Hypnotic drugs reduce tension and anxiety, induce sleep, and in large doses, cause drunkenness and resultant impairment of behavioral controls. There are no specifically susceptible personality patterns, but most patients are either markedly neurotic or have a character disorder, or a mixture of both. Depressive reactions may predispose to hypnotic dependence because of the associated insomnia, and dependence frequently results from medical prescription. Alcoholics and opiate abusers frequently become dependent on hypnotic in attempts to supplement the effects of their usual drugs.
Drugs and Mode of Use.
Hypnotics (class I-B in the table) generally are taken orally. Occasionally, opiate abusers will take them intravenously. The amounts range from 4 to 50 hypnotic doses daily, frequently including several different drugs. Drugs are often obtained by prescription from different physicians, none of whom realizes that the patient has more than one source.
Distribution and Metabolism.
All the hypnotic drugs are well absorbed when taken orally and are generally distributed throughout the body. Only small amounts reach the central nervous system. Most of the drugs are metabolized in the liver by hydroxylation, dealkalization, and conjugation (barbital is an exception) and are excreted in the urine or bile. The metabolites of the drugs do not account for tolerance or physical dependence. The barbiturates that are metabolized in the liver stimulate induction of enzymes concerned with oxidation and hydroxylation, so that the metabolic degradation of barbiturates proceeds more rapidly, and the increased rate of transformation partly accounts for tolerance.
Physiologic Changes.
hypnotic elevate the threshold for excitation of all types of neurons and depress all„ kinds of central reflexes. Cortical neurons and those of the reticular activating system are the most sensitive. Neurons of the cerebellar-vestibular system are the next most sensitive, followed by the spinal neurons. Midbrain centers are the most resistant. In sufficient dose, all drugs of this type cause respiratory and cardiovascular depression.
During addiction partial tolerance develops that is never as complete as tolerance to opiates. Tolerance is due partly to increased metabolic degradation of the drugs and partly to adaptive cellular changes in the central nervous system. As with the opiates, the adaptive changes oppose and outlast drug action so that abstinence manifestations are opposite to acute drug effects. Early in chronic intoxication, thresholds for electrical induction of convulsions are increased. As tolerance develops, the electroconvulsive threshold declines to normal levels. When the drugs are abruptly withdrawn, the convulsive threshold falls below normal.
Theories of Tolerance and Dependence. Cellular tolerance t adaptive i develops by unknown mechanisms so that neurons function almost normally in the presence of high blood concentrations of drugs. Changes in the level of gamma aminobutyric acid in the brain may play a role.
Clinical Manifestations.
The manifestations of chronic hypnotic intoxication resemble those of alcoholic intoxication, and include lethargy, ataxia, nystagmus, slurred speech, impaired judgment, and emotional lability. As chronic intoxication proceeds, partial tolerance develops, and the symptoms on a particular dose become less noticeable. However, tolerance is limited and, if it is exceeded by even a small amount, signs and symptoms of intoxication reappear. Behavioral disturbances range from simple confusion and increased emotional lability to paranoid psychotic states. Patients become untidy and disheveled, neglect their work, suffer from disturbed judgment, and exhibit impulsive behavior.
Abstinence Syndrome,What Happens To The Person Who Takes An Overdose of a Sedative Hypnotic Drugs?
When hypnotics are abruptly discontinued following long-continued ingestion, a stereotyped, self-limited illness occurs. “Minor” symptoms include anxiety, tremors, restlessness, insomnia, postural hypotension, nausea, and vomiting. “Major” symptoms include convulsions, delirium, and high fever. In contrast to opiate abstinence, that from hypnotics is dangerous to life.
Several factors affect the severity of abstinence. Significant dependence usually occurs only in patients taking three to four hypnotic doses daily in whom minor symptoms and, occasionally, a convulsion appear upon withdrawal. When five to six hypnotic doses are taken daily, half the patients convulses and a third suffer delirium upon withdrawal. If eight doses or more are taken daily, convulsions occur in 75 per cent and delirium in 60 per cent. To produce abstinence signs and symptoms requires at least a month of continuous use; the longer the use, the more severe the abstinence syndrome. Signs and symptoms appear quickly following withdrawal of short-acting drugs such as meprobamate, pentobarbital, or chloral hydrate, but develop more slowly and persist longer after withdrawal from barbital, phenobarbital, and glutethimide. Recovery is usually complete in two to three weeks.
When hypnotics are abruptly withdrawn, the patient first “sobers up” and appears to improve. He then complains of nervousness, tremulousness, weakness, and insomnia. Startle responses, muscle twitching, hyperactive stretch reflexes, weakness, and postural hypotension emerge. The syndrome usually terminates in one to five days, either suddenly after a “critical” sleep or gradually. Recovery is complete and without permanent brain damage.
Diagnosis About Sedative Hypnotic Drug.
Diagnosis of dependence is usually made from the history, and should always be suggested by signs of drunkenness without the odor of alcohol. Tests are available for some of the drugs and their metabolites in blood and urine. Abstinence from hypnotics is too dangerous to warrant establishing the diagnosis by withholding drugs, and thus is best established by determining tolerance to test doses of hypnotic drugs (vide infra).
Treatment About Hypnotic Drugs .
Treatment includes withdrawal, rehabilitation, and aftercare, Withdrawal must be conducted in a hospital, nursing home, or other institution. Since abstinence from hypnotics is dangerous to life, it should be prevented if possible and, if present, should be treated vigorously, As mentioned above, the drugs in group I-B are all partially equivalent so that any of them can be used in conducting withdrawal. Pentobarbital is as effective, flexible, and safe as any other member of the group, If the diagnosis is established before signs of abstinence have appeared, the patient is given no drugs until he is sober.
Next, the least amount of pentobarbital that just maintains a mild but manageable degree of intoxication – the “stabilization dose” —must be established by trial and error. After the patient has become sober he is given a test dose of 0.2 gram of pentobarbital orally and is examined one and a half hours later, The desired effect is mild intoxication manifested by inconstant slow nystagmus on lateral gaze, slight dysarthria, and swaying, but not falling, on the Romberg test. If the desired endpoint is attained on the first test, 0.2 gram of pentobarbital is given orally every six hours, but the patient must be re-examined one and a half hours after each dose, since pentobarbital effects may cumulate,
If the patient is tremulous, agitated, and twitchy one and a half hours after the first test, the dose was insufficient and should be immediately reinforced with an additional 0.1 gram of pentobarbital, which may be repeated at hourly intervals until the desired effect has been attained, after which the patient can be placed on a regular schedule, If the patient becomes grossly ataxic, has constant nystagmus, dysarthria, and emotional lability after the test dose or any subsequent dose, too much pentobarbital has been given and the next scheduled dose should be reduced. In this way, the amount of drug required is triturated to the individual’s requirements. The stabilization dose is diagnostic as well as therapeutic. If-the patient can take 0.4 gram of pentobarbital daily without gross intoxication, he is tolerant to,, and mildly dependent on, drugs of type I-B. If he requires 0.6 to 0.8 gram daily, he is strongly dependent; and if he requires more than 0.8 gram daily, he is severely dependent. After the stabilization dose is known, the patient is maintained on that dose for a day or two while necessary examinations are being obtained.
The dose of pentobarbital is then reduced progressively by 0.1 gram or less daily. Withdrawal is usually complete in 4 to 14 days. If the patient cannot or will not take pentobarbital orally, it may be given by intramuscular injection initially in the same fashion as described for oral use. Generally, patients can be switched to oral drugs after a few intramuscular doses.Convulsions, delirium, or fever should be treated as emergencies. The patient should be given 0.2 gram of pentobarbital intramuscularly at once and additional doses of 0.1 gram at hourly intervals until asleep; additional doses should be given as required to maintain sleep for 8 to 12 hours. He is then allowed to awaken and to become sober, after which the stabilization dose is determined as described above.
Fluid and electrolyte losses must be replaced and complicating medical or surgical conditions treated. Increasing fever without evidence of infection requires additional sedation, antipyretic?, sponging, or cooling blankets.The same system of stabilization on pentobarbital to maintain slight drunkenness followed by progressive daily reduction of the pentobarbital can be used in treating abstinence from alcohol (see below).The phenothiazines, reserpine, and the butyrophenones and diphenylhydantoin are ineffective, and should be avoided.
After withdrawal the patient needs two to three weeks for convalescence, during which institution of psychiatric treatment is desirable. Following discharge, the patient should be supervised, preferably for years. Participation in Alcoholics Anonymous may help. Prognosis is guarded and relapse is frequent. Depression and suicide attempts may follow withdrawal.
