Blood flow routes

As stated earlier, inhalation is the main route of absorption for occupational exposure to chemicals. Absorption of gaseous substances depends on solubility ifi blood and tissues (as presented in Sections 2.3.3-2.3.5), blood flow, and pulmonary ventilation. Particle size has an important influence on the absorption of aerosols (see Sections 2.3.7 and 3.1.1). 

FIG. 1 Schematic presentation of pharmacokinetics in the human body. The arrows indicate possible routes of drug adminsitration and the direction of the blood flow in the circulation. 

Thus, if the hepatic clearance for a drug is largely relative to the hepatic blood flow, the extent of availability for this drug will be low when it is given by a route that yields first-pass effects. The decrease in availability is a function of only the anatomical site... 

Describe the route of blood flow through the heart... 

Table 13.1 Route of Blood Flow through the Heart...

The evidence cited here is only a very small sample of the vast quantity of research into putative cognitive enhancers. However, many of these compounds that have demonstrated positive effects are believed to influence cerebral metabolism, whether through increased blood flow, glucose metabolism or other indirect routes, as outlined above. Furthermore, these metabolic effects are hypothesised to be at least partly responsible for the cognitive improvements documented. Indeed, many of the putative cognitive enhancers currently available claim modes of influence (Table 14.1) that would fall in line with a metabolic model of cognitive enhancement. 

The most important sequelae of portal hypertension are the development of varices and alternative routes of blood flow. Patients with cirrhosis are at risk for varices when portal pressures exceed the vena cava pressure by greater than or equal to 12 mm Hg. 

The buccal mucosa, which lines the inside of the cheek, has been investigated as an alternative route for drug delivery, especially for proteins and peptides. There are many advantages associated with the use of the buccal mucosa as a site for the delivery of drugs into the systemic circulation. Since blood flow from the buccal epithelium drains directly into the internal jugular... 

When sweating is inhibited due to poisoning with anticholinergics (e.g., atropine), cutaneous blood flow increases. If insufficient heat is dissipated through this route, overheating occurs (hyperthermia). 

Extrapolation between species should ideally take into account metabolic routes, i.e., the absence or presence of metabolites, as well as the relative rate of formation of the individual metabolites. In PBPK models (Section 4.3.6), both aspects (nonlinearity, formation of active metabolites) are incorporated. This modeling technique uses compartments that correspond to actual tissues or tissue groups of the body. Size, blood flow, air flow, etc. are taken into account, in addition to specific compound-related parameters such as partition coefficients and metabolic rate data. Based on such studies, target-organ concentrations of active metabolites can be predicted in experimental animals and humans, thus providing the best possible basis for extrapolation (Feron et al. 1990). 

Developmental differences in drug absorption between neonates, infants and older children are summarized in Table 1. It must be recognized that the data contained therein reflect developmental differences which might be expected in healthy pediatric patients. Certain conditions and disease states might modify the function and/or structure of the absorptive surface area(s). GI motility and/or systemic blood flow can further impact upon either the rate or extent of absorption for drugs administered by ex-travascular routes in pediatric patients. 

Any volatile material, irrespective of its route of administration, has the potential for pulmonary excretion. Certainly, gases and other volatile substances that enter the body primarily through the respiratory tract can be expected to be excreted by this route. No specialized transport systems are involved in the loss of substances in expired air simple diffusion across cell membranes is predominant. The rate of loss of gases is not constant it depends on the rate of respiration and pulmonary blood flow. 

Reduction of local or regional blood flow is desirable for achieving hemostasis in surgery, for reducing diffusion of local anesthetics away from the site of administration, and for reducing mucous membrane congestion. In each instance, -receptor activation is desired, and the choice of agent depends on the maximal efficacy required, the desired duration of action, and the route of administration. 

Intracoronary, intravenous, or sublingual nitrate administration consistently increases the caliber of the large epicardial coronary arteries except where blocked by concentric atheromas. Coronary arteriolar resistance tends to decrease, though to a lesser extent. However, nitrates administered by the usual systemic routes may decrease overall coronary blood flow (and myocardial oxygen consumption) if cardiac output is reduced due to decreased venous return. The reduction in oxygen consumption is the major mechanism for the relief of effort angina. 

The advantages of administration by intramuscular injection are that the muscle can act as a depot, and the rate of disappearance of drug from the site of injection can be calculated. Inhalational, intranasal, and intratracheal administration are normally reserved for vapors and aerosols including anesthetics. Absorption is facilitated by small-sized particles, high lipid solubility, sufficient pulmonary blood flow, and a large absorptive surface area, as it is present in healthy lungs. Administration by these routes can be very rapid when several of the factors favoring increased absorption are combined. 

Figure 3.8 Blood flow and resulting distribution of a foreign compound from the three major sites of absorption or routes of injection. Abbreviations, i.v., intravenous injection s.c., subcutaneous injection i.m., intramuscular injection i.p., intraperitoneal injection.

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