Effects of benzodiazepines

The fact that single-dose administration of benzodiazepines could have marked amnestic effects was first recognized in anesthesiology where these drugs are used to relax and sedate patients prior to surgery. It was found that, 

4 Amnestic Effects of Benzodiazepines a Clinical Experiment in Anesthesiology 

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 

Golombok et al. (1988) reported on a retrospective study in long-term (more than 1 year) users of benzodiazepines. They found a negative correlation 

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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]... 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

Benzodiazepines (alprazolam) COCs may inhibit oxidative metabolism Increase side effects of benzodiazepines... 

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. 

Compare the neurochemical and behavioural effects of benzodiazepines and barbiturates. 

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... 

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... 

Lorazepam The PK-PD modeling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers showed that the parameter values derived from PK/PD modeling, and especially the EC values, may provide sensitive indices that can be used, rather than the raw data derived from PD measurements, to compare CNS effects of benzodiazepines... 

Side effects of benzodiazepines include sedation, dizziness, poor coordination, and, at higher doses, amnesia. Benzodiazepines also increase the effects of alcohol therefore, alcohol use should be avoided or markedly curtailed. Benzodiazepines can also exacerbate the breathing problems of patients with sleep apnea and other respiratory disorders such as emphysema. Like the barbiturates, long-term use of benzodiazepines can lead to physical dependence, and abrupt discontinuation can produce an unpleasant, or even dangerous, withdrawal syndrome. 

Benzodiazepines. These agents, particularly alprazolam and clonazepam, have been widely used in the treatment of PTSD, despite little evidence to demonstrate their effectiveness. The few studies exploring the effectiveness of benzodiazepines for PTSD suggest that they provide modest relief for anxiety in general but offer no benefit for the core symptoms of PTSD, namely, intrusive recollections and emotional numbing. Furthermore, a small controlled study investigating prophylactic treatment with a benzodiazepine in the immediate aftermath of trauma exposure failed to protect patients from the subsequent development of PTSD symptoms. Consequently, we do not recommend benzodiazepines for the routine management of PTSD. 

Side effects of benzodiazepines include drowsiness and reduced respiratory function. In patients who are severely medically ill, especially those with lung disease, this side effect can be problematic. However, benzodiazepines are much safer in this regard than their predecessors, the barbiturates, and untreated delirium tremens, the most severe form of alcohol withdrawal, can be fatal. 

The development of tolerance is a major drawback to the use of benzodiazepines in the long-term treatment of insomnia. Whereas tolerance to the hypnotic effects of benzodiazepines permits them to be used without excessive sedation when treating anxiety disorders, this is counterproductive when attempting to treat insomnia. Patients often find themselves requiring higher doses to obtain the same sedative-hypnotic effect initially accomplished by lower doses. For this reason, careful consideration must be given before benzodiazepines are used to treat chronic insomnia. 

Flumazenil is a benzodiazepine antagonist that is used in anaesthesia for the reversal of central sedative effects of benzodiazepines. It should not be administered rapidly so as to avoid patient wakening too rapidly, which can lead to agitation, anxiety, fear and convulsions, particularly in high-risk patients, e.g. those with a history of epilepsy or head injury. 

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... 

Labor and delivery - The use of flumazenil to reverse the effects of benzodiazepines used during labor and delivery is not recommended because the effects of the drug in the newborn are unknown. 

Extended-release The usual starting dose is 0.5 mg once/day. Gradually increase if needed and tolerated. The elderly may be especially sensitive to the effects of benzodiazepines. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

The effects of benzodiazepines, and drugs with similar actions, result from interactions with benzodiazepine binding sites on the GABAa receptor com-... 

Several studies have suggested increased sensitivity of older persons to effects of benzodiazepines (Table 3). For example, midazolam, widely used for rapid sedation for procedures, requires lower doses to reach defined end points of sedation that is attributable to a 59% reduction in the EC50 (the concentration that produces 50% of the maximum effect) and not to changes in pharmacokinetics, as shown in Fig. 3. The reasons for this increased sensitivity are not known. Animal studies have not shown any difference in brain benzodiazepine receptor density or affinity or effects on the associated chloride channel function with ageing. In any event, benzodiazepine doses should be reduced in older patients. 

The withdrawal syndrome from ethanol includes anxiety, insomnia, possibly convulsions and visual hallucinations (delirium tremens - the Dts). It is treated or better still prevented by a calm environment, adequate (but not excessive) hydration, and careful monitoring, with the added use of anticon-vulsive/sedative agents, mainly benzodiazepines to prevent or treat convulsions. The preventive effects of benzodiazepines on withdrawal morbidity has been clearly demonstrated. There do not seem to be major differences between benzodiazepines, such as chlordiazepoxide or diazepam or others. Because of the abuse potential in these highly susceptible patients, these should be rapidly weaned, and proper prevention of relapse instituted. Other drugs such as meprobamate and clomethiazole (Hemineurin) are commonly used in some countries. The effectiveness... 

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