Suicides barbiturates

Overdosage, The untoward effects are directly related to the administered amount of drug (e.g., absolute overdosage, as in barbiturate suicide) or to its unexpected accumulation due to some excretory or metabolic abnormality in the patient (e.g., kidney or liver failure). 

Convulsive disorders are still a serious therapeutic problem and new agents are being actively sought. Classical therapy was based upon the barbiturates that are no longer in favor because of their many side effects and their suicide potential. Interestingly, a seemingly minor structural variation of phenobarbital (152, shown as its sodium salt) leads to an anticonvulsant of increased potency and which has less hypnotic activity. In this case, sodium phenobarbital serves as its own base (so the yield is limited to 50%) and reacts readily with... 

Due to their narrower margin of safety (risk of misuse for suicide) and their potential to produce physical dependence, barbiturates are no longer or only rarely used as hypnotics. Dependence on them has all the characteristics of an addiction (p. 210). 

With any hypnotic, the risk of suicidal overdosage cannot be ignored. Since benzodiazepine intoxication may become life-threatening only when other central nervous depressants (ethanol) are taken simultaneously and can, moreover, be treated with specific benzodiazepine antagonists, the benzodiazepines should be given preference as sleep remedies over the all but obsolete barbiturates. 

In humans, early symptoms of intoxication may include headache, dizziness, nausea, vomiting, malaise, and myoclonic jerks of the limbs clonic and tonic convulsions and sometimes coma follow and may occur without the premonitory symptoms. A suicidal person who ingested 25.6mg/kg developed convulsions within 20 minutes that persisted recurrently until large amounts of barbiturates had been administered. Hematuria and azotemia occurred the day after ingestion and continued for 18 days. Liver function studies were within normal limits except for an elevated icterus index an electroencephalogram revealed generalized cerebral dysrhythmia, which returned to normal after 5 months. ... 

The principal disadvantages of barbiturates as hypnotics include the development of physical dependence, a relatively low therapeutic index (and the potential of poisoning, as in suicide), suppression of REM sleep, and possible hangover effects. As mentioned above, benzodiazepines (e.g., flurazepam or brotizolam) are hypnotics as effective as barbiturates and are much safer in terms of their therapeutic index, addiction potential, and REM sleep-deprivation effects. Thus benzodiazepines have displaced barbiturates as sedative hypnotics. 

It produces severe toxic manifestations. Either suicidal or accidental intake of toxic doses of barbiturates is characterized by depressed respiration, circulatory shock, pupils are initially constricted then dilated due to asphyxia, hypothermia, renal failure and pulmonary complications such as acute pulmonary edema. 

Tolerance, physical dependence and addiction are possible with the benzodiazepines but less likely to occur than with barbiturates. In general this class of compounds does not cause induction. The potential for suicide is also lessened with these compounds. It has been estimated that physical dependence occurs in one person out of five million. Withdrawal symptoms are real but usually not life-threatening (fatigue due to REM rebound, dizziness, CNS disturbances). In general, benzodiazepines do not cause induction. 

One reason for Roche s success with Dalmane was that it did not share two undesirable features of the barbiturates, the then reigning class of sedatives REM suppression and suicidal potency. The barbiturates are CNS depressants that can induce unconsciousness, but because they have a very low margin of safety they can also shut down the respiratory control system of the brain stem. That is how they kill, and that is why they are still popular in Oregon and other places where individuals are free to elect a definitive end to unbearably unpleasant conscious awareness. Physician-assisted suicide is sometimes accomplished by turning off breathing, by pulling the plug internally as it were. 

Many cases document the synergistic effect of alcohol and barbiturates as a cause of death in cases appearing to be suicide. Alcohol itself is probably the most frequent cause of death due to poisoning. 

Just how safe the barbiturates are is subject to much debate. For one thing, in high doses, they are lethal, the reason that for many years barbiturate overdose was a common way by which people committed suicide. In addition, the rebound produced... 

A federal district court judge on April 17, 2002 rejected the United States Justice Department s attempt to overturn Oregon s physician-assisted suicide law. The Justice Department had claimed that the state law violated the federal Controlled Substances Act. Oregon was the first state to approve a law that allowed doctors to prescribe lethal dosages of medications like barbiturates to terminally ill patients. 

At the close of the twentieth century, the DEA reported that barbiturates represented about 20% of all depressant prescriptions in the United States. Uses ranged from epilepsy treatment to assisted suicide in Oregon. In 1997, Oregon voters approved the Death with Dignity Act, which allows doctors to prescribe lethal dosages of barbiturates to terminally ill people. 

Barbiturate overdose is a factor in nearly one-third of all reported drug-related deaths in the United States. These deaths include suicides and accidental drug poisonings. Accidental deaths sometimes occur when a user takes one dose, becomes confused, and unintentionally takes additional or larger doses. In the case of barbiturates, there is a narrow margin between the amount that induces sleep and the amount that kills. 

Acute barbiturate poisoning is mostly suicidal but sometimes accidental. There is no specific antidote for barbiturate poisoning. Earlier analeptics such as pentylenetetrazol (Metrazol) and bemegride have been used for the treatment of poisoning. 

Tragically, while the older antidepressant drugs cannot prevent suicide and can cause it, in relatively small amounts, they can become lethal instruments in the hands of suicidal patients. As little as 1 week s supply of most tricyclics can cause death, often due to cardiac dysfunction. In combination with other drugs, their lethality increases. Thus millions of depressed, suicidal patients are given the tool with which to kill themselves. By 1981, the tricyclics were overtaking the barbiturates as the medications most frequently involved in serious overdoses ( Tricyclics, 1981). The tricyclics remain a major public health problem as agents of suicide (Henry et al., 1995). 

Some of the tricyclic antidepressants and barbiturates are probably more lethal than BZs taken alone. But when BZs are combined with other drugs, such as alcohol, their lethality is increased. Overall, the BZs account for many more suicides than most physicians probably realize. 

Unlike barbiturates, benzodiazepine derivatives administered orally lack a general anesthetic action cerebral activity is not globally inhibited (the virtual impossibility of respiratory paralysis negates suicidal misuse) and autonomic functions, such as blood pressure, heart rate, or body temperature, are unimpaired. Thus, benzodiazepines possess a therapeutic margin considerably wider than that of barbiturates. 

Several classes of pharmacologic agents are available for insomnia. Barbiturates are the oldest agents that have been used for insomnia and include pentobarbital, secobarbital, and amobarbital. Barbiturates are currently not recommended because of their high abuse potential (due to rapid development of tolerance) and lethal potential in overdose situations. Barbiturates potentiate the GABAergic-induced increase in chloride ion conductance at low doses, and at high doses they depress calcium-dependent action potentials. Caution should be exercised in patients with marked renal or liver dysfunction, severe respiratory disease, suicidal tendencies, or history of alcohol/drug abuse. 

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