Download Therapeutics Week 2

Chapter 2:
Drug Action and Handling
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 2 Outline

Drug Action and Handling





Characterization of drug action
Mechanism of action of drugs
Pharmacokinetics
Routes of administration and dose forms
Factors that alter drug effects
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
2
Drug Action and Handling

The dental health care worker must be
familiar with some basic principles of
pharmacology to discuss drugs used in
dentistry and those that patients may be
taking

Understanding how drugs work, what effects they
can have, and what problems they can cause can
aid communication
cont’d…
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3
Drug Action and Handling



Haveles (p. 12)
Historically, drugs were discovered by
randomly searching for active components
among plants, animals, minerals, and soil
Today, organic synthetic chemistry
researchers are responsible primarily for
developing new drugs
cont’d…
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4
Drug Action and Handling

Parent compounds that exhibit known
pharmacologic activity are chemically
modified to produce congeners or analogs:
agents of similar chemical structure with
similar pharmacologic effect

This technique of modifying a chemical molecule
to provide more useful therapeutic agents evolved
from studies of the relationship between chemical
structure and the biologic activity, called the
structure-activity relationship (SAR)
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5
Characterization of Drug Action





Haveles (pp. 12-14)
Log dose effect curve
Potency
Efficacy
Chemical signaling between cells
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6
Log Dose Effect Curve


Haveles (pp. 12-13) (Fig. 2-1)
The effect a drug exerts on biologic systems
can be related quantitatively to the dose of
the drug given

A curve will result if the dose of the drug is plotted
against the intensity of the effect
cont’d…
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7
Log Dose Effect Curve


Haveles (pp. 12-13) (Fig. 2-2)
If this curve is replotted using the log of the dose (log
dose) versus the response, another curve is
produced

The potency and efficacy of the drug’s action may be
determined from this curve
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8
Potency


Potency of a drug is a function of the amount of the
drug required to produce an effect


Haveles (p. 13) (Fig. 2-3)
Potency is shown by the location of that drug’s curve along
the log-dose axis (x-axis)
More of a less-potent drug is required to produce a
desired effect equivalent to that of a more potent drug
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9
Efficacy


Efficacy is the maximal intensity of effect or response
that can be produced by a drug


Haveles (pp. 13-14) (Fig. 2-5)
Administering more drug will not increase the efficacy but
can often increase the probability of an adverse reaction
The efficacy of a drug increases as the height of the
curve increases
cont’d…
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10
Efficacy

“The efficacy and the potency of a drug are
unrelated”


Drugs may be equally efficacious, but differ in potency
Death is the endpoint when measuring the lethal
dose

The median lethal dose (LD50) is the dose when one half of
the subjects die
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11
Chemical Signaling Among Cells


Haveles (p. 14)
The brain regulates the body through the autonomic
nervous system


Messages from the brain must be transmitted to many part of
the body commanding the parts to “do something”
Complex mechanisms for transmitting these messages allow
for amplification or damping of the effect
cont’d…
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12
Chemical Signaling Among Cells


Haveles (p. 14)
Neurotransmitters are chemicals responsible for
transporting a wide variety of messages across the
synapse

Chemical signaling involves release of neurotransmitters and
local substances and hormone secretion
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13
Neurotransmitters


Haveles (p. 14) (Fig. 2-6)
Messengers that move the electrical impulses from a
nerve are transmitted across the synapse via
neurotransmitters


The neurotransmitters are released and quickly travel across
the synapse to the receptor
At least fifty different agents can transmit messages
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14
Local Substances

Some organs secrete chemicals that work near them

These chemicals are not released into systemic circulation
cont’d…
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15
Local Substances

Prostaglandins and histamine are examples of local
substances


Histamines can produce a localized allergic reaction
Prostaglandins contract uterine muscles and become
important when a baby is born
• When released in the stomach, they protect its lining
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16
Hormones

Secreted to produce effects throughout the body


Examples include insulin, thyroid hormone, and
adrenocorticosteroids
Reactions are usually slower than the ones associated with
neurotransmitters
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17
Mechanism of Action of Drugs




Haveles (pp. 14-16)
Nerve transmission
Receptors
Agonists and antagonists
cont’d…
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18
Mechanism of Action of Drugs


Drugs elicit pharmacologic effects after they
have been distributed to their sites of action


Haveles (p. 14)
The effect occurs because of a modulation in the
function of an organism
Drugs do not impart a new function to an
organism

They either produce the same action as an
endogenous agent or block the action of an
endogenous agent
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19
Nerve Transmission


Haveles (pp. 14-15)
Transmission of impulses travels along the
nerve producing a nerve action potential

The action potential is triggered by the
neurotransmitter released at the previous synapse
cont’d…
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20
Nerve Transmission

The processes involved in the drug’s effect
begin with the drug-receptor interaction


The receptors interact with both endogenous
substances and drugs
This drug-receptor interaction results in a
conformational (shape) change, which may allow
the drug inside the cell to produce its effect, or it
may cause release of a second messenger, which
then produces the effect
cont’d…
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21
Nerve Transmission

Many of the effects involve altering enzyme-regulated
reactions or regulatory processes for protein
synthesis after a series of reactions

Similar to a chain reaction
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22
Receptors


Haveles (p. 15)
Once a drug passes through a biologic
membrane, it is carried to many different
areas of the body, or site of action, to exert its
therapeutic effect or adverse effect

To do this, the drug must bind with the receptor
site on the cell membrane
cont’d…
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23
Receptors


Haveles (p. 15) (Fig. 2-7)
Drug receptors appear to consist of many large
molecules that exist either on the cell membrane or
within the cell itself


More than one receptor type or identical receptors can be
found at the site of action
Usually, a specific drug will bind with a specific receptor in a
lock-and-key fashion
cont’d…
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24
Receptors


Haveles (p. 15) (Fig. 2-8)
Different drugs often compete for the same receptor
sites


The drug with stronger affinity for the receptor will bind to
more receptors than the drug with weaker affinity
Drugs with stronger affinity for receptor sites are more potent
than drugs with weaker affinity for receptor sites
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25
Agonists and Antagonists


Haveles (pp. 15-16) (Fig. 2-9)
When a drug combines with a receptor, it may
produce enhancement or inhibition of the
function

These drugs are classified as either agonists or
antagonists
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26
Agonist


Haveles (p. 15)
An agonist is a drug that



Has affinity for the receptor
Combines with the receptor
Produces an effect
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27
Antagonists


Haveles (pp. 15-16) (Fig. 2-9)
An antagonist counteracts the action of the
agonist

Three different types of antagonists
• Competitive antagonist
• Noncompetitive antagonist
• Physiologic antagonist
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28
Competitive Antagonist

A drug that




Has affinity for a receptor
Combines with the receptor
Produces no effect
This causes a shift to the right in the dose-response
curve


The antagonist competes with the agonist for the receptor
The outcome depends on the relative affinity and
concentrations of each agent
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29
Noncompetitive Antagonist

Binds to a different receptor site than the agonist

This reduces the maximal response of the agonist
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30
Physiologic Antagonist

Has affinity for a different receptor site than the
agonist

Decreases the maximal effect of the agonist by producing an
opposite effect via different receptors
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31
Agonists and Antagonists


Haveles (p. 16)
Transport carriers are systems available for
moving neurotransmitters or drugs into the
cell

Neurotransmitter precursors must be taken into
the cell by an active transport pump
 The precursor for norepinephrine is tyramine,
therefore it must be pumped into the cell
 After the neurotransmitter is synthesized, it is
placed in granules that await a signal to dump
their contents into the synapse
cont’d…
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32
Agonists and Antagonists

The neurotransmitter can take three paths after it is
released



It can be broken down by enzymes
It can migrate to the receptor and interact to produce an
effect
It can be taken up by the presynaptic nerve ending
• Reuptake is an easy way to recover the neurotransmitter for
future use
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33
Pharmacokinetics








Haveles (pp. 16-22)
Passage across body membranes
Absorption
Distribution
Half-life
Blood-brain barrier
Redistribution
Metabolism (biotransformation)
cont’d…
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34
Pharmacokinetics



Haveles (p. 16)
The study of how a drug enters the body,
circulates within the body, is changed by the
body, and leaves the body
Factors influencing movement are described
in four major steps (ADME)




Absorption
Distribution
Metabolism
Excretion
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35
Passage Across Body
Membranes



Haveles (pp. 16-17)
Passive transfer
Specialized transport
cont’d…
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36
Passage Across Body
Membranes


Haveles (pp. 16-17)
The amount of drug passing through a cell
membrane and the rate at which a drug moves
are important in describing the time course of
action and the variation in individual response to
a drug


Before a drug is absorbed, distributed, metabolized,
and eliminated, it must pass through various
membranes such as cellular membranes, blood
capillary membranes, and intracellular membranes
These membranes share physicochemical
characteristics that influence the passage of drugs
across their borders
cont’d…
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37
Passage Across Body
Membranes


Haveles (p. 16)
Membranes are composed of lipids, proteins,
and carbohydrates



Membrane lipids make the membrane relatively
impermeable to ions and polar molecules
Membrane proteins make up the structural
components of the membrane and help move the
molecules across the membrane during the
transport process
Membrane carbohydrates are combined with
either proteins or lipids
cont’d…
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38
Passage Across Body
Membranes

The lipid molecules orient themselves to form
a fluid bimolecular leaflet with hydrophobic
(lipophilic) ends in and hydrophilic charged
ends out

Throughout the membrane is a system of pores
through which low–molecular-weight and smallsize chemicals can pass
cont’d…
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39
Passage Across Body
Membranes

The physicochemical properties of drugs that
influence their passage across biologic membranes
are lipid solubility, degree of ionization, and molecular
size and shape

Mechanisms of transfer are passive transfer and specialized
transport
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40
Passive Transfer
 Haveles (pp. 16-17) (Fig. 2-10)

Lipid-soluble substances move across the
lipoprotein membrane by a passive transfer
process called simple diffusion

Directly proportional to concentration gradient of
the drug across the membrane and the degree of
lipid solubility
cont’d…
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41
Passive Transfer

Water-soluble molecules small enough to pass
through membrane pores may be carried through
pores by bulk flow of water


This process of filtration through single-cell membrane may
occur with drugs having a molecular weight of 200 or less
Drugs with molecular weights of 60,000 can “filter” through
capillary membranes
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42
Specialized Transport


Haveles (pp. 16-17) (Fig. 2-14)
Certain substances are transported across
cell membranes by processes more complex
than simple diffusion or filtration

Active transport is a process by which a substance
is transported against a concentration or
electrochemical gradient
 Facilitated diffusion does not move against a
concentration gradient
 Pinocytosis may explain the passage of
macromolecular substances into cells
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43
Absorption


Effect of ionization




Haveles (p. 17)
Weak acids
Weak bases
Oral absorption
Absorption from injection site
cont’d…
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44
Absorption


Haveles (p. 17)
The process by which drug molecules are
transferred from the site of administration to
the circulating blood

Requires the drug to pass through biologic
membranes
cont’d…
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45
Absorption

The rate of absorption of a drug involves these
factors



Physicochemical factors
The site of absorption, which is determined by the route of
administration
The drug’s solubility
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46
Effect of Ionization


Haveles (p. 17) (Fig. 2-10)
Drugs that are weak electrolytes dissociate in
solution and equilibrate into a nonionized
form and an ionized form


The nonionized, or uncharged, portion acts similar
to a nonpolar, lipid-soluble compound that readily
crosses body membranes
The ionized portion will traverse these membranes
with greater difficulty because it is less lipid
soluble
cont’d…
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47
Effect of Ionization


Haveles (p. 17)
The pH of tissues at the site of administration
and dissociation characteristics (acid
dissociation constant, or pKa) of the drug will
determine the amount of drug in the ionized
and nonionized state

The proportion in each state will determine the
ease with which the drug will penetrate tissue
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48
Weak Acids

When the pH at the site of absorption
increases, the hydrogen ion concentration
falls


This results in an increase in the ionized form (A–),
which cannot easily penetrate tissues
If the pH of the site falls, the hydrogen ion
concentration will rise

This results in an increase in the un-ionized form
(HA), which can more easily penetrate tissues
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49
Weak Bases

If the pH of the site rises, the hydrogen ion
concentration will fall


This results in an increase in the un-ionized form
(B), which can more easily penetrate tissues
If the pH of the site falls, the hydrogen ion
concentration will rise

This results in an increase in the ionized form
(BH+), which cannot easily penetrate tissues
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50
Effect of Ionization

In summary


Weak acids are better absorbed when the pH is
less than the pKa
Weak bases are better absorbed with the pH is
greater than the pKa
cont’d…
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51
Effect of Ionization


Haveles (p. 17)
In the presence of infection, the acidity of the
tissue increases (and the pH decreases), and
the effect of local anesthetics decreases


In the presence of infection, the (H+) increases
because of accumulating waste products in the
infected area
The increase in (H+) leads to an increase in
ionization and a decrease in penetration of the
membrane by local anesthetic
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52
Oral Absorption



Haveles (p. 17)
Unless the drug is administered as a solution,
the absorption of the drug in the gastrointestinal
(GI) tract involves release from a dose form such
as a tablet or capsule
This release requires the following steps before
absorption can take place




Disruption: initial disruption of coating or shell
Disintegration: contents must break apart
Dispersion: particles must spread
Dissolution: drug must be dissolved in GI fluid
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53
Absorption from Injection Site


Haveles (p. 17)
Depends on solubility of the drug and the
blood flow at that site



Drugs with low water solubility are absorbed very
slowly after intramuscular injection
Drugs in suspension are absorbed much more
slowly than those in solution
Drugs that are the least soluble will have the
longest duration of action
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54
Distribution



Haveles (pp. 17-19)
Basic principles
All drugs occur in two forms in blood: bound
to plasma proteins and the free drug

The free drug is the form that exerts the
pharmacologic effect
 The bound drug is a reservoir for the drug
cont’d…
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55
Distribution

The proportion in each form is dependent on
the properties of that specific drug (percent
protein bound)


Within each body compartment, the drug is split
between the bound drug and the free drug
Only the free drug can pass across cell
membranes
cont’d…
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56
Distribution

For a drug to exert its activity, it must be made
available at its site of action in the body


The mechanism by which this is accomplished is
distribution—the passage of the drug into various
body fluid compartments such as plasma, interstitial
fluids, and intracellular fluids
The manner in which a drug is distributed in the body
will determine how rapidly it produces the desired
response, the duration of that response, and, in some
cases, whether a response will occur at all
cont’d…
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57
Distribution

Drug distribution occurs when a drug moves
to various sites in the body, including its site
of action in specific tissues



Drugs are also distributed to areas where no
action is desired (nonspecific tissues)
Some drugs are poorly distributed to certain
regions
Some drugs are distributed to their site of action
and then redistributed to another tissue site
cont’d…
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58
Distribution

The distribution is determined by several
factors

Size of the organ
 Blood flow to the organ
 Solubility of the drug
 Plasma protein–binding capacity
 Presence of barriers (blood-brain barrier, placenta)
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59
Distribution by Plasma


After absorption from the site of
administration, a drug is distributed to its site
of action by blood plasma


Haveles (p. 18)
Biologic activity is related to the concentration of
free, unbound drug in plasma
Drugs are bound reversibly to plasma
proteins such as albumin and globulin


The bound drug is considered a storage site
Only the unbound form is biologically active
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60
Half-Life


Haveles (p. 18) (Fig. 2-11)
The amount of time that passes for the
concentration of a drug to fall to one half of its
blood level (t1/2)

When the half-life is short, the duration of action is
short
 When the half-life is long, the duration of action is
long
cont’d…
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61
Half-Life

Only 3% to 6% of the drug remains after four or five
half-lives; we can say the drug is essentially gone

Conversely, about four or five half-lives of repeated dosing
are needed for a drug’s level to build up to a steady state in
the body
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62
Blood-Brain Barrier


The tissue sites of distribution should be
considered before administration of a drug


Haveles (pp. 18-19)
To penetrate the central nervous system, a drug
must cross the blood-brain barrier
Passage of a drug across this barrier is
related to the drug’s lipid solubility and degree
of ionization

To diffuse transcellularly, the drug must penetrate
the epithelial and basement membrane cells
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63
Placenta


Haveles (p. 19)
Involves simple diffusion according to the
degree of lipid solubility


The placenta may act as a selective barrier
against a few drugs; most drugs pass easily
across the placental barrier
When agents are administered to the mother, they
are concomitantly administered to the fetus
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64
Enterohepatic Circulation


Haveles (p. 19)
Most drugs are absorbed in the intestines,
distributed through serum, pass to specific
and nonspecific sites of action, and then go to
the liver, where they are metabolized before
being excreted via the kidneys

For enterohepatic circulation, the steps are the
same until the drug is metabolized
cont’d…
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65
Enterohepatic Circulation

With enterohepatic circulation, after the drug
is metabolized, the metabolite is secreted via
bile into the intestine

The metabolite is broken down by enzymes and
releases the drug
 The drug is then absorbed again and the process
continues
 After being taken up by the liver a second time,
these drugs are again secreted into the bile
 This circular pattern continues, with some drug
escaping with each passing
 This process prolongs the effect of a drug
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66
Redistribution


The movement of a drug from the site of
action to nonspecific sites of action


Haveles (p. 19)
The drug’s duration of action can be affected by
redistribution of the drug from one organ to
another
If redistribution occurs between specific sites
and nonspecific sites, a drug’s action will be
terminated
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67
Metabolism
(Biotransformation)


First-pass effect



Haveles (pp. 19-22)
Phase I
Phase II
Excretion







Kinetics
Renal route
Extrarenal routes
Biliary excretion
Other
Saliva
Gingival crevicular fluid
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68
Metabolism


Haveles (p. 19)
The body’s way of changing a drug so that it can
be more easily excreted by the kidneys

Many drugs undergo metabolic transformation or
change, most commonly in the liver
 The metabolite formed is usually more polar and less
lipid soluble than the parent compound
 This means renal tubular absorption of the metabolite
will be reduced because renal tubular absorption
favors lipid-soluble compounds
cont’d…
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69
Metabolism


Haveles (p. 19) (Fig. 2-12)
Drugs can be metabolized by three different
means

Active to inactive
• An inactive metabolite is formed from an active parent
drug (most common process)

Inactive to active
• An inactive parent drug (prodrug) may be transformed to
an active compound

Active to active
• An active parent drug may be converted to a second
active compound, which is then converted to an inactive
product
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70
First-Pass Effect


Haveles (pp. 19-20)
Metabolism of drugs may be divided into two
general types: phase I and phase II

If the drug has no functional groups with which to
combine, then it must undergo a phase I reaction
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71
Phase I Reaction
 Haveles (pp. 19-20)

In phase I reactions, lipid molecules are
metabolized by the three processes of



Oxidation
Reduction
Hydrolysis
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72
Oxidation

When a drug that is administered does not
possess an appropriate functional group that
is suitable for combining with body acids
(conjugation), the body has more difficulty
detoxifying the drug


An enzyme system responsible for the oxidative
metabolism of many drugs is located in the liver
The enzymes are located in the endoplasmic
reticulum and are called microsomal enzymes
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73
Hydrolysis

Some ester compounds are metabolized by
hydrolysis


Hydrolytic enzymes found in plasma and in a
variety of tissues break up esters and add water
Ester local anesthetics are inactivated by plasma
cholinesterases
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74
Reduction

Many reduction reactions are mediated by
enzymes found in hepatic microsomes
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75
Microsomal Enzymes


Haveles (pp. 20-21) (Fig. 2-13; Table 2-1)
Phase I reactions are carried out by
microsomal or cytochrome P-450 enzymes,
known as mixed function oxidases in the liver

Phase I metabolism may be affected by other
drugs that alter microsomal enzyme inhibition or
induction
cont’d…
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76
Microsomal Enzymes

Induction: the P-450 hepatic microsomal
enzymes can be induced (the amount of
enzyme increased) by some drugs and by
smoking tobacco


Hepatic enzymes can be divided into many
categories called isoenzymes
Inhibition: inhibition of the metabolism of
certain drugs may occur through several
mechanisms

With inhibition, the blood levels and action of the
drugs metabolized by these enzymes will be
increased
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77
Phase II Reactions


Haveles (p. 20)
Phase II reactions involve conjugation with
the following agents: glucuronic acid, acetic
acid, or an amino acid

The most common conjugation, called
glucuronidation, occurs with glucuronic acid
 The enzymes that mediate the conjugation are
called transferases
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78
Excretion


Drugs may be excreted by any of several
routes, but renal excretion is most important


Haveles (pp. 20-22)
Extrarenal routes include the lungs, bile, GI tract,
sweat, saliva, and breast milk
Drugs may be excreted unchanged or as
metabolites
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79
Kinetics


Haveles (pp. 18, 20) (Fig. 2-11)
The mathematical representation of the way
in which drugs are removed from the body

The most common mechanism is first-order
kinetics
cont’d…
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80
Kinetics


Haveles (pp. 20, 22) (Fig. 2-14)
A few drugs, such as aspirin and alcohol, exhibit
zero-order kinetics


With zero-order kinetics, the rate of metabolism remains
constant over time, and the same amount of the drug is
metabolized per unit of time, regardless of dose
With high doses, the metabolism of the drug cannot
increase, and the duration of action of the drug can be
greatly prolonged
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81
Renal Route


Haveles (pp. 20-21)
Elimination of substances in the kidney can
occur through three routes

Glomerular filtration (most common)
• The unchanged drug or its metabolites are filtered through
the glomeruli and concentrated in renal tubular fluid

Active tubular secretion
• The drug is transported from the bloodstream, across renal
tubular epithelial cells, and into renal tubular fluid

Passive tubular diffusion
• Favors resorption of nonionized, lipid-soluble compounds
• More ionized metabolites have more difficulty penetrating
the cell membranes of the renal tubules and are likely to be
retained in tubular fluid and eliminated in urine
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82
Extrarenal Routes


Haveles (p. 21)
Gases used in general anesthesia are
excreted across lung tissue by simple
diffusion

Alcohol is partially excreted by the lungs
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83
Biliary Excretion


Haveles (p. 21)
The major route by which systemically
absorbed drugs enter the GI tract and are
eliminated in feces

Drugs excreted in bile may be reabsorbed from
the intestines (enterohepatic circulation)
 This enterohepatic circulation prolongs a drug’s
action
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84
Other


Haveles (p. 21)
Breast milk and sweat


Minor routes of elimination
Distribution of drugs in breast milk may be a
potential source of undesirable effects for the
nursing infant
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85
Saliva


Drugs can be excreted in saliva



Haveles (p. 21)
They are usually swallowed and their fate is the
same as drugs ingested orally
Most drugs secreted in the salivary glands
enter saliva by simple diffusion
Drug levels in saliva have been studied to
see if they can be used to monitor therapy
with certain agents
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86
Gingival Crevicular Fluid (GCF)


Haveles (p. 22)
Drugs excreted in the GCF produce a higher
level of drug in the gingival crevices, which
can increase their usefulness in the treatment
of periodontal disease

Tetracycline is concentrated in GCF
 This means that the drug level in GCF will be
several times higher than the blood level
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87
Routes of Administration and Dose
Forms


Routes of administration












Haveles (pp. 22-25)
Oral route
Rectal route
Intravenous route
Intramuscular route
Subcutaneous route
Intradermal route
Intrathecal route
Intraperitoneal route
Inhalation route
Topical route
Other routes
Dose forms
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88
Routes of Administration


Haveles (pp. 22-23) (Fig. 2-15)
Route of administration affects both the onset
and duration of response


Onset: the time required for the drug to begin to
have its effect
Duration: the length of a drug’s effect
cont’d…
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89
Routes of Administration

The routes can be classified as enteral or parenteral


Drugs given by the enteral route are placed directly into the
GI tract by oral or rectal administration
The parenteral route bypasses the GI tract and includes
injection routes, inhalation, and topical administration
• In practice, parenteral usually means injection
cont’d…
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90
Routes of Administration


Haveles (p. 22)
Oral administration is considered safest, least
expensive, and most convenient, but the
parenteral route has certain advantages
cont’d…
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91
Routes of Administration


Haveles (p. 22)
Advantages of the parenteral route



Injection results in fast absorption, which produces
a rapid onset and more predictable response than
oral administration
Useful for emergencies, unconsciousness, lack of
cooperation, or nausea
Some drugs must be administered by injection to
remain active
cont’d…
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92
Routes of Administration


Haveles (pp. 22-23) (Fig. 2-15)
Disadvantages of the parenteral route







Asepsis must be maintained to prevent infection
An intravascular injection may occur by accident
Administration by injection is more painful
Removing the drug is difficult
Adverse effects may be more pronounced
Self-medication is difficult
More dangerous and expensive than oral medication
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93
Oral Route


Haveles (pp. 22-23)
The simplest way to introduce a drug into the
body

Allows for many different dose forms: tablets,
capsules, and liquids are conveniently given
cont’d…
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94
Oral Route

Advantages of the oral route


A large absorbing area present in the small intestine
Slower onset of action than parenterally administered agents
cont’d…
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95
Oral Route

Disadvantages of the oral route






Stomach and intestinal irritation may result in nausea and
vomiting
Certain drugs, such as insulin, are inactivated by GI tract acidity
or enzymes
Some orally administered drugs may be inactivated by the
hepatic (liver) portal circulation (first-pass effect)
Blood levels after oral administration are less predictable than for
parenteral administration
Drug interactions can occur when two drugs are in the stomach
The oral route necessitates greater patient cooperation
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96
Rectal Route


Haveles (p. 23)
Drugs may be given as suppositories, creams, or
enemas


May be used if the patient is vomiting or unconscious
May be used for either a local or systemic effect, but
because most drugs are poorly and irregularly absorbed
rectally, this route is not often used to achieve a systemic
drug effect
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97
Intravenous Route


Produces the most rapid drug response




Haveles (p. 23)
The absorption phase is bypassed
More predictable drug response than oral
administration
The route of choice for an emergency situation
Disadvantages include phlebitis caused by local
irritation, drug irretrievability, allergy, and side effects
related to high plasma concentration of the drug
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98
Intramuscular Route


Absorption of drugs injected into the muscle occurs
as a result of high blood flow through skeletal muscle


Haveles (p. 24)
Somewhat irritating drugs may be tolerated if given by the
intramuscular route
May be used for injection of suspensions for a
sustained effect

Injections are usually into the deltoid or gluteal mass
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99
Subcutaneous Route


Injection of solutions or suspensions of drugs into
subcutaneous tissue to gain access to systemic
circulation


Haveles (p. 24)
If irritating solutions are injected, sterile abscesses may
result
Commonly used for administration of insulin
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100
Intradermal Route


Small amounts of drugs, such as local anesthetics,
may be injected into the epidermis


Haveles (p. 24)
Produces a small bump (bleb) as the liquid is injected just
under the skin
Used for tuberculin skin test
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101
Intrathecal Route


Haveles (p. 24)
Injection of solutions into the spinal subarachnoid
space

May be used for spinal anesthesia or for the treatment of
certain forms of meningitis
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102
Intraperitoneal Route


Placing fluid into the peritoneal cavity, where
exchange of substances can occur


Haveles (p. 24)
A drug may be absorbed through mesenteric veins
May be used for peritoneal dialysis

Used as a substitute for the failing kidney to manage
patients with renal failure
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103
Inhalation Route


Haveles (pp. 24-25)
May be used in the administration of gaseous,
microcrystalline, liquid, or powdered form of drugs


An example of inhalers being used for their local effects are
those used to treat asthma
General anesthetic in the form of volatile liquids or gases are
examples of the use of the inhalation route for systemic
effects
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104
Topical Route


Haveles (p. 25)
Application to body surfaces



May administered to skin, oral mucosa, and even
sublingually
May be intended to produce either local or
systemic effects
Generally used on skin for local effect
cont’d…
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105
Topical Route

Rarely, systemic side effects can occur from
topical administration of drugs for their local
effect



An example is administration of topical
corticosteroids over a large portion of the body,
resulting in symptoms of systemic toxicity
Interruptions in the mucous membranes or
mucosal inflammation increase the likelihood
of a systemic effect
Examples of drugs applied topically for a
systemic effect include transdermal patches
and sublingual spray or tablet administration
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106
Subgingival Strips and Gels


Haveles (p. 25)
Dental-specific topical application involves the
placement of drug-impregnated strips or gels
subgingivally

Doxycycline gel (Atridox), and the chlorhexidine-containing
chip (PerioChip) are examples of agents administered into
the gingival crevice
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107
Transdermal Patch


Designed to provide continuous controlled release
through a semipermeable membrane over a given
period after application of drug to the intact skin


Haveles (p. 25) (Fig. 2-16)
Eliminates the need for repeated oral dosing
The most common problems with transdermal
patches are local irritation, erythema, and edema
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108
Topical Anesthesia


Haveles (p. 25)
Applied directly to mucous membranes and rapidly
absorbed into systemic circulation

An example is the combination of lidocaine and prilocaine
(Oraqix)
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109
Sublingual and Buccal Routes


Haveles (p. 25)
Two ways in which drugs can be applied topically


The mucous membranes of the oral cavity provide a
convenient absorbing surface for the systemic administration
of many drugs
Absorption of many drugs into systemic circulation occurs
rapidly
• Avoids both first-pass effect and GI acid and enzymes
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110
Other Routes



Haveles (p. 25)
Drugs such as progestins (Norplant), can be
implanted under the skin to release a drug over a
long duration (5 years)
Pumps that deliver intravenous drugs can be
implanted in the body

When insulin pumps are used, they can be programmed
externally
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111
Dose Forms


The most commonly used dose forms in dentistry are
the tablet and capsule given orally


Haveles (pp. 25-26) (Table 2-2)
Liquid solutions or suspensions are often prescribed for
children
For injection, the drug may be in solution, such as
local anesthetic, or it may be in suspension, such as
procaine penicillin G
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112
Factors that Alter Drug Effects













Haveles (pp. 25-27)
Patient compliance
Psychologic factors
Tolerance
Pathologic state
Time of administration
Route of administration
Sex
Genetic variation
Drug interactions
Age and weight
Environment
Other
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113
Patient Compliance


Haveles (p. 25)
Through either lack of understanding or
motivation, patients often do not take their
medication as prescribed or not at all

May result from faulty communication, inadequate
patient education, or the patient’s health belief
system
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114
Psychologic Factors

The attitude of the prescriber and the dental
staff can affect the efficacy of the drug
prescribed


A placebo is a dose form that looks similar to the
active agent but contains no active ingredients
The magnitude of the placebo effect depends on
the patient’s perception; individual variation is
large
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115
Tolerance

Defined as the need for an increasingly larger
dose to get the same effect as with the original
dose, or a decreased effect after repeated
administration of a given dose of a drug



Cross-tolerance may occur with related compounds
People under stress may need a larger dose for an
effect
Tachyphylaxis is the very rapid development of
tolerance
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116
Pathologic State

Diseased patients may respond to medication
differently than other patients


Patients with hyperthyroidism are extremely
sensitive to the toxic effects of epinephrine
Patients with liver or kidney disease may
metabolize or excrete drugs differently, potentially
leading to increased duration of drug action
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117
Time of Administration

The time of administration, especially in
relation to meals, may alter the response to
the drug

Certain drugs with a sedative action are best
administered at bedtime
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118
Route of Administration

Enteral routes are slower, less predictable, and safer
than parenteral routes
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119
Sex


Women may be more sensitive than men to
certain drugs, perhaps because of their
smaller size or their hormones
Pregnancy alters the effects of certain drugs

Women of child-bearing age should avoid
teratogenic drugs
 The health care provider should determine
whether the patient is pregnant before
administering any agent
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120
Genetic Variation

Differences in patient responses to drugs
have been associated with variations in ability
to metabolize certain drugs

Certain populations have a higher incidence of
adverse effects to some drugs—a genetic
predisposition
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121
Drug Interactions

A drug’s effect may be modified by previous
or concomitant administration of another drug

Many mechanisms exist by which drug
interactions may modify a patient’s treatment
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122
Age and Weight

The child’s weight should be used to
determine the child’s dose


The manufacturer’s recommendations for
children’s dosing would be best
Older patients may respond differently to
drugs than younger patients

Whether it is caused by changes in renal or liver
function or whether being elderly predisposes this
sensitivity is controversial
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123
Environment

The environment contains many substances
that may affect the action of drugs


Smoking induces enzymes; therefore higher
doses of benzodiazepines are needed to produce
the same effect as compared with nonsmokers
Chemical contaminants such as pesticides or
solvents can have an effect on a drug’s action
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124
Other

The action of drugs can be altered by the
patient-provider interaction


If the patient “believes” in the substance or
process, then the patient’s opinion will enhance
the drug’s effect
The attitude of both the patient and the provider
can alter the physiology of the body
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125