Central nervous system depressants benzodiazepines

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

The benzodiazepines such as diazepam, oxazepam, and temazepam are common causes of acute poisoning, but rarely cause serious toxicity by themselves, even in enormous doses. They can potentiate central nervous system depression from other drugs, including alcohol. 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

Although it is widely claimed that the benzodiazepine drugs have a specific calming or anxiolytic effect, their most prominent and easily quantifiable action is central nervous system depression. In very low therapeutic doses, this depression manifests as relief of anxiety that is often accompanied by a feeling of sluggishness or drowsiness. As the dose is increased, the degree of depression is intensified such that muscle relaxation, hyp-... 

A significant advantage of the benzodiazepines over other central nervous system depressants (e.g., the barbiturates) is that they possess a much greater separation between the dose that produces sleep and the dose that produces death. This increased margin of safety has been one of the major reasons benzodiazepines have largely replaced the barbiturates and other types of sedative-hypnotics in the treatment of anxiety and insomnia. In addition, benzodiazepine aclministration is associated with few side effects. 

Nearly all central nervous system depressants have some capacity to suppress seizures by virtue of their depressant activity on the brain and spinal cord. Clonazepam and diazepam are two benzodiazepines that depress epileptiform activity and are used in the treatment of epilepsy and seizure disorders (see Chapter 32). 

Benzodiazepines have the capacity to depress polysynaptic reflexes and have been shown to decrease decerebrate rigidity in cats and spasticity in patients with cerebral palsy. What is not clear is whether they can, in humans, relax voluntary muscles in doses that do not cause considerable central nervous system depression. Nevertheless, benzodiazepines, such as diazepam, are often prescribed for patients who have muscle spasms and pain as a result of injury. In these circumstances, the sedative and anxiolytic properties of the drug also may promote relaxation and relieve tension associated with the condition. 

As with other central nervous system depressants, the effects of benzodiazepines are additive with those of ethanol. Patients should be warned that ethanol-containing beverages may produce a more profound depression when taken simultaneously with a benzodiazepine. 

One of the major reasons for the popularity of the benzodiazepines is their relative safety. Overdoses with the benzodiazepines occur commonly, but fatal toxic occurrences are rare. Fatal intoxications are more likely in children, in individuals with respiratory difficulties, and in individuals who have consumed another central nervous system depressant, such as alcohol. After an overdose, the patient begins a deep sleep that may last for 24 to 48 hours, depending on the dose. However, even with large overdoses, the patient can usually still be aroused. 

When used with other sedative-hypnotics or alcohol, the benzodiazepines will produce additive central nervous system depression. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

The most commonly abused prescription drugs are opioids and opiates such as oxycodone and morphine, central nervous system depressants such as barbiturates and benzodiazepines, and stimulants such as dextroamphetamine and methylphenidate. Brand-name painkillers such as Vicodin and OxyContin, depressants such as Valium and Xanax, and stimulants such as Ritalin and Dexedrine are commonly abused (as are some OTC cough remedies). Although helpful and safe when used appropriately, these drugs can cause serious harm when taken in unapproved ways. 

PCP has a sedative effect on certain systems in the body and interactions with other central nervous system depressants such as alcohol and benzodiazepines may lead to coma or accidental overdose. 

Most of the sedative-hypnotics are capable of inhibiting the development and spread of epileptiform activity in the central nervous system. Some selectivity exists in that some members of the group can exert anticonvulsant effects without marked central nervous system depression (although psychomotor function may be impaired). Several benzodiazepines—including clonazepam, nitrazepam, lorazepam, and diazepam—are sufficiently selective to be clinically useful in the management of seizure states (see Chapter 24 Antiseizure Drugs). Of the barbiturates, phenobarbital and metharbital (converted to phenobarbital in the body) are effective in the treatment of generalized tonic-clonic seizures. 

Buspirone causes less psychomotor impairment than diazepam and does not affect driving skills. The drug does not potentiate the central nervous system depressant effects of conventional sedative-hypnotic drugs, ethanol, or tricyclic antidepressants, and elderly patients do not appear to be more sensitive to its actions. Tachycardia, palpitations, nervousness, gastrointestinal distress, and paresthesias may occur more frequently than with benzodiazepines. Buspirone also causes a dose-dependent pupillary constriction. Blood pressure may be elevated in patients receiving MAO inhibitors. A number of buspirone analogs have been developed (eg, ipsapirone, gepirone, tandospirone) and are under study. 

The benzodiazepine antagonist flumazenil is sometimes used to accelerate recovery from excessive sedative actions of intravenous benzodiazepines, but reversal of respiratory depression by flumazenil is less predictable. Its short duration of action (< 90 minutes) may necessitate multiple doses to prevent recurrence of central nervous system depressant effects of longer-acting benzodiazepines. 

Central nervous system depressants include the barbiturates, such as phenobarbital, and the antianxiety drugs, including diazepam (VaUum), chlordiazepoxide Odbrium), oxazepam (Serax), flurazepam hydrochloride (Dalmane), and lorazepam (Ativan). The benzodiazepines, including diazepam, occasionally cause mydriasis, presumably because of their anticholinergic side effects. 

Central nervous system depressant drugs including benzodiazepines, several Hj-receptor antihistamines, alcohol, phenothiazines, antiepilepsy drugs interact to augment their sedative effects. 

Benzodiazepines are involved in many intentional overdoses. While these overdoses are rarely fatal when a benzodiazepine is the sole ingestant, they often complicate overdoses with other central nervous system depressants (e.g., ethanol and sedatives) due to their synergistic activity. Flumazenil finds its greatest utility in the reversal of benzodiazepine-induced sedation from minor surgical procedures. The initial flumazenil dose is 0.2 mg and should be administered intravenously over 30 s. If no response occurs after an additional 30 s, a second dose is recommended. Additional incremental doses of 0.5 mg may be administered at 1 min intervals until the desired response is noted or until a total of 3 mg has been administered. Flumazenil should not be administered... 

Obstructive sleep apnea and central sleep apnea patients should avoid central nervous system depressants such as alcohol, benzodiazepines, and zolpidem. 

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

A second major consideration for social workers when a client is taking benzodiazepines is the potential for addiction and abuse. In addition to the potential abuse, the benzodiazepines are central nervous system depressants that when combined with another depressant such as alcohol can result in significant depression or have a lethal effect (Dulcan, 1999 ... 

Potentiation Actions of drugs with similar actions are additive Central nervous system depression with benzodiazepines and alcohol... 

Rohypnol s chemical name is flunitrazepam. It is a type of benzodiazepine, a drug that acts as a central nervous system depressant and is used to manage anxiety. Rohypnol is similar to the well-known sedative Valium, but it is 5 to 10 times more powerful. 

CENTRAL NERVOUS SYSTEM While benzodiazepines affect activity at aU levels of the neuraxis, some structures are affected preferentially. The benzodiazepines do not produce the same degrees of neuronal depression as do barbiturates and volatile anesthetics. Although the benzodiazepines have similar pharmacological profiles, the drugs differ in selectivity and thus in clinical utility. 

Although workers are often exposed to a variety of solvents with Stoddard solvent, there are no available studies specifically characterizing the interactions of Stoddard solvent with other chemicals. Since Stoddard solvent may have adverse effects on the nervous system, it may compound the effects of other chemicals that cause central nervous system depression, such as alcohol, barbiturates, benzodiazepines, or medical anesthetics. Guinea pigs with a diet high in vitamin C survived a high exposure to Stoddard solvent vapors better than those with a diet low in vitamin C (Jenkins et al. 1971) however, it is not known how vitamin C levels might affect humans exposed to Stoddard solvent. 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

A. Benzodiazepines potentiate inhibitory gamma-aminobutyric acid (GABA) neuronai activity in the centrai nervous system. Pharmacologic effects include reduction of anxiety, suppression of seizure activity, central nervous system depression (possible respiratory arrest when given rapidly intravenously), and inhibition of spinal afferent pathways to produce skeletal muscle relaxation. 

A. Benzodiazepines will potentiate the central nervous system-depressant effects of opioids, ethanol, and other sedative-hypnotic and depressant drugs. 

---