Barbiturates pharmacologic effects

Barbiturates are rare these days but these depressants produce their pharmacological effects by increasing the duration of CU channel opening associated with GABAa receptors (see Chapter 11). 

Although PCP was developed as an anesthetic, its profile as an anesthetic is very different from typical general anesthetics of the CNS-depressant class (Domino 1964). Nonetheless, PCP has a number of behavioral and pharmacological effects similar to those of depressants such as the barbiturates (Balster and Wessinger 1983). PCP has profound motor effects, as evidenced by effects on rotorod performance and similar measures (Kalir et al. 1969 ... 

As with all of the examined drugs in this chapter, methyprylon is intended for treating insomnia. The pharmacological effects of methyprylon are similar to those of barbiturates. However, barbiturates are beginning to give way, thanks to the introduction of benzodiazepines into medical practice. Synonyms for this drug are noctar, noludar, and others. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Estazolam potentiates the CNS depressant effects of phenothiazines, narcotics, antihistamines, MAOIs, barbiturates, alcohol, general anesthetics, and TCAs. Use with cimetidine, disulfiram, oral contraceptives, and isoniazid may diminish hepatic metabolism and result in increased plasma concentrations of estazolam and increased CNS depressant effects. Fleavy smoking (more than 20 cigarettes/day) accelerates estazolam s clearance. Theophylline antagonizes estazolam s pharmacological effects. 

The chemical structures of some older and less commonly used sedative-hypnotics, including several barbiturates, are shown in Figure 22-3. Glutethimide and meprobamate are of distinctive chemical structure but are practically equivalent to barbiturates in their pharmacologic effects. They are rarely used. The sedative-hypnotic class also includes compounds of simpler chemical structure, including ethanol (see Chapter 23) and chloral hydrate. 

Most sedatives and hypnotics achieve concentrations in breast milk sufficient to produce a pharmacologic effect in some infants. Barbiturates taken in hypnotic doses by the mother can produce lethargy, sedation, and poor suck reflexes in the infant. Chloral hydrate can produce sedation if the infant is fed at peak milk concentrations. Diazepam can have a sedative effect on the nursing infant, but, most importantly, its long half-life can result in significant drug accumulation. 

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-... 

Severe anaphylactic reactions following intravenous administration of diazepam have been reported. Meprobamate causes toxicity similar to that of a barbiturate overdosage. Death may result from respiratory failure or hypotension. Limited information is available about the acute toxicity of Buspirone. Effects are merely extensions of pharmacological effects. Nausea, vomiting, dizziness, drowsiness, miosis, and gastric distention may be seen. 

To reach this goal, the first step was to establish a predictive parameter for the volatility of drugs. Underscoring the importance of volatility is the practice of smoking various drugs of abuse in combination or with other agents in an effort to enhance their volatility and thereby increase their pharmacological effects. For example, the addition of either caffeine or barbiturates has been shown to improve the volatilization of heroin (Huzier 1987). 

When used concomitantly, theophylline increases the excretion of lithium. Also, cimetidine, allopurinol (high dose), propranolol, erythromycin, and troleandomycin may cause an increase in serum concentrations of theophylline by decreasing the hepatic clearance. Barbiturates and phenytoin enhance hepatic clearance and hepatic metabolism of theophylline, decreasing plasma levels. Beta-adrenergic blockers exert an antagonistic pharmacologic effect. 

The pharmacological effects of the barbiturates is invariably marked by a decrease with regard to the normal functional activities in the brain. It has been duly observed that at the prevailing therapeutic dose levels in vivo the barbiturates cause a distinct marked enhancement of the GABAergic inhibitory response, in a mechanism very much akin to that shown by the benzodiazepines, that is, by influencing conductance at the site of chloride channel. It is pertinent to mention here that at comparatively higher concentration barbiturates would display six marked and pronounced pharmacological actions ... 

The barbiturates also cause a physical dependence different from the opioid narcotics. In an individual addicted to barbiturates, the barbiturates should not be withdrawn abruptly but, rather, tapered slowly. Sudden withdrawal of the barbiturates can precipitate extreme agitation and grand mal seizures. This can lead to a spasm of the respiratory musculature, producing impaired respiration, cyanosis, and possibly, death (42). As a rule, drug dependence is followed by tolerance, in which increasing doses are required to obtain the same pharmacological effect. Because barbiturates cause tolerance and, often, dependence, their use as a hypnotic rarely is justified. 

The MAOIs interfere with the hepatic metabolism of many prescription and nonprescription (over-the-counter) drugs and may potentiate the actions of their pharmacological effects (i.e., cold decongestants, sympathomimetic amines, general anesthetics, barbiturates, and morphine). 

Tranquillisers and muscle relaxants—As a consequence of studies which demonstrated the pronounced modifications in pharmacological effects that result from V-substitution of the barbiturates [167, 175-177], a series of... 

Secobarbital exhibits the same pharmacologic properties as other members of the barbiturate class. Most nonmedical use is with short-acting barbiturates, such as secobarbital. Although there may be considerable tolerance to the sedative and intoxicating effects of the drug, the lethal dose is not much greater in addicted than in normal persons. Tolerance does not develop to the respiratory effect. The combination of alcohol and barbiturates may lead to fatalities because of their combined respiratory depressive effects. Similar outcomes may occur with the benzodiazepines. Severe withdrawal symptoms in epileptic patients may include grand mal seizures and delirium. 

---