Benzodiazepines CNS depressants

Precautions Use benzodiazepines cautiously in treating patients with liver disease. They potentiate alcohol and other CNS depressants. Benzodiazepines are, however, considerably less dangerous than other anxiolytic and hypnotic drugs. As a result, a drug overdose is seldom lethal, unless other central depressants, such as alcohol, are taken concurrently. 

Table IV-1-10 summarizes the properties of drugs of abuse. These include the CNS stimulants (cocaine j and amphetamines), the CNS depressants (benzodiazepines, barbiturates, and ethanol), the opioids j (morphine, heroin, methadone, fentanyl, and others), the hallucinogens (marijuana and other j...

The elimination of most benzodiazepines involves their metabolism by liver enz5Tnes, including cytochrome P450 isozymes. In a patient with liver dysfunction, lorazepam, which is metabolized extrahepatically, is less hkely to cause excessive CNS depression. Benzodiazepines are not eliminated via the kidneys or lungs. Flumazenil is used to reverse excessive CNS depression caused by benzodiazepines. The answer is (C). 

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. 

Figure 19.4 The activity spectrum of the benzodiazepines. Motor impairment and CNS depression increases with drug dose. (Based on data for chlordiazepoxide (Sternbach, Randall and Gustafson 1964))...

Withdrawal of CNS depressants (abrupt) Alcohol, barbiturates, benzodiazepines... 

The most common side effects associated with benzodiazepine therapy include central nervous system (CNS) depressive effects (e.g., drowsiness, sedation, psychomotor... 

It is interesting to note that some 1,5-benzodiazepines such as 29 also possess CNS depressant activity. Treatment of substituted diphenylamine 26 with methyl malonyl chloride and reduction with Raney nickel led to orthophenylenediamine analogue 27. Sodium alkoxide treatment led to lactam formation (28), and alkylation in the usual way with NaH and methyl iodide produced clobazam (29). °... 

Overdose fatalities are rare unless benzodiazepines are taken with other CNS depressants. 

CNS depressants (e.g., barbiturates, narcotics, benzodiazepines, short-term use of large doses of alcohol)... 

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. 

No health hazards are known with the proper use of kava (Gruenwald et al. 1998). Kava has been approved by the German Commission E for treatment of anxiety and insomnia. In clinical studies of kava for anxiety, adverse effects were uncommon and did not differ across placebo and kava groups. There do not appear to be any studies published on the effects of acute overdosage with kava. Given its CNS depressant effects, it should not be taken with other similar drugs, including benzodiazepines, barbiturates. 

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. 

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. 

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

Drugs that may affect benzodiazepines include alcohol/CNS depressants, cimetidine, oral contraceptives, disulfiram, isoniazid, probenecid, rifampin, smoking, theophyllines, and macrolides. 

Sedation Although traditionally used as nonspecific CNS depressants for daytime sedation, the barbiturates have generally been replaced by the benzodiazepines. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

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