Diazepam absorption

The intentional adsorption of dmgs such as diazepam onto solid substrates should be mentioned, the object being to minimise taste problems. Desorption of the dmg in vivo is essential but should not occur during the shelf-life of the preparation. Desorption may be a rate-limiting step in absorption. Diazepam adsorbed onto an inorganic colloidal... 

The nurse monitors the patient for signs and symptoms of acute salicylate toxicity or salicylism (see Display 17-1). Initial treatment includes induction of emesis or gastric lavage to remove any unabsorbed drug from the stomach. Activated charcoal diminishes salicylate absorption if given within 2 hours of ingestion. Further therapy is supportive (reduce hyperthermia and treat severe convulsions with diazepam). Hemodialysis is effective in removing Hie salicylate but is used only in patients with severe salicylism. 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

Oxazepam is available in oral form only, so it is useful only for uncomplicated withdrawal. Other benzodiazepines are available in injectable form and will be further described below. Diazepam and lorazepam are more lipophilic than chlordiazepoxide and oxazepam, resulting in quicker gastrointestinal absorption and passage across the blood-brain barrier, which makes them valuable in an inpatient setting, especially to treat or prevent seizures. However, their faster onset of action maybe associated with feeling high, which can be a disadvantage of their use. 

IM diazepam and chlordiazepoxide should be avoided because of variability in rate and extent of absorption. IM lorazepam provides rapid and complete absorption. 

Diazepam, a long-acting benzodiazepine can be used either intravenously (risk of thrombophlebitis) or intramuscularly or rectally (both of the last two routes are associated with slow absorption). 

The low pH of the gastric contents (pH 1-2) may have consequences for absorption because it can dramatically affect the degree of drug ionization. For example, the weak base diazepam (pK 3.3) will be highly protonated in the gastric juice, and consequently, ab-... 

Benzodiazepines are usually given orally and are well absorbed by this route. Since the benzodiazepines are weak bases, they are less ionized in the relatively alkaline environment of the small intestine, and therefore, most of their absorption takes place at this site. For emergency treatment of seizures or when used in anesthesia, the benzodiazepines also can be given parenter-ally. Diazepam and lorazepam are available for intravenous administration. 

This pattern is not true for all drugs, however. For example, diazepam and chlordiazepoxide are unstable at a pH of 7.4 and tend to crystallize in tissue when given intramuscularly (14, 17, 18). Therefore, they are less bioavailable when given intramuscularly versus orally. Their absorption also tends to be erratic and variable, depending on where the injection was given (i.e., near blood vessels, in fat, or in muscle), as well as slower and less complete. 

The more lipid-soluble the BZD, the more readily it passes from the plasma through the lipophilic blood-brain barrier and, thus, the more rapid its onset of action. BZDs can be subdivided on the basis of lipophilicity-a factor that plays an important role in absorption. Midazolam, quazepam, and diazepam are among the more lipophilic of the BZDs. Because increasing lipophilicity also increases the rate of redistribution from blood and brain into adipose tissue, BZDs that are less lipophilic may have more persistent brain concentrations due to reduced peripheral distribution ( 97, 184). 

BZDs with rapid absorption produce a more rapid onset of clinical activity than those with slower absorption. BZDs given orally differ in their speed of absorption from the gastrointestinal tract. For example, absorption time is 0.5 hours for clorazepate, 1 hours for diazepam, 1.3 hours for triazolam, 2 hours for alprazolam and lorazepam, 2 to 3 hours for oxazepam, and 3.6 hours for flurazepam. Absorption, however, may be influenced by the presence or absence of food in the gastrointestinal tract. Thus, patients who take a BZD hypnotic with a bedtime snack may experience a slower onset of hypnotic activity than if the same drug were taken several hours after a meal. 

The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration. 

Lin, S. Y. 1987. Pluronic surfactants affecting diazepam solubility, compatibility, and absorption from i.v. admixture solutions Parenteral Sci. Technol. 41 83-87. 

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