Administration, routes brain

Pharmacokinetics - labeling of a potential drug candidate. This study includes distribution studies of drug passage over the blood-brain barrier and selective accumulation in critical organs. Apart from intravenous administration, oral and nasal administration routes are other important applications employed for quantification of the deposition and disposition of a drug formulation. 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

Ricaurte, G.A. DeLanney, L.E. Irwin, L and Langston, J.W. Toxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in the primate Importance of route and frequency of drug administration. Brain Res 446 165-168, 1988a... 

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. 

However, for certain routes of injection, such as intrathecal, intraocular, or into any part of the brain, isotonicity and physiological pH are critical in order to minimize potential nerve damage. Absence of preservatives is also critical for these routes of administration for the same reason. 

The identification of the morphine receptor spurred an effort in many laboratories to find an endogenous agonist for which that receptor was normally intended. Ultimately, a pair of pentapeptides that bound quite tightly to opiate receptors were isolated from mammalian brains. These peptides, called enkephalins (2, 3), show many of the activities of synthetic opiates in isolated organ systems. They do in fact show analgesic activity when injected directly into the brain. It is thought that lack of activity by other routes of administration is due to their rapid inactivation by peptide cleaving enzymes. 

Route of administration may account for wide variations in the toxic action of fenvalerate. Most authorities agree that fenvalerate is most toxic to rodents when administered by intercere-broventricular injection relative to other routes — indicating the importance of the brain in the Type II poisoning syndrome. Fenvalerate was decreasingly toxic when administered intravenously, intraperitoneally, orally, and dermally (Lawrence and Casida 1982 Flannigan et al. 1985 Grissom etal. 1985 Bradbury and Coats 1989a Williamson etal. 1989). 

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