Overdoses of barbiturates

A thiazole derivative that incorporates a fragment of the amphetamine molecule shows some CNS stimulant activity more specifically, the compound antagonizes the depression caused by overdoses of barbiturates and narcotics. Reaction of benzalde-hyde with sodium cyanide and benzenesulfonyl chloride gives the toluenesulfony1 ester of the cyanohydrin (141). Reaction of this with thiourea leads directly to aminophenazole (143) It is probable the reaction proceeds by displacement of the tosylate by the thiourea sulfur to give 142 addition of the amino group to the nitrile followed by tautomerization affords the observed product. ... 

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. 

Nikethamide is a respiratory and heart stimulant, used beneficially against overdoses of barbiturates and morphine, Also known as Coramine, this compound (A, A-diethylnicolinamide) is made by reaction of nicotinic add esters or the add chloride with diethylamine. Its... 

Movie actress and sex symbol of the 1950s, Marilyn Monroe died of an overdose of barbiturates in 1962. 

Succinylcholine is an ultra-short-acting depolarizing skeletal muscle relaxant. The neuromuscular block remains for as long as sufficient quantities of succinylcholine remain. After i.v. administration, the onset of action is typically within Imin and lasts for 2-3 min. Succinylcholine is metabolized by plasma cholinesterases to choline and the weakly active succinylmono-choline, which is primarily excreted in the urine (Plumb 1995). Succinylcholine should be administered i.v. at a dose rate of 0.088mg/kg (Plumb 1995). Succinylcholine can also be added to an overdose of barbiturate to produce euthanasia in horses. This is accompanied by a minimal amount of postmortem muscular contraction, making the addition of succinylcholine desirable for use during euthanasia when the client is present. 

In normal human being the cerebral electrical activity is directly proportional to anxiety, emotional excitement, or administration of a potent central nervous system stimulant e.g., caffeine, dexamphetamine, lysergic acid diethylamide LSD to name a few). At this juneture the administration of a reasonably overdose of barbiturates would cause a calming effect, which could be measured demonstrably with the help of an electroencephalogram, (EEG). Thus, barbiturates depress the reticular activating system by impairing the synaptic transmission. 

The side effects of barbiturates include sedation, poor physical coordination, and impaired mental performance. They also potentiate the intoxicating effects of alcohol. Barbiturates can be extremely dangerous in overdose, causing anesthesia, coma, and even death. In addition, barbiturates can cause dangerous suppression of breathing in patients with sleep apnea or other respiratory disorders. With repeated use over just a few weeks, physical dependence and tolerance to their effects can develop, leading to increasing doses to maintain the desired therapeutic effect. If a... 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

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). 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

The amount of a fatal dosage of barbiturate will vary with the individual. However, the lethal dose is usually 10 to 15 times as large as a usual dose. A fatal overdose starts with cardiovascular collapse followed by respiratory depression. The person then falls into a coma and dies. 

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. 

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. 

By 1972, luding out —taking methaqualone with wine—was popular on college campuses. Excessive use of the drug leads to tolerance, dependence, and withdrawal symptoms similar to those of barbiturates. Overdose by methaqualone is more difficult to treat than barbiturate overdose, and deaths have frequently occurred. In the United States, the marketing of methaqualone pharmaceutical products was discontinued in 1984, and the drug became a Schedule I controlled substance. However, some level of occasional abuse has continued. 

Amphetamines and cocaine (Figure 6.11), tricyclic antidepressants (see imiprimine hydrochloride in Figure 6.12), phenylcyclidines, and belladonna alkaloids at toxic levels increase blood pressure. Overdoses of antihypertensive agents decrease blood pressure, as do toxic doses of opiates, barbiturates, iron, nitrite, cyanide, and mushroom toxins. 

The BZDs are also safer than the barbiturates because there is a large difference between the amount needed for sedation and the amount that would cause an overdose. Studies have shown that the rate of drug overdose decreased after the use of barbiturates began to decline and the BZDs were substituted. -... 

There is no drug or magic remedy that can help reverse the effects of barbiturates. For example, with an overdose of a narcotic, such as morphine, the drug naloxone can be given. With barbiturates, only time makes the overdose patient get better. Following overdose, the blood levels will go down and with this, the comatose state and the shallow breathing will lessen. 

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