Benzodiazepines administration route

Ross J, Darke S Hall W (1997). Transitions between routes of benzodiazepine administration among heroin users in Sydney. Addiction, 92, 697-705... 

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. 

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. 

Although diazepam has a high bioavailability after oral administration (approaching 100%), it is administered in equine practice primarily by the i.v. route. Because of its low water solubility, diazepam is solubilized in propylene glycol for injection. The bioavailability of this formulation is poor after i.m. administration and diazepam is not recommended for i.m. use. When i.m. administration of a benzodiazepine is desired, the more water-soluble agent midazolam is recommended. In contrast to diazepam, midazolam has a poor oral bioavailability (42%) because of its high hepatic clearance and first-pass metabolism. Zolazepam, in combination with tiletamine, can also be administered i.m. 

The most common route of exposure to the benzodiazepines is ingestion of oral dosage forms. Several of these agents are also available for parenteral administration (intramuscular or intravenous). Diazepam may be administered through an... 

Intranasal drug delivery This drug delivery provides fast and direct access to systemic circulation without first-pass metabolism. Administration is not easy especially with uncooperative children, but small volumes involved, rapidity of execution, feasibility at home has made it more attractive, particularly for no-needle approach to acute Illnesses. Aerosols with an appropriate device can avoid swallowing and is more precise in terms of dose. Drugs such as benzodiazepines, fentanyl, diamorphine, and ketamine have been used successfully via this route (90). 

The therapeutic uses and routes of administration of individual benzodiazepines marketed in the... 

Names, Routes of Administration, and Therapeutic Uses of Benzodiazepines ... 

The barbiturates have a different pharmacological and binding profile from that of the benzodiazepines. They exert a depressant effect on the cerebrospinal axis and depress neuronal activity as well as skeletal muscle, smooth muscle, and cardiac muscle activity. Depending on the compound, dose, and route of administration, the barbiturates can produce different degrees of CNS depression and have found use as sedatives, hypnotics, anticonvulsants, or anesthetics. 

Fosphenytoin sodium (Fig. 20.5) is a soluble pro-drug disodium phosphate ester of phenytoin (142 mg/mL) that was developed as a replacement for parenteral phenytoin sodium to circumvent the pH and solubility problems associated with parenteral phenytoin sodium formulations (36,37). Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions and is rapidly absorbed by the IM route. It is rapidly metabolized (conversion half-life, 8-15 minutes) to phenytoin by in vivo phosphatases. Therapeutic free (unbound) and total plasma phenytoin concentrations are consistently attained following IM or IV administration of fosphenytoin (26). It is administered IV following benzodiazepines for control of status epilepticus or whenever there is a need to rapidly achieve therapeutic plasma concentrations. Severe bradycardiac adverse events to fosphenytoin, including some fatalities, have been reported (38). A dose reduction in patients who are elderly or have renal or hepatic impairment has been suggested. 

This chapter deals with preparations for nasal administration, with a local or a systemic effect. Classical nasal preparations were always associated with local ailments, but nowadays the interest in the nasal route for systemi-cally acting substances and direct nose to brain delivery is increasing. Fast absorption, the possibility of high blood levels and a patient friendly dosage form are the reasons. Nasal administration of medicines with local effect is the first choice for the treatment of topical nasal disorders. It is also an attractive route for low dose active substances with a systemic effect, such as peptides or benzodiazepines (e.g. midazolam). When compared to parenteral administration nasal administration is more easily applied and causes less risk of infection. 

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