Chemistry Reference
In-Depth Information
the cell,
the equilibrium must re-establish to give a further 1% free base
.
This unionised free base can diffuse into the cell easily, the equilibrium re-
establishes, and so on. These so called 'sink conditions' mean that a
substantial portion of a drug dose can reach the site of action even though,
at first glance, there appears to be insufficient unionised drug to partition
across the membrane. This system is an example of a
dynamic equilibrium
and should be studied carefully. Dynamic equilibria occur in many sites in
the body and are responsible for a significant amount of drug absorption.
Excretion and reabsorption of drugs
Previously in this chapter, the pH partition hypothesis was applied to the
absorption of drugs across biological membranes following administration
by the oral route. The same types of physicochemical processes occur when
drugs are reabsorbed into the bloodstream following excretion by the
kidneys.
The two kidneys are situated at the back of the abdomen on either
side of the vertebral column. They carry out many functions in the body,
the most important of which is the production of urine and the excretion
from the body of low-molecular-weight (relative molecular mass less than
68 000 daltons) water-soluble compounds, including many drugs. Each
kidney contains approximately one million urine-producing structures
called nephrons. The nephron in turn consists of a bundle of blood capil-
laries termed a
glomerulus
, which functions as a very efficient filter to
remove waste products and impurities from the blood, and a long tube-like
structure called a
tubule
(see Figure 2.10).
The kidneys receive a large blood flow (approximately a quarter of the
total cardiac output of 5 litres per minute) and from this volume of blood
approximately 170 litres of filtrate are produced every day. Clearly, the body
would quickly become dehydrated if this volume of fluid were lost to the
sewage system, so most of it is reabsorbed from the kidney tubule and
returned to the bloodstream. Small molecules that are dissolved in the
glomerular filtrate are also reabsorbed back into the bloodstream, either by
passive diffusion (which obeys Fick's law) or by the utilisation of energy in
an active transport process similar to the mechanisms for gut absorption
discussed previously. It should be realised that reabsorption from the
glomerular filtrate and return to the bloodstream are involved in the
duration of action of many drugs, and a drug molecule may be filtered and
reabsorbed many times before it is finally excreted from the body.
In cases of drug overdose it is desirable to eliminate the toxic drug
from the body as quickly as possible and techniques have been devised to
