Hypnotics overdose

Patients with the lethargy pattern of PCP toxicity may be clinically indistinguishable from patient with mild sedative/hypnotic intoxication, although hypertension and grand mal seizures which may occur with PCP intoxication, are not expected with sedative/ hypnotic overdose. The remaining minor patterns are differentiated as follows. 

Patients with ethanol or sedative-hypnotic overdose may be euphoric and rowdy ("drunk") or in a state of stupor or coma ("dead drunk"). Comatose patients often have depressed respiratory drive. Depression of protective airway reflexes may result in aspiration of gastric contents. Hypothermia may be present because of environmental exposure and depressed shivering. Ethanol blood levels greater than 300 mg/dL usually cause deep coma, but regular users are often tolerant to the effects of ethanol and may be ambulatory despite even higher levels. Patients with GHB overdose are often deeply comatose for 3-4 hours and then awaken fully in a matter of minutes. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Analeptics are drugs that have a stimulatory effect on the respiratory and vasomotor centers of the medulla. Analeptics are primarily used as antagonists in depressant drug overdose (hypnotics, narcotics). Having a relatively small range of therapeutic action, they can stimulate other parts of the CNS even in minor overdoses, causing a number of undesirable side effects such as stimulation of the cardiovascular system, hyperreflexia, vomiting, and seizures. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

Anxiolytics and Sedative-Hypnotics. Because of their large therapeutic index, measurement of anxiolytic or sedative-hypnotic serum concentrations is not usually necessary in clinical practice, unless abuse, overdose, or inadvertent toxicity are suspected. Some data indicate that plasma alprazolam levels of 40 ng/mL may be required to manage panic disorder ( 51) (see the sections Adverse Effects of Anxiolytics and Adverse Effects of Sedative-Hypnotics in Chapter 12). 

The benzodiazepines (BZDs), which were introduced nearly 40 years ago, were hailed as a breakthrough because they have fewer of the drawbacks of prior anxiolytics and sedative-hypnotics, are effective in a range of disorders, and are safe in combination with most drugs (except other sedatives), as well as alone in overdose, and are generally mild in terms of side effects. For these reasons, BZDs quickly became, and remain, among the most widely prescribed drugs worldwide. 

More recently, non-BZD anxiolytics, such as buspirone, and nonbarbiturate, non-BZD hypnotics, such as zolpidem and zaleplon, have been developed. The more recent anxiolytics and hypnotics offer equal efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose. Unfortunately, these compounds have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they do have a lower abuse potential than their predecessors. 

Barbiturates and barbiturate-like drugs, such as chloral hydrate, although effective hypnotics, are considered far less safe than BZDs in terms of tolerance, interaction with alcohol, and lethality in overdose. Therefore, their use is not generally recommended. 

At hypnotic doses in healthy patients, the effects of sedative-hypnotics on respiration are comparable to changes during natural sleep. However, even at therapeutic doses, sedative-hypnotics can produce significant respiratory depression in patients with pulmonary disease. Effects on respiration are dose-related, and depression of the medullary respiratory center is the usual cause of death due to overdose of sedative-hypnotics. 

Nontolerant individuals who consume alcohol in large quantities develop typical effects of acute sedative-hypnotic drug overdose along with the cardiovascular effects previously described (vasodilation, tachycardia) and gastrointestinal irritation. Since tolerance is not absolute, even chronic alcoholics may become severely intoxicated if sufficient alcohol is consumed. 

An understanding of common mechanisms of death due to poisoning can help prepare the care-giver to treat patients effectively. Many toxins depress the central nervous system (CNS), resulting in obtundation or coma. Comatose patients frequently lose their airway protective reflexes and their respiratory drive. Thus, they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdoses of narcotics and sedative-hypnotic drugs (eg, barbiturates and alcohol). 

Phenobarbital, mephobarbital and metarbital are the only oral anticonvulsants which are effective at sub-hypnotic levels. Many barbiturates are classified as Schedule II, III, or IV due to their high potential for overdose and dependence. Abrupt withdrawal may cause seizures, restlessness, trembling, and insomnia and may be fatal. Phenobarbital is used as an anticonvulsant for the treatment of epilepsy and in some combination medications for the relief of irritable bowel syndrome. 

Benzodiazepines are a family of compounds that share the same basic chemical structure and pharmacological effects. Although the more famous members of this family are associated with treating anxiety (e.g., diazepam [Valium] see later in this chapter), several benzodiazepines are indicated specifically to promote sleep (Table 6-1). These agents exert hypnotic effects similar to those of nonbenzodiazepines—such as the barbiturates—but benzodiazepines are generally regarded as safer because there is less of a chance for lethal overdose.22 Benzodiazepines, however, are not without their drawbacks, and they can cause resid-... 

Barbiturates Nembutal Seconal Others Sedative-hypnotic Oral or injected (IM, IV] Relaxation and a sense of calmness drowsiness Physical dependence possible death from overdose behavior changes (irritability, psychosis] following prolonged use See Chapter 6... 

Glutethimide (Doriden), a highly lipid-soluble drug classified as a sedative-hypnotic, was introduced in 1954 as a safe barbiturate substitute. However, its addiction potential and the severity of withdrawal symptoms were similar to those of barbiturates. In 1991, glutethimide was classified as a Schedule II controlled substance in response to an upsurge in the prevalence of diversion, abuse, and overdose deaths. The drug is illegal in the United States and in several other countries. It is classified as a sedative-hypnotic. 

Any new hypnotic should induce and maintain natural sleep without producing residual sedative effects during the day it should not cause dependence or interact adversely with other sedatives, including alcohol. The ideal hypnotic should not cause respiratory depression or precipitate cardiovascular collapse when taken in overdose. So far no drug fulfils all these criteria. 

Overdosing An overdose of a hypnotic drag causes a user to fall unconscious for 2d6 hours. 

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