. Katzung, pp 430-431.) Midazolam is useful for sedation because it produces a higher incidence of amnesia and has a more rapid onset of action and a shorter half-life than other benzodiazepines used in anesthesia... 

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... 

Benzodiazepines. The benzodiazepines were developed in the 1950s and introduced into the U.S. market in the 1960s. They have found a variety of uses including the treatment of several anxiety disorders, insomnia, seizure disorders, alcohol withdrawal, surgical anesthesia, and others. The benzodiazepines have also been used to calm agitated patients and are therefore useful during the acute treatment phase of bipolar mania. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

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. 

The synthesis of these compounds will be described in Section 3.1, Opioid analgesics. Besides opioids, benzodiazepines (diazepam, lorazepam, and midazolam), which have anxiolytic, sedative, and anticonvulsant effects, that cause amnesia and muscle relaxation, are frequently used to relieve patients anxiety during anesthesia. 

Reversal of benzodiazepine sedation For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced or maintained with benzodiazepines, where sedation has been produced... 

Hypoventilation Monitor patients who have received flumazenil for the reversal of benzodiazepine effects (after conscious sedation or general anesthesia) for resedation, respiratory depression or other residual benzodiazepine effects for an appropriate period (120 minutes or less) based on the dose and duration of effect of the benzodiazepine employed, because flumazenil has not been established as an effective treatment for hypoventilation due to benzodiazepine administration. Flumazenil may not fully reverse postoperative airway problems or ventilatory insufficiency induced by benzodiazepines. In addition, even if flumazenil is initially effective, such problems may recur because the effects of flumazenil wear off before the effects of many benzodiazepines. 

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. 

Midazolam (Versed), diazepam (Valium), and lo-razepam (Ativan) are benzodiazepine derivatives that are useful in anesthesia. Midazolam is the most popular of these agents for the induction of anesthesia. Its popularity is related to its aqueous solubility and to its short duration of action, which permits a prompt return of psychomotor competence. Unlike midazolam, lor-azepam and diazepam are not water soluble and must be formulated in propylene glycol the latter is irritating to the vasculature on parenteral administration. 

Benzodiazepines are usually given orally and are well absorbed by this route. Since the benzodiazepines are weak bases, they are less ionized in the relatively alkaline environment of the small intestine, and therefore, most of their absorption takes place at this site. For emergency treatment of seizures or when used in anesthesia, the benzodiazepines also can be given parenter-ally. Diazepam and lorazepam are available for intravenous administration. 

Benzodiazepines have the capacity to produce a calming effect and to cause anterograde amnesia, in which the patient cannot recall events that took place for some time after the drug was administered. Benzodiazepine-induced sedation and amnesia are deemed useful in the preparation of patients for anesthesia, surgery, and other frightening or unpleasant medical and dental procedures and diagnostic tests. Midazolam is a frequently used anesthetic benzodiazepine (see Chapter 25). 

The acute effects of depressants can include euphoria, anxiety reduction, anticonvulsant activity, sedation, ataxia, motor incoordination, impaired judgment, anesthesia, coma, and respiratory depression resulting in death. The benzodiazepines are rarely involved in lethality, but all CNS depressants enhance the effects of other depressant drugs. The physiological effects of high-dose depressants include miosis, shallow respiration, and reduction in reflex responses. 

Clinical experiments such as that conducted by George and Dundee (1977) allow the following interpretation intravenous (and, similarly, high oral) doses of benzodiazepines cause sleepiness and eventually induce sleep. Despite being sleepy immediately after the injection, the patients were able to perceive and correctly name pictures shown to them before full anesthesia, but they had only a limited ability to remember the pictures later, once the effect of the substance had... 

Benzodiazepines—including diazepam, lorazepam, and midazolam—are used intravenously in anesthesia (see Chapter 25), often in combination with other agents. Not surprisingly, benzodiazepines given in large doses as adjuncts to general anesthetics may contribute to a persistent postanesthetic respiratory depression. This is probably related to their relatively long half-lives and the formation of active metabolites. However, such depressant actions of the benzodiazepines are usually reversible with flumazenil. 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

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