For barbiturate overdose

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... 

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-... 

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

Ethchlorvynol, USP. Ethchlurvynol. l-chloro-.A-cthyl-l-penten-4-yn-.A-ol (Placidyl). is a sedative-hypnotic with a rapid on.sct and short duration of action. Metabolism, probably involving the hydroxyl group, accounts for about 90% of a dose. Acute overdo.se shares several features with barbiturate overdose. 

Methods are avahable for detecting barbiturate overdose and abuse. To detect overdose, semiquantitative immunoassays suitable for detection of barbiturates in serum are avaUable and useful for this purpose. Capillary GC is also useful for this purpose, and a capillary GC procedure is described in the Chapter 34 Appendix that is formd on this book s accom-... 

Capillary Gas Chromatography. To detect barbiturate overdose, a serum sample can be analyzed for several barbiturates using the capillary GC technique described in the Chapter 34 Appendix that is found on this book s accompanying Evolve site (http //evolve.elsevier.com/Tietz/text-book/). In this method, aprobarbital is first added to an aliquot of the sample as an internal standard. Barbiturates in the aliquot are then extracted twice with diethyl ether, and the ether is dehydrated with solid sodium sulfate and then evaporated to dryness. The residue is dissolved in 50)uL of ethyl acetate, and an aliquot is injected into the gas chromatograph. 

Sedative-hypnotics (barbiturates, benzodiazepines, ethanol) Disinhibition initially, later lethargy, stupor, coma. Nystagmus is common. Decreased muscle tone, hypothemiia. Small pupils, hypotension, and decreased bowel sounds in severe overdose Provide airway and respiratory support. Avoid fluid overload. Use flumazenil for benzodiazepine overdose... 

IV. Diagnosis is usually based on a history of ingestion and should be suspected in any epileptic patient with stupor or coma. Although skin bullae are sometimes seen with barbiturate overdose, these are not specific for barbiturates. Other causes of coma should also be considered (see p 19). 

The various barbiturates differ m the time required for the onset of sleep and m the duration of their effects All the barbiturates must be used only m strict accordance with instructions to avoid potentially lethal overdoses Drug dependence m some mdi viduals IS also a problem... 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

Thalidomide, a prescription drng nsed as a tranqniUzer and flu medicine for pregnant women in Enrope to replace dangerous barbiturates that cause 2000 to 3000 deaths per year by overdoses, was found to cause birth defects. Thalidomide had been kept off the market in the United States because of the insistence that more safety data be produced for the drug. 

Effects of pH on urinary drug elimination may have important applications in medical practice, especially in cases of overdose. For example, one can enhance the elimination of a barbiturate (a weak acid) by administering bicarbonate to the patient. This procedure alka-linizes the urine and thus promotes the excretion of the now more completely ionized drug. The excretion of bases can be increased by making the urine more acidic through the use of an acidifying salt, such as ammonium chloride. 

Historically, alcohol has been used as an anxiety-reducing agent, both casually and in professional medical settings. In 1903, barbital was introduced as the first barbiturate to treat anxiety, and phenobarbital followed a few years later. Barbiturates have many side effects and addictive properties, and overdose can lead to coma and death. For these reasons, they are rarely used today, except to treat some forms of epilepsy. This class of drugs was eventually replaced by the benzodiazepines (see Chapter 4). 

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. 

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