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P A R T 1
Introduction to nursing pharmacology
(the blood vessels that flow through the liver on their
way back to the heart). Aspirin and alcohol are two
drugs that are known to be absorbed from the lower end
of the stomach. The portal veins deliver these absorbed
molecules into the liver, which immediately transforms
most of the chemicals delivered to it by a series of liver
enzymes. These enzymes break the drug into metabo
lites, some of which are active and cause effects in the
body and some of which are deactivated and can be
readily excreted. As a result, a large percentage of the
oral dose is destroyed at this point and never reaches
the tissues. This phenomenon is known as the
first-pass
effect
. The portion of the drug that gets through the
first-pass effect is delivered to the circulatory system for
transport throughout the body.
Injected drugs and drugs absorbed from sites other
than the GI tract undergo a similar biotransformation
when they pass through the liver. Because some of the
active drug already has had a chance to reach the respon
sive tissues before reaching the liver, the injected drug is
often more effective at a lower dose than the oral equiva
lent. Thus, the recommended dose for oral drugs can be
considerably higher than the recommended dose for par
enteral drugs, taking the first-pass effect into account.
Bioavailability and bioequivalence
Bioavailability
refers to the proportion of drug that
passes through to systemic circulation after oral admin
istration, taking into account both absorption and
metabolic degradation. It relates to the total proportion
of drug that reaches the systemic circulation. The use
of the concept of bioavailability is limited as it relates
only to the total proportion of the drug that reaches the
systemic circulation and neglects the rate of absorption.
Regulatory authorities make decisions about the “generic
equivalence” of patented products. The concept of bio
availability may be used to provide evidence that a new
product behaves sufficiently similar to the existing one
to be substituted for without causing clinical problems
(
bioequivalence
).
Distribution
Distribution
involves the movement of a drug to the
body’s tissues (Figure 2.2). As with absorption, factors
that can affect distribution include the drug’s lipid solu
bility and ionisation, and the perfusion of the responsive
tissue.
For example, tissue perfusion is a factor in caring
for a person with diabetes who has a lower-leg infec
tion and needs antibiotics to destroy the bacteria in the
area. In this case, systemic drugs may not be effective
because part of the disease process involves changes in
the vasculature and decreased blood flow to some areas,
particularly the lower limbs. If there is not adequate
blood flow to the area, little antibiotic can be delivered
to the tissues and little antibiotic effect will be seen.
In the same way, people in a cold environment may
have constricted blood vessels (vasoconstriction) in the
extremities, which would prevent blood flow to those
areas. The circulating blood would be unable to deliver
drugs to those areas and the person would receive little
therapeutic effect from drugs intended to react with
those tissues.
Many drugs are bound to proteins and are not lipid
soluble. These drugs cannot be distributed to the central
nervous system (CNS) because of the effective blood–
brain barrier (see later discussion), which is highly
selective in allowing lipid soluble substances to pass into
the CNS.
Pharmacology:
Distribution
Protein binding
Most drugs are bound to some extent to proteins in the
blood to be carried into circulation. The protein–drug
complex is relatively large and cannot enter into capil
laries and then into tissues to react. The drug must be
freed from the protein’s binding site at the tissues.
Many drugs are extensively bound to proteins and
it should be noted that only the unbound fraction of the
drug can reach the site of action in responsive tissues.
Some drugs compete with each other for protein binding
sites, altering effectiveness or causing toxicity when the
two drugs are given together. The toxicity is attributed
to sudden increase in the fraction of the previously pro
tein-bound drug that is now free.
Pharmacology:
Drug binding
Blood–brain barrier
The blood–brain barrier is a protective system of cellular
membranes that keep many things (e.g. foreign invaders,
poisons) away from the CNS. The fundamental structural
difference of the membranes forming the blood-brain
barrier is the use of so called tight-junctions between
cells, leaving no gaps between the cells. Drugs that are
highly lipid soluble are more likely to pass through the
blood–brain barrier and reach the CNS. Drugs that are
not lipid soluble are not able to pass the blood–brain
barrier. This is clinically significant in treating a brain
infection with antibiotics. Almost all antibiotics are not
lipid soluble and cannot cross the blood–brain barrier.
Effective antibiotic treatment can occur only when the
infection is severe enough to damage the blood–brain
barrier and allow antibiotics to cross.
Although many drugs can cause adverse CNS
effects, these are often the result of indirect drug effects
and not the actual reaction of the drug with CNS tissue.
For example, alterations in glucose levels and electro
lyte changes can interfere with nerve functioning and
produce CNS effects such as dizziness, confusion or
changes in thinking ability.
