Administration, drug routes

A wide variety of animal species are subjected to the administration of drugs during their lifetime.The various animal species can encounter drugs and other dietary additives by different routes and this is dependent on the environment in which they are kept. Intensively reared animals tend to have considerable consistency in the components of their diets and thus are much less likely to encounter the range of naturally produced compounds that extensively produced animals encounter. The desire for less expensive dietary constituents and increased efficiency of use has induced feed manufacturers and producers to add enzyme supplements to diets of most farmed animals to reduce the negative effects of indigestible dietary carbohydrates, refactory proteins and unavailable minerals such as phosphorus. This use of dietary additives to improve nutrient utilization and environmental consequences of feeding animals intensively has been the subject of intense research activity in the last five years. " The... 

For the majority of drugs, the preferred administration route is by oral ingestion which requires good intestinal absorption of drug molecules. Intestinal absorption is usually expressed as fraction absorbed (FA), expressing the percentage of initial dose appearing in a portal vein [15]. 

Convenient intraperitoneal route of administration of drugs such as antibiotics and insulin. 

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

Liposomes tend to remain at the injection site when they are administered intramuscularly or subcutaneously. Therefore, these administration routes are useful for slow and sustained release of drugs at the injection site. 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

The major routes of parenteral administration of drugs are subcutaneous, intramuscular, and intravenous. Other more specialized routes are intrathecal, in-tracistemal, intra-arterial, intraspinal, intraepidural, and intradermal. The intradermal route is not typically used to achieve systemic drug effects. The major routes will be discussed separately. Definitions of the more specialized routes, along with additional information concerning needle sizes, volumes typically administered, formulation constraints, and types of medication administered, are summarized in Table 1. 

Nanoparticles show great promise as devices for the controlled release of drugs, provided that the choice of material for nanoparticle formation is made with the appropriate considerations of the drug cargo, administration route, and the desired site of action. The use of nano- and microparticles as controlled drug-delivery devices has recently been extensively reviewed [97]. 

Rectal Administration. The administration of drugs by a solid rectal dosage form (i.e., suppositories) results in a wide variability in the rate and extent of absorption in children [79]. This fact, coupled with the inflexibility of a fixed dose, makes this a route that should not be promoted for pediatric patients. At least one death involving a 7-month-old infant can be directly attributed to the use of solid rectal dosage form of a therapeutic dose of morphine [80]. 

In neurochemical terms, amphetamine and cocaine boost monoamine activity. Amphetamine has a threefold mode of action first, it causes dopamine and noradrenaline to leak into the synaptic cleft second, it boosts the amount of transmitter released during an action potential and third, it inhibits the reuptake of neurotransmitter back into presynaptic vesicles. These three modes all result in more neurotransmitter being available at the synapse, thus generating an increase in postsynaptic stimulation. Cocaine exerts a similar overall effect, but mainly by reuptake inhibition. The main neurotransmitters affected are dopamine and noradrenaline, although serotonin is boosted to a lesser extent. These modes of action are outlined in Chapter 3, and the neurochemical rationale for drug tolerance is covered more fully in Chapter 10. The main differences between amphetamine and cocaine are their administration routes (summarised above) and the more rapid onset and shorter duration of action for cocaine. 

Almost 30 routes exist for administration of drugs to patients, but only a handfbl of these are commonly used in preclinical safety studies (Gad, 1994). The most common deviation from what is to be done in clinical trials is the use of parenteral (injected) routes such as IV (intravenous) and SC (subcutaneous) deliveries. Such injections are loosely characterized as bolus (all at once or over a very short period, such as five minutes) and infusion (over a protracted period of hours, days, or even months). The term continuous infusion implies a steady rate over a protracted period, requiring some form of setup such as an implanted venous catheter or infusion port. 

The oral route is the most commonly used route for the administration of drugs both because of ease of administration and because it is the most readily accepted route of administration. Although the dermal route may be as common for occupational... 

Perocular Route. The administration of drugs or accidental exposure of chemicals to the eyes is not commonly a concern in systemic toxicity due to the small surface area exposed and the efficiency of the protective mechanisms (i.e., blink reflex and tears). As long as the epithelium of the eyes remains intact, it is impermeable to many molecules, but, if the toxicant has a suitable polar-nonpolar balance, penetration may occur (Kondrizer et al., 1959 Swan and White, 1972). 

Borlak J, Blickwede M, Hansen T, Koch W, Walles M, Levsen K (2005) Metabolism of verapamil in cultures of rat alveolar epithelial cells and pharmacokinetics after administration by intravenous and inhalation routes. Drug Metab Dispos 33(8) 1108-1114... 

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