Both of these classes of medications have broad uses in various conditions and are effective when used at proper dosages and under the guidance of trained medical professionals. However, these drugs also run a high risk of misuse and abuse and frequently lead to untoward consequences. Benzodiazepines (BZDs) are among the most commonly prescribed psychoactive drugs by clinicians in primary care. 34 Individuals with sedative, hypnotic, or anxiolytic use disorders are frequently treated in the outpatient setting. BZDs are Food and Drug Administration (FDA) indicated for a number of conditions such as anxiety disorders, insomnia, acute status epilepticus, induction of amnesia, spastic disorders, and agitation. Non-FDA-approved indications include Tourette’s syndrome, delirium, delirium tremens, sleep disorders, and abnormal movements associated with other medications. 37 Sedative drugs decrease activity, diminish excitement, and calm the individual. Sedatives are often used to alleviate unwanted side effects of other substances. Hypnotic drugs produce drowsiness and facilitate the onset and maintenance of a state of sleep that resembles natural sleep in its electroencephalographic characteristics and from which the recipient can be easily aroused. 35 These medications have varying mechanisms of action but generally exert their most significant effect on the central nervous system. They act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS. 36 Nonbenzodiazepines including zolpidem, zaleplon, and eszopiclone, referred to as Z-drugs, were developed as alternatives to BZDs and have clinical effects similar to BZDs but may be more prone to misuse and dependence. Anxiolytics or sedative-hypnotic drugs can be viewed on a continuum based on sedating properties of the class. Physical and psychological dependence does occur, and all have withdrawal symptoms. Alcohol take along with drugs in this class has additive effects. The essential features of this drug class are maladaptive behavioral or psychological changes. In some, memory impairment causes anterograde amnesia similar to blackouts .
BZDs are contraindicated in angle-closure glaucoma and have a black box warning with concomitant use with opioids, which lead to severe respiratory depression, coma, and death. However, in a supervised setting, BZDs can be used to quell the significant anxiety associated with stimulant intoxication and opioid withdrawal. Several groups are at high risk for abuse, and caution is essential when prescribing BZDs. Individuals who consume large amounts of alcohol often present for treatment of anxiety and insomnia, and there is an elevated likelihood of abuse of this class of drug. Individuals may self-medicate for insomnia, anxiety, and withdrawal. Additionally, benzodiazepines increase the hedonistic effects of methadone. 39 Older individuals are at unique risk of significant cognitive impairment while using benzodiazepines, which may lead to gait disturbances and sedation causing injury. A risk versus benefit analysis must be calculated when deciding to use BZDs in clinical scenarios. Sedative, Hypnotic, or Anxiolytic Intoxication Relatively low doses of sedatives, hypnotics, or anxiolytics can lead to intoxication during or shortly after use. Patients should be monitored closely for signs of intoxication, which include the following: • Drowsiness or sedation Treatment of acute sedative intoxication and overdose is primarily supportive and requires close monitoring of hemodynamic and respiratory status and observation until the drug is fully metabolized. A reversal agent exists. Flumazenil is a benzodiazepine antagonist. It competitively inhibits the activity of benzodiazepine and nonbenzodiazepine substances that interact with benzodiazepine receptors site on the GABA/ benzodiazepine receptor complex. It must be used with extreme caution to prevent acute precipitated withdrawal in the patient with sedative habituation. Complications may include intractable seizures. The use of flumazenil should be limited to those clinicians with familiarity with the drug. • Slurred speech • Incoordination • Unsteady gait • Nystagmus • Impaired cognition • Stupor or coma
Sedative, Hypnotic, and Anxiolytic Withdrawal The severity of withdrawal varies with dose and duration; however, it can occur with short- term, relatively low dose use of BZDs. Withdrawal symptoms include: • Autonomic hyperactivity (diaphoresis, tachycardia) • Hand tremors • Insomnia • Nausea/vomiting • Transient visual, tactile, or auditory hallucinations • Psychomotor agitation • Anxiety • Grand mal seizures Deprescribing BZDs is an important clinical skill, and the first goal of treatment in detoxification. Certain individuals may not require long-term BZDs. When deprescribing BZDs, consider duration of treatment, dose, and half-life of the BZD. Consider a taper over several weeks or months. Often switching to a long-acting BZD is an effective method in an individual who has serious abuse problems. Tapering is effective in cases of long-acting benzodiazepines but is not as effective in short- acting benzodiazepines. For example, an individual who has been taking a BZD for 12 weeks should be monitored closely while implementing a reduction of 10-25% of the dose per week. 40 Sedative Use Disorder Treatment No standard exists for determination of the appropriateness of inpatient versus outpatient settings for the management of patients who are suffering withdrawal symptoms or who are attempting to manage their long-term sedative use. Tapering doses of benzodiazepines can be managed effectively in the outpatient setting in stable healthy patients using the strategies discussed earlier. Substitution of a long-acting benzodiazepine such as Clonazepam for a short-acting drug such as Valium would eliminate the associated euphoria and illicit market value of the medication and may assist in detoxification and inappropriate use. Acute withdrawal that may be associated with delirium, abnormal vital signs, seizures, or patients with multiple comorbidities that may be at risk from labile vital signs during the withdrawal period would be more appropriately managed in a supervised inpatient setting. 145 Stimulant-Related Disorders Stimulant use disorders include a range of issues related to illicit cocaine, methamphetamine, and ecstasy, as well as prescription stimulants that include methylphenidate and amphetamine. The general mechanism of stimulants revolves around increased catecholamine levels and increased agonistic activity at adrenergic receptors. Acute adverse effects can cause acute conditions including tachycardia, vasoconstriction, and bronchodilation, as well as hyperthermia.
Table 3. FDA Approved Benzodiazepines 38
Generic
Trade
Common Indication
Alprazolam
Xanax
Anxiety, panic disorders, agoraphobia
Chlordiazepoxide
Librium Alcohol withdrawal syndrome
Clonazepam Quazepam Temazepam Diazepam Lorazepam
Klonopin Panic disorder and agoraphobia; myoclonic and absence seizures
Doral
Chronic insomnia
Restoril
Onset and sleep maintenance in insomnia
Valium Alcohol withdrawal management
Ativan Anxiety disorders Midazolam (in-patient) Versed Procedural sedation Triazolam Halcion Sleep onset in insomnia
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