Foreign compound toxicity blood

Many toxic substances and other foreign compounds are removed from the blood as it passes through the kidneys. The kidneys receive around 25% of the cardiac output of blood, and so they are exposed to and filter out a significant proportion of foreign compounds. However, excretion into the urine from the bloodstream applies to relatively small, water-soluble molecules large molecules such as proteins do not normally pass out through the intact glomerulus, and lipid-soluble molecules such as bilirubin are reabsorbed from the kidney tubules (Fig. 3.31). 

Once absorbed, foreign compounds may react with plasma proteins and distribute into various body compartments. In both neonates and elderly human subjects, both total plasma-protein and plasma-albumin levels are decreased. In the neonate, the plasma proteins may also show certain differences, which decrease the binding of foreign compounds, as will the reduced level of protein. For example, the drug lidocaine is only 20% bound to plasma proteins in the newborn compared with 70% in adult humans. The reduced plasma pH seen in neonates will also affect protein binding of some compounds as well as the distribution and excretion. Distribution of compounds into particular compartments may vary with age, resulting in differences in toxicity. For example, morphine is between 3 and 10 times more toxic to newborn rats than adults because of increased permeability of the brain in the newborn. Similarly, this difference in the blood-brain barrier underlies the increased neurotoxicity of lead in newborn rats. 

Figure 6.1 The interrelationships between the disposition and toxicity of a foreign compound. The parent compound may undergo distribution out of the blood (d) to other tissues, and there cause toxicity by reaction with receptors (r). Alternatively, metabolism (m) may also occur and give rise to toxic metabolites (a), which react with critical targets (r). Metabolites may also distribute back into the blood (b) and be excreted (e).

Many toxic substances and other foreign compounds are removed from the blood as it passes through the kidneys. The kidneys receive around 25 % of the cardiac output of blood and so they are exposed to and filter out... 

FIGURE 6.1 The interrelationships between the disposition and toxicity of a foreign compound. The parent compound may undergo distribution out of the blood (d) to other tissues and there cause toxicity by reaction with receptors... 

As almost all foreign compounds are distributed via the bloodstream, the components of the blood are exposed at least initially to significant concentrations of toxic compounds. Damage to and destruction of the blood cells results in a variety of sequelae such as a reduced ability to carry oxygen to the tissues if red blood cells are destroyed. Aromatic amines such as aniline and the drug dapsone (4,4-diaminodiphenyl sulphone) are metabolized to hydroxylamines, and in the latter case the metabolite is concentrated in red blood cells. Also, nitro compounds such as nitrobenzene, which can be reduced to hydroxylamines, are similarly toxic to red blood cells. These hydroxylamines are often unstable and can be further oxidized to reactive products, in the presence of oxygen in the... 

Drastic changes in blood pressure may occur as a toxic response to a foreign compound, such as the hypotension caused by hydrazoic acid and sodium azide. There may be various mechanisms involved such as vasodilation, /1-adrenoceptor blockade or altered water balance. Anti-hypertensive drugs will clearly cause dangerous hypotension if given in large doses, but such an exaggerated response may also be due to reduced metabolism in some individuals, as in the case of debrisoquine (see Chapter 5). 

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