Sedative-hypnotic drugs abuse

Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) is a sedative-hypnotic drug that is now rarely used therapeutically because of wide variation in gastrointestinal absorption, fast development of pharmacodynamic tolerance, a fairly severe discontinuation syndrome, and potential for abuse. Reports of... 

Allgulander, C. History and current status of sedative-hypnotic drug use and abuse. Acta Psychiatr. Scand. 73, 465-478, 1986. 

All of the neuroleptics are consumed in their pure form and are rarely abused. Most of the sedative-hypnotics of abuse are diverted from legitimate sources and remain in their pure form. However, occasionally powdered forms of illegal drugs (such as ketamine hydrochloride), which are often manufactured in clandestine laboratories, are mixed with tobacco, marijuana, or other drugs. 

Cross-tolerance means that tolerance to any sedative-hypnotic drug will extend to other drugs in the same class. Cross-dependency means that use of any drug in this class, or any opioid drug will enhance the effects and abusers may turn to other drugs in either category to either supplement their drugs of choice or stand in for them if they are not readily available. 

Benzodiazepines show less tendency to tolerance and dependency than other older sedative-hypnotic drugs, especially barbiturates. Also, benzodiazepines produce less abuse potential. 

Ethanol, a sedative-hypnotic drug, is the most important alcohol of pharmacologic interest. It has few medical applications, but its abuse as a recreational drug is responsible for major medical and socioeconomic problems. Other alcohols of toxicologic importance are methanol and ethylene glycol. 

Comparable findings for lifetime prevalence of psychiatric disorders were obtained in another study of 133 persons, which also found that 47% received a concurrent DSM-III diagnosis of substance abuse or dependence (Khantzian and Treece 1985). The most frequently abused substances were sedative-hypnotics (23%), alcohol (14%), and cannabis (13%). Similar rates of psychiatric disorders were found in other studies of drug abusers (Mirin et al. 1986 Woody et al. 1983). Although such diagnoses do not imply causality, and, in many cases, opioid dependence causes or exacerbates psychiatric problems, some causal link seems likely (Regier et al. 1990). 

Uni 1ke other drugs of abuse, the diagnosis of PCP intoxication is often difficult because of the wide spectrum of clinical findings that occurs with this drug. PCP toxicity sometimes can be mistaken for delirium tremens, acute psychiatric illness, sedative/ hypnotic overdosage, amphetamine intoxication, or sedative/ hypnotic withdrawal syndromes. 

Drug abuse and dependence Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Zolpidem does not reveal any clear evidence for withdrawal syndrome. 

Compared to the benzodiazepine sedative-hypnotics, secobarbital is more lethal in overdosage, has a higher tendency for abuse and addiction, and is more likely to cause drug interactions via induction of hepatic microsomal enzymes few advan-fages if any in safety or efficacy over benzodiazepines... 

Psychotic symptoms may also occur with the withdrawal of alcohol, sedatives, hypnotics, and anxiolytics The following symptoms may occur persecutory delusions, perceptual distortions, and vivid hallucinations in any modality, most classically visual and tactile hallucination of insects crawling under the skin (formication) Substance abuse history may be elicited from the history and confirmed by finding urinary metabolites Confirmation of schizophrenia can only be made if the psychotic symptoms persist for at least a month following drug withdrawal... 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

One of the first quinazolone-based drugs, the sedative hypnotic methaqualone (83-4), gained considerable notoriety as a drug of abuse under the alias ludes after the original tradename Quaalude. The compound is prepared in a straightforward fashion by fusion of anthranilamide (83-1) with orf/zo-toluidine (83-2) [93] the reaction can be envisaged as proceeding via the di-amide (83-3). 

Barbiturates, which preceded benzodiazepines as the most commonly abused sedative hypnotics (after ethanol), are now rarely prescribed to outpatients and therefore constitute a less common prescription drug problem than they did in the past. Street sales of barbiturates, however, continue. Management of barbiturate withdrawal and addiction is similar to that of benzodiazepines. 

Jasinski, D.R., Assessment of the abuse potentiality of morphinelike drugs (methods used in man), in Drug Addiction 1 Morphine, Sedative/Hypnotic and Alcohol Dependence, W.R. Martin, Ed., Springer-Verlag, Berlin, 1977. 

Finally, long-term insomnia is not only persistent but disabling. Studies suggest that almost all of these patients have either an associated psychiatric disorder, an associated drug use, abuse, or withdrawal problem, or an associated medical disorder. As mentioned above, treatment of these associated disorders may be sufficient to treat the insomnia as well. However, if the underlying disorder is not treatable or if there is a requirement to relieve the symptom of insomnia before the underlying condition can be relieved, it may be necessary to treat the insomnia symptomatically with a sedative-hypnotic agent. 

---