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Introduction to
Drug Action
The Interplay of Pharmacotherapeutics,
Pharmacokinetics and
Pharmacodynamics
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Pharmacotherapeutics
Pharmacotherapeutics is the achievement of
the desired therapeutic goal from drug therapy.
• Pharmacotherapeutics is the study of the clinical
purpose—the indication—for giving a drug.
• The clinical purpose can be to induce a cure or
prevent a problem.
Nurses should question medication orders if the
intended pharmacotherapeutics of a drug does
not correlate with the patient’s reason for
receiving drug therapy.
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Off-label Medications
• Off-label use is defined as the use of a
medication for any purpose that is not
FDA studied or approved.
• May be off-label for:
• Non-approved Diagnosis
• Non-approved dosage of medication
(higher or lower than approved)
• Non-approved client population
(child, pregnancy, etc.)
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Pharmacokinetics (Kinetic=Movement)
Pharmacokinetics is the movement of the drug
particles throughout the body.
• Absorption - The movement of the drug from
the site of administration into the
bloodstream.
• Distribution - The movement of the drug
into the cells.
• Metabolism - The conversion of the drug into
another substance or substances.
• Excretion - is the removal of the drug from
the body.
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Process by Which Drugs Move
Through the Body
Drugs cross cell membranes in one of three
ways:
1. They can pass between the spaces or
channels between the molecules in the
membrane.
2. Drugs can pass through the cell membrane
with the help of a transport system.
3. Drugs can penetrate the cell membrane
directly.
The chemistry of the drug particles also affects
the movement of particles throughout the body.
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Absorption
• Several variables affect the rate of drug
absorption.
– Absorption is dependent partly on the
route of administration
– Absorption is affected by the speed at
which the drug dissolves
• Drugs that are administered orally generally
take the longest to be absorbed.
– Food or other drugs can interfere with
absorption.
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Absorption (cont.)
Drugs given parenterally (IM, IV, SubQ) are
absorbed more rapidly than drugs given orally.
– Intramuscular absorption is somewhat more
rapid than subcutaneous absorption.
– Drugs that are administered intravenously are
placed directly into the bloodstream.
• Lipid (fat) solubility alters absorption.
• pH affects absorption.
• Blood flow also affects the rate of absorption—the
greater the volume of blood flow > the faster the
rate of absorption.
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Distribution
The distribution of a drug throughout the body
depends on three factors:
1. Blood flow to the tissues,
2. The drug’s ability to leave the blood, and
3. The drug’s ability to enter cells.
• The drug is transported to the tissues and cells
through the circulatory system.
• Most drugs do not produce their effect while in
the blood.
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Protein-Bound Drugs
Protein binding of drugs affects the distribution
of a drug.
• When the drug is bound to protein, it is unable
to pass through the capillary walls as protein
molecules are large.
• The bonds will dissolve in time, and the drug
molecules will become free and active.
• When the patient has a lower-than-expected
protein level, the distribution of the drug is
altered.
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The Effects of Administering ProteinBound Drugs
Highly Protein
Bound Drug
Loosely Protein
Bound Drug
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Blood–Brain Barrier
• The capillary bed that services the
brain is different from other capillary beds.
• Instead of wide spaces between the cells in the
capillary walls, the cells are packed tightly
together.
• This prevents drug molecules & other foreign
substances from passing through and entering
the brain.
• The purpose of the blood–brain barrier is to
keep toxins and poisons from reaching the
brain.
• This can prevent medication distribution.
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Placental Membrane
• The placental membrane separates
maternal circulation from fetal
circulation.
• It is not a barrier like the blood–brain
barrier.
• Any drug that can pass through a
membrane can pass through the
placenta.
• In order to pass through the placenta, a
drug must be lipophilic (lipid-soluble) and
not protein bound.
12
Metabolism (Biotransformation)
Metabolism of drugs occurs primarily in
the liver.
• Physiologic factors that impair the functioning of
the liver decrease the ability of the liver to
metabolize drugs.
• When drugs are metabolized, they
are changed from their original form to a
new form.
• Drugs are generally metabolized from substances
that are lipophilic into substances that are
hydrophilic (water soluble) for easy excretion.
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Metabolites
A product of metabolism is called a metabolite.
• Drugs that are metabolized are generally
changed into an inactive form.
• Metabolism can convert a drug that has little or
no therapeutic effect in its original form into an
active form.
• Drugs that are inactive until metabolized into an
active form are called pro-drugs.
• An active metabolite may cause a different and
potentially harmful effect.
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First-Pass Effect
Metabolism occurs at different rates for different
drugs.
• The % of drug that is metabolized each time the
drug passes through the liver is the same
• Drugs that are highly metabolized lose
much of their effectiveness after this first
pass through the liver.
• This loss of effectiveness is called the first-pass
effect.
• Drugs that experience a high first-pass effect
may need higher or more frequent oral doses to
achieve a therapeutic level of circulating drug.
15
P-450 System
• Liver metabolism is predominantly achieved by
specific enzymes. These enzymes make up the
cytochrome P-450 system.
• P-450 metabolism is genetically determined.
When a large quantity of one of these enzymes
is present, more metabolism can occur through
this pathway.
• This increase in metabolism rapidly decreases
the amount of circulating drug.
• Some drugs either induce or inhibit the P-450
system, altering metabolism of other drugs.
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Excretion
• Excretion is the process of removing a drug, or
its metabolites, from the body.
• The most common route for drug excretion is
through the urine.
• Drugs are also excreted through feces,
sweat, tears and bile.
• Diseases and pathological changes in the kidney
decrease the effectiveness of the kidney in drug
excretion.
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Half-Life of a Drug
The combined processes of metabolism and
excretion are responsible for the elimination of a
drug from the body.
• The amount of time that is required to remove
half (50%) of the blood concentration of a drug
is called half-life.
• Drugs have various half-lives, based on their
pharmacologic properties.
• In one half-life rotation, a percentage of the
drug molecules present in the blood is
eliminated.
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Steady State
The point at which the amount of drug
being administered and the amount being
eliminated are equal
• Increasing the dose has no effect on how quickly
steady state can be achieved.
• Steady state is achieved based on the amount of
time required for 4-5 half-lives to occur.
• The full pharmacotherapeutic response of a
particular drug dose is measured when the drug has
achieved steady state.
19
Clearance
The rate at which drug molecules disappear from
the circulatory system is effected by several
factors.
• This rate is called clearance or clearance rate of
a drug.
• Renal excretion and hepatic metabolism are the
major modes of clearance.
• Age & gender of the patient can also alter the
clearance of some drugs.
• Even though a drug’s clearance is shown to be
statistically altered, this statistical difference
does not necessarily create a clinical difference.
20
Pharmacodynamics
Pharmacodynamics is the biologic,
chemical, and physiologic actions of
a particular drug within the body.
• The pharmacodynamics of a drug
are responsible for its therapeutic
effects and sometimes its adverse
effects.
• Drugs cannot create new
responses in the body; they can
only turn on, turn off, promote, or
block a response that the body is
inherently capable of producing.
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Drug–Receptor
Interactions
Most drugs create their effects in the body by
attaching to special sites called receptors.
• At the receptor site, the drug is able to stimulate
the cell to act in a way that the cell is designed to
act.
• Each type of receptor is responsible for producing
a particular effect in the cell.
• An agonist causes the cell to act, or “turn on”.
• An antagonist prevents something else from
attaching to the cell therefore blocking an action.
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Receptor Occupancy Theory
• Single-occupancy theory
– The intensity of the body’s response to the
drug is directly related to the number of
receptors occupied by the drug.
– The maximum response occurs when all of
the receptors have drug molecules attached.
• Modified occupancy theory
– Different drugs have different strengths of
attractions, or affinity, for receptor sites.
– Once a drug is attached to a receptor, it has
different abilities to stimulate the receptor.
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Receptor Sensitivity
• Changes in receptor sensitivity
– Receptors are not static.
– Continual stimulation from an agonist
usually makes the drug less effective.
– Continual blockage from an antagonist
usually makes the drug more likely to
react.
• Non-receptor responses
– Drugs exert their effect by reacting
physically or chemically with other
molecules in the body.
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Variables that Influence the Dose of a
Drug
• Potency and efficacy
– The level of the drug needed in the body to
produce an effect
• Maintenance and loading doses
– Maintenance dose—daily dose
– Loading dose—larger than usual dose to
reach a therapeutic effect quicker
• Therapeutic index
– The difference between an effective dose and
a toxic dose
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Potency and Efficacy
A certain level of drug must be present in the body
to produce any effect at all.
• This level is called the minimum effective
concentration.
• The strength of the response to a drug increases
proportionately as more drug is given.
• The amount of a drug that must be given in order
to produce a particular response is called the
potency of a drug.
• How well a drug produces its desired effect is
called efficacy.
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Maintenance and Loading Doses
• Because people are unique, how individuals
respond to a drug dose varies.
• The dose that is required to produce the
therapeutic response in 50% of the
population is called the effective dose 50%
(ED50).
• The dose that is given consistently over time is
called the maintenance dose.
• Patients who are started on drug therapy using
the standard maintenance dose arrive at steady
state after 4-5 half-lives.
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Maintenance and Loading Doses (cont.)
• The patient’s medical condition may warrant
immediate and full drug effect.
– If this is the case, a larger dose than usual is
given initially.
– This initial large dose is called a loading
dose.
– The loading dose is computed so that after
some of the drug is eliminated, the drug
concentration in the body is still in the
therapeutic range.
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Therapeutic Index
• A lethal dose is computed in a laboratory setting
and analyzed statistically.
• The point at which the dose would be fatal in
50% of the population receiving that dose is
called lethal dose 50% (LD50).
• To determine the safety of a drug, the ED50
is compared with the LD50.
• The relation of ED50 to LD50 is called the
therapeutic index.
TI = ED50 / LD50
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Therapeutic Index (cont.)
• If the ED50 is close to the LD50, the mathematical
ratio of the two values will equal a number close
to one.
• When the ED50 and the LD50 are close to 1, the
drug is considered to have a very narrow
therapeutic index.
Questions
• Would a drug with TI close to 1 be a safe
drug?
• Why would we use such a drug?
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Drug Dosage and Blood Concentration
• As drug levels within the body increase, the
patient is more likely to experience adverse
effects from drug therapy.
Drug Dosage =
Adverse Effects
• To help determine whether a drug’s dose is
sufficient to be in the therapeutic range, but not
so high as to cause adverse effects, blood levels
of the drug may be measured.
 Narrow T.I. drugs are more likely to use
blood levels
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Assessment and Evaluation
The Nursing Process
Assess
Evaluate
Plan
Implement
32
Question
One aspect of pharmacotherapeutics is the study of the
clinical indications of drug therapy.
– A. True
– B. False
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Question
One aspect of pharmacotherapeutics is the study of the
clinical indications of drug therapy.
– A. True
– B. False
Pharmacotherapeutics is the study of desired
therapeutic goal from drug therapy, the clinical
purpose—the indication—for giving a drug and the
desired effect of the drug.
34
Question
What will be the result of administering a highly
protein-bound drug to a patient with liver failure?
– A. There will be no significant difference in the
distribution of the drug.
– B. The drug will reach the target cells more
quickly and therefore will not be as effective.
– C. The drug will reach the target cells more
quickly, which could result in a toxic effect.
– D. The drug will take longer to reach the target
cells, delaying the onset of action.
35
Question
What will be the result of administering a highly
protein-bound drug to a patient with liver failure?
– A. There will be no significant difference in the
distribution of the drug.
– B. The drug will reach the target cells more
quickly and therefore will not be as effective.
– C. The drug will reach the target cells more
quickly, which could result in a toxic effect.
– D. The drug will take longer to reach the target
cells, delaying the onset of action.
36
Rationale
Patients with liver failure have lower levels of
protein and albumin in their blood than patients
without liver failure;
Therefore, the drug will reach the target cells
more quickly, which could lead to a toxic effect.
Remember that all recommended drug dosages
are calculated based on a patient with normal
protein levels and liver functioning!
37
Question
All drugs have some type of adverse effect(s).
– A. True
– B. False
38
Question
All drugs have some type of adverse effect(s).
– A. True
– B. False
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