Depressants benzodiazepines

Benzodiazepines are a potent class of antianxiety agents. Compared with many other types of depressants, benzodiazepines are relatively safe and rarely produce... 

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). 

The role of ChCMs as anxiolytic agents has not been extensively investigated. Clinical data have shown reduced anxiety in smokers and decreased anxiety induced by a stress-producing movie. With many patients suffering from anxiety, there is a concurrent overlap of depression, where two thirds of patients diagnosed with depression are anxious and almost all anxious patients will encounter an episode of depression. Benzodiazepines, such as diazepam, have long been the treatment of choice for anxiety. However, they are depressants and therefore could contribute to the depression in many patients, thereby limiting their use. 

Leeb-Lundberg F, Napios C, and Olsen R. W (1981) Dihydropicrotoxinm binding sites in mammalian brain interaction with convulsant and depressant benzodiazepines Brain Res 216,399-408... 

Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

BENZODIAZEPINES Carbamazepine may cause aplastic anemia and agranulocytosis. During treatment blood studies are performed frequently If evidence of bone marrow depression is obtained (eg, the patient s platelet... 

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. 

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. 

Benzodiazepines and other anxiolytics. Although benzodiazepines are widely used in the treatment of acute alcohol withdrawal, most nonmedical personnel involved in the treatment of alcoholism are opposed to the use of medications that can induce any variety of dependence to treat the anxiety, depression, and sleep disturbances that can persist for months following withdrawal. Researchers have debated the pros and cons of the use of benzodiazepines for the management of anxiety or insomnia in alcoholic patients and other substance abuse patients during the postwithdrawal period (Ciraulo and Nace 2000 Posternak and Mueller 2001). 

Despite the risks of benzodiazepine dependence and overdose among alcoholic patients beyond the period of acute withdrawal, there may be a role for the judicious use of benzodiazepines in treating these patients. To the degree that early relapse, which commonly disrupts alcoholism treatment, is a result of continued withdrawal-related symptoms (e.g., anxiety, depression, insomnia) that can be suppressed by low doses of benzodiazepines, retention in treatment could be enhanced by the use of benzodiazepines (Kissin 1977). Moreover, for some patients, benzodiazepine dependence, if it does occur, may be more benign than alcoholism. 

Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146—150, 1981 Ciraulo DA, Nace E Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Jaffe JH, et al Intravenous pharmacokinetics of 2-hydroxy-imipramine in alcoholics and normal controls. J StudAlcohol 51 366-372, 1990 Ciraulo DA, Knapp CM, LoCastro J, et al A benzodiazepine mood effect scale reliability and validity determined for alcohol-dependent subjects and adults with a parental history of alcoholism. Am J Drug Alcohol Abuse 27 339—347, 2001 Collins MA Tetrahydropapaveroline in Parkinson s disease and alcoholism a look back in honor of Merton Sandler. Neurotoxicology 25 117-120, 2004 COMBINE Study Research Group Testing combined pharmacotherapies and behavioral interventions in alcohol dependence rationale and methods. Alcohol Clin Exp Res 27 1107-1122, 2003a... 

Fyer AJ, Liebowitz MR, Gorman JM, et al Effects of clonidine on alprazolam discontinuation in panic patients a pilot study. J Clin Psychopharmacol 8 270—274,1988 Garvey MJ, Tollefson GD Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. Am J Psychiatry 143 1601-1603, 1986... 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

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))...

Setting aside the general anaesthetics, which do not directly modify the function of any particular neurotransmitter, all the drugs that are used to induce sleep, i.e. the hypnotics , augment the function of GABA and so directly depress neuronal function and probably facilitate cortico-thalamic synchrony. Most of them are benzodiazepines... 

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