Drug Action: Pharmaceutic,
Pharmacokinetic, and
Pharmacodynamic Phases
A tablet or capsule taken by mouth goes through
three phases—pharmaceutic, pharmacokinetic,
and pharmacodynamic—as drug actions occur.
In the pharmaceutic phase, the drug becomes a
solution so thatit can cross the biologic
membrane. When the drug is administered
parenterally by subcutaneous (subQ),
intramuscular (IM), or intravenous (IV) routes,
there is no pharmaceutic phase. The second
phase, the pharmacokinetic phase, is composed
of four processes: absorption, distribution,
metabolism (or biotransformation), and
excretion (or elimination). In the
pharmacodynamics phase, a biologic or
physiologic response results.
PHARMACEUTIC PHASE
Approximately 80% of drugs are taken by
mouth. The pharmaceutic phase (dissolution) is
the first phase of drug action. In the
gastrointestinal (GI) tract, drugs need to be in
solution so they can be absorbed. A drug in solid
form (tablet or capsule) must disintegrate into
small particles to dissolve into a liquid, a process
known as dissolution. Drugs in liquid form are
already in solution. Figure 1-1 displays the
pharmaceutic phase of a table.
Tablets are not 100% drug. Fillers and inert
substances, generally called excipients, are used
in drug preparation to allow the drug to take on a
particular size and shape and to enhance drug
dissolution. Some additives in drugs, such as the
ions potassium (K) and sodium (Na) in penicillin
potassium and penicillin sodium, increase the
absorbability of the drug. Penicillin is poorly
absorbed by the GI tract because of gastric acid.
However, by making the drug a potassium or
sodium salt, penicillin can then be absorbed.
Disintegration is the breakdown of a tablet into
smaller particles. Dissolution is the dissolving
of the smaller particles in the GI fluid before
absorption. Rate of dissolution is the time it
takes the drug to disintegrate and dissolve to
become available for the body to absorb it.
Drugs in liquid form are more rapidly available
for GI absorption than are solids. Generally,
drugs
are both disintegrated and absorbed faster in
acidic fluidswith a pH of 1 or 2 rather than in
alkaline fluids. Alkaline drugs would become
ionized and have difficulty crossing cell
membrane barriers. Both the very young and
older adults have less gastric acidity; therefore,
drug absorption is generally slower for those
drugs absorbed primarily in the stomach.
Enteric-coated drugs resist disintegration in the
gastric acid of the stomach, so disintegration
does not occur until the drug reaches the alkaline
environment of the small intestine. Enteric-
coated tablets can remain in the stomach for a
long time; therefore, their effect may be delayed
in onset. Enteric-coated tablets or capsules and
sustained-release (beaded) capsules should not
be crushed. Crushing would alter the place and
time of absorption of the drug. Food in the GI
tract may interfere with the dissolution of certain
drugs. Some drugs irritate the gastric mucosa, so
fluids or food may be necessary to dilute the
drug concentration and to act as protectants.
PHARMACOKINETIC PHASE
Pharmacokinetics is the process of drug
movement toachieve drug action. The four
processes are absorption, distribution,
metabolism (or biotransformation), and
excretion
(or elimination). The nurse applies knowledge of
pharmacokinetics when assessing the patient for
possible adverse drug effects. The nurse
communicates assessment findings to members
of the health care team in a timely manner to
promote safe and effective drug therapy for the
patient.
Absorption
Absorption is the movement of drug particles
from the GI tract to body fluids by passive
absorption, active absorption, or pinocytosis.
Most oral drugs are absorbed into the surface
area of the small intestine through the action of
the extensive mucosal villi. Absorption is
reduced if the villi are decreased in number
because of disease, drug effect, or the removal of
small intestine. Protein-based drugs such as
insulin and
growth hormones are destroyed in the small
intestine by digestive enzymes. Passive
absorption occurs mostly by diffusion
(movement from higher concentration to lower
concentration). With the process of diffusion, the
drug does not require energy to move across the
membrane. Active absorption requires a carrier
such as an enzyme or protein to move the drug
against a concentration gradient. Energy is
required for active absorption. Pinocytosis is a
process by which cells carry a drug across their
membrane by engulfing the drug particles
(Figure 1-2). The GI membrane is composed
mostly of lipid (fat) and protein, so drugs that
are lipid soluble pass rapidly through the GI
membrane. Water-soluble drugs need a carrier,
either enzyme or protein, to pass through the
membrane. Large
particles pass through the cell membrane if they
are nonionized (have no positive or negative
charge). Weak acid drugs such as aspirin are less
ionized in the stomach, and they pass through
the stomach lining easily and rapidly. An
infant’s gastric secretions have a higher pH
(alkaline) than those of adults; therefore, infants
can absorb more penicillin. Certain drugs such
as calcium carbonate and many of the
antifungals need an acidic environment to
achieve greater drug absorption; thus food can
stimulate the production of gastric acid.
Hydrochloric acid destroys some drugs such as
penicillin G; therefore a large oral dosage of
penicillin is needed to offset the partial dose
loss. Drugs administered by many routes do not
pass through the GI tract or liver. These include
parenteral drugs, eyedrops, eardrops, nasal
sprays, respiratory inhalants, transdermal drugs,
and sublingual drugs. Remember, drugs that are
lipid soluble and nonionized are absorbed faster
than water-soluble and ionized drugs.
Blood flow, pain, stress, hunger, fasting, food,
and pH affect drug absorption. Poor circulation
to the stomach as a result of shock,
vasoconstrictor drugs, or disease hampers
absorption. Pain, stress, and foods that are solid,
hot, or high in fat can slow gastric emptying
time, so the drug remains in the stomach longer.
Exercise can decrease blood flow by causing
more blood to flow to the peripheral muscle,
thereby decreasing blood circulation to the GI
tract. Drugs given IM are absorbed faster in
muscles that have more blood vessels (e.g.,
deltoids) than in those that have fewer blood
vessels (e.g., gluteals). Subcutaneous tissue has
fewer blood vessels, so absorption is slower in
such tissue.
Some drugs do not go directly into the systemic
circulation following oral absorption but pass
from the intestinal lumen to the liver via the
portal vein. In the liver, some drugs may be
metabolized to an inactive form that may then be
excreted, thus reducing the amount of active
drug. Some drugs do not undergo metabolism at
all in the liver, and
others may be metabolized to drug metabolite,
which may be equally or more active than the
original drug. The process in which the drug
passes to the liver first is called the first-pass
effect, or hepatic first pass. Most drugs given
orally are affected by first-pass metabolism.
Lidocaine and some nitroglycerins are not given
orally because they have extensive first-pass
metabolism and therefore most of the dose
would be destroyed. Bioavailability is a
subcategory of absorption. It is the percentage of
the administered drug dose that reaches the
systemic circulation. For the oral route of drug
administration, bioavailability occurs after
absorption and first-pass metabolism. The
percentage of bioavailability for the oral route is
always less than 100%, but for the IV route it is
100%. Oral drugs that have a high first-pass
hepatic metabolism may have a bioavailability
of only 20% to 40% on entering systemic
circulation. To obtain the desired drug effect, the
oral dose could be higher than the drug dose for
IV use.
Factors that alter bioavailability include (1) the
drug form (e.g., tablet, capsule, sustained-
release, liquid, transdermal patch, rectal
suppository, inhalation), (2) route of
administration (e.g., oral, rectal, topical,
parenteral), (3) GI mucosa and motility, (4) food
and other drugs, and (5) changes in liver
metabolism caused by liver dysfunction or
inadequate hepatic blood flow. A decrease in
liver function or a decrease in hepatic blood flow
can increase the bioavailability of a
drug, but only if the drug is metabolized by the
liver. Less drug is destroyed by hepatic
metabolism in the presence of liver disorder.
With some oral drugs, rapid absorption increases
the bioavailability of the drug and can cause an
increase in drug concentration. Drug toxicity
may result. Slow absorption can limit the
bioavailability of the drug, thus causing a
decrease in drug serum concentration.
Distribution
Distribution is the process by which the drug
becomes available to body fluids and body
tissues. Drug distribution is influenced by blood
flow, the drug’s affinity to the tissue, and the
protein-binding effect (Figure 1-3). In addition,
volume of drug distribution (Vd) is dependent
on drug dose and its concentration in the body.
Drugs with a larger volume of drug distribution
have a longer half-life and stay in the body
longer. See the section on metabolism, or
biotransformation, later in this chapter.
Protein Binding
As drugs are distributed in the plasma, many are
bound to varying degrees (percentages) with
protein (primarily albumin). Drugs that are
greater than 89% bound to protein are known as
highly protein-bound drugs; drugs that are 61%
to 89% bound to protein are moderately highly
proteinbound; drugs that are 30% to 60% bound
to protein are moderately protein-bound; and
drugs that are less than 30% bound to protein are
low protein-bound drugs. Table 1-1 lists selected
highly protein-bound drugs and moderately
highly protein-bound drugs. The portion of the
drug that is bound is inactive because it is not
available to receptors, and the portion that
remains unbound is free, active drug. Only free
drugs (drugs not bound to protein) are active
and can cause a pharmacologic response. As the
free drug in the circulation decreases, more
bound drug is released from the protein to
maintain the balance of free drug. Drugs bound
to proteins cannot leave the systemic circulation
to get to the site of action. This is why only free
drug is active.
When two highly protein-bound drugs are given
concurrently, they compete for protein-binding
sites, thus causing more free drug to be released
into the circulation. In this situation, drug
accumulation and possible drug toxicity can
result. Also, a low serum protein level decreases
the number of protein-binding sites and can
cause an increase in the amount of free drug in
the plasma. Drug toxicity may then result. Drug
dose is prescribed according to the percentage in
which the drug binds to protein. Patients with
liver or kidney disease or those who are
malnourished may have an abnormally low
serum albumin level. This results in fewer
protein-binding sites, which in turn leads to
excess free drug and eventually to drug toxicity.
Older adults are more likely to have
hypoalbuminemia. With some health conditions
that result in a low serum protein level, excess
free or unbound drug goes to nonspecific tissue
binding sites until needed and excess free drug
in the circulation does not occur. Consequently,
a decreased drug dose is needed as there is not as
much protein circulated for the drug
to bind to. Some drugs bind with a specific
protein component such as albumin or globulin.
Most anticonvulsants bind primarily to albumin.
Some basic drugs such as antidysrhythmics (e.g.,
lidocaine, quinidine) bind mostly to globulins.
To avoid possible drug toxicity, checking the
proteinbinding percentage of all drugs
administered to a patient is important. The nurse
should also check the patient’s plasma protein
and albumin levels, because a decrease in
plasma
protein (albumin) decreases protein-binding
sites, permitting more free drug in the
circulation. Depending on the drug, the result
could be life-threatening. Abscesses, exudates,
body glands, and tumors hinder drug
distribution. Antibiotics do not distribute well at
abscess and exudate sites. In addition, some
drugs accumulate in particular
tissues such as fat, bone, liver, muscle, and eye
tissues. The blood-brain barrier (BBB) is a
semipermeable membrane in the central nervous
system (CNS) that protects the brain from
foreign substances. Highly lipid-soluble drugs
are able to cross the BBB. Drugs that are not
bound to proteins and are not lipid soluble are
not able to cross the BBB, which makes it
difficult to distribute the drug (Figure 1-4).
During pregnancy, both lipid-soluble and lipid-
insoluble
drugs are able to cross the placental barrier,
which can affect the fetus and the mother. The
risk-benefit ratio should be considered before
drugs are given during pregnancy (Figure 1-5;
see also Chapter 53). During lactation, drugs can
be secreted into breast milk, which could affect
the nursing infant. The nurse needs to check
which drugs may cross into breast milk before
administering to a lactating patient.
Metabolism, or Biotransformation
Metabolism is the process by which the body
inactivates or biotransforms drugs. Drugs can be
metabolized in several organs; however, the liver
is the primary site of metabolism. Most drugs
are inactivated by liver enzymes and are then
converted or transformed by hepatic enzymes to
inactive metabolites or water-soluble substances
for excretion. A large percentage of drugs are
lipid soluble; thus the liver metabolizes the
lipid-soluble drug substance to a water-soluble
substance for renal excretion. However, some
drugs are transformed into active metabolites,
causing an increased pharmacologic response.
Liver diseases such as cirrhosis and hepatitis
alter drug metabolism by inhibiting the
drugmetabolizing enzymes in the liver. When
the drug metabolism rate is decreased, excess
drug accumulation can occur and lead to
toxicity.
The half-life (t 1 2 ) of a drug is the time it takes
for one half of the drug concentration to be
eliminated. Metabolism and elimination affect
the half-life of a drug. For example, with liver or
kidney dysfunction, the half-life of the drug is
prolonged and less drug is metabolized and
eliminated. When a drug is taken continually,
drug accumulation may occur. Table 1-1 shows
the half-life of selected drugs. A drug goes
through several half-lives before more than
90% of the drug is eliminated. If the patient
takes 650 mg of aspirin and the half-life is 3
hours, it takes 3 hours for the first half-life to
eliminate 325 mg, 6 hours for the second half-
life to eliminate an additional 162 mg, and so on
until the sixth half-life (or 18 hours), when 10
mg of aspirin is left in the body (Table 1-2). A
short half-life is considered to be 4 to 8 hours,
and a long one is 24 hours or longer. If the drug
has a long half-life (such as digoxin at 36 hours),
it takes several days for the body to completely
eliminate the drug. By knowing the half-life, the
time it takes for a drug to reach a steady state of
serum concentration can be computed.
Administration of the drug for three to five half-
lives saturates the biologic system to the extent
that the intake of drug equals the amount
metabolized and excreted. An example is
digoxin, which has a half-life of 36 hours with
normal renal function. It would take
approximately 5 days to 1 week (three to five
half-lives) to reach a steady state for digoxin
concentration.
Excretion, or Elimination
The main route of drug elimination is through
the kidneys (urine). Other routes include bile,
feces, lungs, saliva, sweat, and breast milk. The
kidneys filter free unbound drugs, water-soluble
drugs, and drugs that are unchanged. The lungs
eliminate volatile drug substances and products
metabolized to carbon dioxide (CO2) and water
(H2O). The urine pH influences drug excretion.
Urine pH varies from 4.5 to 8. Acidic urine
promotes elimination of weak base drugs, and
alkaline urine promotes elimination of weak acid
drugs. Aspirin, a weak acid, is excreted rapidly
in alkaline urine. If a person takes an overdose
of aspirin, sodium bicarbonate may be given to
change the urine pH to alkaline to promote
excretion of the drug. Large quantities of
cranberry juice can decrease urine pH, causing
acidic urine and thus inhibiting the elimination
of aspirin.
With a kidney disease that results in decreased
glomerular filtration rate (GFR) or decreased
renal tubular secretion, drug excretion is slowed
or impaired. Drug accumulation with possible
severe adverse drug reactions can result. A
decrease in blood flow to the kidneys can also
alter drug excretion. Common tests used to
determine renal function are creatinine
clearance (CLcr) and blood urea nitrogen
(BUN). Creatinine is a metabolic by-product of
muscle that is excreted by the kidneys. The
creatinine clearance test compares the level of
creatinine in the urine with the level of
creatinine in the blood. Creatinine clearance
varies with age and gender. Lower values are
expected in older adult and female patients
because of their decreased muscle mass. GFR
may be the best test, but it is expensive and not
so commonly used. A decrease in GFR results in
an increase in serum creatinine level and a
decrease in urine creatinine clearance. With
renal dysfunction either in older adults or as a
result of kidney disorders, drug dosage usually
needs to be decreased. In these cases, the
creatinine clearance needs to be determined to
establish appropriate drug dosage. When the
creatinine clearance is decreased, drug dosage
likewise may need to be decreased. Continuous
drug dosing according to a prescribed
dosing regimen without evaluating creatinine
clearance could result in drug toxicity.
PHARMACODYNAMIC PHASE
Pharmacodynamics is the study of the way
drugs affect the body. Drug response can cause a
primary or secondary physiologic effect or both.
The primary effect is desirable, and the
secondary effect may be desirable or
undesirable. An example of a drug with a
primary and secondary effect is
diphenhydramine (Benadryl), an antihistamine.
The primary effect ofdiphenhydramine is to treat
the symptoms of allergy, and the secondary
effect is a central nervous system depression that
causes drowsiness. The secondary effect is
undesirable when the patient drives a car, but at
bedtime it could be desirable because it causes
mild sedation.
Dose Response and Maximal Efficacy
Dose response is the relationship between the
minimal versus the maximal amount of drug
dose needed to produce thedesired drug
response. Some patients respond to a lower drug
dose, whereas others need a high drug dose to
elicit the
desired response. The drug dose is usually
adjusted to achieve the desired drug response.
All drugs have a maximum drug effect (maximal
efficacy). For example, morphine and tramadol
hydrochloride (Ultram) are prescribed to relieve
pain. The maximum efficacy of morphine is
greater than tramadol hydrochloride, regardless
of how much tramadol hydrochloride is given.
The pain relief with the use of tramadol
hydrochloride is not as great as it is with
morphine.
Onset, Peak, and Duration of Action
One important aspect of pharmacodynamics is
knowing the drug’s onset, peak, and duration of
action. Onset of action is the time it takes to
reach the minimum effective concentration
(MEC) after a drug is administered. Peak action
occurs when the drug reaches its highest blood
or plasma concentration. Duration of action is
the length of time the drug has a pharmacologic
effect. Figure 1-6 illustrates the areas in which
onset, peak, and duration of action occur. Some
drugs produce effects in minutes, but others may
take hours or days. A time-response curve
evaluates three parameters of drug action: the
onset of drug action, peak action, and duration of
action. Figure 1-6 indicates these parameters by
using T (time) with subscripts (e.g., T0, T1, T2,
T3). It is necessary to understand the time
response in relationship to drug administration.
If the drug plasma or serum level decreases
below threshold or MEC, adequate drug dosing
is not achieved; too high a drug level above the
minimum toxic concentration (MTC) can result
in toxicity.
Receptor Theory
Drugs act through receptors by binding to the
receptor to produce (initiate) a response or to
block (prevent) a response. The activity of many
drugs is determined by the ability of the drug to
bind to a specific receptor. The better the drug
fits at the receptor site, the more biologically
active the drug is. It I similar to the fit of the
right key in a lock. Figure 1-7 illustrates a drug
binding to a receptor.
Most receptors, which are protein in nature, are
found in cell membranes. Drug-binding sites are
primarily on proteins,glycoproteins, proteolipids,
and enzymes. There are four receptor families:
(1) kinase-linked receptors, (2) ligand-gated ion
channels, (3) G protein–coupled receptor
systems, and (4) nuclear receptors. The ligand-
binding domain is the site on the receptor at
which drugs bind. Kinase-linked receptors. The
ligand-binding domain for drug binding is on the
cell surface. The drug activates the enzyme
(inside the cell), and a response is initiated.
• Ligand-gated ion channels. The channel spans
the cell membrane and, with this type of
receptor, the channel opens, allowing for the
flow of ions into and out of the cells. The ions
are primarily sodium and calcium.
• G protein–coupled receptor systems. There are
three components to this receptor response: (1)
the receptor, (2) the G protein that binds with
guanosine triphosphate (GTP), and (3) the
effector that is either an enzyme or an ion
channel. The system works as follows: drug
__activ_ate_s_receptors __activ_ate_s_G
protein__activ_ate_s_effect
• Nuclear receptors. Found in the cell nucleus
(not on the surface) of the cell membrane.
Activation of receptors through the transcription
factors is prolonged. With the first three receptor
groups, activation of the receptors is rapid.
Agonists and Antagonists
Drugs that produce a response are called
agonists, and drugs that block a response are
called antagonists. Epinephrine (Adrenalin)
stimulates beta1 and beta2 receptors, so it is
anagonist. Atropine, an antagonist, blocks the
histamine (H2)
receptor, thus preventing excessive gastric acid
secretion. The
effects of an antagonist can be determined by the
inhibitory
(I) action of the drug concentration on the
receptor site. IC50
is the antagonist drug concentration required to
inhibit 50%
of the maximum biological response.
Nonspecific and Nonselective Drug Effects
Many agonists and antagonists lack specific and
selective effects. A receptor produces a variety
of physiologic responses, depending on where in
the body the receptor is located. Cholinergic
receptors are located in the bladder, heart, blood
vessels, stomach, bronchi, and eyes. A drug that
stimulates or blocks the cholinergic receptors
affects all anatomic sites of location. Drugs that
affect various sites are nonspecific drugs and
have properties of nonspecificity. Bethanechol
(Urecholine) may be prescribed for
postoperative urinary retention to increase
bladder contraction. This drug stimulates the
cholinergic receptor located in the bladder, and
urination occurs by strengthening bladder
contraction. Because bethanechol affects the
cholinergic receptor, other cholinergic sites are
also affected. The heart rate decreases, blood
pressure decreases, gastric acid secretion
increases, the bronchioles constrict, and the
pupils of the eye constrict (Figure 1-8). These
other effects may be either desirable or harmful.
Drugs that evoke a variety
of responses throughout the body have a
nonspecific response. Drugs may act at different
receptors. Drugs that affect various receptors are
nonselective drugs or have properties of
nonselectivity. Chlorpromazine (Thorazine) acts
on the norepinephrine, dopamine, acetylcholine,
and histamine receptors, and a variety of
responses result from action at these receptor
sites. Epinephrine acts on the alpha1, beta1, and
beta2 receptors (Figure 1-9). Drugs that produce
a response but do not act on a receptor may act
by stimulating or inhibiting enzyme activity or
hormone production.
Categories of Drug Action
The four categories of drug action include (1)
stimulation or depression, (2) replacement, (3)
inhibition or killing of organisms, and (4)
irritation. In drug action that stimulates, the rate
of cell activity or the secretion from a gland
increases. In drug action that depresses, cell
activity and function of a specific organ are
reduced. Replacement drugs such as insulin
replace essential body compounds. Drugs that
inhibit or kill organisms interfere with bacterial
cell growth (e.g., penicillin exerts its bactericidal
effects by blocking the synthesis of the bacterial
cell wall). Drugs also can act by the mechanism
of irritation (e.g., laxatives irritate the inner wall
of the colon, thus increasing peristalsis and
defecation).
Therapeutic Index and Therapeutic Range
(Therapeutic Window)
The safety of drugs is a major concern. The
therapeutic index (TI) estimates the margin of
safety of a drug through the use of a ratio that
measures the effective (therapeutic) dose (ED) in
50% of people (ED50) and the lethal dose (LD)
in 50% of people (LD50) (Figure 1-10). The
closer the ratio is to 1, the greater the danger of
toxicity. TI
LD
ED
= 50
50
In some cases, the ED may be 25% (ED25) or
75% (ED75).
Drugs with a low therapeutic index have a
narrow margin of safety (Figure 1-11, A). Drug
dosage might need adjustment, and plasma
(serum) drug levels need to be monitored
because of the small safety range between the
ED and LD. Drugs with a high therapeutic index
have a wide margin ofsafety and less danger of
producing toxic effects (Figure 1-11, B). Plasma
(serum) drug levels do not need to be monitored
routinely for drugs with a high TI. The
therapeutic range (therapeutic window) of a
drug concentration in plasma is the level of drug
between the minimum effective concentration in
the plasma for obtaining desired drug action and
the minimum toxic concentration (the toxic
effect). When the therapeutic range is given, it
includes both protein-bound and unbound
portions of the drug. If the therapeutic range is
narrow, such as for digoxin (0.5 to 1 ng/mL), the
plasma drug level should be monitored
periodically to avoid drug toxicity. Monitoring
the therapeutic range is not necessary if the drug
is not considered highly toxic. When the
therapeutic range is given, itincludes both
protein-bound and unbound portions of the drug.
Table 1-3 lists the therapeutic ranges and toxic
levels for anticonvulsants.
Peak and Trough Drug Levels
Peak drug levels indicate the rate of absorption
of the drug and trough drug levels indicate the
rate of elimination of the drug. Peak and trough
levels are requested for drugs that have a narrow
therapeutic index and are considered toxic, such
as the aminoglycoside antibiotics (Table 1-4). If
either the peak or trough level is too high,
toxicity can occur. If the peak is too low, no
therapeutic effect is achieved. Peak drug level
is the highest plasma concentration of drug at a
specific time.
Peak drug levels indicate the rate of absorption.
If the drug is given orally, the peak time might
be 1 to 3 hours after drug administration. If the
drug is given IV, the peak time might occur in
10 minutes. If a peak drug level is ordered, a
blood
sample should be drawn at the proposed peak
time, according to the route of administration.
The trough drug level is the lowest plasma
concentration of a drug, and it measures the rate
at which the drug iseliminated. Trough levels are
drawn immediately before the next dose of drug
is given, regardless of route of administration.
Loading Dose
When immediate drug response is desired, a
large initial dose, known as the loading dose, of
drug is given to achieve a rapid minimum
effective concentration in the plasma. After a
large initial dose, a prescribed dosage per day is
ordered. Digoxin (Digitek, Lanoxicaps,
Lanoxin), a digitalis preparation, requires a
loading dose when first prescribed.
Digitalization is the process by which the
minimum effective concentration level for
digoxin is achieved in the plasma within a short
time.
Side Effects, Adverse Reactions,
and Toxic Effects
Side effects are physiologic effects not related to
desired drug effects. All drugs have desirable or
undesirable side effects. Even with a correct
drug dosage, side effects occur and are
predicted. Side effects result mostly from drugs
that lack specificity, such as bethanechol
(Urecholine). In some health problems, side
effects may be desirable (e.g., the use of
diphenhydramine HCl [Benadryl] at bedtime
when its side effect of drowsiness is beneficial).
At times, however, side effects are called
adverse reactions. The terms side effects and
adverse reactions are sometimes used
interchangeably in the literature and in speaking,
but they are different. Some side effects are
expected as part of drug therapy. The occurrence
of these expected but undesirable side effects is
not a reason to discontinue therapy. The nurse’s
role includes teaching patients to report any side
effects. Many can be managed with dosage
adjustments, changing to a different drug in the
same class of drugs, or implementing other
interventions. It is important to know that the
occurrence of side effects is one of the primary
reasons patients stop taking the prescribed
medication. Adverse reactions are more severe
than side effects. They are a range of untoward
effects (unintended and occurring at normal
doses) of drugs that cause mild to severe side
effects, including anaphylaxis (cardiovascular
collapse). Adverse reactions are always
undesirable. Adverse effects must always be
reported and documented because they represent
variances from planned therapy. Toxic effects,
or toxicity, of a drug can be identified by
monitoring the plasma (serum) therapeutic range
of the drug. However, for drugs that have a wide
therapeutic index, the therapeutic ranges are
seldom given. For drugs with a narrow
therapeutic index, such as aminoglycoside
antibiotics and anticonvulsants, the therapeutic
ranges are closely monitored. When the drug
level exceeds the therapeutic range, toxic effects
are likely to occur from overdosing or drug
accumulation.
Pharmacogenetics
Pharmacogenetics is the scientific discipline
studying how the effect of a drug action varies
from a predicted drug response because of
genetic factors or hereditary influence. Because
people have different genetic makeup, they do
not always respond identically to a drug dosage
or planned drug therapy. Genetic factors can
alter the metabolism of the drug in converting its
chemical form to an inert metabolite; thus, the
drug action can be enhanced or diminished.
Some persons are less or more sensitive to drugs
and their drug actions because of genetic factors.
For example, African Americans do not respond
as well as Caucasians to some classes of
antihypertensive medications such as ACE
inhibitors. (See Chapter 3 for a discussion of
pharmacogenetics.)
Tolerance and Tachyphylaxis
Tolerance refers to a decreased responsiveness
over the course of therapy. In contrast,
tachyphylaxis refers to a rapid decrease in
response to the drug. In essence, tachyphylaxis is
an “acute tolerance.” Drug categories that can
cause tachyphylaxis include narcotics,
barbiturates, laxatives, and psychotropic agents.
For example, drug tolerance to narcotics can
result in decreased pain relief for the patient. If
the nurse does not recognize the development of
drug tolerance, the patient’s request for more
pain medication might be interpreted as drug-
seeking behavior associated with addiction.
Prevention of tachyphylaxis should always be
part of the therapeutic regimen (see Chapter 42).
Placebo Effect
A placebo effect is a psychological benefit from
a compound that may not have the chemical
structure of a drug effect. The placebo is
effective in approximately one third of persons
who take a placebo compound. Many clinical
drug studies involve a group of subjects who
receive a placebo. The nurse can increase the
therapeutic effect of the drug (e.g., narcotics for
pain management) but violate the truth-telling
ethical
principle if a nontherapeutic drug is presented as
a therapeutic agent. Hence, it is required that
participants in drug trials be told from the start
that they might receive a placebo. To review, the
phases of drug action are pharmaceutic,
pharmacokinetic, and pharmacodynamic. Figure
1-12 illustrates
these three phases for drugs given orally, but
drugs given by injection are involved only in the
pharmacokinetic and pharmacodynamic phases.
Nurses should be aware that tablets must
disintegrate and go into solution (the
pharmaceutic phase) to be absorbed. To avoid
toxic effects, the nurse must know the half-life,
protein-binding percentage, normal side effects,
and therapeutic ranges of the drug. This
information can be obtained from drug reference
books.
Nursing Process
Patient-Centered Collaborative Care
Assessment
■ Take patient history to identify factors that
may affect drug pharmacokinetics (e.g., gastric
surgery will affect absorption; low serum
albumin will affect protein binding; peripheral
vascular disease may affect drug distribution to
extremities). Examine the patient’s history to
identify factors that may affect
pharmacodynamics (e.g., a G6PD deficiency
may cause hemolytic anemia if some common
drugs are given)
■ Collect a medication history.
■ Perform a physical exam to identify problems
that may
affect pharmacodynamics (e.g., elevated BP,
dysrhythmias,
or other abnormal findings may be an indication
for drug therapy).
■ Identify side effects of drugs that are
nonspecific (same
receptor at different tissue and organ sites). For
example, when atropine is the drug to be
administered, assess for tachycardia, dry mouth
and throat, constipation, urinary retention, and
blurred vision. If nonspecific drugs are given in
large doses or at frequent intervals,
many side effects are likely to occur.
■ Check peak levels and trough levels of drugs
such as
aminoglycosides that have a narrow therapeutic
range. If the trough level is high, toxic effects
can result.
■ Check the drug literature for the protein-
binding percentage of the drug. Drugs with a
high protein-binding effect have a large portion
of drug bound to protein. This causes the drug to
become inactive until it is released from the
protein. The portion not bound to protein is a
free and active drug.
Nursing Interventions
■ Advise patient not to eat high-fat food before
ingesting an enteric-coated tablet, because high-
fat foods decrease absorption rate.
■ Report to the health care provider if drugs with
a long half-life (i.e., greater than 24 hours) are
given more than once a day. Some drugs with a
long half-life (e.g., the anticoagulant warfarin
[Coumadin]) can be more dangerous than others
and must be monitored frequently.
■ Monitor the therapeutic range of drugs that are
more toxic or have a narrow therapeutic range
(e.g., digoxin).
Cultural Considerations
■ Be aware that individuals of some ethnic or
racial heritage metabolize drugs differently than
the general population.
Assess for adverse effects that may result from
this variation in metabolism.
Evaluation
■ Evaluate the determinants that affect drug
therapy
according to Figure 1-13.
■ Assess for signs and symptoms of drug
toxicity when giving two drugs that are highly
protein-bound. The drugs compete for protein-
binding sites, and displacement of drugs occurs.
More free drug is in circulation because there are
not enough protein-binding sites. Too much of a
free drug can result in drug toxicity.
FIGURE 1–13 Determinants that affect drug
therapy.
Which components of pharmacokinetics does the
nurse need to understand before administering a
drug? (Select all that apply.)
a. Drugs with a smaller volume of drug
distribution have a longer half-life.
b. Oral drugs are dissolved through the process
of
pinocytosis.
c. Patients with kidney disease may have fewer
proteinbinding
sites and are at risk for drug toxicity.
d. Rapid absorption decreases the bioavailability
of the drug.
e. When the drug metabolism rate is decreased,
excess drug accumulation can occur, which can
cause toxicity.
2. The nurse will question the health care
provider if a drug with a half-life (t 1 2 ) of more
than 24 hours is ordered to be given more than
how often?
a. Once daily
b. Every other day
c. Twice weekly
d. Once weekly
3. The nurse is explaining drug action to a
nursing student. Which statement made by the
nurse is correct?
a. “Water-soluble and ionized drugs are quickly
absorbed.”
b. “A drug not bound to protein is an active
drug.”
c. “Most receptors are found under the cell
membrane.”
d. “Toxic effects can result if the trough level is
low.”
4. The nurse is caring for a patient with
congestive heart failure who is receiving digoxin
(Digitek, Lanoxicaps, Lanoxin). The nurse plans
to take which action when administering
digoxin?
a. Check the peak levels of digoxin.
b. Check the trough levels digoxin.
c. Monitor for tachyphylaxis.
d. Monitor the therapeutic range of digoxin.
5. The nurse anticipates that the health care
provider will order which laboratory test for an
older adult with renal dysfunction?
a. Creatinine clearance
b. Glomerular filtration rate
c. Urine specific gravity
d. Urine pH
6. When reviewing the patient’s medication
regimen, the nurse understands that the interval
of drug dosage is related to what?
a. Half-life
b. Stimulation of receptors
c. Therapeutic index
d. Trough level
7. Which nursing assessment(s) will the nurse
include when developing a patient medication
plan? (Select all that apply.)
a. Check peak and trough levels of drugs.
b. Check the drug literature for the protein-
binding percentage of a drug.
c. Identify side effects of drugs that are
nonspecific.
d. Evaluate the patient’s reaction to a drug.
e. To enhance absorption, advise the patient to
crush an enteric-coated tablet before taking.
8. A student nurse is studying the phases of drug
action. Which statement by the student indicates
to the nursing instructor that the student
understands the pharmaceutic phase?
a. “To achieve drug action, drugs are moved by
four processes.”
b. “For the drug to cross the biologic membrane,
the drug becomes a solution.”
c. “In this phase, drugs are concentrated and a
biologic or physiologic response occurs.”
d. “The pharmaceutic phase is the process by
which the drug becomes available to body fluids
and tissue.”
9. The nurse plans to advise the patient to avoid
which
food(s) before ingesting an enteric-coated
medication?
(Select all that apply.)
a. Bananas
b. Baked lamb chops
c. Broiled fish
d. Ice cream
e. Fried chicken