Diazepam route

Diazepam Being extremely lipophilic, diazepam penetrates quickly into the CNS, but can rapidly redistribute into body fat and muscle. This results in a faster decline in CNS levels and early recurrence of seizures. It is dosed at 5 to 10 mg (or 0.15 mg/kg) and infused no faster than 5 mg/minute. Repeated doses can be given every 5 minutes until seizure activity stops or toxicities are seen (e.g., respiratory depression). Diazepam can also be administered as a rectal suppository, making it possible for non-medical personnel to provide rapid therapy for seizures that develop at home or in public areas.11 The adult dose is 10 mg given rectally and this dose may be repeated once if necessary. Diazepam is erratically absorbed via the intramuscular route therefore, IM administration is not recommended. 

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. 

For example, rectal diazepam may be administered to people undergoing continuous seizures (status epilepticus), because other oral and parenteral routes would not be feasible. 

In addition, other drugs such as alosetron (2), cyproheptadine (12), diazepam (13) or tamoxifen (49) are AT-demethylated by various microorganisms as a major metabolic route. The carboxylic acid resulting from the oxidative cleavage of the piperidine ring of phencyclidine (36), probably proceeding through an... 

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). 

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. 

Most BZs are completely absorbed from the gastrointestinal (GI) tract. The one exception is clorazepate, a pro-drug that undergoes acid hydrolysis in the stomach and is decarboxylated to form N-desmethyl-diazepam, which is then completely absorbed into the bloodstream (Bellantuono et ak, 1980 Hobbs et ak, 1996 Chouinard et ak, 1999). In contrast, most BZs, with the exception of lorazepam and midazolam, are not consistently absorbed from intramuscular injection (Chouinard et ak, 1999). Lorazepam is available as a sublingual form that reaches clinical effect at the same rate as an oral dose. In general, intravenous administration is used only for anesthesia or for the acute management of seizures. When BZs are given via this route, the onset of action is almost immediate (Chouinard et ak, 1999). 

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

In patients unable to take medication by the oral route, diazepam may be administered by intramuscular or slow intravenous injection (into a large vein, at a rate of not more than 5 mg/min), at a dose of 10 mg, repeated if necessary after not less than 4 hours. Alternatively, diazepam may be administered via the rectal route as a rectal solution or suppository. The intramuscular route should only be used when both the oral and intravenous routes are not possible. 

Although intravenous diazepam is the preferred route, the undiluted intravenous solution of diazepam can be given rectally, and is effective in the emergency management of seizures in children (29). Rectal gel is an alternative, and can be given by non-medical personnel (30). Adverse effects of rectal diazepam are rare and mild. Animal studies and clinical experience have not shown damage to the rectal mucosa. 

The benzodiazepines, one of the most widely prescribed groups of drugs, undergo extensive metabolism by routes already described for the barbiturates, namely 7V-dealkylation and hydroxylation. However, unlike the barbiturates, metabolic conversion yields derivatives which have similar pharmacological activities and potencies to those of the parent compounds. For example, the three major metabolites of diazepam are desmethyl-diazepam (nordazepam), 3 -hydroxydiazepam (temazepam), and desmethyl-3-hydroxydiazepam... 

Enzymatic hydrolysis is a primary route for elimination of nerve agents. Specifically, treatment for OP intoxication includes atropine, a muscarinic receptor antagonist, an anticonvulsant such as diazepam, and a cholinesterase reactivator, an oxime. It has been found that drag-induced inhibition of ACh release and accumulation in the synaptic cleft, such as adenosine receptor antagonist early in the OP intoxication, improves the chances of survival. Some AChE reactivators, such as bispyridinum oximes, HI 6 and HLo 7 with atropine, are quite effective. 

SAFETY PROFILE Poison by ingestion and intraperitoneal routes. Moderately toxic by subcutaneous route. Human systemic effects by ingestion wakefulness, withdrawal, nausea and vomiting. An experimental teratogen. Other experimental reproductive effects. A tranquilizer. When heated to decomposition it emits very toxic fumes of NOx and Cl". See also DIAZEPAM. 

Rectal absorption is efficient with an appropriate formulation and has been used for diazepam and theophyllines this route may be preferred with an uncooperative infant. 

If an i.v. line cannot be placed, the intraosseous drug administration route can be used for pediatric patients during, for example, cardiopulmonary resuscitation (CPR) because drug delivery by this route is similar to that for i.v. administration.If drug or fluid deliver by this route is sluggish, a saline flush can be used to clear the needle. Intraosseous administration is used to deliver medications such as epinephrine, atropine, sodium bicarbonate, dopamine, diazepam, isoproterenol, phenytoin, phenobarbital, dexametha-sone, and various antibiotics. ... 

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... 

Roche converted 2-amino-5-chlorobenzophenone (147) into the first benzodiazepine antianxiety agent, chlorodiazepoxide (148) (Scheme 30). The ring enlargement was unexpected, and was soon incorporated into similar products. The same intermediate, 147, is the starting point for diazepam (149), and provides one of two routes to oxazepam (150) discovered at Wyeth (Scheme 31)82. The full range of benzodiazepines exceeds fifteen different drugs used as tranquillizers, and in some case as hypnotics. 

Diazepam (Valium) Route Pregnancy Pharmacokinetic Well absorbed... 

Diazepam. The side effects of diazepam for intravenous administration are similar to those of phenytoin when administered by this route, that is, cardiovascular collapse when administered too rapidly. 

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