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2
General Principles of Pharmacology
KEY TERMS
Affinity: The force of attraction of a molecule to a receptor
site
Agonist: A drug that has a direct stimulatory effect on a
receptor
Antagonist: A drug that interferes with the action of an
agonist
Ceiling dose: The dose above which no further beneficial
drug effect will occur
Enteral: The administration of a drug through the
gastrointestinal (GI) tract, by mouth
Efficacy: The magnitude of response obtained from
optimal receptor site occupancy by a drug
Half-life: The time it takes for half the drug to be removed
from the body
Intrinsic activity: The ability to cause an effect or action
Parenteral: The administration of a drug bypassing the GI
tract, usually through injection into the body in various
ways but also including inhalation and topical
administration
Partial agonist: A drug with affinity for the receptor site,
but unable to produce a strong effect or action
Pharmacodynamics: The mechanisms of drug action
involving biochemical and physiologic effects of drugs
Pharmacokinetics: The absorption, distribution,
metabolism, and excretion of a drug
Pharmacotherapeutics: The use of pharmacologic
agents to diagnose, treat, or prevent disease
Potency: The concentration at which the drug elicits 50%
of its maximal response, related to the drug’s affinity for
the receptor
Receptor site: A specialized area on a cell or within a cell
where a drug acts to initiate a series of biochemical and
physiologic effects
Strong agonist: Drug that produces a significant
physiologic response when only a relatively small
number of receptors are occupied
Toxicity: Overdose, undesirable effects, or poisoning
KEY ACRONYMS
IM: Intramuscular
IV: Intravenous
ROA: Route of administration
SC: Subcutaneous
The science of pharmacology is the study of drugs. The science developed when early individuals observed the effects
of herbs and plant extracts on themselves or others. Historically, the clinician was responsible for information about the
sources, physical and chemical properties, and compounding
and dispensing of drugs. These activities are now delegated
to pharmacologists and pharmacists. Today, the practitioner’s
responsibility relates to the clinical application of this knowledge. Oral health professionals must understand basic prin-
ciples of pharmacology as they apply to drugs used in oral
health care as well as other drugs taken by the dental patient.
This understanding provides for more efficient communication when explaining drug effects to the patient or when medical consultation is necessary. Important principles include:
r knowing how a drug works, called the mechanism of action;
r the potential adverse (or side) effects (ADEs) that are pos-
sible;
11
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r oral health education information related to drug effects;
r the risks of taking a drug.
AG I
AT II
These principles apply to all therapeutic agents (including vitamins, herbs, and nutritional supplements) and pertain to a
drug’s mechanism of action (pharmacodynamics), the movement of the drug through the body (pharmacokinetics), and
potential adverse effects when the drug is taken (pharmacotherapeutic variables).
I
AT
AT III
AG II
Self-Study Review
1. List four principles of pharmacology that the oral
health professional must understand in order to
provide information on drug effects.
2. Define pharmacodynamics and pharmacokinetics as
they apply to drugs.
PHARMACODYNAMICS
Pharmacodynamics is the science of molecular interac-
tions between drugs and body constituents. It relates to the
biochemical and physiologic actions of drugs. When a drug
is delivered to the tissue cells, it goes through several steps.
The first step in initiating a drug-induced effect is the formation of a complex, or bond, between the drug molecule
and a cell component called the drug receptor. The receptor
site where a drug acts to initiate a series of biochemical and
physiologic effects is that drug’s site of action. The molecular event that follows this drug-receptor interaction is called
the drug’s mechanism of action. An example of this process is the action of epinephrine in local anesthetic agents.
Following the injection of a local anesthetic solution (delivery), epinephrine binds to its receptor on vascular smooth
muscle (complex formation) and causes the muscle cell to
constrict (drug-receptor interaction), resulting in vasoconstriction (mechanism of action). Most drugs go through a
similar process; however, it should be understood that not all
drugs produce their effects by interacting with specific receptors. This concept will become apparent as one considers
drug action in future chapters. A number of drugs form chemical bonds with small molecules, chelating agents, or metallic
cations. A practical example of this type of drug-receptor interaction is the therapeutic neutralization of gastric acid by
antacids. Many other drugs act by mechanisms that are not
yet understood.
Receptors
Drug receptors are large, highly specialized molecules, which
are components of the plasma membrane or are located intracellularly. A single cell may have hundreds of different
receptor sites, and a drug may interact with a variety of different receptor types or subtypes, producing different pharmacologic effects. Drug molecules and their receptors must
have similar structures (structural specificity), described as
“lock and key” complementary fits. Figure 2-1 illustrates the
AT IV
Figure 2-1 Complementary Receptor-Molecule Fit. Major features of classical receptors. Drug molecules (AG,
agonist; AT, antagonist) and their receptors must have
a similar structure (structural specificity), described as a
“lock and key” complementary fit. AT I and AG I compete for the same receptor site, AG I to enhance and AT
I to block signal; AG II and AT III enhance or block signal,
respectively, by binding to alternative sites that influence
signal transmission; AT II binds to an alternative site and
blocks AG I activation site. AT IV blocks signal at intracellular signal reception site.
complementary fit and the interaction with different receptors. Only one molecule can bind to a receptor at a time; i.e.,
two drugs cannot occupy the same receptor at the same time.
Receptors have a variety of other features that determine their
function, location in the body, relationship to cellular membranes, and binding capacity (Box 2-1), including:
r electrochemical force (either electropositive or electroneg-
ative) that functions to attract the drug molecule to the receptor
r the trait of being hydrophilic or hydrophobic to attract or
repel a molecule
r are cellular macromolecules
BOX 2-1. Characteristics of Drug Receptors
r
r
r
r
r
r
r
Cellular macromolecules
Location on the cell surface or within the cell
Hundreds of different receptors on a single cell
Complementary fit between drug and receptor
Electrochemical charge
Hydrophilic or hydrophobic
Only one drug molecule can occupy a receptor at one
time
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The drug molecule binds to the complementary receptor and
stimulates the receptor to produce a definable pharmacologic
response.
13
tors. The following forces govern the potential for a complex
to form.
Affinity
Chemical Bonds
Drugs attach to or interact with these receptor sites through
various types of chemical bonds. These include ionic, hydrogen, and covalent bonds, and van der Waals forces. Hydrogen bonding and ionic bonding are the most common
types between drugs and receptors. The bonds are similar in that both involve an electrochemical attraction. These
interactions require little energy and are made and broken
easily.
Ionic Bonds
Ionic interactions occur between atoms with opposite
charges. An atom with an excess of electrons imparts a negative charge, which causes an attraction to an atom with a deficiency of electrons. A simple example of this type of interaction is reflected in the attraction between sodium and chloride
ions (sodium chloride [Na+ /Cl– ]). Applying the concept to
the attraction between drug molecules and receptor sites, a
positively charged drug molecule is attracted to a negatively
charged receptor site. These bonds are weak and are easily
reversed.
Hydrogen Bonds
When bound to nitrogen or oxygen, hydrogen atoms become
positively polarized and bind to negatively polarized atoms
such as oxygen, nitrogen, or sulfur. These bonds are generally
weaker than ionic bonds.
Covalent Bonds
Covalent bonds are the strongest type of bond between a
drug and its receptor, resulting from the sharing of electrons
by two atoms. The energy required to overcome such interactions can be so great that the bond is often irreversible. Fortunately, such drug–receptor interactions are not common.
A good example of a covalent bond is the complex formed
between tetracycline and dentin to produce a permanent intrinsic discoloration.
van der Waals Forces
These nondescript forces contribute to the mutual attraction
between organic molecules through a shifting of electron density in or around a molecule that results in the generation of
transient positive or negative charges. This provides for a
weak attractive force between some drugs and their receptors.
Attractive Forces Between Drugs
and Receptors
Drug molecules move in constant random motion in the cellular area, binding to receptors and breaking away from recep-
When a drug molecule moves so close to its receptor that
the attractive force between them becomes great enough to
overcome the random motion of the drug molecule, the drug
binds to the receptor. This phenomenon is called affinity.
The affinity of a drug for a particular receptor and the type of
binding that occurs is intimately related to the drug’s chemical structure. Because two drug molecules cannot occupy
the same receptor site at the same time, the drug with the
greater affinity will bind more readily to the receptor. Affinity is expressed by its dissociation constant (KD ), which is
the concentration of a drug required in solution to achieve
50% occupancy of its receptors. When two drugs of equal
concentrations are competing for the same receptor population, the drug with the greater affinity will bind with more
receptors (and stimulate the receptor to cause an action) at
any given instant (Fig. 2-2). Thus, a lower concentration of
that drug will produce the same level of pharmacologic effect. This means that drugs with good affinity have greater
potency; i.e., they require a smaller dose to cause a specific
effect. Consequently, potency is related to the affinity of a
drug.
Figure 2.2 illustrates that when equal concentrations of
two drugs are in equilibrium with the same receptor population (square indentations), the drug with the greater affinity
(Drug A) will make a greater number of effective bindings at
any given instant. The result is that Drug A is more potent,
and a lower concentration of Drug A is required to produce
the same level of pharmacologic effect as that produced by
Drug B.
Agonists
Drugs that have direct stimulatory effects on receptors are
called agonists. A strong agonist produces a significant
physiologic response when only a relatively small number
of receptors are occupied. The ability of an agonist to interact with a receptor and initiate a response is the function of its
intrinsic activity. Using these terms in an example, when
a small dose of a drug (agonist) produces a desired effect,
the drug has good affinity and good intrinsic activity. A weak
agonist must be bound to many more receptors to produce
the same effect, so a much larger dose of a weak agonist will
be required to produce the desired effect—i.e., the drug has
lower affinity and/or lower intrinsic activity. A partial agonist
has affinity for the receptor, but very low intrinsic activity.
Therefore, it will never produce the same effect as a strong
agonist or a weak agonist, even when all receptors are occupied. This can be illustrated with the log dose–response of
three different drugs with affinity to the same receptors, as
shown in Figure 2-3, where a low dose of Drug A (strong
agonist) produces a full effect, Drug B (weak agonist) must
have a higher dose to reach that effect, and Drug C (partial
agonist) never reaches the effect produced by Drugs A or B.
An example of the above concept would be the use of 5 mg
of morphine to relieve strong pain, compared with 50 mg
of meperidine (Demerol) to relieve the same degree of pain,
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Relationship of Affinity and Potency
A
A
A
A
A
B
A
A
B
B
B
A
B
A
B
B
B
B
A
B
A
A
Drug B
Drug A
Equal Concentration
Figure 2-2 Relationship between Drug Affinity to Receptor and Potency. When equal concentrations of two drugs
are in equilibrium with the same receptor population (square indentations), the drug with the greater affinity (Drug A)
will make a greater number of effective bindings at any given instant. Thus, a lower concentration of Drug A will be
required to produce the same level of pharmacologic effect as that produced by Drug B.
and further compared with 65 mg of propoxyphene (Darvon),
which will not relieve strong pain, no matter how high the
dose given. Thus the affinity and the intrinsic activity of an
agonist determine efficacy of a drug.
Efficacy
Efficacy is the maximum response produced by a drug. It is
a state of optimal receptor occupancy by the drug molecules;
additional doses would produce no further beneficial effect.
This concept is often referred to as the ceiling dose. As seen
with the affinity of a drug for a particular receptor, the efficacy of a drug is also related to its chemical structure. This
Log Dose-Response Curve
concept is referred to as the intrinsic activity relationship.
The quantification of a specific response elicited by a drug
given in a range of doses (5 mg, 10 mg, 50 mg, etc.) is called
the graded dose–response relationship. This relationship is
expressed visually and mathematically with a dose–response
curve. The curve is established by placing the logarithmic
value for the dose (or log dose) on the x-axis and the quantified response on the y-axis (Fig. 2-4). The upper plateau of
the dose–response curve represents the efficacy or the maximal effect of a drug associated with a specific dose. A good
example of this concept is acetaminophen, which has a ceiling dose of about 1,000 mg for pain relief. Taking 2,000 mg
in a single dose will not produce greater pain relief and may
lead to toxicity (overdose). The lowest dose of a drug that will
produce a measurable response is called the threshold dose.
The dose range of acetaminophen for pain relief is 325 mg
to 1,000 mg. Therefore, 325 mg would be the threshold dose
of acetaminophen.
Efficacy
Maximum effect
y-axis
Drug A
5 mg
Drug B
50 mg
Drug C
65 mg
Log dose
Figure 2-3 Log Dose-Response Curve Illustrating Three
Different Drugs (a Strong Agonist, a Weak Agonist, and
a Partial Agonist) with Affinity for the Same Receptors.
Drugs A and B have the same efficacy, but it takes more
of Drug B to produce the effect. Drug C does not have the
same efficacy of Drugs A and B, even at a higher dose.
x-axis
Figure 2-4 Log Dose Curve for Efficacy. A drug’s efficacy,
or maximum effect, is represented by the upper plateau
of the dose–response curve.
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A1
B1
Figure 2-5 Log Dose of Potency and Efficacy. This shows
two drugs with same efficacy (A, B), but different potency
(A, B). Potency relates to two or more drugs by comparing
the doses required to produce a given effect.
Potency
Potency is defined as the relative pharmacologic activity
of a dose of a compound compared with a dose of a different agent producing the same effect. The concept provides a
mechanism by which to compare the ability of two or more
drugs, with affinity for the same receptor, to produce a given
effect as a function of dose. Potency is related to the affinity of a drug to its receptor, whereas efficacy is related to
the intrinsic activity of that drug once a drug–receptor complex is formed. It is determined by the relative position of the
dose-response curve along the dose axis as illustrated in Figure 2-5. Note that for the maximum effect, the dose of Drug
A is smaller than that required for Drug B, illustrating that
Drug A is more potent than Drug B, yet they have the same
efficacy. An example is the ability of two nonsteroidal agents
(ketorolac and ibuprofen) to relieve dental pain. Ketorolac
at 20 mg relieves dental pain to the same degree as 400 mg
of ibuprofen. Therefore, ketorolac has greater potency and
equal efficacy.
Antagonists
An antagonist is a drug that interferes with the action of
an agonist, but has no effect in the absence of an agonist.
Antagonists can be classified as receptor or nonreceptor antagonists.
Receptor Antagonists
Receptor antagonists can bind at the active site (called agonist
binding domain) and prevent the binding of the agonist, or
they may bind to an adjacent site (overlapping with the agonist binding domain) and prevent the conformational change
required for receptor activation by an agonist. Receptor antagonism can be either reversible (competitive) or irreversible
(noncompetitive):
r A competitive antagonist binds reversibly to the active site
of the agonist and maintains the receptor in its inactive
15
conformation. In other words, it has affinity for a receptor
but no efficacy (i.e., it cannot cause an effect). It competes
with the agonist for the receptor, and the outcome depends
on the degree of affinity of the competitive antagonist compared with the agonist. A competitive antagonist forms a
reversible drug-receptor complex, which can be overcome
by increasing the dose of the agonist. Consequently, the inhibition is surmountable. In effect, the presence of a competitive antagonist reduces the potency of the agonist. A
practical example of this type of antagonism with relevance to dentistry is the reversal of respiratory depression
caused by excessive doses of an opioid analgesic (agonist)
with naloxone, an opioid antagonist.
r A noncompetitive antagonist binds either to the active site
or to an allosteric (adjacent) site of the receptor. It binds
to the active site either covalently or with very high affinity, both of which are effectively irreversible. An allosteric
noncompetitive antagonist prevents the receptor from being activated, even when the agonist is bound to the active
site. In effect, the presence of a noncompetitive antagonist
reduces the efficacy of the agonist. Aspirin is a practical
example of a noncompetitive antagonist. It irreversibly affects cyclooxygenase, the enzyme responsible for the process that causes platelets to clump together and produce a
clot. This reduces clotting and increases the bleeding time.
Normal platelet function can be reestablished only by the
generation of new platelets in the bone marrow.
Nonreceptor Antagonists
A nonreceptor antagonist may be either a chemical or physiologic antagonist.
Chemical Antagonist
A chemical antagonist may either bind a molecule at some
point in the activation pathway or directly inhibit the agonist.
A practical example of this type of antagonism with relevance to dentistry is the one produced by local anesthetic
agents. They block sodium channels in the activation pathway of chemicals that promote depolarization of nerve fibers.
By blocking depolarization, information about tissue damage
(in the form of electrical impulses) is not transmitted to the
cortex, and the patient will not experience pain.
Physiologic Antagonist
A physiologic antagonist activates pathways that oppose the
action of the agonist. An example of this type of antagonism is
reflected in the action of epinephrine on blood vessels (vasoconstriction) following an allergic reaction (anaphylaxis) and
histamine release. The effect of epinephrine overcomes the
effect of histamine (vasodilation) on the same blood vessel,
and the vessel becomes constricted.
Mixed Agonist–Antagonists
Mixed agonist–antagonists are drugs that have both agonistic and antagonistic properties. When used alone, such a drug
behaves as an agonist. However, when another drug that competes for the same receptor site is administered concurrently,
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the agonist–antagonist will also act as an antagonist. A practical example of an agonist–antagonist is pentazocine, an opioid analgesic; when used alone, it interacts with its opioid
receptor to produce analgesia, but it antagonizes the action
of other opioid agonists.
Receptor Classification
Receptors are classified according to the type of drug they
interact with or according to the specific physiologic response
produced by the drug–receptor complex. Receptor sites may
also be subclassified by evaluating the effects of different
agonists in the presence of a given antagonist. The previous
example of using epinephrine to counteract the effects of
histamine illustrates this concept. Earlier in this chapter, it
was noted that drugs can interact with different receptors.
Epinephrine can bind to receptors in the bronchioles of the
lungs to cause bronchodilation, and it can bind to different
receptors on blood vessels to cause vasoconstriction; hence,
one drug interacts with two different receptors and causes
two different actions.
Similarly, receptors and receptor subtypes exist for many
other agents. The number of any given receptor types or
subtypes on a cell also may vary. Certain disease states or
drugs taken long term and/or in large doses may increase
(up-regulate) or decrease (down-regulate) the number of receptors and provide a degree of adaptability in the face of
changing physiologic events. Developing tolerance to a drug
so the former dose no longer causes an adequate effect and
a higher dose is needed to cause the effect illustrates this
concept.
Figure 2-6 Effective Dose in 50% of Subjects.
death is the measured end point, the ED50 is expressed as
the median lethal dose (LD50). A steep dose–response curve
indicates a narrow dosage range between minimal and maximal effects. Consequently, the risk for toxic or even lethal
dosage levels can be greater because of the narrower dosage
range. Similarly, the median toxic dose (TD50) is the dose
of a drug that produces a specific toxic response in 50% of
the individuals within the same population. These concepts
are used during drug development to determine the safety of
doses. Fortunately, laboratory animals are used to determine
the LD50 in drug research centers! The relative safety of a
drug for humans is extrapolated from animal data and clinical
data during new drug’s clinical trials.
Therapeutic Index
Toxicity
Any drug at a high-enough concentration can produce a toxic
effect (overdose). In the context of this discussion, toxicity
refers to undesirable effects associated with the administration of therapeutic dosages of drugs. These adverse effects
may be:
When evaluating potential therapeutic agents, dose–response
curves provide valuable information relative to their safety.
The margin of safety of a drug is expressed by the Therapeutic
Index (TI). For example, if the slope of the dose–response
curve is steep, it indicates a narrow range between dosages
that produce minimal and maximal effects, or between a safe
dose and a toxic dose (Fig. 2-7). Using the dose–response
r An exaggeration of direct effects seen at higher doses. For
example, barbiturates may produce sedation, drowsiness,
and reduced rate of respiration at therapeutic levels (direct
effect), but cause death (exaggerated effect of respiratory
depression) at increased dose levels. This is an extension
of the intended therapeutic effect of central nervous system
(CNS) depression.
r Multiple concurrent adverse, or side, effects occurring at
therapeutic dosage levels. For example, the administration
of certain antihistamines for hay fever, intended to antagonize histamine action at H1 -histaminic receptors in the respiratory system, can also bind to H3 -histaminic receptors
in the CNS and cause drowsiness. In this case, the drowsiness is a concurrent side effect, not an intended response.
ADEs are discussed in detail in Chapter 5.
Median Effective Dose or Lethal Dose
The dose of a drug required to produce a desired response
in 50% of the individuals within the same population is the
median effective dose (ED50), as shown in Figure 2-6. If
Figure 2-7 ED50 and LD50. The margin of safety of a
drug may be expressed by its therapeutic index, the actual
ratio of LD50 and ED50, or by comparing the 99% dose–
response curve for the therapeutic effect with the curve
for the toxic effect.
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curve, the risk of a toxic effect may also be calculated and
expressed as the drug’s TI. The TI is the actual ratio of the
LD50 and ED50 (LD50/ED50). The same concept applies to
any toxic effect in that the higher the numerical value of this
ratio (or the higher the TI), the safer the drug. The margin
of safety also may be established by comparing 99% dose–
response curve for the therapeutic effect to the curve for a
toxic or lethal effect (Fig. 2-7). The farther apart these two
curves are, the wider the margin of safety.
17
and pKa of the drug). In an acid environment, an acidic drug
exists mainly in the nonionized form. Nonionized molecules
are lipid soluble and pass through biologic membranes easily.
In the same acid environment, a basic drug exists mainly in
the ionized form. Ionized drugs are water soluble and must
pass through water pores of the biologic membrane or be
transported through the membrane by specialized transport
mechanisms. These movements are accomplished in a variety
of ways.
Filtration
Self-Study Review
3. Describe the steps a drug follows after being
delivered to body cells.
4. List seven features of receptors.
5. Describe the features of the four types of chemical
bonds between a drug molecule and the
complementary receptor. Which type is most
common in drug–receptor complexes?
6. Define the roles of affinity and intrinsic activity in
drug action. Which is related to potency?
7. What is the difference in the effect of a weak
agonist when compared to a partial agonist?
Identify both in a log dose curve illustration.
8. Describe the relationship of efficacy and the ceiling
dose concept.
9. Compare the ceiling dose with the threshold dose.
10. Define ED50 and LD50.
11. What is the therapeutic index (TI), and how is it
used? What is the formula to determine the TI, and
what is the significance of a high number?
Small, water-soluble substances may pass through aqueous
channels or water pores in cell membranes by a process
known as filtration. Larger water-soluble molecules are in
the ionized form and are blocked from moving through small
water pore openings. They must rely on specialized transport
mechanisms (discussed below) to move through the biologic
membrane.
Passive Diffusion
Most drugs are weak acids or weak bases, and drug molecules
are too large to pass through most aqueous channels. However, as a function of their lipid solubility, the nonpolar (nonionized) forms of these drugs readily can cross biologic membranes by passive diffusion along a concentration gradient
(from high concentration to low concentration) until equilibrium is reached across the membrane. Therefore, nonionized lipid-soluble molecules can easily pass through biologic
membranes.
Specialized Transport Mechanisms
Large ionized, water-soluble drug molecules require more
complex processes to cross biologic membranes. These include facilitated diffusion and active transport mechanisms.
PHARMACOKINETICS
Facilitated Diffusion
Pharmacokinetics deals with the movement of drugs
through the body. Therefore, pharmacokinetics relates to a
drug’s absorption; distribution in the body, including to the
site of action; metabolism to prepare the drug for removal
from the body; and excretion, where the drug is ultimately
removed from the body and its effect is terminated. As drugs
progress through these various phases within the body to be
delivered to their sites of action and, ultimately, to be eliminated from the body, they must pass through biologic barriers
(e.g., cell walls, blood vessels) in various tissues.
Passage across Biologic Membranes
To produce an effect, most drugs must pass through cell membranes to gain access to their receptor(s). Passage through biologic membranes affects the amount of the drug that reaches
the site of action and influences the time it takes the drug to
get to the site of action. The physicochemical properties that
influence the movement of drug molecules across biologic
membranes are molecular size, lipid solubility, and the degree of ionization (a function of the pH of the environment
The concept of facilitated diffusion assumes that the drug
forms a complex with a component of the cell membrane on
one side. The complex is then carried through the membrane,
the drug is released, and the carrier returns to the original
surface to repeat the process. Vitamins are known to participate in facilitated diffusion, furnishing the energy to carry
large, water-soluble drug molecules across membranes. Facilitated diffusion does not require energy and does not proceed against a concentration gradient. One example is the
movement of glucose across cell membranes; it is thought to
be facilitated by insulin. Another example is that some waterinsoluble substances, such as fat-soluble vitamins (vitamins
A, D, E, and K), are engulfed by the cell membrane and are
released unchanged in the cytoplasm by a process known as
endocytosis, a form of facilitated diffusion.
Active Transport
Active transport is the movement of drug molecules across
biologic membranes against both a concentration and an
electrochemical gradient. This activity requires energy. The
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BOX 2-2. Factors That Influence Absorption
r
r
r
r
r
r
Degree of ionization
Formulation (liquid or solid)
Concentration
Circulation to area
Area of absorptive surface
Route of administration
transfer of some drugs through biologic membranes in the
kidneys and intestines relies on an active transport mechanism.
Absorption
Regardless of the process by which a drug moves through
biologic membranes, it first must be dissolved in the fluids
encircling the cells. For this reason, a drug must have some
degree of both lipid and water solubility—water solubility to
get it to the cell, and lipid solubility to get it through the cell
membrane. Factors that influence the rate of absorption of
drugs include
r the degree of ionization and pH of tissues;
r the formulation of the drug (liquid or solid);
r the drug’s concentration (the greater the concentration of a
drug, the faster the rate of absorption);
pH at which a drug is 50% ionized and 50% nonionized. For
example, in the highly acidic environment of the stomach,
drugs with a low pKa will exist primarily in their nonionized forms (weak acids in an acidic environment). Ionization
occurs when different charges (acids mixed with bases) exist together. Similarly, in the small intestine where the pH
is more basic, the same drugs with a low pKa will be more
ionized.
Formulation of Drug
The form in which a drug is administered can affect the rate
of absorption. To illustrate this point, let us consider the form
in which a drug is administered to a patient. Aqueous formulations of drugs (such as Alka-Seltzer) do not require time to
dissolve after oral administration and, therefore, will cover
a wider area of the absorptive surface in the gastrointestinal
(GI) tract much faster than a tablet, which must go through
stages of a dissolving process. In general, the liquid formulation results in an increased rate of absorption of the drug
(and more rapid onset of action) than solid formulations of
the same drug.
Enteric Coating
Drugs can be modified in various ways that result in delayed
absorption. Enteric-coated formulations delay dissolution of
tablets until they have moved from the stomach into the upper
small intestine, thereby reducing adverse gastric side effects.
r circulation to the area (the greater the blood flow to tissue,
Other Modifications
the faster the rate of absorption);
r the area of absorptive surface (the greater the area to which
the drug is exposed, the faster the rate of absorption);
r the route of administration (ROA; Box 2-2).
A strategy involved in formulating intraoral topical agents
is to combine them with an insoluble agent. This strategy
prevents agents applied to the oral mucosa from dissolving
in saliva and being removed (e.g., corticosteroid mixed with
an insoluble agent [Kenalog in Orabase]). New doseforms
and delivery systems are being developed every day. For example, in 2006 the Food and Drug Administration (FDA)
approved the very first inhaled insulin, a drug formerly only
administered by injection.
Degree of Ionization
As mentioned earlier, the ionized form of a drug tends to be
more water soluble, and nonionized forms tend to be more
lipid soluble. Biologic membranes are composed of
r layers of lipid material and proteins that allow for passage
of lipid-soluble molecules;
r small openings or water pores that allow for the passage of
water-soluble molecules.
Consequently, the nonpolar, nonionized form of a drug will
diffuse across biologic membranes more readily than its polar, ionized form. This phenomenon has clinical implications.
For example, if the patient is taking an antacid, which increases the pH of the stomach and upper small intestine, the
administration of a weak acid (such as aspirin) may result
in increased ionization and poor absorption of the aspirin,
giving less-than-optimal pain relief.
pKa and Ionization
The pH of the area affects drugs’ degrees of ionization. Drugs
will be ionized or nonionized primarily as a function of their
pKa and the pH of the environment. The pKa is defined as that
Drug Concentration
Highly concentrated drugs are absorbed faster than the same
drugs in low concentrations. Absorption of drugs through
skin and mucosa by passive diffusion is proportional to the
drugs’ concentration and lipid solubility. This concept is discussed further when ROAs are presented.
Circulation to Area
The greater the blood flow to tissue, the faster the rate of
absorption. Organs with significant blood flow include the
heart, the GI tract, and the liver. This concept is illustrated in
the discussion related to ROAs.
Area of Absorptive Surface
The upper small intestine has a large surface area and is the
site of absorption for most orally administered drugs. Drugs
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r the presence of food in the stomach, which slows the rate of
BOX 2-3. Routes of Administration
Enteral
r oral
r rectal
Parenteral
r various injections
r inhalation
r topical (sublingual, drops, patches, intrasulcus)
absorption because the drug competes for absorption with
food components in the GI mucosa;
r gastric motility, which can move the drug through the intestines so fast that it does not have time for complete absorption;
r the degree of splanchnic blood flow (blood flow through
intestinal viscera)—i.e., the intestinal viscera have a large
surface area and significant vascularity;
r patient compliance in taking the prescribed drug regimen.
First-Pass Effect
must pass through the wall of the small intestine and be
absorbed into the bloodstream to be distributed to the body
tissues and their receptors.
Routes of Administration
ROAs are classified as enteral or parenteral. Enteric drugs
are placed directly into the GI tract by oral or rectal administration and must pass through the liver before distribution
to the site of action. This reduces the bioavailability of some
drugs by a process called first-pass metabolism. Parenteral
drugs bypass the GI tract and include various injection, inhalation, and topical routes, such as direct application to the
skin or mucosa and sublingual administration (Box 2-3).
Enteral
The oral route is the safest, most common, most convenient,
and most economical method of drug administration. It is
also the most unpredictable route because many factors can
affect the rate of absorption between the GI tract (Box 2-4).
The rectal route, which is a form of enteric drug administration, may be useful in young children who have trouble
swallowing tablet doseforms, and for unconscious or vomiting patients. However, absorption with this route is unpredictable. When a drug is administered enterally, its rate of
absorption into the systemic circulation is influenced by
r the inherent characteristics of the drug (lipid soluble, water
The close anatomical relationship between the liver and the
GI tract, and the abundant blood supply of these organs, has
important effects on the bioavailability of some drugs. Because the liver is situated between enteric sites of absorption
and the systemic circulation, it can profoundly influence the
amount of drug in circulation when the drug is administered
orally—an action that has been described as the first-pass
effect. A drug given orally is absorbed mainly in the upper
small intestine and enters the splanchnic circulation supplying that mucosa. Rectally administered drugs are absorbed via
the lower intestinal mucosa. Within the circulation, the drug
molecules attach to plasma proteins, called albumin. Drugs
bind at various ratios to plasma proteins. When the drug binds
at a 90:10 ratio, this means that 90% of the molecules are
bound to albumin and 10% exist in an unbound form. Albumin serves to carry the molecule in the circulation to be
distributed to the site of action. The protein-bound drug is
protected from metabolism as the blood moves through the
liver. Drugs that are removed efficiently from the liver during
“first pass” will have a low bioavailability. Consequently, only
that fraction of the drug that reaches the systemic circulation
after first-pass metabolism is bioavailable to its receptor site.
Parenteral
Parenteral drugs bypass the GI tract and include various injectable routes, such as intravenous (IV), subcutaneous (SC),
intramuscular (IM); inhalation; and topical routes. This ROA
often is used for agents susceptible to degradation in the
GI tract and those adversely affected by hepatic first-pass
metabolism.
soluble, molecular weight, pKa of the drug);
r the pH of the GI tract, which can change the ionization
characteristics of a drug molecule;
BOX 2-4. Features of the Oral Route
r
r
r
r
r
Safest route
Most common route
Most convenient route
Most economical route
Most unpredictable route
Intravenous Administration
The IV route provides for accurate and immediate deposition
of drugs into the circulation, bypassing the absorption phase.
The effect is rapid, with almost immediate onset of action.
This route is considered to be the most predictable ROA. The
IV route often is used in emergency situations. The dose of
injected drugs can be adjusted to the patient’s response; however, once a drug is injected, there is no recall. This makes the
IV route less safe than the oral route, where absorption can be
manipulated. Sterile formulations of soluble substances and
an aseptic technique are required. Local irritation, often referred to as injection site reactions, and damage to the inner
blood vessel wall can result in thromboembolic complications (Box 2-5).
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BOX 2-5. Features of IV Route
r
r
r
r
r
Bypasses absorption, causing immediate effect
Most predictable route
Used in emergency situations
Less safe than oral route
Injection site reactions are possible
diffusion is proportional to their concentration and lipid solubility. Drugs’ concentrations may be increased for topical
products because the skin is a barrier to absorption. Warnings
related to applying topical anesthetic agents include
r limiting the area of application in order to reduce the ab-
sorption of these concentrated local anesthetic agents;
r avoiding placement of an occlusive dressing;
r avoiding application over abraded areas or where skin is
not intact;
r considering the allergic potential.
Subcutaneous Injection
Following SC injection, a drug’s rate of absorption into the
bloodstream is slow and sufficiently constant to provide a
sustained effect. The incorporation of a vasoconstrictor into
a drug formulation, such as in a local anesthetic agent used in
dentistry, can further retard the rate of absorption. Local tissue
irritation characterized by sloughing, necrosis, and severe
pain are potential complications. Insulin is administered by
SC injection.
Intramuscular Injection
The IM injection allows for rapid absorption of aqueous solutions into the bloodstream. Oily or other nonaqueous formulations may provide for slow, constant absorption. This is
another example that illustrates the role of drug formulation
in the drug’s absorption. Substances considered too irritating
to administer by IV and SC routes in some instances may be
given intramuscularly. The IM injection is usually given in
the deltoid or gluteal muscle.
Other Parenteral-Injectable Routes
Intradermal, intrathecal, and intraperitoneal routes are other
types of parenteral ROAs given by injection. The tuberculosis
skin test uses the intradermal route.
Inhalation
Inhaled drugs are considered to be delivered topically—the
drug is inhaled and attaches to pulmonary tissues, where absorption occurs. This direct topical absorption also has an
advantage over enteric administration because it circumvents
the metabolic first-pass breakdown in the liver. The large pulmonary absorptive surface in the lungs allows for rapid access
of gaseous, volatile agents to the circulation. Drugs administered by inhalation may act locally or they may cross the
alveoli, enter the circulation, and act at the appropriate receptor site. Concentration is controlled at the alveolar level
because most of these drugs are exhaled immediately. Asthma
often is treated with inhaled drugs.
Topical Application
This ROA is used to apply drugs directly to tissue. It includes
those placed sublingually, supplied via patches, inserted by
drops in the eyes or ears, or placed within the gingival sulcus. Absorption of drugs through skin and mucosa by passive
Systemic adverse effects can occur if occlusive dressings are
placed over the drug or if the drug is applied to abraded or
inflamed areas. In these situations, the concentrated drug is
absorbed more easily, leading to overdose. For unexplained
reasons, the topical ROA is more likely to cause allergic drug
reactions.
Sublingual
Topical application of a drug placed under the tongue is absorbed into the lingual venous system through nonkeratinized
mucosa. Because venous drainage from the mouth flows into
the superior vena cava, and because of the rich vascularity
of the oral area, sublingually administered drugs enter the
circulation quickly. This direct absorption also has an advantage over enteric administration because it circumvents the
metabolic first-pass breakdown in the liver. Absorption of
many drugs is immediate, and this ROA is often used when a
rapid response is needed, such as when nitroglycerin is used
to treat anginal pain.
Transdermal Patch
Transdermal delivery systems are designed to provide for a
slow, continued release of medication. The patch is applied
to the skin, eliminating the need for multiple doses of the
drug. Most patches consist of several layers: An adhesive to
stick to the skin, a membrane to control the rate of drug release, a reservoir where the drug is placed, and a backing
that keeps the drug from evaporating. Common adverse effects with patches include local erythema and irritation. These
are minimized by rotating the location of the patch when it
is reapplied. Patches are changed daily, every few days, or
weekly, depending on the specific drug.
Other Topical Routes
The recent introduction of locally applied antimicrobial
agents into the gingival sulcus utilizes a polymer-based formulation. This keeps the antimicrobial product from leaving
the area and increases the duration of the effect. This is discussed in detail in Chapter 9.
Self-Study Review
12. Describe the stages a drug goes through from the
time of administration to the elimination of the
drug.
13. Compare the features of ionized molecules with
those of nonionized forms as the molecule moves
through tissues to cause an effect.
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14. What is the role of specialized transport mechanisms
in moving drug molecules across the membrane?
Give an example of a specialized transport vehicle.
15. Identify three factors that affect the absorption of a
drug.
16. From where in the GI tract are most drugs
absorbed?
17. Describe how taking a drug that alters the pH of the
stomach can affect the absorption of a drug.
18. Describe two means to alter a drug’s absorption
through modifying the formulation.
19. Identify features of enteral and parenteral ROAs.
20. How does food in the stomach affect drug
absorption?
21. Describe how the first-pass effect influences the
onset of drug action.
22. List parenteral routes and identify the route used in
most emergency situations.
23. What is the most predictable ROA?
24. What are the precautions to follow when using
topical agents?
21
tent by plasma protein (albumin) binding of drugs. Plasma
protein binding is a nonselective process. Many drugs compete with each other and with endogenous substances for
albumin-binding sites. Plasma protein binding tends to reduce
the availability of drugs for diffusion into target organs because, in general, only the free or unbound drug is capable of
crossing biologic membranes. Because highly protein-bound
drugs cannot leave the circulation, their rate of metabolism
and excretion also is reduced. The therapeutic consequence
of this phenomenon is taken into consideration when drug
dosages are determined. Highly protein-bound drugs, such as
aspirin, are also an important mechanism for some drug–drug
interactions. When administered concurrently with another
drug, highly bound drugs will compete for albumin-binding
sites, and the drug with the greatest affinity (e.g., aspirin)
will tend to “bump” the other drug off the albumin receptor,
effectively increasing its free, unbound form. The increased
blood level of the free drug molecules can lead to increased
therapeutic and/or toxic effects, even though the drug was
administered in therapeutic doses.
Blood–Brain Barrier
Distribution of Drugs
Drug absorption is a prerequisite for establishing adequate plasma levels. Next, drugs must reach their target
organ(s) in therapeutic concentrations to produce effects.
Drug distribution is achieved primarily through the circulatory system. In most cases, the therapeutic effect of a
drug in tissues correlates well with the concentration in the
circulation.
Tissues and organs vary greatly in their abilities to absorb various drugs and in the proportion of systemic blood
flow that they receive. Highly perfused organs, such as the
liver, kidney, heart, and CNS, tend to receive the drug within
minutes of absorption. Muscles, most viscera, skin, and fat
may require a longer amount of time before equilibrium is
achieved. When the patient has excess body fat, those drugs
that tend to accumulate in fat are slowly released from these
fat stores, which can result in high blood levels when multiple doses of the drug are taken. Redistribution may affect
the duration of a drug effect. For example, if a drug of high
lipid solubility accumulates rapidly in the brain and then is
redistributed to other tissues, the drug effects in the brain
are reduced. The distribution of drugs—their ability to cross
biologic membranes and leave the vascular compartment,
and ultimately to accumulate in tissues and at their sites of
action—relies on the same factors that affect absorption (i.e.,
molecular weight, concentration in plasma, lipid solubility,
pH of the vascular compartment, and pKa of the drug). In addition, in the circulation, many drugs are bound to plasma
proteins and, therefore, are unable to bind to therapeutic
receptors.
Plasma Protein Binding
The capacity of tissues (i.e., muscle and fat) to bind and store
drugs increases the tendency of drugs to leave the vascular
compartment, but this tendency is counteracted to some ex-
The distribution of drugs to the CNS and cerebrospinal fluid
is restricted by the blood–brain barrier. However, cerebral
blood flow is the only limiting factor associated with highly
lipid-soluble, uncharged (nonpolar) drugs.
Placenta as a Barrier
In a pregnant woman, drugs pass across the placenta by simple diffusion (once again, as a function of their concentration
in plasma, molecular weight, lipid solubility, pH of the vascular compartment, and their pKa ). The result is that the fetus
becomes medicated along with the mother. This is the reason
for the restriction of drugs, except prenatal vitamins, during
pregnancy.
Metabolism
Rarely does a drug enter the body and leave it without modification. A number of organs (liver, kidneys, GI tract, skin,
lungs) are capable of metabolizing drugs using a variety of
enzymatic reactions. However, the liver contains the greatest
diversity and quantity of metabolic enzymes, and the majority of drug metabolism occurs there. The liver preferentially metabolizes highly lipophilic drugs, rendering the drugs
in their metabolite state and inactive, although some drug
metabolites maintain a degree of pharmacologic activity. The
kidneys easily eliminate the metabolite form, which is ionized (water soluble). These enzymatic reactions, classified
as Phase I and Phase II processes, are collectively referred
to as biotransformation and can alter drugs in four different
ways:
1.
2.
3.
4.
Convert an active drug to an inactive drug
Convert an active drug to an active or toxic metabolite
Convert an inactive drug to an active drug
Convert an unexcretable (more lipophilic) drug into an
excretable (more hydrophilic) metabolite
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Phase I Reactions
Cytochrome P450 Induction and Inhibition
The CYP450 enzyme system can be induced to increase
drug metabolism or inhibited to reduce the rate of a drug’s
metabolism, and it is responsible for many adverse drug–
drug interactions. For example, chronic ethanol toxicity induces the metabolism of barbiturates, whereas acute ethanol
toxicity inhibits the metabolism of barbiturates. Alcohol and
barbiturates are additive CNS depressants. These potential
drug–drug interactions are the basis for the “DO NOT DRINK
ALCOHOL WITH THIS DRUG” warning on a barbiturate
prescription. Other drugs (erythromycin, omeprazole, cimetidine, ciprofloxacin) inhibit CYP450 enzymes and decrease
the metabolism of many other drugs. This increases the drugs’
blood levels and effectively increases their therapeutic and/or
toxic effects.
Excretion
Renal excretion is the most common and important mechanism of drug elimination from the body. Biotransformation prepares the molecule, and the kidney eliminates it via
urination. Consequently, following biotransformation, drugs
are intrinsically hydrophilic (ionized) and are excreted more
readily than lipophilic (nonionized) compounds. A relatively
small number of drugs are excreted primarily in the GI
tract via the bile, and only minor quantities are excreted
through respiratory (exhalation) and dermal routes (perspiration). Lactation is responsible for minor amounts of drug
excretion.
collecting duct
pH 4.6 to 8.2
proximal tubule
ul e
The chemical structure of a drug is modified by conjugation
to a large polar endogenous molecule. Some metabolites of
Phase I reactions can undergo additional Phase II metabolism.
In contrast to a Phase I reaction, Phase II biotransformation
almost always results in inactivation of the parent drug. Virtually all Phase II metabolites are pharmacologically inactive.
reabsorption to circulation
c
mole
Phase II Reactions
glomerulus
drug
A drug’s chemical structure is modified through oxidation,
reduction, or hydrolysis, which require very little energy.
The most commonly used pathway is the hepatic microsomal cytochrome P450 (CYP450) enzyme system, which oxidizes lipophilic molecules. Some drugs are biotransformed
by CYP450-independent oxidation, hydrolysis, or reduction.
These reactions are not limited to the hepatic endoplasmic reticulum. A practical example is the hydrolysis of ester and amide local anesthetic agents and the oxidation of
epinephrine, which may be hydrolyzed or oxidized, respectively, at their sites of administration within tissues, thereby
limiting their systemic toxicity.
excretion arterioles
distal
tubule
urine
loop of Henle
Figure 2-8 Elimination of a Drug in the Kidney
into the glomeruli. The glomerulus is the primary location for
drug elimination to occur. Typically, only the free drug is filtered by the glomeruli. A drug may be filtered at the renal
glomerulus or secreted into the proximal tubule, and, subsequently, either may be reabsorbed into the tubular lumen and
returned to the circulation or may be excreted into the urine
where, via urination, it is removed from the body (Fig. 2-8).
The mechanism includes these processes:
r Glomerular filtration depends on renal blood flow,
glomerular filtration rate, and plasma protein binding. Reduced renal blood flow, reduced glomerular filtration rate,
and increased plasma protein binding all contribute to reduced drug elimination.
r Active tubular secretion facilitates the movement of the
drug from the bloodstream into the renal tubular fluid by a
nonselective carrier system for organic ions. Some drugs,
such as penicillin, aspirin, and probenecid, are actively secreted at the proximal tubule and compete with each other
for the same secretory transport mechanisms.
r Passive tubular reabsorption of nonionized drugs results
in net passive reabsorption. Although reabsorption can decrease the elimination rate of drugs, many drugs exhibit pH
trapping in the distal tubules and are efficiently eliminated
in the urine. When drugs need to be retained in the body,
the pH of the urine can be manipulated. By alkalinizing
the urine (via administration of sodium bicarbonate), the
plasma level of weak acids can be decreased; alternatively,
by acidifying the urine (via administration of ammonium
chloride), the plasma level of weak bases can be decreased.
In summary, drug molecules are removed from the circulation into renal proximal tubules by the glomeruli, or they
may be secreted into renal proximal tubules from peritubular capillaries and, if not reabsorbed in the collecting tubules
of the kidney, excreted in the urine. Although the kidneys
excrete most drugs via glomerular filtration, there are other
mechanisms whereby the body eliminates drugs.
Glomerular Filtration, Tubular Secretion,
and Reabsorption from the Tubular Lumen
Enterohepatic Recirculation
Renal blood flow represents about 25% of total systemic
circulation. Therefore, afferent arterioles in the kidney constantly bring free, unbound, and plasma-protein–bound drugs
Some metabolites formed in the liver are excreted via the
bile into the intestinal tract to be eliminated in the feces. If these metabolites are subsequently hydrolyzed and
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Chapter 2 General Principles of Pharmacology
reabsorbed from the gut (a process called enterohepatic recirculation), drug action can be re-established. One could say
this is the body’s contribution to recycling! Enterohepatic recirculation can result in a significant delay in the elimination
of drugs from the body.
Exhalation
Pulmonary excretion is important mainly for the elimination
of anesthetic gases and vapors.
Other Mechanisms
Drugs can be excreted in lactation and are potential sources
of unwanted pharmacologic effects in nursing infants. Other
routes, such as saliva, sweat, and tears, are quantitatively
unimportant.
Half-Life of a Drug
The removal of most drugs from the body follows exponential
or first-order kinetics. Assuming a relatively uniform distribution of a drug within the body (considered to be a single compartment), first-order kinetics implies that a constant
fraction (%) of the drug is eliminated per unit time. The rate of
exponential kinetics may be expressed by its constant (k), the
fractional change per unit time, or its half-life (expressed as
t1/2 ), which is the time required for the plasma concentration
of a drug to decrease by 50%. This occurs in several ways,
such as
r the distribution half-life, which represents the rapid de-
cline in plasma–drug concentration as 50% of the drug is
distributed throughout the body;
r the elimination half-life, which reflects the time required
to excrete 50% of the drug from the system.
Following the administration of multiple therapeutic dosages
of a drug at time intervals equal to or shorter than the drug’s
half-life, a plateau level of drug accumulates. This is called
steady-state concentration and involves over four halflives. For example, if the t1/2 of a drug is 1 hour, then it will
require the administration of four therapeutic doses at 1-hour
intervals to reach steady state (Fig. 2-9). The plateau rep-
Time (t1/2)
Figure 2-9 Drug Half-Life. This shows the effects of dosing on plasma concentration.
23
resents a rate of drug administration that is equal to the rate
of drug elimination. Consequently, fluctuations in the plasma
concentration of drugs occur as a function of the dosage interval and the drug’s elimination half-life. Assuming first-order
kinetics, it takes approximately four half-lives to eliminate
a drug from the body. The elimination of some drugs (such
as alcohol) may follow zero-order kinetics, implying that a
constant amount of the drug is eliminated per unit time. In
this case, the enzymes that metabolize the drug become saturated and cannot absorb more drug, resulting in a constant
amount of drug being metabolized per unit of time. Small
changes in the dose of drugs with this type of kinetics can
lead to large serum concentrations and increase the risk for
toxicity.
Self-Study Review
25. Describe features of distribution that affect a drug
molecule reaching the receptor.
26. What is the role of albumin in the blood?
27. Identify the organ responsible for most drug
metabolism.
28. Describe the four ways drugs are altered during
biotransformation.
29. What are the differences between Phase I reactions
and Phase II reactions in biotransformation?
30. Which enzyme system is the primary pathway for
drug metabolism?
31. In which organ are most drugs excreted? What is
the primary area of the organ where this
occurs?
32. Describe the process of drug excretion.
33. Define a drug’s half-life.
CONCLUSION
After initial administration of a drug, there is a period of
time before any perceptible effect of the drug is observed in
the patient. The time of onset is determined mainly by the
rate and degree of absorption. The effect increases with time
until the drug reaches the peak effect. Movement through
biologic membranes and drug redistribution influences the
peak effect. The effect diminishes as the drug is metabolized and eliminated from the body. The duration of action
is affected primarily by the rate of inactivation and excretion
of the drug by the liver and kidneys. The onset of action,
the peak effect, and the duration of action are all dependent
upon the dose administered—i.e., the larger the dose, the
shorter the time to reach the peak effect, and the longer the
duration of action. An important clinical use of time-effect
relationships involves multiple dosing schedules over a period of time that depends on the drug’s half-life. To eliminate adverse events, the dosage schedule must be designed to
avoid giving more drug than has been eliminated since the last
dose.
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24 PART 1 General Principles of Pharmacology
CLINICAL APPLICATION EXERCISES (CAE)
Exercise 1. During the review of the health history,
it is noted that the patient lists Tums as a current overthe-counter (OTC) medication. The current appointment
is for periodontal débridement of one quadrant. The diagnosis of the case is severe chronic periodontal disease,
and a recommendation will be made for “saltwater rinse
in evening, plus OTC medication for pain relief.” How will
the current drug history information affect your recommendation for pain relief?
Exercise 2. During oral examination, your patient
gasps, clutches his chest, and cries out in pain. He reports
taking anticholesterol medication due to a recently identified problem with high cholesterol. You tell the receptionist to call 911, and you secure the medical emergency kit.
What ROA should be used to get the vasodilating drug
to the coronary arteries quickly?
Exercise 3. Your patient is an elderly, overweight
person who presents to the office in pain. The dentist decides to prescribe a narcotic agent. What considerations
are important in determining dosage, and why?
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