Benzodiazepines toxicity

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. 

There is a broad spectrum of signs and symptoms associated with acute benzodiazepine toxicity. Lethargy,... 

Flumazenil (Romazicon) is a benzodiazepine antagonist that can reverse the CNS depressant effects of these agents. It should be used with caution in acute intentional benzodiazepine overdoses. Because acute benzodiazepine overdoses generally result in only mild toxicity, it has limited clinical utility in this setting. Flumazenil s use in the acute benzodiazepine intoxicated patient may lead to an unnecessarily long observation period after fumazenil s infusion. This observation is necessary to be certain that reoccurrence of benzodiazepine toxic effects do not occur... 

Gait disturbances (attributed to benzodiazepine toxicity) occurred in two patients given triazoiam and lorazepam or flu-razepam with omeprazoie, and another patient taking diazepam and omeprazole became wobbly and sedated. Lansoprazole, pan-toprazole, or rabeprazole appear not to interact to a clinically relevant extent with diazepam. Diazepam serum levels are increased by esomeprazole but the clinical relevance of this is unknown. 

Cardiac arrest following heroin and benzodiazepine toxicity in a 29-year-old man was managed with therapeutic hypothermia [76" ], which improves neurological outcomes and may benefit comatose victims of toxin-mediated cardiac arrest. 

Benzodiazepines are excreted more slowly in older adults causing a prolonged drug effect. The drugs may accumulate in the blood, resulting in an increase in adverse reactions or toxicity. For this reason, the initial dose should be small, and the nurse should increase dosages gradually until a therapeutic response is obtained. 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Many CNS depressants have some liability for dependence. This is typically greater with barbiturates, but lesser with benzodiazepines, and perhaps nonexistent in many antiseizure medications. CNS depressants produce tolerance when administered chronically, where increasingly larger doses are required to sustain the same level of effect. Further, a cross-tolerance often develops, where the tolerance is generalized to other CNS depressants. For example, a person with an ethanol tolerance will also display some tolerance to barbiturates. The therapeutic index tends to decrease as tolerance increases, so that the difference between an effective and toxic dose diminishes. Thus, tolerance to CNS depressants is accompanied by a smaller safety margin. 

There have been no formal studies of the toxicity of passionflower, but adverse effects have not been reported. There is one report of a case of inflammatory vasculitis associated with a preparation of passionflower (Smith et al. 1993). Like other herbs in this category, its putative benzodiazepine action contraindicates its combined use with other CNS depressants. 

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-... 

The only medication that blocks GABA activity is flumazenil (Mazicon). Flumaze-nil is used only in the emergency room or in an inpatient hospital setting to treat benzodiazepine overdose. It quickly and reliably reverses the toxic effects when a patient has accidentally or purposefully taken an overdose. Restricted to emergency situations, flumazenil is never used on a routine basis. 

Since GABA-ergic synapses are confined to neural tissues, specific inhibition of central nervous functions can be achieved for instance, there is little change in blood pressure, heart rate, and body temperature. The therapeutic index of benzodiazepines, calculated with reference to the toxic dose producing respiratory depression, is greater than 100 and thus exceeds that of barbiturates and other sedative-hypnotics by more than tenfold. Benzodiazepine intoxication can be treated with a specific antidote (see below). 

Zopiclone is a chiral cyclopyrrolone with hypnotic properties, possessing a pharmaceutical profile of high efficacy and low toxicity, similar to that of benzodiazepines. Zopiclone has been commercialized as a racemic mixture however, the (S)-enantiomer is more active and less toxic than the (R)-enantiomer [11]. Although enzymatic hydrolysis of esters or transesteriflcation processes of alcohols have been widely applied for enzymatic resolution or desymmetrization... 

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. 

The sedative hypnotic ethchlorvynol has approximately the same activity and toxicity as phenobarbital however, its hypnotic effect develops and dissipates qnicker. It is nsed mnch less than benzodiazepines in treating insomnia for a nnmber of reasons. 

Mixed drug overdosage Particular caution is necessary when using flumazenil in cases of mixed drug overdosage toxic effects of other drugs taken in overdose (especially cyclic antidepressants) may emerge with reversal of the benzodiazepine effect by flumazenil. 

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