Critical Care and
Emergency Medicine
Pharmacology
Jassin M. Jouria, MD
Dr. Jassin M. Jouria is a medical doctor,
professor of academic medicine, and medical
author. He graduated from Ross University
School of Medicine and has completed his
clinical clerkship training in various teaching
hospitals throughout New York, including
King’s County Hospital Center and Brookdale Medical Center, among others. Dr.
Jouria has passed all USMLE medical board exams, and has served as a test prep
tutor and instructor for Kaplan. He has developed several medical courses and
curricula for a variety of educational institutions. Dr. Jouria has also served on
multiple levels in the academic field including faculty member and Department Chair.
Dr. Jouria continues to serves as a Subject Matter Expert for several continuing
education organizations covering multiple basic medical sciences. He has also
developed several continuing medical education courses covering various topics in
clinical medicine. Recently, Dr. Jouria has been contracted by the University of
Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module
training series for trauma patient management. Dr. Jouria is currently authoring an
academic textbook on Human Anatomy & Physiology.
Abstract
Safe administration of medication in critical care and emergency
settings is paramount to ensure optimal outcomes for patients. The
most experienced medical and nursing clinicians are well aware of the
fragility of critical care patients and the potential for the smallest
mistake to result in serious consequences. Understanding the purpose,
administration, monitoring, and potential consequences of
pharmacological agents available to critical care and emergency
department clinicians is necessary for them to make use of potentially
life-saving treatments.
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Policy Statement
This activity has been planned and implemented in accordance with
the policies of NurseCe4Less.com and the continuing nursing education
requirements of the American Nurses Credentialing Center's
Commission on Accreditation for registered nurses. It is the policy of
NurseCe4Less.com to ensure objectivity, transparency, and best
practice in clinical education for all continuing nursing education (CNE)
activities.
Continuing Education Credit Designation
This educational activity is credited for 4 hours. Nurses may only claim
credit commensurate with the credit awarded for completion of this
course activity. Pharmacology content is 4 hours.
Statement of Learning Need
Critical care and emergency medicine is a relatively recent
phenomenon in health care, and the role of pharmacists, physicians
and certified nurses trained to work in critical care and emergency
settings have expanded over recent years. As the intensive care units
and emergency departments in hospital increasingly develop to include
computerized equipment and software supporting unit-based services
and highly trained interdisciplinary staff delivering care to patients
diagnosed with critical conditions, so too does the highly important
need of the right medication, dose and route to initially treat, stabilize
and progress patients to a healthier state.
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Course Purpose
To provide advanced learning in critical care and emergency
pharmacology for clinicians working in hospital emergency and
intensive care unit settings.
Target Audience
Advanced Practice Registered Nurses and Registered Nurses
(Interdisciplinary Health Team Members, including Vocational Nurses
and Medical Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA,
Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures
Acknowledgement of Commercial Support
There is no commercial support for this course.
Please take time to complete a self-assessment of knowledge,
on page 4, sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge
learned will be provided at the end of the course.
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1. ________________ is a process that is sometimes given the
abbreviation ADME.
a.
b.
c.
d.
Pharmacodynamics
Biopharmaceutics
Pharmacokinetics
Pinocytosis
2. True or False: Studies that assess how drug act in the body
after administration, such as rates of absorption, volume
distribution, or rates of elimination, are often generated
from clinical research studies on healthy volunteers.
a. True
b. False
3. Which of the following processes describes the movement of
a drug from its point of administration to its target location,
i.e., the bloodstream?
a.
b.
c.
d.
Absorption
Pinocytosis
Diffusion
Transportation
4. Which of the following forms of drug administration
generally has the slower rate of absorption?
a.
b.
c.
d.
Intravenous administration
Intramuscular injection
Subcutaneous injection
All the above have similar absorption rates
5. ______________ occurs when a cell membrane surrounds
and encloses the particles of the drug.
a.
b.
c.
d.
Passive diffusion
Pinocytosis
Absorption
Active transport
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Introduction
Medication administration is a common element of medical and nursing
clinical care, and prescribed drugs are typically given to patients in all
areas of medicine. Clinicians working in emergency departments and
critical care units may administer many drugs from different classes.
These medications may sometimes be routine prescription medications
needed for general care of the patient, but often, the drugs are also
given in emergency or life-threatening situations. In the intensive care
unit (ICU) or emergency department (ED), clinicians must be familiar
with the purposes, effects, and appropriate routes of administration of
medications so that they can quickly give them to patients in need.
Overview: Medication Safety
Medication administration involves accounting for the safety of the
patient from the time the dose is prescribed until after it has been
given. Assessing the patient’s clinical status and ensuring the correct
dose and route have been ordered, administering the drug correctly
(and sometimes very rapidly), and observing the patient for the drug’s
effects or for changes in clinical status are all major steps in the
process of giving drugs in the critical care setting. Before discussing
the purposes of common types of critical care medications and their
potential complications, it is important to know how the body responds
to a drug once it has been given as well as what the drug does once it
enters the body to exert its therapeutic effects.
A key element of drug administration is the clinical interventions
necessary during the time surrounding their administration. Often,
drugs given in the critical care environment can have great potential
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for complications because of their physiological effects. When
administered rapidly for emergency purposes, many drugs start to
work almost immediately and their effects can impact almost all body
systems. Nitroglycerin, a vasodilator medication often administered for
the management of angina, is an example of a drug that can cause a
rapid drop in the patient’s blood pressure because it relaxes the
smooth muscles of the blood vessels.1 The clinician who administers
nitroglycerin must not only monitor for the effects of the drug on
controlling angina, but also for complications that can develop because
of hypotension, such as dizziness or syncope. In order to understand
drug effects and side effects, the clinician needs to know the
pharmacokinetics and pharmacodynamics.
Pharmacokinetics
When a drug is given for any type of illness or medical condition, it is
regulated in the body through pharmacokinetics, which describes the
processes of absorption, distribution, metabolism, and excretion of a
drug within the body.2 The process is sometimes given the
abbreviation ADME. The term pharmacokinetics is also sometimes
described as what the body does to a drug when it is given. Overall, it
is important to have a basic understanding of pharmacokinetics when
administering drugs in the critical care setting, as changes in the
pharmacokinetics of a drug within the body, whether due to such
factors as a patient’s deteriorating health condition or the presence of
chronic disease, can lead the healthcare provider to make associated
changes in patient care and in the dosage, timing, and even the route
of drug administration.
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Each category of pharmacokinetics has a corresponding
pharmacokinetic parameter. Each parameter consists of measurable
factors that can be determined through the calculation of certain
statistical formulas. When a drug is assessed by how it acts in the
body after administration, corresponding pharmacokinetic parameters
can be calculated to determine factors such as the rate of its
absorption, the volume of its distribution, or the rate of its elimination.
This information is often generated from clinical research studies in
which volunteers, who are often healthy, take the drugs for specified
periods and then scientists such as biostatisticians and
pharmacokineticists study the information, apply the formulas, and
determine the results of the drug’s pharmacokinetics based on how it
behaves after being administered to study participants. This allows
those who are manufacturing, dispensing, and administering the drug
to have a better understanding of how it will act in the body and how
differences in factors such as drug concentration or the coadministration of other drugs or substances will affect
pharmacokinetics.
While this information is extremely valuable, the health clinician
working in the ICU or emergency department and administering
medications to the critically ill patient must keep in mind that since
studies of pharmacokinetics are often done on healthy adults, the
measurements of factors such as volume of distribution or rate of
elimination typically reflect that factor. Among critically ill patients,
however, these parameters may not be the same since illness and
injury often affect how the body processes certain drugs. While the
bedside clinician cannot be expected to understand the exact
pharmacokinetic formulas for parameters and the effects of critical
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illness on these items, it makes sense to know how common drugs are
absorbed, distributed, metabolized, and excreted, so that any
alterations in the body systems that perform these functions can be
expected to have a corresponding effect on the pharmacokinetics of
the drug.
Drug Absorption
When a medication is prescribed, it is always given a route through
which it is to be administered. The route of which each drug is given
affects how it will be absorbed into circulation. Absorption is the
process of moving the drug from its initial location after it has been
given (for instance, the stomach or intestinal tract for oral drugs, or
the skeletal muscle tissue for an intramuscular injection) and
transitioning its particles into circulation.
Any drug that is given through an extravascular route, including such
routes as oral tablets or capsules, as an intramuscular or
subcutaneous injection, or via inhalation, must be absorbed into
circulation before it can begin to take effect. This is because drugs that
are not given intravenously are not given directly into the
bloodstream. Alternatively, medications that are given via the
intravenous route are administered directly into the bloodstream and
do not require the additional step of absorption. Therefore, this section
describing the absorption process is mainly focused on extravascular
routes of drug administration that require absorption for the drug to
eventually reach the bloodstream.
The rate and method of absorption depends on several factors,
including the route in which the drug is administered. Drugs that are
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given via subcutaneous injection are absorbed through nearby
capillaries that are close to the subcutaneous tissue and the site of
administration. Because there is less vascular access to the
subcutaneous tissue when compared to skeletal muscle tissue used for
an intramuscular injection, the absorption rate of a subcutaneous
injection is slower. Alternatively, medications given orally often first
pass through the stomach, as most drugs are not absorbed in the
stomach cavity, and then enter the small intestine, where they are
eventually absorbed. The rate at which a drug is absorbed also
depends on the type of drug and its overall constitution. Some drugs
are rapidly absorbed based on their chemical compositions, while
others must first be broken down and their chemical makeup
separated before they are able to be absorbed. Other factors, including
the molecular size of the drug particles, as well as the overall solubility
at the site of absorption also affect the rate at which a drug is
absorbed into circulation.
To best facilitate absorption after a drug has been administered, the
drug components must first be broken down from the original form
when it was given. This may mean the dissolution of the substance of
the drug, such as when an oral medication is given in capsule form
that dissolves in the stomach. Some drugs, such as intramuscular or
subcutaneous injections, are prepared within a solution, known as a
vehicle in which the drug is suspended. The vehicle solution is usually
classified as being either aqueous, in which is contains mostly water,
or non-aqueous, which may be oil-based. Injections may also contain
other solvents along with the medication and the solution, particularly
when the drug has low solubility.60,61 After giving an injection, all of
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these components must be broken down or dissolved before the drug
can be absorbed.
The term biopharmaceutics refers to the physical and chemical
properties of drugs, as well as their effects in the body.
Biopharmaceutics may be referred to in conjunction with
pharmacokinetics, as the two concepts are interrelated because of how
the drug behaves in the body.5 The intensity of a drug’s effects after it
is absorbed and distributed within the body, the formulation of the
drug, and the solution or vehicle in which the drug is suspended for
administration are just some of the factors involved with how a drug is
absorbed and then used in the body.
Drugs that have very slow rates of absorption are often less desirable
for use when compared to those that can be absorbed rapidly. When a
drug must be administered to combat a critical and potentially lifethreatening situation, drugs that are rapidly absorbed exert their
effects more quickly than those with slower processes of absorption.
Sometimes, a slow rate of absorption cannot be avoided and the
drug’s effects are much more important than the amount of time it
takes for the drug to be absorbed. As an example, drugs that are
administered orally must pass through the intestinal membrane of a
part of the small intestine, often the duodenum, before they can be
absorbed into circulation.
The rate of absorption of oral medications can be affected by various
factors, including the pH of the gastrointestinal system or first-pass
metabolism by the liver, which is a type of filtration process in which
the concentration of the drug is significantly reduced before it ever
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reaches systemic circulation.3 Other factors, such as administration of
enteric coated capsules or by giving medications through enteral
feeding tubes can also impact the rate of absorption. Note that some
drugs are specifically given to affect the gastrointestinal system and
are administered enterally for their effects on the stomach and
intestinal tract.
When a drug is administered orally, the majority of absorption takes
place in the small intestine, similar to the absorption of food. Most
medications are not absorbed in the stomach because of the thick
lining of the stomach wall. The rate at which an oral drug is absorbed
is affected by how much time it spends in the stomach before being
transported into the small intestine. Delayed gastric emptying can
ultimately cause a delay in movement of the drug for it to be
absorbed; this is why there are some drugs that must be taken on an
empty stomach, as the presence of food in the stomach can affect
transit time of the drug into the small intestine.
There are four main types of absorption processes. The activity of
absorption is basically a movement of the drug particles across a
membrane into the circulatory system where it can then be
distributed. This movement of particles occurs as passive diffusion,
facilitated passive diffusion, active transport, or pinocytosis.2
• Passive diffusion describes the movement of drug particles across a
membrane from an area of higher concentration to an area of lower
concentration. For example, the fluids that make up the
gastrointestinal tract have a higher concentration than the blood in
circulation. Drugs can be absorbed via passive diffusion using little
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to no excess energy and a carrier molecule is not required. Passive
diffusion is the method of absorption by which most drugs are
transferred into systemic circulation.
• Facilitated passive diffusion also does not require energy. It
involves the movement of drug particles across a membrane with
the help of a carrier molecule. It is thought that a carrier molecule
within the membrane combines with a molecule of the drug; this
molecule combination then rapidly crosses the membrane barrier
where the molecule of the drug is then released on the other side.
• Active transport describes the active movement of molecules across
a membrane; the process requires energy to occur. Active transport
utilizes specific molecules, sometimes referred to as carrier
molecules, that can cross the membrane. This process is drug
selective and usually occurs only at specific sites, including within
the small intestine for absorption of oral medications. Because
active transport uses energy, it is able to facilitate the movement of
drug molecules against a concentration gradient, if needed. In this
way, active transport can move drug particles from an area of lower
concentration to one of higher concentration.
• Pinocytosis occurs when a cell membrane surrounds and encloses
the particles of the drug. Once the drug particles are confined, a sac
or cavity is formed that moves toward the center part of the cell
and then is separated. The process requires energy to occur, as it is
an active process, however there are only a few drugs that are
absorbed through pinocytosis.
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These methods of absorption by the movement of particles occur not
only with orally administered drugs. As stated, there are various other
techniques of drug administration, and all have different methods of
being absorbed after they are given, but the process of moving
particles across a membrane through diffusion or active transport
remains the same.
Extravascular injections of medications that are given subcutaneously
or intramuscularly involve direct injection of the drug and its
surrounding solution into the tissue, which may include the
subcutaneous fat just under the surface of the skin or deep into the
skeletal muscle tissue. Because these methods administer drugs into
different types of tissue, their methods of absorption also differ. In
general, intramuscular medications are absorbed more quickly than
subcutaneous injections, as muscle tissue contains more blood vessels.
When a drug is given as an intramuscular injection, the substance of
the medication gathers together within the muscle tissue to form a
pocket called a depot. The medication is then absorbed into the
surrounding blood vessels as it is released from the depot, the rate at
which can be affected by various factors, including viscosity of the
medication, the number of blood vessels present along with local blood
supply, and the type of muscle into which the drug was administered.4
Absorption of medications from subcutaneous injections takes longer
because there is less of a blood supply within the subcutaneous tissue
when compared to skeletal muscle tissue. If there is local blood flow
nearby, the drug may be absorbed quickly, particularly if it is not an
overly viscous solution. Drugs that are given in aqueous solutions are
absorbed faster than those that contain oil-based solutions;
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medications with high solubility also tend to be absorbed more slowly
than those with low solubility. Some drugs need to exert their effects
quickly and so rapid absorption is preferable to slow; alternatively,
when drugs are meant to work slowly and to exert their effects over a
longer course of time, it is preferable to have longer absorption times.
Other types of medication administration, including intrathecal,
sublingual, rectal, or through inhalation all require the drugs to be
absorbed through a process so that they can enter the circulatory
system. For example, when a drug is administered transdermally as a
patch or ointment applied to the skin, it comes into contact with the
stratum corneum, which is the outermost layer of the epidermis. The
stratum corneum acts as a barrier on the skin surface, therefore, only
a percentage of the drug applied is actually able to breach this initial
barrier and enter the body, passing the skin.61
The size and type of molecules that make up the drug affect the rate
of transdermal absorption. A discussion of the pharmacokinetics of
topical products in the journal Dermatological Nursing conferred that
drugs with small molecules that are better absorbed in fatty tissues
(lipophilic molecules) can be transported well across the stratum
corneum and into its intercellular lipids. When these drugs have
hydrophilic properties, meaning they are better dissolved in water,
they are best able to penetrate the skin to reach the lower layers.61
Underneath the stratum corneum, the skin layers are much more
permeable; penetration of the layers of skin takes place by passive
diffusion. The dermis contains a variety of structures, including hair
follicles and sweat glands, and it also contains blood vessels, into
which the medication is absorbed.
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Other factors may influence the rate at which topical preparations are
absorbed into the skin. For example, when an ointment is applied to
the skin and covered by an occlusive dressing, the medication may be
absorbed more quickly than when a layer of the medication is applied
without any cover. The presence of an occlusive dressing on the skin
prevents water loss from the site and supports hydration, causing the
stratum corneum layer to swell and expand slightly, thereby increasing
permeability and the capacity for the drug to enter.61 Other factors
that may affect the rate and amount of drug absorbed transdermally
include the presence of hair at the site, whether any skin conditions or
diseases are present at the affected site, and the variations in skin
permeability seen in different areas of the body.
Regardless of the method of extravascular administration of drugs, in
order for medications to enter systemic circulation, they must all be
released into the fluid or tissues into which they were administered
and then cross the membrane of the circulatory system through one of
the absorptive processes described. Although there are many factors
that can affect the rate of absorption and the amount of the drug that
actually enters circulation, the process of drug absorption is one step
of pharmacokinetics that all drugs, except intravenously administered
drugs, must undergo to exert their effects and to be therapeutically
useful.
Drug Distribution
Once a drug has been absorbed into circulation, the body distributes
the medication to various sites for its own purposes. Bioavailability
refers to exactly how much of a drug enters the circulation and the
rate at which it is absorbed and therefore available to be distributed.
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Drugs that are administered extravascularly are generally not
completely absorbed. There are usually traces of the medication that
remain unabsorbed. This reduces bioavailability since there is less of
the drug available for distribution from its original dose. By
comparison, drugs that are administered intravascularly have greater
bioavailability because they do not need to undergo absorption first.
The composition of a drug impacts its rate of absorption and can affect
the bioavailability of the drug within the circulation system. For
example, there are differences between drugs that are administered as
capsules and as tablets, even though they may be the same drug at
the same dose. Their composition as either capsules or tablets can
impact their qualities of absorption because of their formulations. This,
in turn, affects their bioavailability in the bloodstream as well as the
amount to be distributed.
Clinical illness can also affect the rate and bioavailability of a drug
reaching systemic circulation. Changes in the gastrointestinal wall,
such as due to inflammatory bowel disease or gastrointestinal illness,
can affect the lining of the small intestinal tract and its ability to
properly absorb the medication. Other changes related to illness, such
as alterations in circulation or capillary damage can also affect how
drugs are absorbed when they are administered through other routes
as well, including intramuscular or subcutaneous injections.
Drug distribution begins once the medication has entered systemic
circulation. When a drug is administered intravenously, distribution
begins relatively rapidly because the medication is already present in
circulation. When a drug is given through another extravascular route,
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it begins to be distributed once absorption has taken place. The
administration of intravenous medications has its benefits and
limitations. It can cause complications associated with infection, tissue
extravasation, phlebitis, or hematoma formation; however, the direct
administration of medication into the bloodstream bypasses the step of
absorption and the bioavailability of the drug is much higher so that it
can be rapidly distributed across the body’s tissues to take effect
quickly. The rate of distribution so that the drug can exert its effects is
a very important element to consider when the drug is given in the
critical care setting, as the outcomes of the drug’s effects often need
to take place very quickly.
Through the circulatory system, the drug is able to be distributed to all
parts of the body that receive blood flow, including all tissues and
organs where the drug exerts its effects. The drug is transported to
sites of action by either binding to elements within the blood that will
carry the drug components, or by traveling as an unbound particle.
How much of the drug is actually distributed depends on plasma
proteins and the amount of tissue binding.62 Typically, when a drug
binds to components in the bloodstream, it is to plasma proteins,
including albumin, alpha-1 acid glycoprotein, and lipoproteins.
However, when a drug is bound nonspecifically to a protein in the
bloodstream, it cannot exert its therapeutic effects. The drug is said to
bind nonspecifically when it binds to a component that is not its
intended receptor. For instance, when a drug is a specific type of
receptor agonist but it binds to protein instead, it is said to be binding
nonspecifically. The unbound part of the medication, though, is free to
cross over into the interstitial space through passive diffusion where it
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will reach tissue-binding sites and it will begin to exert its
pharmacological effects.
Just as some factors affect the rate and degree of a drug’s absorptive
processes, there are also some issues that impact the rate of a drug’s
distribution. Different drugs may be distributed at a faster or slower
rate through the bloodstream; the rate of distribution is affected by
factors such as blood flow and the tissue where the drug is being
distributed. When blood flow is slow and perfusion is poor, a drug is
not distributed as rapidly. A drug is distributed more quickly to areas
that receive more blood flow, such as to the lungs or the kidneys.6
Blockages in the circulatory system, including blood clots or
atherosclerotic lesions, can decrease the overall rate of blood flow.
Obstructions that affect the direction of the blood vessels can also slow
the rate of drug distribution if the blood is rerouted around a
physiological barrier to circulation.
The characteristics of a drug can also affect the rate at which it is
distributed. Some drugs are more likely to bind to plasma proteins in
the bloodstream, which affects their rate of distribution. A drug that is
particularly lipophilic may accumulate in areas with high body fat,
which typically has poor perfusion.
There are several sites where the drug can be distributed in addition to
the plasma of the bloodstream, including intracellular fluid and the
interstitial spaces. When a drug is in the bloodstream, it moves from
the plasma into the tissues through the process of diffusion. The
concentration of the drug is initially much higher in the plasma than in
the tissues just after intravenous drug administration or absorption of
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an extravascular administration of the drug. Consequently, the drug
moves from an area of higher concentration within the bloodstream to
an area of lower concentration found in the tissues through diffusion.
Once more of the drug has entered the tissues, the process of diffusion
slows when the areas of concentration between the plasma levels and
tissue levels of the drug are more in balance. This point is known as
the post-distribution phase, in which drug concentrations in plasma
and in the tissues are in balance. This is more often true of drugs that
are administered routinely and continuously, such as in the case of an
ongoing prescription drug, where plasma drug levels are constant, as
opposed to an individual administration of a drug. Once a drug reaches
the post-distribution phase, the plasma and tissue concentrations of
the drug are balanced as the drug is eliminated from the body.7
Note that there are some barriers present that affect how well the
drug reaches its target receptor sites; examples include the bloodbrain barrier (BBB) and the placental barrier. The BBB affects how well
a drug is distributed to the brain; it separates the brain from systemic
circulation. In order for a drug to enter the brain, it must be
transported through capillaries of the central nervous system through
the BBB, which is made up of tightly bound cells that act as a semipermeable membrane. Some drugs are more readily able to pass
through this barrier than others. For instance, some lipid-soluble drugs
can quickly pass through to enter the brain. Alternatively, some
solutions pass through the BBB much more slowly because the large
size of their molecules make it difficult to move past the barrier’s tight
junction of endothelial cells.
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Each drug given has a particular volume of distribution, which
describes how much it will be distributed throughout the body. Most
drugs are not distributed at the same rates or in even concentrations,
and while there are often barriers that affect drug distribution, the
process is a distinct element of pharmacokinetics that moves the drug
from its original site of administration toward exerting its intended
effects.
Drug Metabolism
Once distributed, the drug is metabolized, which describes how the
chemical compound of the drug is converted into an active chemical
substance through the work of enzymes. Most drugs are metabolized
in the liver, but other body areas, including the lungs, plasma, and the
wall of the gastrointestinal tract have the capacity to metabolize drugs
as well.8 The majority of drugs given must be metabolized before they
can be excreted. When metabolism takes place in the liver, the
hepatocytes contain the enzymes needed to complete the metabolic
process.
The metabolism of a drug generally takes place in two stages; in some
cases, a drug will undergo only one of the two phases, but for most,
the metabolic process in the liver involves the drug undergoing Phase
1 followed by Phase 2. During the first phase, the most common
change that takes place is when the drug undergoes oxidation. Within
the liver, certain enzymes are responsible for initiating oxidation; the
most frequent group of enzymes responsible for drug metabolism
within the liver are those of cytochrome P450 (CYP450). Some other
substances that either inhibit or increase their activity can affect these
enzymes. Consequently, a drug that is known to affect CYP450 should
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not be administered with a drug that requires the enzyme for
metabolism.
The CYP450 enzymes from this group start the process of oxidation,
which occurs when electrons from the drug are removed. At this point,
the drug becomes a metabolite. Other processes that may occur
during the first phase of drug metabolism and that result in the
breakdown of the drug are reduction, in which there is the removal of
oxygen from the drug; or hydrolysis, in which there is the addition of
water molecules to the drug.
Once the medication has passed through Phase 1, conjugation occurs
in the second phase of metabolism, in which a group of ions binds to
the metabolite. This process occurs within the cytoplasm of the
hepatocyte. Typically, ionized groups that conjugate to the drug
metabolite come from glutathione, acetyl, or methyl groups. The
process of conjugation contributes toward the eventual excretion of
the drug from the body’s system, as the binding of an ionized group
makes the metabolite more water soluble and therefore easier to
excrete.8 The most common reaction that occurs during Phase 2 of
metabolism is glucuronidation, in which enzymes known as UDPglucuronosyltransferases catalyze the conjugation reactions that occur
during Phase 2 of metabolism. This process leads to the detoxification
of certain substances and the formation of glucuronides, which are
more water-soluble and facilitate easier excretion of drugs.
While glucuronidation is one of the most common conjugation
reactions of metabolism, there are other forms that can occur as well,
in which a functional group is added to the molecule to facilitate
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metabolism. Such examples include acetylation, which is the addition
of an acetyl group, and sulfation, which is the conjugation of a sulfo
group to the molecule.10 As the process of metabolism continues, the
drug’s therapeutic effects are decreased.
Rates of drug metabolism can vary, depending on several factors,
including the age, weight, and hydration status of the patient, the
overall health of the liver or the organ metabolizing the medication,
and the presence of any comorbid conditions that would otherwise
affect the patient’s general state of health.9 When a drug is
metabolized at an abnormal rate, it impacts the therapeutic effects of
the drug on the patient’s body. If a drug is metabolized very rapidly,
the patient may not experience the desired effects of the medication.
Alternatively, if a drug is metabolized too slowly, the patient may be at
risk of toxicity because of buildup of the drug within the body.
The overall outcome of metabolism is to take the parent compound —
which is the initial state of the drug after it has been distributed — and
break it down through metabolism so that it becomes
pharmacologically inactive for eventual excretion. The body must
metabolize drugs for excretion to avoid the buildup of medication
within the system that leads to toxicity and potential organ damage.
Most drugs become pharmacologically inactive through the process of
metabolism, but note that some drugs, when undergoing metabolism,
remain pharmacologically active. This is sometimes called a prodrug;
the initial drug may actually have a weaker effect until it is partially
metabolized, and then its metabolite is more active. An example of a
prodrug is the antihypertensive drug enalapril, a metabolite whose
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parent drug is enalaprilat, which does not become pharmacologically
active until it has undergone metabolism.8
Metabolism of a drug is also affected by its half-life, which is the
amount of time that it takes for the concentration of a drug to
decrease by one-half within the body. A drug that has a long half-life
will be present in the body for a longer period and will take longer to
metabolize than a drug with a comparably shorter half-life. This is
important to remember as well, as the rate of a drug’s half-life can
affect its elimination and may lead to a state of toxicity if another dose
of the drug is administered before its half-life has decreased to an
appropriate level. A drug that is distributed through circulation so that
it can undergo metabolism will eventually be eliminated from the
plasma. The removal of a drug from the plasma is known as drug
clearance, which is a factor used in pharmacokinetic formulas to
determine the half-life of a drug and its steady state of concentration.
The half-life therefore describes how long the drug is active in the
body, which may be referred to as the drug’s duration of action. The
half-life of the drug is related to the amount of the drug present in
plasma. It is important to be familiar with the half-life of certain drugs
when giving them to better understand total duration. If plasma
concentrations are measured to determine the amount of drug
present, knowing the half-life of the drug can tell the clinician how
much longer the drug is expected to be at its present concentration in
the plasma before being reduced. Once a drug is administered and it
reaches the bloodstream, the concentration of the drug initially peaks
at the greatest amount that will be present in the plasma before it
begins to decrease. As stated, different drugs have different lengths of
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half-lives, so administration of one drug may result in a peak plasma
concentration that lasts longer before the drug is reduced when the
half-life is longer, compared to a shorter period of peak plasma
concentration with a drug that has a short half-life.
To determine whether a drug is exerting its intended effects and the
concentration of the amount of the drug in the body, clinicians often
draw plasma levels. When a drug is being distributed through
circulation, it is often dispensed to more than one site at a time;
consequently, attempting to assess the drug’s concentration within
specific targeted tissues is often not possible. Instead, plasma levels
are typically measured to determine the drug’s concentration in the
body.9 A drug that is administered once or twice will not build up much
of a concentration in the bloodstream and will be cleared from the
plasma after distribution. However, in cases where a drug is
administered routinely, the goal is to develop a steady state within the
bloodstream, or a certain amount of the drug that is constant within
the plasma so that it is therapeutically effective. An example of this is
with the administration of digoxin, which is given for the treatment of
heart failure or chronic atrial fibrillation. Digoxin is administered
routinely, typically on a daily basis. Because of this, its concentration
within the blood plasma is maintained and it can exert its therapeutic
effects. Clinicians can test for digoxin levels in the bloodstream by
assessing plasma values because its chronic administration leads to a
plasma steady state.
The time it takes to reach the steady state of a drug is considered to
be approximately five half-lives of the drug.8 In other words, if the
half-life of a drug is one hour, it would take approximately five hours
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for the drug to reach a steady state within the bloodstream. Again,
when a drug’s half-life is longer, it takes longer to reach a steady state
than when a drug has a short half-life. This is also why it is important
to be familiar with a drug’s half-life when administering it to a patient
so as to better understand how long it will take to reach a therapeutic
concentration within the bloodstream.
There may be times when it is preferable to achieve a steady state of a
drug’s concentration quickly, in order to gain the drug’s therapeutic
effectiveness more quickly. A loading dose given at the beginning of a
drug regimen can achieve a steady state in the bloodstream at a faster
pace. This loading dose is then followed by maintenance doses to
sustain a suitable concentration of the drug over time.
Therapeutic drug monitoring of plasma levels is commonly performed
on those drugs that need to achieve a steady state in the bloodstream.
In addition to digoxin, some other examples of drugs that may require
this type of monitoring include lithium, given for treatment of bipolar
disorder, and the anti-seizure medication carbamazepine. In some
cases, peak and trough levels are measured to assess plasma
quantities and the levels of therapeutic effectiveness. For example,
when administering gentamicin as an antibiotic, the patient requires
peak and trough levels, which are performed after dose administration
and just prior to dose administration, respectively. Measuring the peak
involves collecting a blood sample within approximately 30 minutes
after the drug has been given and has had a chance to be distributed.
Alternatively, the trough is measured just prior to giving the drug,
when the concentration of the drug in the body from the last point of
administration would be at its lowest.
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There are several considerations to think through when using
therapeutic drug monitoring for patients in the ICU. First, this type of
monitoring is only appropriate for those drugs that require therapeutic
monitoring to check plasma levels, but it does not need to be
performed every day or with each dose. The critical care patient’s
disease state can also affect how the drug is distributed, as well as the
steady state concentration, and so therapeutic drug monitoring may
not be totally accurate in some cases; as a result, it should not be
relied upon as the sole mechanism of determining drug effectiveness.
To sum up, therapeutic drug monitoring in critical care can be a
valuable tool in some cases, but often when there are other indicators
of the patient’s clinical response that are difficult to interpret
otherwise.45 In the case of assessing plasma levels of antibiotics to
determine therapeutic effectiveness, the health clinician should also
consider other signs and symptoms that the patient is responding to
the drugs, including an improved clinical state and resolving signs of
infection.
There are many factors to consider when evaluating a drug’s
distribution and metabolism. The bedside caregiver cannot be
expected to know and remember the rates of metabolism for all of the
drugs being administered, but should understand the basic routes of
metabolism and what can affect its rate of tissue distribution, plasma
concentrations, and conversion to exert its effects so that
accommodations for critical care patients can be made, if needed.
Drug Excretion
Technically, the elimination of a drug from the body begins as soon as
it is administered and it enters the body. When a drug is first being
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absorbed, the body is also simultaneously eliminating it, but the rate
of absorption is greater than the rate of elimination, so more of the
drug is absorbed initially.5 Over time, the processes balance out and
eventually, more of the drug is metabolized and excreted when there
is less of the initial drug to be absorbed.
The term clearance describes how a drug is eliminated from the body.
Drug clearance occurs when the drug is brought to the organ of
elimination, often either the liver for metabolism or the kidneys. The
rate of clearance is directly proportional to the amount of drug present
in the plasma, so if there is a large plasma drug concentration, the
rate of drug clearance is increased. When clearance occurs via liver
metabolism, it is known as hepatic clearance. This type of clearance
occurs as a result of liver metabolism of the drug as well as biliary
excretion, which is the transfer of drug metabolites into the bile.64
Hepatic clearance can be affected by such factors as the amount of
hepatic enzymes needed for metabolism, as well as the presence of
any biliary obstructions.
Alternatively, renal clearance describes the elimination of the drug
through the kidneys via the urine. Drugs are excreted by the kidneys
when they enter the renal circulatory system and portions of the drug
are transferred into the urine following glomerular filtration or tubular
secretion within the proximal tubule.64,65 Various factors can also
impact renal excretion of drugs, however, one of the most common
issues with poor renal excretion is because of impaired renal function,
often due to illness or disease, which results in an inability of the
kidneys to properly filter the drug.
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As with other elements of pharmacokinetics, drug excretion can be
affected when the patient’s body is unable to adequately eliminate
appropriate amounts of the drug. This increases the risk of a buildup of
the drug within the system and the potential for toxicity. For instance,
a patient with poor kidney function as a result of disease may have
difficulties excreting certain drugs and the health clinician may need to
assess kidney function prior to drug administration or the continuation
of the current dose. There are several formulas that can be used to
estimate kidney function through measurement of creatinine, as
elevated creatinine levels can indicate impaired kidney function.
Historically, the standard of measurement of creatinine levels was the
Cockcroft-Gault equation, which was developed in the 1970s but has
since been replaced by more standardized measurements of
creatinine.
Because many drugs administered within healthcare facilities today are
removed from the body through the work of the liver or the kidneys, it
is important to understand basic tests of liver or kidney function to
determine the effects that critical illness can play on the metabolism
and excretion of drugs. When estimating kidney function, a clinician
should consider the patient’s estimated glomerular filtration rate
(GFR). Besides the change in use of the Cockcroft-Gault formula
(which may still be used in some locations), clinicians have other
formulas that can also determine patient kidney function, including the
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the
Modification of Diet in Renal Disease (MDRD) formulas that are
standardized and that can accurately determine kidney function.45
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While many clinicians, such as those who provide direct patient care,
do not necessarily calculate the GFR of specific patients, nor
implement specific formulas to determine kidney function, they should
still be familiar with the effects of the GFR on a patient’s system to
adequately excrete the drug. Additionally, the health clinicians who are
prescribing orders and making changes in the patient’s plan of care
may be using these formulas to alter the prescription amounts based
on the patient’s condition. Further, it should be noted that many
formulas that estimate kidney function are based on the patient
achieving a steady state of the drug in the plasma, which may or may
not be reflective of a patient in critical care. These are just some of the
factors to take into account when considering how critical care impacts
the pharmacokinetics of various drugs.
Pharmacodynamics
In contrast to pharmacokinetics, the concept of pharmacodynamics
describes a drug’s actions or what a drug does in the body after it is
administered. The action of a drug is determined by its
pharmacodynamic properties; these factors are related to the drug’s
pharmacokinetic factors, and each drug has different properties in how
it behaves once it has been administered. In essence,
pharmacodynamics considers the drug concentration at the site of
action and its therapeutic effects, including any adverse effects that
may occur.
Drugs have sites of action in the body, which are the locations of
where they are expected to exert their effects.5 For example, a betablocker drug’s sites of action are the beta-adrenergic receptors that
they effectively block to prevent the action of some neurotransmitters.
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The drug’s action in the body is affected by how it is able to bind with
its specific receptor. There are receptors located throughout the body,
and they have various functions. Nociceptors are those associated with
pain, while thermoreceptors impact body temperature. There are
receptors located in areas such as the heart and the muscles; they are
on the neurons of the central nervous system, and they can be found
inside of cell walls.
Most receptors are made up of amino acids and protein structures. As
such, they can be sensitive to changes in the pH of the surrounding
environment. When this occurs, it could change the receptor’s ability
to bind to different substances. This can then affect a drug’s ability to
bind to certain receptors and therefore, its overall effectiveness. In
general, drugs that interact with receptor sites are classified as being
either agonists or antagonists in their behavior. Receptor agonists
react with the receptor to stimulate it and to cause a change. Often,
there is already a substance in the body that also reacts with the
receptor; the receptor agonist drug therefore acts in a manner similar
to the endogenous substance. When the drug acts on the receptor, it
is said to occupy it, meaning that it takes over the site and prevents
the endogenous substance from affecting the receptor. This occurs for
only as long as the drug compound is in the body. An example of a
receptor agonist is isoproterenol, which works by stimulating betareceptors that are normally stimulated by epinephrine.
In contrast, a receptor antagonist blocks the activity of the receptor,
which produces an opposite effect of what agonist activity would be.
As with agonist activity, the receptor antagonist also occupies the
receptor for a period of time while the drug is present and prevents
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other substances from interacting with the same receptor. Receptor
antagonists may compete with agonists to be able to occupy certain
receptor sites. The higher the concentration of the drug (receptor
antagonist) within the body then the greater the likelihood the
antagonist will be the substance to occupy the receptor. Receptor
antagonists may also be non-competitive, in that they do not compete
for receptor sites, but they ultimately do not allow the surrounding
agonists to have any effect on the receptor.
A drug is able to exert its effect based on how much of the drug
reaches the receptors. Consequently, when there are issues that
disrupt the pharmacokinetics of the drug, such as its potential for
absorption, there may be less of the drug available at receptor sites to
take action and the drug will not exert as powerful of an effect.
Additionally, some receptor sites have greater density than others and
there are more locations for the drug to act on, meaning the drug is
more likely to exert more of its effects.
Individual patient characteristics will also affect the pharmacodynamics
of a drug. Factors such as a person’s age, overall health or the
presence of chronic illness, and weight or body mass can all impact
drug pharmacodynamics.9 Some people are more sensitive to drug
effects than others. This can occur when there are more drug
receptors available in a location for the drug; as a result, one patient
may have a more pronounced drug effect than the next person with a
slightly lower density of receptors at a similar site.
Each drug also has a specific duration, which is the time that it will
exert its effects in the body. This is perhaps most well known in the
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case of insulin, which is typically administered in relation to when and
how long it will be therapeutic compared to a patient’s blood glucose
levels. The duration of insulin, for instance, is how long the drug will
be taking action in the body, which is important to know to be able to
determine the appropriate time for the next dose. The duration of
action of a drug is impacted by how long it is exerting its effects
against its specific receptors. Further, drug tolerance can develop
when a repeated administration of the same drug requires more of the
drug to affect its receptors; the drug, when given normally, does not
exert as strong of an effect at the receptor site and so requires more
to achieve the same results.
The appropriate dose of the drug is decided, in part, by
pharmacodynamics. Because this segment of drug pharmacology is
concerned with drug concentration and its effects in the body, the
appropriate dose of the drug is calculated based on the knowledge of
these two factors, to ensure that the person taking the drug does not
take too much as to cause toxicity, and also to ensure that the person
receives enough to experience the drug’s therapeutic benefits. Proper
dosing is, in fact, achieving a balance that maintains the correct drug
concentration in the body.
While a drug is typically given to exert therapeutic effects and to be
helpful, there are times when unintended effects may also develop as
a result of the drugs actions. Drugs are given because of their
intended actions in the body, meaning, their specificity for certain
receptor sites leads to their therapeutic effects. However, no drug has
absolute specificity; instead, it just acts more on certain receptors
than in other areas.67 As a result, drugs can also cause adverse effects
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that can be uncomfortable for the patient and that may require further
monitoring and care. Note that the term side effects are often used
only as a general term for the public when describing adverse drug
reactions.
The different mechanisms that occur when a drug enters the body and
undergoes the process of being absorbed and distributed to its
intended receptor site can cause a number of reactions along the way.
The drug may bind to the appropriate receptor, but it may do so at the
wrong concentration, or it may not produce enough of a reaction.
Almost all drugs cause reactions in the body that are different from,
but that occur in addition to, their intended effects. The severity of
these adverse effects can be mild and imperceptible, or they can be so
significant that they predominate over the desired drug effects.
Adverse effects may also develop when a drug acts as an agonist for a
receptor site that is different from its target site. This phenomenon is
sometimes known as an off-target adverse effect.68 The drug may
have specificity for one type of receptor, but by also acting as an
agonist for other receptors, it can cause different effects. A drug’s
target receptors may be located in more than one area, so the adverse
effects that occur can affect different body systems. A study by Kim, et
al. in the journal Biochemical and Biophysical Research
Communications used a prediction method for identifying unintended
drug effects based on off-target events and found that in most cases,
the drug’s target proteins were located in more than one tissue and
the drug could cause effects impacting multiple tissue areas.68 This
information may be related to why some drugs, while having one
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intended effect, can cause adverse effects that seem unrelated to their
original intent.
Another type of adverse event that can occur with drug administration
is an idiosyncratic drug reaction. This describes an adverse effect that
is rare and unpredictable. It generally does not develop with normal
drug administration, but if it does, it is an adverse effect that can be
very serious and even life-threatening for the patient. Whether or not
a drug causes an idiosyncratic reaction is based partly on the drug’s
composition and characteristics, but it is also based on some patient
factors as well, including immune receptors that affect the cell-surface
antigens.69
The random and varied nature of idiosyncratic drug reactions can lead
to some uncertainty with drug administration. Because the health
clinician does not know if or when an idiosyncratic reaction will occur,
the patient could be placed in a state of harm without anyone being
aware of it. Idiosyncratic reactions are difficult to study because they
do not necessarily follow a pattern.69 The clinician who administers any
drugs to patients must then be aware of the possibility of idiosyncratic
reactions at all times, even though they are rare.
Idiosyncratic drug reactions seem to occur in any area of the body,
however, the skin, liver, and the blood cells are areas most often
affected.69 There is often a delay between the time of drug
administration and the onset of symptoms, and the reaction for a
specific drug does not appear to be dose-dependent. An example of an
idiosyncratic drug reaction is the development of drug reaction with
eosinophilia and systemic symptoms (DRESS) syndrome, which is
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thought to occur in up to 1 in 10,000 drug exposures. DRESS has
occurred following administration of a variety of drugs; some examples
include phenytoin, minocycline, allopurinol, and sulfasalazine.70
However, the exact cause seems to be associated with a number of
factors, including both immune and non-immunologic elements.
The pharmacodynamics of a drug can also be impacted by patient
factors, and within the critical care setting, the potential for severe
acute or chronic illnesses that affect physiological drug activity is high.
As an example, patients with diabetes often have cardiovascular
complications, and they are often prescribed more medications for
therapeutic management of not only of their diabetes, but for other
consequences as well. An article published in Podiatry Today discussed
the effects of diabetes on both pharmacodynamic and pharmacokinetic
responses and said that while current research related to the effects of
diabetes on pharmacodynamic processes is somewhat limited and still
ongoing, clinical assessments have shown that patients with diabetes
tend to have altered drug responses, particularly following
administration of certain classes of medications, including lipidlowering agents and antihypertensives.71 Other chronic diseases or
conditions that have been suggested to affect the pharmacodynamic
processes following drug administration include thyrotoxicosis,
myasthenia gravis, Parkinson’s disease, and malnutrition.72
Undoubtedly, the pharmacodynamic processes that occur within the
body following drug administration are a significant part of how drugs
work, their potential for adverse events, and the overall bodily
response. Just as pharmacokinetic effects are a complex progression of
activity that involve many different formulas and systems, the
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pharmacodynamic effects of drugs are also complex and multifaceted.
The clinician who provides direct care and who administers
medications to patients in the emergency department or ICU should
have at least a basic understanding of pharmacodynamics and how
these processes instigate various biochemical and metabolic processes
in the body.
Common Medication Types In Critical Care
When a patient needs intensive care for an illness or severe injury, the
clinician often must know to act quickly, giving drugs to respond to
changes in the patient’s condition or clinical status. The clinician
working in a critical care setting may be faced with administering a
variety of different drugs and it may be challenging to remember the
varied drug classes, common dosages, potential side effects, and
implications for administration. Drugs are often given based on each
patient’s condition and may be used to manage specific symptoms that
affect different organ systems within each person. For example, one
patient in the emergency department may require cardiac medications
to stabilize a potentially life-threatening arrhythmia, while another
may need analgesia to control pain associated with a severe injury.
Often, patients require more than one type of medication.
Prior to administering any drugs, it is important to know some of the
patient’s pertinent medical history, whether any allergies are present,
and the presence of comorbid conditions. Sometimes, this information
is not available and the clinician must quickly respond to the situation
at hand, such as in the case of life-threatening events. Alternatively,
many patients who are managing severe illnesses or who are
overcoming major surgery have well-documented histories and their
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caregivers carefully administer medications and monitor clinical
responses over a period of days or weeks of care. In these cases,
patient care plans may be complex and filled with a number of
different drugs and prescribed treatments. Despite the variety of drugs
available for therapy and symptom control, there remain several
classes of medications that are commonly administered in the
emergency department or the ICU, including sedatives, analgesics,
neuromuscular blocking agents, and pressors.
Sedative Medications
Sedative medications are drugs that work by physiologically reducing
excitement, agitation, or anxiety by inducing a state of calm.
Sometimes called tranquilizers, sedatives typically consist of those
drugs classified as barbiturates or benzodiazepines, although some
other drugs may have sedating side effects or may be used as an offlabel method of causing sedation.73 Some of their most common
purposes for administration are for control of anxiety or as an aid for
sleep, however, they are also prescribed as anticonvulsants,
amnesiatics, and as muscle relaxants.
Benzodiazepines work by augmenting the action of the
neurotransmitter gamma-amino butyric acid (GABA), which primarily
has an inhibitory effect on the motor neurons. Benzodiazepines target
GABA receptors, which are some of the most common receptors in the
body. Normally, these receptors respond to GABA, but when
benzodiazepines are given, they act as agonists for these receptors as
well, increasing the effects of GABA and slowing motor activity.73
Benzodiazepines may be considered short-acting or long-acting drugs.
Short-acting preparations are given to exert their effects during a
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specific condition and over a brief period of time, whereas long-acting
benzodiazepines may be administered repeatedly and are designed to
build up in concentration within the bloodstream. Although they
primarily are used in controlled situations and are able to achieve
calming effects, the primary adverse effects often seen with
benzodiazepines include poor motor coordination, drowsiness,
confusion, slurred speech, slowed reflexes, and respiratory depression.
Barbiturates are another type of sedative agent that were once more
commonly administered for their calming effects; however, many
barbiturates are no longer used because of safety issues and they
have been replaced with other drugs that are more appropriate.
Barbiturates are made up of barbituric acid and they are typically
classified according to their duration of action. The range of
barbiturate classification spans from ultrashort-acting drugs, which are
most commonly given prior to surgery, to long-acting barbiturates,
which may take up to two hours to produce effects. As with
benzodiazepines, barbiturates act as GABA receptor agonists to slow
motor activity. They are often used for inducing sleep, and many of
the ultrashort-acting preparations are administered during induction of
anesthesia. Long-acting barbiturates are used as sleep aids or for
anxiety, but also to control migraines and as anticonvulsants.74 Due to
their potential for abuse, harmful adverse effects, and significant
withdrawal symptoms, barbiturates used within healthcare are
typically highly controlled and are less often used if other sedatives are
available.
There are other drugs that are administered for their sedating effects
that are not classified as benzodiazepines or barbiturates. Some of
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these drugs have been approved for other purposes but they also have
a sedating effect and so are administered in an off-label manner. An
example is the use of some neuroleptic agents, also referred to as
antipsychotics. These drugs, such as haloperidol, produce sedation as
an adverse effect to their intended use for control of psychotic
symptoms. For a patient with no history of mental illness,
antipsychotic medications are often not used as a first choice for
calming, despite their ability to achieve sedation. However, for some
patients in the ICU and ED who are already struggling with delirium
and agitation as a result of psychosis, neuroleptic agents can control
anxiety and can promote sleep.75
Other drugs that are used as induction agents with anesthesia
successfully cause sedation and induce sleep for the patient
undergoing surgery. These drugs are almost always given
intravenously and they not only induce sedation, but can also cause
memory loss of the event. Examples include ketamine and etomidate.
Ketamine is actually a type of anesthetic that produces sedating
effects that include hypnosis, analgesia, and increased sympathetic
activity while maintaining an effective airway and respiratory drive.
Ketamine works as an antagonist to the N-methyl-D-aspartate (NMDA)
receptors to decrease excitability.78 Etomidate is an anesthetic and
hypnotic drug that exerts its effects rapidly after administration; it is
used during induction of general anesthesia, but may also be
administered just prior to certain medical procedures, such as rapidsequence intubation. Etomidate supports the action of GABA, leading
to a decrease in overall motor activity, but maintains cardiac and
respiratory functions. It may be administered as an adjuvant to
neuromuscular blocking agents to decrease excitement and anxiety.
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Within the emergency department, sedation is often administered
quickly and rapidly, yet its use must be handled in a safe and effective
manner. The American College of Emergency Physicians (ACEP) has
issued recommendations for the specific use of sedatives in the
emergency department in order to provide timely and safe sedation for
patients in need. These guidelines include14 1) the administration of
sedatives only by those who have been appropriately trained and who
have the credentials to be able to care for patients requiring
emergency care, 2) the specific type and amount of sedation should be
individualized to each patient depending on circumstances, 3) each
member of the emergency team who administers sedative medications
should be familiar with their purposes and side effects, 4) patients who
receive sedation should be thoroughly monitored and continually
evaluated before, during, and after their administration, and 5) there
should be appropriate protocols developed for the use of sedation and
the competency of the staff who administer these drugs in each
healthcare facility where they are given.
Sedatives have the potential to cause harmful complications to the
patients for whom they are administered, which means their use in
healthcare must be tightly controlled. Despite their potential
drawbacks, they serve important purposes in the emergency and
critical care environments because they enable clinicians to adequately
assist with calming and reducing patient anxiety. The ICU or
emergency department can be frightening for patients who do not
necessarily understand what is happening. Administration of sedatives
can calm anxiety and fears about the patient’s well-being. Additionally,
patients in critical care often undergo various procedures, which can
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cause anxiety and agitation. They often benefit from sedatives to feel
calmer about the procedure or sometimes to sleep through the event.
The majority of sedatives are administered intravenously or orally,
depending on the type of drug and the circumstances during which
they are given. Many patients who take benzodiazepines, for example,
take oral preparations at home. A patient in the hospital who has
difficulty sleeping may be given an oral sedative if he/she can tolerate
taking medication by mouth. Alternatively, sedatives administered
intravenously are typically given to those patients who cannot take
oral drugs or where rapid sedation is needed, such as prior to a
procedure or when a person requires mechanical ventilation. The
distinct purposes of sedatives, as well as their potential problems and
need for monitoring is discussed further below.
Purpose
As stated, sedatives are administered because of their depressant
effects on the central nervous system and their ability to slow down
motor neuron activity. They often leave a person feeling sleepy, calm,
or peaceful. While they are commonly prescribed in the general
population and are usually taken by oral prescription, sedatives are
also commonly administered in critical care. Because of the potentially
unstable nature of these patients, sedative administration requires
thoughtful planning and careful monitoring throughout the entire
process.
While most sedatives are used as sleep aids or for control of anxiety,
their use in critical care may also include management of significant
agitation as well as for patient comfort. Because emergency care may
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entail procedures that can be frightening and uncomfortable for the
patient, the administration of a sedative just prior to performing a
procedure can help the individual to relax. As an example, rapid
sequence intubation, which is the process of quickly securing an
airway in a patient who is clinically unstable, requires that the patient
be quickly sedated and calmed prior to intubation in order to better
facilitate the process. Just before starting, the patient may be given an
induction agent as a sedative, which will blunt responses to the
process and which can be used in addition to neuromuscular blocking
agents.
In cases of rapid sequence intubation, the patient is most commonly
given a drug such as etomidate or ketamine, although some
benzodiazepines may be used as well, including midazolam.76 Note
that these drugs are given for sedation prior to the process of rapid
intubation because of their short-acting properties and their
availability. Other drugs, including long-acting benzodiazepines, may
also be given to maintain sedation after the patient has been intubated
and placed on mechanical ventilation.
Sedative medications are also important to control anxiety and
agitation that commonly accompanies a patient’s stay in the ICU. In
addition to the potentially painful procedures that are often necessary
for a critically ill patient, the experience of receiving intensive care can
be frightening and confusing. Many patients in the ICU suffer from
severe agitation and distress, whether due to anxiety and fear or
because of confusion or alterations in levels of consciousness due to
their injuries. Agitation may lead some patients to become aggressive
toward their caregivers and can increase the risk of inadvertent
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removal of equipment, such as endotracheal tubes or central venous
catheters. Administration of sedative medications can promote
relaxation and can be calming to reduce some of the agitation and
delirium commonly experienced by patients in the ICU.
The sedatives administered can have varying effects on the patient,
depending on the amount given and the type of drug administered;
when sedatives are given, the amounts and their effects are often
described on a continuum that ranges from very mild effects that are
calming to general anesthesia that induces a complete loss of
consciousness. Mild or minimal sedation, also referred to as anxiolysis,
provides some amount of sedation so that the patient is calmed and
comforted but not so much that it alters his/her level of consciousness.
A patient who receives anxiolysis can still respond to verbal
commands, has normal reflexes, and can breathe spontaneously.14
Moderate sedation may be administered for purposes of keeping a
patient comfortable and subdued, often during the process of
performing a medical procedure. Moderate sedation is sometimes also
referred to as conscious sedation. The patient has not lost
consciousness and is still able to respond to verbal cues. The patient is
still able to breathe independently but has an altered level of
consciousness that is more depressed than an alert state, and may
require some gentle physical stimulation to acquire a response.
Deep sedation induces a greater degree of suppressed levels of
consciousness. When under deep sedation, the patient can be aroused
to respond to verbal or physical stimulation, but it often requires more
aggressive maneuvers to achieve a response. The patient under deep
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sedation may or may not maintain a patent airway and, if breathing is
slowed because of the medication, the patient needs respiratory
assistance through endotracheal intubation. Typically, a patient who
undergoes deep sedation has no memory of the events that occurred.
According to an Expert Opinion report by McGrane, et al. in Minerva
Anestesiologica, sedation is prescribed in 42% to 72% of patients
admitted to an ICU, and its use has only been increasing within the
last decade.77 The increases in complexity of procedures performed in
this environment, combined with the technical capabilities of medical
systems have led to many critically ill patients receiving more frequent
administration of sedation. Whether these drugs are given quickly to
control patient responses during critical procedures, or as ongoing
therapy to maintain patient comfort and safety while in the ICU,
sedative use helps health clinicians to achieve overall goals of
providing effective care to those who are critically ill.
Monitoring
While sedative administration is common and their effects serve a
number of purposes, there are still drawbacks to their use.
Inappropriate use of sedatives, whether intentional or not, could cause
serious adverse effects in the patient, some of which can be lifethreatening. Therefore, patient monitoring is an integral part of
sedative administration throughout the timing of each drug dose.
The best, initial step in monitoring patients who receive sedation as
part of critical treatment is for the health facility to have a protocol in
place regarding the process. The actual method of monitoring patients
who have been given sedatives may vary slightly, depending on the
facility’s policies and standards; however, in order for protocols that
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guide clinicians monitoring sedated patients to be accurate and
appropriate, they must include guidance on the necessary time
intervals of drug administration, the acceptable depth of sedation, and
the use of further interventions, such as with the administration of
concomitant analgesia. Ideally, the level of sedation should be limited
to the amount necessary to maintain the patient’s comfort, without
causing an unnecessary loss of consciousness.
There are many sedatives that are classified according to schedules,
based on the Controlled Substances Act. Controlled substances are
categorized within one of five schedules, based on their potential for
causing dependency or their risk of being abused. The schedules range
from Schedule I, which consists of powerful, illicit drugs that have no
medical value, such as heroin, to Schedule V drugs, which have limited
quantities of narcotics and have the lowest potential for abuse. While
most sedative medications given within the critical care environment
are administered and controlled by medical clinicians, the use of these
types of drugs should still be closely monitored for signs of increased
tolerance and physical or psychological dependency.
There are no sedative medications that are given by prescription that
are classified as Schedule I. These drugs have no acceptable medical
use and would not be administered in the critical care setting.
Schedule II drugs have a high potential for abuse; sedative
medications that are classified as Schedule II drugs include
secobarbital (Seconal®) and pentobarbital. Examples of sedative
medications that are Schedule III drugs are midazolam (Versed®) and
talbutal (Lotusate®), while sedatives that are in Schedules IV or V
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include eszopiclone (Lunesta®), zolpidem (Ambien®), and suvorexant
(Belsomra®).
High concentrations of sedative medications can lead to significant
drowsiness to the point of a loss of consciousness and may slow
respiratory efforts or cause apnea. Other issues associated with
oversedation include insomnia and sleep prevention, hypotension,
constipation, deep vein thrombosis, and increased risk of ventilatorassociated pneumonia, impaired gastrointestinal motility, increased
length of required mechanical ventilation and lengthened weaning
times, amnesia of the hospital event, and muscle wasting.15 Because
of the large number of potential side effects and their significance, the
clinician who administers sedative medications must be familiar with
signs or symptoms that can indicate that the patient has received too
much.
Continual assessment of the patient’s clinical status will help the
clinician to better understand the level of sedation the patient is
experiencing and whether he/she has received the right amount of the
drug. Additionally, clinical assessments can determine if the patient
needs more medication because of discomfort and possibly being
undersedated, so assessing for signs of agitation or vocalization is
warranted. Frequent monitoring also considers whether the patient has
been given too much medication and is experiencing ill effects, as
evidenced by slowed breathing or periods of apnea, changes in levels
of consciousness, and an inability to rouse with stimulation.
Monitoring of sedation can also take place through sedation scales,
which are assessment measures used in a manner similar to
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assessment of pain. Many patients are unable to adequately
communicate or explain how they are feeling, particularly if they are
oversedated. An assessment scale to evaluate sedation levels helps
the clinician to closely monitor the patient and can prevent
complications associated with oversedation. One of the more common
tools available for use in critical care is the Richmond AgitationSedation Scale (RASS); this scoring system can be used for any
patient who is at risk of delirium, agitation, or anxiety and who is
receiving sedative medications, but it is particularly useful for those
who have difficulty with communication, such as patients who have
mechanical ventilation.
The RASS requires observation of the patient’s behavior and responses
to stimuli. The responses are scored on a scale that ranges from -5
(unarousable) to +4 (combative, violent, dangerous to staff), with a
score of “0” described as being “alert and calm.”12 The clinician should
first observe the patient to determine alertness; if so, the patient
should receive a score that falls between 0 and +4. If the patient is
not alert, his score will fall between 0 and -5, based on levels of
responsiveness to stimuli, eye opening, or spontaneous movement. A
score of -5 indicates that the patient is unresponsive to any
stimulation. Based on the patient’s RASS score, the caregiver can
titrate sedative medications accordingly to ensure that the patient
needs more or less intervention.
The Riker Sedation-Agitation Scale is another intervention that may be
used to monitor sedation levels and to determine whether a patient is
receiving enough or too much sedative medications for his condition.
The Riker Scale requires patient assessment to evaluate his behavior,
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activity, and cognition and then assigns a score based on the outcome.
The scores for the Riker Scale range from 1, in which the patient
cannot be aroused and does not follow any commands, to a score of 7,
in which the patient is considered to have “dangerous agitation” and is
pulling at tubes or catheters, trying to climb out of bed, or is a danger
to staff. An appropriate target score on the Riker Scale is between 3
and 4, in which the patient is calm and cooperative, and follows
commands appropriately.13
Sedatives should not be administered as a method of keeping a patient
constantly subdued and controlled. Historically, sedatives were given
around the clock to patients who required mechanical ventilation in
order to maintain such deep sedation that the individual was relatively
unaware of his condition until he was able to successfully breathe on
his own. Today, sedatives are still commonly administered, but are
often given as adjuvant drugs to promote comfort alongside
analgesics; they should be given as a method of controlling anxiety
and insomnia in the critical care environment, instead of just being
used to keep a ventilated patient restrained and confined. According to
Reade, et al., in the New England Journal of Medicine, sedatives should
only be used when the patient’s pain and delirium have already been
addressed through medication and non-pharmacologic interventions.11
In cases where a patient receives continuous sedative medications
over a longer period, he will eventually need to be weaned from the
drugs in order to achieve a fully conscious and alert state. As an
example, a patient who requires a mechanical ventilator for several
days to assist with respiratory efforts may also receive sedative
medications to reduce anxiety and agitation. When considering
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whether the patient can be extubated and removed from the
ventilator, the clinician may need to perform a brief trial of stopping
the sedatives to determine the patient’s neurological state. This period
of rest from the drug is sometimes called sedation cessation or
sedation interruption, and it is done intentionally and on a scheduled
basis to best determine the patient’s response.15 The patient’s
sedation is interrupted for a brief period so the clinician can assess the
person’s neurological status, his ability to communicate, and his
overall levels of agitation. This assessment helps the clinician to
evaluate, along with other factors, whether the patient may be ready
for extubation or if he still requires sedative medications for a longer
period.
The time period for how often to perform sedation interruption varies,
depending on the individual patient’s needs. Some facilities perform
sedation interruption on a daily basis, and there have been some
benefits associated with this practice, including a decreased amount of
time required for the patient to use the ventilator. However, the daily
practice of sedation cessation is not implemented in all locations and
there may also be some complications involved with its routine
performance, including an increased risk of ventilator associated
pneumonia, patient barotrauma, and venous thromboembolic disease.
Healthcare guidelines vary for timing of sedation interruption between
facilities and locations.
As described, the intensity of sedation can vary from mild levels of
intervention that promote comfort and cooperation, to deep sedation
that induces a state of unconsciousness. Deep sedation may be
implemented for some very painful procedures that the patient would
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otherwise be unable to tolerate. However, despite the need for deep
sedation in some critical care situations, the majority of patients who
receive emergency or ICU care benefit from mild sedation.
Analgesic Medications
A significant number of patients who require care in the ICU or the
emergency department experience some form of pain, as well as
stress and anxiety. In addition to administration of sedatives to reduce
excitement, analgesic medications are commonly administered to
uphold patient comfort and to keep patients calm. Analgesic
medications are primarily administered to control pain. Uncontrolled
pain can lead to many complications, including an increased length of
stay, severe patient anxiety, and delirium.30 The appropriate use of
analgesics makes a considerable difference in the health and wellbeing of the patient in the ICU. The dose, route of administration, and
rate at which the drug is given are all factors that impact the patient’s
levels of comfort and support healing, thereby ultimately affecting
patient outcomes.
There are different classes of analgesic agents available; each of these
drugs may also have more than one route in which it can be
administered, creating a variety of choices when selecting the best
option for pain control. Analgesics may be classified according to the
intensity of pain they are designed to treat; for instance, opioid
analgesics, which can have strong effects, manage moderate or severe
pain, while non-opioid analgesics are typically designed to treat mild
pain, and their effects are not as powerful. The patient in critical care
may experience a range in severity of pain, depending on his current
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condition, and often, different strengths of analgesic medications are
available as needed.
Purpose
Pain is an individual experience. What one person considers as very
mild discomfort may be described as intensely painful to another.
Although the experience of pain differs for each person, there are
certain situations that are known to cause pain at certain intensity. For
example, an accident that causes an open leg fracture is understood to
be quite painful for someone experiencing it. Two people with the
same injury may describe their pain at different levels of intensity, but
the experience is somewhat similar in that they feel the same type of
pain; in the case of an open leg fracture, the pain experienced comes
from damage to the soft tissues of the leg.
Analgesics are administered to relieve many different types of pain.
The pain that healthcare providers see and treat in critical care
situations may vary significantly in duration, location, and intensity.
Acute pain describes the feeling of discomfort that has a relatively
short duration (lasting from several hours to days) and that has
developed quickly, often because of the event that caused the pain.
Acute pain often develops as a result of injuries or accidents and is
experienced with soft tissue trauma, inflammation due to an infection,
broken bones, or because of surgery. An individual who seeks care for
treatment of an injury or who is recovering from surgery and who feels
pain is most likely experiencing an acute form.
Chronic pain is described as pain that has been present for longer than
12 weeks.79 In contrast to acute pain, chronic pain is often persistent
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and may or may not respond to medication or therapy as treatment. It
may arise initially from an injury or event that caused acute pain, but
may then persist despite efforts at treatment. Untreated chronic pain
can lead to feelings of depression, fatigue, mood changes, and
insomnia. Over time, it may be so debilitating to the affected person
that it impacts his ability to complete normal daily activities. Some
patients who receive care in the hospital already suffer from chronic
pain due to a previous situation; when this occurs, the chronic pain
must also be managed in addition to any acute pain that has
developed as a result of the hospitalization. For example, a patient
who has cancer may have endured chronic pain for months; when
hospitalized for another painful procedure, the patient’s comfort levels
must be addressed by providing pain medication that helps to control
both acute and chronic pain.
In addition to acute and chronic pain, patients may suffer from
different types of pain based on the affected area; these types may
involve neuropathic pain, which can occur following an injury to the
nerves; somatic pain, which often occurs with soft tissue or
musculoskeletal injuries; and visceral pain, which describes pain from
damage to the internal organs. Patients in the ICU may experience any
of these kinds of pain, or more than one type at once. The body
experiences pain through stimulation of nociceptors, which are sensory
receptors located throughout the body, including in the skin, muscles,
joints, and viscera; these receptors are responsible for perceiving
unpleasant stimuli. When stimulated, the nociceptors transmit signals
of pain to the brain via the spinal cord. When the brain perceives the
pain, the reaction can be affected by various factors, including a
person’s genetic composition, personal beliefs about pain, and level of
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cognition, among other items. This is why people experience pain
differently and a painful event for one person may be perceived as
excruciating, while the same type of pain causes moderate discomfort
in someone else.
Analgesics are given primarily for the control of pain; there are a
variety of analgesics available on the market and some drugs have
been found to be more beneficial for certain types of pain than others.
For example, non-steroidal anti-inflammatory drugs (NSAIDs) are
beneficial in relieving pain of inflammation, but they also can be
helpful for controlling the pain of muscle cramps.
When tissue damage occurs, the body releases inflammatory
mediators in response. These mediators, including bradykinin,
cytokines, and prostaglandins, can also stimulate nociceptors to send a
signal about pain, which is why inflammation can also be painful for
the affected person. Some drugs are specifically designed to reduce
this pain associated with inflammation, such as inflammatory pain in
the joints because of arthritis. For example, the non-opioid drug
ibuprofen is often used to manage pain and inflammation; it may be
given intravenously, known as Caldolor®. Additionally, some opioids
also affect peripheral nerve receptors and may reduce inflammation,
and these drugs may be more appropriate in cases of severe pain.
Many studies have shown that pain is a very common element
associated with time spent in the ICU and that most patients who
receive intensive care treatment experience pain. Analgesic
medications are therefore significant as part of the overall treatment
plan for many patients receiving emergency and critical care. Ayasrah,
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et al., in the International Journal of Health Sciences state that
inadequate pain assessment and treatment is associated with an
increased morbidity and mortality for the patient in the ICU.80 When
time in the critical care environment is extensive and the patient
suffers from poor pain control, he is more likely to experience
complications, necessitating further treatment and resulting in a longer
length of hospital stay. Additionally, patients in the ICU who
experience ongoing, untreated pain are at greater risk of experiencing
distress and discomfort, resulting in post-traumatic stress.11 Routine
assessment of the patient’s pain, from the first contact while providing
emergency care and throughout the patient’s hospital stay is essential
for controlling comfort levels and preventing further complications.
Opioids vs. Non-Opioids
Analgesics are typically classified as being either opioids or nonopioids, based on whether they contain a natural or synthetic extract
from the opium poppy. Opiates are drugs that are directly derived
from opium extract; opioids are technically the synthetic versions of
opiates in that they produce the same effects and are chemically
similar but not entirely the same. The term “opioid” is now used to
describe both the synthetic and natural versions of these drugs. They
may also be referred to as “narcotics” because of their effects, but
keep in mind that this word also is used to describe illicit drugs that
have no medical value but that produce some of the same effect as
opioids.
Opioids are used to treat moderate to severe pain; they may be given
on a short-term basis in cases of acute pain, but they can also be
prescribed for long-term use for cases in which a patient is
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experiencing chronic pain, such as with cancer. Opioids may be
classified as being short-acting or long-acting medications; the
healthcare provider should prescribe and schedule these drugs
accordingly, based on the patient’s condition and whether he requires
immediate pain relief for acute pain, such as within the emergency
department, or whether the patient is suffering from ongoing pain.
Short-acting opioid medications include morphine (Roxanol®),
oxycodone (Oxycontin®), hydromorphone (Dilaudid®), and
hydrocodone (Vicodin®, Norco®). Long-acting opioids include fentanyl
(Duragesic® patch), as well as morphine and oxycodone.28
As with sedatives, opioids are classified according to the Schedule of
Controlled Substances because of their powerful effects and potential
for misuse. In addition to their analgesic effects, opioids can cause
mood changes and alterations in levels of consciousness. Some
patients are at higher risk of physical dependence and abuse of opioids
because of these effects. Additionally, because pain is affected by a
number of factors within each person, including personal response to
painful stimuli and emotional reactions associated with pain, the
effects of opioids can be somewhat sedating and can induce calm in
the patient, which may regulate some of his emotional responses to
the pain.
Opioids work in both the central and peripheral nervous systems by
acting on opioid receptors found in the cell membranes of neurons.
There are four main types of opioid receptors: the mu opioid receptor
(MOP), the kappa opioid peptide receptor (KOP), the delta opioid
receptor (DOP), and the nociceptin orphanin FQ peptide receptor
(NOP), located in various areas of the brain and in the spinal cord. The
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different opioids available have affinities for the various opioid receptor
sites; for example, morphine has a high affinity for the MOP, but less
so for KOP or DOP. When an opioid medication is given and it binds to
one of these receptors, it can inhibit the release of some
neurotransmitters as well as by inhibiting the transmission of pain
information released from sensory neurons. This complex process can
occur very quickly following the administration of opioid analgesics,
particularly when the drugs are given intravenously.
Once administered, opioids can exert pain-control effects rather
quickly, depending on the route of administration. It is estimated that
when given intravenously, opioids can peak in their pain control within
10 minutes of administration. When given as an intramuscular
injection, effects typically occur within 30 to 45 minutes, while effects
occur within 60 to 90 minutes after oral administration because of the
extra time that it takes for absorption of the drug into circulation.28
In contrast to opioid analgesics, non-opioid drugs may be given in
cases where the patient is experiencing mild or moderate pain. They
may be administered to control acute pain or may be given on a longterm basis for chronic pain, depending on patient circumstances.
Additionally, non-opioid analgesics may be the sole drug given for pain
control when it is mild, but they are also beneficial as adjuvant
medications when given with opioids for cases of severe pain. Many
non-opioid analgesics are also effective in relieving inflammation and
swelling. Non-steroidal anti-inflammatory drugs such as ibuprofen or
ketorolac are examples of non-opioid analgesics that control pain and
inflammation. Acetaminophen is another type of non-opioid analgesic
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that is commonly administered for mild pain and is particularly useful
in cases of musculoskeletal pain or with minor injuries.
Two types of non-opioid analgesics, salicylates and non-salicylates,
comprise a large number of these drugs. Salicylates come from
salicylic acid, and work to reduce fever and inflammation in addition to
controlling pain. Examples of salicylates include aspirin and
magnesium salicylate (Doan’s® Pills). Salicylates exert their effects by
inhibiting prostaglandins, which decreases the sensation of pain and
alleviates some inflammation. They also have vasodilatory effects, and
some salicylates, particularly aspirin, prevent platelet aggregation, so
they may be prescribed for prevention of blood clots.
Non-salicylates typically have similar abilities as salicylate medications
in that they reduce fever and control mild pain. The most commonly
used non-salicylate medication is acetaminophen, which may be used
among patients who otherwise do not tolerate salicylate medications,
those who have bleeding tendencies, and children. Acetaminophen
also exerts its effects to control pain and fever by reducing synthesis
of prostaglandins, although its exact mechanism of action is still
unclear.29
Non-opioid drugs such as NSAIDs control elements such as pain,
inflammation, and fever by inhibiting cyclooxygenase (COX), which is
an enzyme that promotes the conversion of some substances within
cell walls into prostaglandins that can cause pain, fever, and
inflammation. Note that aspirin, while classified as a salicylate
medication is also considered to be an NSAID. Other examples of
these drugs include celecoxib (Celebrex®), ibuprofen (Advil®,
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Motrin®), naproxen (Aleve®, Naprosyn®), and indomethacin
(Indocin®).
Non-opioid analgesics also differ from opioids in that they do not
produce the same side effects of drowsiness or euphoria and they do
not lead to tolerance and addiction. Non-opioid analgesics are not
listed in the Schedule of Controlled Substances and are considered to
be very safe, such that while a healthcare provider may administer
them within the hospital, they can also be purchased without a
prescription.
Analgesics should not be used unless the patient’s comfort level has
been adequately assessed. Monitoring of patient comfort levels is an
ongoing process that involves assessing the patient’s level of pain prior
to giving medication, selecting the most appropriate analgesic for the
patient’s level and intensity of pain, administering the medication
through the correct route and at the correct rate, and continuing to
assess the patient following drug administration to ensure the drug’s
effectiveness.
It may be difficult to adequately assess patient pain, particularly if the
individual has an altered level of consciousness or has difficulty
communicating because of medical equipment. Changes in vital signs,
as evidenced by an increase in heart rate or blood pressure, were once
standard options for assessing pain in the nonverbal patient, but vital
sign changes are no longer considered accurate measures of pain
assessment. Instead, there are several tools that clinicians can
implement to assess pain in the patient who is nonverbal or otherwise
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unable to communicate his discomfort. Examples include the
Behavioral Pain Scale and the Critical Care Pain Observation Tool.
Additionally, some critical care patients may have difficulty explaining
the extent and intensity of their pain if they have been given other
drugs to combat their immediate issues. For example, a patient who
has been given sedative medications to control anxiety just prior to
undergoing a procedure may experience changes in his level of
consciousness because of the sedation but he is still experiencing pain.
Still, the healthcare provider in this situation may have a difficult time
determining the extent of his pain and may rationalize that because
the patient is sedated, he is comfortable. This further emphasizes the
critical need for using a pain observation tool if the patient is nonverbal, even if he has received another type of medication. Continuous
and ongoing assessment of the patient’s behavior and signs or
symptoms of distress is the only way to determine whether further
analgesia is needed.
For patients who can talk and express how they are feeling, use of a
scale, such as a 0 – 10 pain intensity rating, is valuable in assessing
the patient’s level of comfort. The patient may rate his pain on a scale
of 0 to 10, with 0 describing “no pain” and 10 being “the worst pain
imaginable”. This type of intensity rate helps the healthcare provider
to better determine the type of analgesia to use and how much to
give. The patient may be asked again approximately 30 minutes after
receiving the medication to clarify whether the medication is
controlling his pain or if he needs another dose. While the best method
of assessing for pain is through patient self-reporting, there are
obvious times when the patient cannot communicate verbally, such as
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with mechanical ventilation or with altered levels of consciousness, and
the caregiver must rely on other cues that signify pain. Utilizing
assessment tools that evaluate patient pain are essential for those
individuals who cannot verbalize or communicate.
A tool designed specifically to assess pain among patients in the
critical care environment is the Critical Care Pain Observation Tool
(CPOT), which can be used quickly and easily and which assesses the
patient’s behaviors that would indicate the presence of pain. The
clinician assesses the indicators of facial expression and whether the
patient appears relaxed, tense, or is grimacing; body movements, in
which the patient may demonstrate agitation and restlessness,
cautious and protective movements, or the absence of movement; and
muscle tension, in which the patient may appear relaxed, tense or
rigid, or may demonstrate a strong resistance to any sort of
movement. Additionally, the CPOT assesses patient vocalization if he is
not intubated, including talking, crying, or sobbing; if the patient is
intubated, the tool assesses for ventilator compliance, and whether he
is tolerating the ventilator, coughing, or fighting ventilation.31
Each patient behavior is given a score from 0 to 2; the highest total
score is 8 points. The closer to a score of 8 that a patient receives
indicates greater pain levels and an increased need for analgesia. To
use the CPOT, the patient should first have a baseline assessment in
which he is observed at rest for one minute. When considering
analgesia use, the patient should then be evaluated during any
procedure that could potentially cause pain, such as with endotracheal
suctioning, turning, or with dressing changes; depending on the
patient’s response, analgesic medications should be administered
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according to their prescribed route and time. The caregiver should
then assess the patient both before and at the time of the peak effect
of the analgesic to determine the drug’s overall effectiveness in
relieving the patient’s pain.
The Behavioral Pain Scale (BPS) is another method of assessing for
pain or discomfort among patients who are in the ICU and who cannot
vocalize or communicate how much pain they are experiencing. The
BPS is also a scoring system that considers the patient’s facial
expression and whether it is relaxed, tightened, or grimacing; upper
limb movements, with scoring ranging from being relaxed to slightly
flexed to permanently retracted; and ventilator compliance, which can
include total compliance and relaxation to coughing to fighting the
ventilator and causing asynchrony.32 The BPS is often a simpler
method to use and can be employed quickly and effectively; it is
commonly reserved for intubated patients who have no verbal
communication. Each item on the scale is scored to quantify how much
pain the patient is experiencing so as to guide analgesia use.
Administration of analgesic medications is a common practice in critical
care; based on the numbers of patients in the ICU who experience
some amount of pain during their stay, the probability that a nurse will
need to administer analgesics in this area is quite high. It is therefore
very important to remain familiar with the most common types of pain
medications, as well as their usual routes of administration, common
side effects, and mechanisms of action. By understanding these
principles, the caregiver will be better able to recognize the most
appropriate medication to give in each situation and to maintain the
patient’s comfort.
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Paralytic Medications
Paralytic medications are used in the critical care environment to
induce such deep muscle relaxation that the individual is unable to
move. Also known as neuromuscular blocking agents because of their
mechanisms of action, paralytic drugs may be administered during
surgery or short-term procedures to prevent the patient from moving,
they may be given to those who require mechanical ventilation, or
they may be utilized in cases where it is important that the patient
remain still during treatment, such as when an individual has
increased intracranial pressure.
Neuromuscular blocking agents are typically classified as one of two
types: depolarizing agents or non-depolarizing agents. The drugs work
on nicotinic acetylcholine receptors at the post-synaptic junction of
nerve impulses. One of the only depolarizing drugs in current use is
succinylcholine, which works to cause significant muscle relaxation by
acting as an agonist at the nicotinic receptor site. Succinylcholine is
made up of two acetylcholine molecules and when these bind to the
receptor site, they act in the same way, but with a longer duration
than acetylcholine. Acetylcholine is normally metabolized by
acetylcholinesterase however succinylcholine is not. This leads to
depolarization of the membrane, in which there is a shift in the electric
charge within the cell and it temporarily becomes more positive. This
shift causes an initial rapid muscle contraction, but the membrane
potential must be reset before depolarization occurs again. The
muscles then become slack and remain so through the length of the
effects of the drug.17
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Succinylcholine is administered as an intravenous infusion and its
effects of neuromuscular blockade are quite rapid. When used,
succinylcholine may be infused for very short periods, such as during a
brief treatment or procedure that only lasts a few minutes. However,
use of depolarizing agents in critical care is becoming less common
because of the risk of certain complications, including malignant
hyperthermia as well as hypokalemia.18 Because it causes complete
muscle paralysis, succinylcholine should always be administered with a
sedative agent that will induce unconsciousness.
In contrast to depolarizing neuromuscular blockade agents, nondepolarizing agents work in a slightly different manner. Nondepolarizing agents act as antagonists to the acetylcholine receptor
sites. With administration, they competitively bind to acetylcholine
receptors and prevent depolarization from occurring. Because
acetylcholine is responsible for skeletal muscle contractions, the
patient will develop flaccid paralysis when acetylcholine is blocked
from its receptor sites. In order to stop the effects of non-depolarizing
blockade, either the drug must be metabolized and excreted from the
body without adding a further dose, or a reversal agent may be given
to stop the effects. Typically, this is an anticholinesterase drug such as
neostigmine.
Non-depolarizing agents are further divided into two types:
benzylisoquinolinium compounds and aminosteroid compounds.
Benzylisoquinolinium drugs are made up of short chains of ammonia
molecules that can cause histamine release when they break down in
the bloodstream. Examples of these types of paralytics include
atracurium and cisatracurium.
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Aminosteroid compounds consist of one or more ammonia groups
connected to a steroid. They typically do not cause a release of
histamine, which may otherwise cause hypotension and tachycardia.
Some types of aminosteroid compounds include pancuronium and
vecuronium.18
Neuromuscular blockade through the use of paralytics is often
warranted in critical care, particularly in cases where a patient is
undergoing a procedure where excess movement would otherwise be
detrimental. Inducing paralysis must be done for some patients to
uphold their safety and to support their treatment, even if the process
is frightening. In order to maintain patient safety and comfort,
paralytic drugs must always be administered with concomitant
sedatives or anesthesia to avoid awareness or memory of the event.
Purpose
Neuromuscular blocking agents are primarily used when skeletal
muscle paralysis would most benefit the patient. The administration of
these drugs is significant and is not taken lightly; rather, each
situation in which paralytic drugs may be valuable should be
thoroughly assessed for the risks and benefits to the patient, and the
most appropriate type of drug selected based on its duration of action
and overall patient outcomes.
Paralytic drugs are given in many varied situations. During anesthesia
induction for surgery, a patient is often given a paralytic along with a
sedative or induction agent to cause muscle relaxation and sedation.
Paralytics are sometimes administered to patients who have severe
neurologic conditions that cause significant muscle twitching or
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spasticity. These drugs are also often administered just prior to
endotracheal intubation to prevent the patient from moving during the
procedure and possibly making the process much more difficult. For
many people, the introduction of a tracheal tube is frightening and
painful and it is a natural response to attempt to block the procedure.
The administration of a neuromuscular blocking agent causes such
muscle relaxation in the patient that the healthcare provider can
complete the intubation much more rapidly when the patient is not
struggling. Additionally, the muscles of the respiratory system and the
vocal cords are relaxed after paralytic administration, making
endotracheal intubation easier with a decreased risk of tissue trauma
with introduction of the tube.
Use of paralytic agents is also commonly associated with mechanical
ventilation of patients, and in these cases, the drugs are administered
over longer periods during the time that ventilation is required. While
this is not its primary purpose, administration of paralytics can be a
practical measure when working with patients who are intubated to
prevent excess movement and possible tube dislodgement. Studies
have shown that of healthcare providers who administer paralytic
agents among patients who require mechanical ventilation, the main
reasons for administration were to combat asynchrony between a
patient’s breathing and ventilator rate, to prevent poor patient
compliance with the ventilator, to reduce patient hypercapnia, and to
inhibit patient hypoxemia.18
Within the ICU, neuromuscular blocking agents have also been
employed for other common reasons, including the control of
intracranial pressure, control of patient agitation and aggression, and
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to decrease a patient’s metabolic demand when extremely ill.18 Use of
paralytic agents may facilitate improved oxygenation in some patients,
particularly if the person is otherwise agitated and requires
supplemental oxygen or mechanical ventilation. Induced paralysis,
combined with sedation, reduces the patient’s muscle activity levels
and decreases oxygen consumption.
A study by Price, et al., in the Annals of Intensive Care showed that
use of neuromuscular blocking agents is beneficial among patients
diagnosed with acute respiratory distress syndrome (ARDS). The study
showed that patients with ARDS who received paralytics experienced
improved oxygenation, as evidenced by a decrease in oxygen
requirements and a decrease in lung trauma often associated with
mechanical ventilation. Additionally, the patients showed a statistically
significant decrease in the amount of inflammatory markers present,
including interleukin, which demonstrates that these patients have a
decreased inflammatory response and a potentially improved overall
mortality after a diagnosis of ARDS.18
Research continues about other possible benefits of using paralytics as
part of treatment in the critical care setting. When protocols are in
place that guide and shape their use, paralytics can be safely
administered and may prevent some potentially significant
complications that would otherwise develop because of patient
agitation and distress.
Complications
Use of paralytic agents is not without the potential for complications,
as has been seen across many groups of patients to whom these drugs
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are given. Although the neuromuscular blocking effects of these drugs
can better facilitate completion of some procedures, there are
drawbacks to inducing paralysis, some of which may be widespread
and can affect major body systems. Use of paralytics requires
continuous monitoring to observe for complications and to closely
track the patient’s clinical status.
Paralytics cause complete muscle relaxation and paralysis that affects
all muscle groups, including the muscles required for breathing. As a
result, the patient who has been given neuromuscular blocking
medications will be unable to breathe on his own. Most people who are
given paralytic medications require breathing assistance, often through
endotracheal intubation and mechanical ventilation. The inability to
breathe spontaneously and the subsequent need for mechanical
ventilation can lead to a number of respiratory problems, including
barotrauma and ventilator-associated lung injury.
Additionally, because paralytic agents prevent the use of the
respiratory muscles to breathe, the patient also typically lacks the
effective mechanisms of protecting his own airway. Normally, the gag
reflex is present in conscious patients, as well as the routine ability to
swallow. The body normally prevents food and mucus from being
aspirated, but when the muscles are paralyzed, the patient no longer
has this capacity. The gag and swallowing reflexes are not present and
the vocal cords are paralyzed. This can increase the patient’s risk of
aspiration of mucus or stomach contents into the lungs, which can lead
to decreased oxygenation and aspiration pneumonia.
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In addition to the possible respiratory complications associated with
neuromuscular blockade, there are some concerns that paralytic
agents increase the risk of patients developing critical illness
polyneuropathy (CIP), a disease state in which a patient is weakened
and suffers from long-term muscle paralysis. The condition is most
often seen following a period where a person spent time in the ICU
and may have received paralytic drugs. CIP causes the muscles to
become flaccid and the patient is often too weak to move, even though
he is no longer receiving paralytics; he may experience paralysis of
certain muscle groups and if intubated, may have difficulties being
weaned off the ventilator due to weakness or paralysis of the
respiratory muscles.19
There have been concerns that prolonged use of neuromuscular
blocking agents contributes to the development of CIP, since the
repeated administration of these drugs and the prolonged, induced
state of muscle paralysis seem to increase the risk of neuromuscular
damage that causes symptoms of CIP. The increased risk seems to be
more commonly associated with aminosteroid drugs instead of
benzylisoquinolinium compounds. Use of paralytics for an extended
period does carry higher risks of complications when compared to the
limited use of these drugs, but research has not shown that use of
neuromuscular blocking agents for less than 48 hours prevents CIP.18
Regardless, clinicians who use paralytic drugs with their patients must
be familiar with the potential for development of CIP and be on guard
to prevent potentially irreversible damage.
As discussed, neuromuscular blocking agents can be beneficial among
patients diagnosed with ARDS, which occurs as fluid build up in the
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lungs that significantly compromises breathing and oxygenation in
critically ill patients. Although paralytics have been shown to be
valuable when used as part of ARDS management, there is also some
evidence that they may contribute to pulmonary complications,
particularly during the post-operative period. Many patients receive
paralytic drugs with sedation during surgery so that they will not move
during the procedure. A study by McLean, et al., in the journal
Anesthesiology showed that the use of neuromuscular blocking agents
was associated with an increase in respiratory complications, including
pulmonary edema, respiratory failure, pneumonia, and reintubation.
The study showed that the increase in complications was dose
dependent, in that larger doses of paralytics contribute to greater risks
of complications. However, proper training in the administration of
paralytic drugs and thorough monitoring throughout their use may
diminish some of these risks.20
Other potential complications found to be associated with paralytic
drugs stem from the lack of movement on the patient’s part. When a
person receives a neuromuscular blocking agent, all body systems
must be closely monitored to prevent some of the consequences of
immobility. For example, a patient who is paralyzed cannot turn
himself while in bed and is at risk of skin breakdown, particularly on
areas where there are bony prominences. Lack of movement can lead
to sluggish circulation and an increased risk of deep vein thrombosis.
All patients who are paralyzed need regular eye care and to have the
eyelids closed to prevent drying on the surface of the eye and possible
corneal abrasions.
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One of the more disturbing complications that may develop with the
use of paralytic medications is anesthesia awareness, in which a
patient has not been given enough sedative or anesthetic medications
with the neuromuscular blocking agents and is awake and aware of his
surroundings. Due to the neuromuscular weakness and paralysis
involved with these medications, the patient is unable to notify
personnel or even move at all and may remain awake during painful
and frightening procedures. The development of awareness during
such procedures as surgery, while undergoing painful treatments, or
utilizing mechanical ventilation has been described as terrifying by
those who have endured these processes and were unable to move or
speak about what was happening.
While awareness occurs infrequently in most patient care situations, it
is a potential complication that must be considered when administering
paralytics. Situations in which a patient is more likely to experience
awareness include the excessive use of paralytic drugs, a history of
drug addiction in the patient, failure of one or more medical devices
being used for patient care, and inappropriate monitoring techniques.21
Not all patients who experience awareness with paralytics will have the
same feelings. Some people have memories of the time of being
awake or undergoing a procedure but they do not feel pain. There are
some people who also experience an altered level of consciousness in
that they are not fully awake; their encounter is more like that of a
dream in which they are aware of their surroundings but their memory
of the event is inconsistent.
The best methods of guarding against awareness in the patient who
requires paralytic medications is to evaluate the patient’s medical
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history, provide the appropriate amount of neuromuscular blockade in
combination with analgesia and sedative medications, and to
continuously monitor the patient throughout the entire time that he
receives these types of medications. The patient’s medical history may
indicate a condition that could increase the risk of awareness with
procedures. A patient with a history of drug abuse may require larger
amounts of medications to elicit a therapeutic effect if he has
developed a tolerance for some kinds of drugs. Patients who take beta
blockers for hypertension are at greater risk of awareness if they
receive low doses of general anesthetic to avoid hypotension.21 As
stated, all patients who receive neuromuscular blocking agents require
concomitant use of medications that induce amnesia, analgesia, and
sedation to avoid development of awareness; appropriate monitoring
techniques for patients receiving paralytic agents are essential in
inducing muscular weakness and paralysis while avoiding other
complications.
Monitoring
Paralytics must always be administered with sedative drugs to calm
the patient and to induce sleep. Paralytics can work without the use of
sedatives and will still cause muscle paralysis. Without the use of
sedatives, the patient would remain awake but would be unable to
move. This is particularly traumatizing for anyone undergoing a
medical procedure and should be avoided as much as possible. The
clinician caring for the patient who receives paralytics must continue to
monitor his level of consciousness to ensure that he is sedated while
paralysis is in effect.
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When paralytic drugs are administered continuously, their rate of
administration and depth of paralysis must also be analyzed and
monitored frequently. This can be challenging, particularly when other
drugs are also exerting their effects. However, part of the process of
monitoring paralytic use is to ensure that the patient receives the right
amount of the drug. There is a distinct balance in providing
neuromuscular blockade so that the individual does not receive so
much that the effects are long lasting and there is no ability to move,
versus too little of the drug, in which the patient has purposeful
movements that could be disruptive toward his treatment.
There are various methods of analyzing whether a patient is receiving
the right amount of neuromuscular blocking agents. One method often
employed is known as the ‘train of four’, which is a process in which a
healthcare clinician applies a nerve stimulator to the patient’s skin to
test nerve function. The train of four process can help the clinician to
determine whether the patient is receiving too much of the paralytic
and also if he is not getting enough. To accurately perform the train of
four, the clinician must first have a baseline measurement of the
patient’s nerve function; this involves testing nerve function prior to
administration of any neuromuscular blocking agents. In cases of
emergency when the paralytic drugs are administered quickly, a
baseline measurement may not be available.
Having a baseline measurement helps the provider to better know how
much nerve stimulation to apply when performing the train of four.
The caregiver applies electrodes connected to a nerve stimulator on
the skin near a specific nerve, such as the median or the ulnar nerves.
The machine is set to a low level of impulse delivery and it gives the
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electrical stimulus four times in a row. These mild shocks should
stimulate the nearby nerve and cause the muscles to twitch or spasm.
For example, when assessing the ulnar nerve, the electrodes would be
placed on the patient’s forearm. When delivering the four impulses,
one or more of the patient’s fingers may twitch slightly in response to
the stimulation.
The patient is said to have an adequate amount of paralytic
medications on board if his muscles twitch twice out of the four
impulses. If the muscles twitch more than twice out of four impulses,
the patient may need more medication because his muscles do not
appear to be paralyzed. Alternatively, if the patient’s muscles do not
respond to any of the impulses given, he may have been receiving too
much of the paralytic drugs to the point that he is unresponsive.16 The
drugs may be titrated to increase or decrease the dose depending on
the patient’s response to the nerve stimulation, however, each facility
that administers neuromuscular blocking agents should have a
protocol in place for monitoring paralytic use and assessing
responsiveness.
Monitoring use of paralytics through such practices as the train of four
is useful in determining the right balance of what the patient needs for
neuromuscular blockade. When giving these drugs, it is always better
to administer the least amount necessary to induce paralysis, rather
than exceeding the minimum dose and giving too much at once. It
should be noted that not all patients respond to paralytic drugs in the
same way. While monitoring techniques are similar between patients,
each person often requires a different dose and may need more or less
of the drug to achieve adequate paralysis. While there is a range of
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acceptable doses and the amounts to give have limits, clinicians
administering paralytics should be aware that patients often require
different amounts and should titrate accordingly. Because of these
differences, it is extremely important to be familiar with the process of
administration, the appropriate methods of monitoring paralysis, and
the effects of monitoring outcomes on medication titration to ensure
the utmost safety for these patients.
Vasopressor Drugs
Vasopressor drugs, commonly referred to as pressors, act on the
circulatory system to improve the overall tone of the blood vessels.
Generally, pressors are administered to increase blood pressure,
particularly in cases where a patient is suffering from hypotension and
poor perfusion and is at risk of developing shock.
Shock occurs when the organs and tissues do not receive as much
blood as they need. All areas of the body have their own metabolic
requirements to continue working properly and they require a certain
amount of blood perfused through the circulatory system. When blood
flow is inadequate, such as because of very low blood pressure,
significant bleeding, abnormal cardiac activity, or an obstruction
somewhere within the circulatory system, the major organs cannot
continue to work in a normal manner and they can develop hypoxia
and eventual ischemia from a lack of blood flow. When this occurs, the
organs shut down from tissue damage and cell death occurs. The cells
of the peripheral tissues, in order to try to maintain metabolic
demands, utilize anaerobic respiration to make energy. This process
creates more carbon dioxide and puts the body into a state of
metabolic acidosis. The progression takes on a cyclical nature in that
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increasing acidosis contributes to a worsening of blood pressure and
the affected patient remains hypotensive.22
There are several types of shock that may develop within the critically
ill patient; kinds of shock are typically classified according to their
causes. A patient who needs aggressive treatment for low blood
pressure that causes shock may be suffering from one of three main
types: cardiogenic shock, hypovolemic shock, or septic shock.
Cardiogenic shock develops when the organs do not receive adequate
perfusion because of inadequate cardiac output. The cause of the
decreased cardiac output is usually due to one or more problems with
the heart, including myocardial infarction, cardiac tamponade,
inflammatory myocarditis; valve disorders, including mitral
regurgitation, or cardiac arrhythmia. It may also develop as a result of
ineffective respiratory function that impairs blood flow to the heart,
leading to decreased output and circulation, such as in cases of
pulmonary embolism or drug overdose. An individual who has
developed cardiogenic shock will exhibit significant hypotension,
evidenced by low systolic blood pressure levels and the need for
vasopressor medications to maintain adequate blood pressure;
elevated left-ventricular filling pressures or pulmonary congestion; and
clinical signs of poor organ perfusion, evidenced by pale, clammy skin;
decreased urine output, or altered mental status.81
Cardiogenic shock originally develops due to tissue ischemia from poor
cardiac output, which leads to a cycle of decreased cardiac
contractility, hypotension, and then further tissue ischemia. The
cardiac compromise eventually impacts the entire circulatory system
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to the distal capillary beds. Poor perfusion of tissues may lead to
systemic inflammation and capillary vessel leakage. Approximately 80
percent of cases of cardiogenic shock originally stem from myocardial
infarction. The condition can have up to a 50 percent mortality rate.81
The treatment involves improving blood flow by relieving obstructions
in the blood vessels that originally contributed to early ischemia, such
as through percutaneous coronary intervention as treatment of
stenotic coronary vessels.
Typically, a combination of medications and interventions is needed to
control cardiogenic shock and to prevent deterioration of the patient’s
clinical condition. Blood clot development, such as that which causes
pulmonary embolism leading to cardiogenic shock is often treated
through thrombolytic therapy. The patient often requires medications
that improve cardiac contractility and that further cardiac output while
simultaneously increasing blood pressure levels to facilitate perfusion.
Other medical procedures may also be implemented, including
administration of fluids and electrolytes, management of cardiac
arrhythmias, revascularization through surgery, or left-ventricular
support.
Hypovolemic shock describes a state in which there is severely
inadequate tissue perfusion due to a low volume of blood within the
cardiovascular system. The low blood volume is often due to
hemorrhage, and bleeding may be internal or external. Excessive
bleeding is often seen following traumatic injury, but it may also occur
after surgery. Patients who have suffered severe burns are also at risk
of hypovolemia due to loss of plasma volume. Some people who
experience severe vomiting or diarrhea may develop hypovolemia as a
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result of shifts in electrolyte levels in circulation. The patient with
hypovolemic shock typically exhibits a very low blood pressure, and
increased heart rate with a thready pulse. Additional signs or
symptoms often include hyperventilation, pallor, and mental status
changes.82
The main goals of treatment of hypovolemic shock are to restore some
of the circulatory volume to be able to provide adequate blood
perfusion to pertinent organs and tissues. This process often involves
fluid resuscitation through rapid administration of crystalloid solutions,
repletion of oxygenated blood volume through administration of blood
products, and the use of medications such as vasopressors to improve
blood pressure. The administration of vasopressor medications is not
indicated until the circulatory volume has been at least partially
restored. In the case of hemorrhagic shock, in which a patient
experiences hypovolemic shock due to blood loss, a research review by
Beloncle, et al., in the Annals of Intensive Care showed that most
experimental data do not indicate the administration of vasopressors
early during treatment and that vasopressors should not be used in
place of fluid resuscitation.83 Further, use of vasopressors too early
during treatment of hemorrhagic shock when the patient has otherwise
not received appropriate fluid resuscitation is associated with an
increased risk of patient mortality.84 Alternatively, once a patient who
is experiencing shock has had cardiovascular volume repletion through
fluid resuscitation, vasopressor medications can be therapeutically
effective in stabilizing blood pressure so that the blood volume that is
available can be better perfused to vital organs.
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Septic shock is a specific type of shock that develops following
infection. Sepsis describes a condition in which the organs are
inadequately perfused because of the effects of infection; septic shock
can then develop when perfusion is so limited that the patient
develops organ failure. In the United States, severe sepsis accounts
for 10 percent of all hospital ICU admissions.85 A patient with septic
shock typically exhibits dangerously low blood pressure and often has
an altered mental status. The skin is often cool and clammy and pallor
is present. The rate of progression from severe sepsis to septic shock
may depend on several factors, including the type of causative
infection and the presence of underlying illness in the patient. The
condition can become rapidly fatal if not promptly recognized and
treated.
Initial treatment involves fluid resuscitation, however, one of the
hallmarks of septic shock is that the condition often does not respond
to rapid fluid administration. Vasopressors are often added as part of
treatment when the patient continues to have significant hypotension
despite fluid administration. Vasopressor therapy, including
administration of norepinephrine or epinephrine, can be given
simultaneously with fluids. According to the Surviving Sepsis
Campaign, norepinephrine is the vasopressor of choice to use for
hypotension treatment associated with septic shock, and vasopressin,
given at a low dose concomitantly with norepinephrine can be added to
increase the patient’s mean arterial pressure.86 Additional measures
utilized in the treatment of septic shock may include the administration
of blood products, inotropic therapy to improve cardiac output, and
antimicrobial therapy to control the infection. Many patients with this
type of shock also need mechanical ventilation, insulin administration
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for unstable blood glucose levels, and ongoing sedation and analgesia
to maintain comfort.
Vasopressors stimulate adrenergic receptors to improve the tone of
the blood vessels and to cause vasoconstriction, thereby improving
blood pressure and circulation through increased pulmonary vascular
resistance. There are different types of receptors as well as different
kinds of vasopressors. When given, a vasopressor may act as a
receptor agonist or an antagonist to exert its effects. These
baroreceptors are found within the walls of the blood vessels and they
constantly monitor blood pressure and send messages to the brain to
help maintain a normal pressure balance.
The exact hemodynamic responses following administration of pressors
can vary slightly, depending on the drug and its dose, as well as the
patient’s condition. The variations develop because of some of the
differences of the effects on the receptors between the drugs. Some
examples of vasopressors that may be given for management of shock
states among patients in critical care include norepinephrine,
metaraminol bitartrate, and vasopressin. In order to facilitate the best
outcomes among individual patients, selection and use of vasopressors
requires careful monitoring and observation.
Purpose
The main purpose of pressors is to improve the blood circulation of
patients and increase hemodynamic stability. Pressors are most often
given to patients who are hemodynamically unstable in that they have
abnormally low blood pressure and are at risk of shock. Administering
pressors in these situations can cause the blood vessels to constrict
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and can help to stabilize blood pressure. When a patient is brought to
the emergency room or is in the ICU and has low blood pressure and
such poor perfusion that he is unable to meet metabolic demands, he
is at risk of a potentially irreversible state of shock and organ damage.
In emergent cases, pressors can be rapidly administered to improve
blood pressure and organ perfusion.
Because pressors are most often given in cases where a patient has
significant hypotension, they may be considered as an early form of
therapeutic treatment to correct hypotension and to prevent tissue
ischemia from a lack of blood flow. However, in cases where patients
are seen with hypotension due to low circulatory volume, such as in
cases of massive blood loss, the individual first requires fluid
resuscitation to correct some of the circulatory volume before
administration of pressors can be considered.
As discussed, vasopressors are often necessary and beneficial, but
guidelines typically recommend that they are initiated once fluid
resuscitation has been started.40 Vasopressors, while powerful in their
effects, could lead to a reduction in blood flow and subsequent
ischemia in other parts of the body. Additionally, when there is
massive fluid loss, such as in the case of hypovolemic shock,
constriction of the blood vessels will not necessarily impact blood
pressure when fluid volume is too low to begin with. Fluid volume
levels must first be corrected enough that vasoconstriction will work in
conjunction with blood flow to correct blood pressure.
Pressors can also be beneficial in protecting blood pressure levels
when extra volumes of fluid are not necessary or would actually be
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detrimental to the patient’s care. In some cases where hypotension
occurs that is not necessarily related to volume depletion, rapid
administration of large amounts of fluid is not warranted. In fact, there
are some cases where fluid resuscitation may be injurious to the
patient’s condition when extra volume is not needed, as too much fluid
can promote edema and may damage pulmonary function.40
Pressors improve blood pressure by increasing systemic vascular
resistance (SVR), which describes how much the blood vessels comply
with or constrict against blood flow. This increase then raises arterial
blood pressure. The mean arterial blood pressure (MAP) describes the
relationship between cardiac output and SVR; if the MAP is low, then
the vital organs are not being well perfused, and if the MAP is too high,
it indicates that the heart may be working too hard. In addition to
causing vasoconstriction to improve blood pressure, some pressors
increase cardiac contractility to promote cardiac output. When pressors
stimulate alpha-1 receptors, they improve blood pressure and increase
SVR, and when they stimulate beta-1 receptors, they increase the
heart rate and cardiac contractility.
Some drugs that are considered vasopressin analogs may also be used
for vasoconstriction when given in larger amounts. Vasopressin, also
known as antidiuretic hormone, is a specific hormone normally found
in the hypothalamus. It acts on particular vasopressin (V) receptors to
exert its effects, including V1, V2, and V3 receptors. V1 receptors are
found in smooth muscles of the blood vessels, as well as in the
kidneys, hepatocytes, platelets, and spleen and they control
vasoconstriction. V2 receptors are mainly found in the kidneys and
they exert antidiuretic effects. V3 receptors play a role in temperature
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regulation and memory and are primarily located in the pituitary
gland.88
Vasopressin, through its antidiuretic effects, reduces urine output by
helping the kidneys to reabsorb water. During cases of hypovolemia,
vasopressin can help to control further volume loss by exerting
antidiuretic effects; the body often naturally releases antidiuretic
hormone in response to a drop in blood volume anyway, such as with
the case of dehydration or hypotension. Vasopressin acts in the same
manner as anti-diuretic hormone except that it is a synthetic version.
Research regarding the effects and timing of administration of pressors
is ongoing and over time, guidelines as to the type and amount of
pressors to give in cases of shock have evolved. The health clinician
who works with critical care patients who are experiencing any type of
shock and who have severe hypotension should be familiar with the
effects of vasopressors and should stay up to date about changes in
administration guidelines to be able to provide the safest and most
current form of care available.
Summary
The clinician who works in a critical care setting must often be
prepared to act quickly to administer drugs to respond to changes in a
patient’s condition or clinical status. The clinician may be faced with
administering a variety of different drugs and it may be challenging to
remember the varied drug classes, common dosages, potential side
effects, and implications for administration. Drugs are often given
based on each patient’s condition and may be used to manage specific
symptoms that affect different organ systems within each person. For
example, one patient in the emergency department may require
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cardiac medications to stabilize a potentially life-threatening
arrhythmia, while another may need analgesia to control pain
associated with a severe injury. Often, patients require more than one
type of medication.
Often, drugs given in the critical care environment can have great
potential for complications because of their physiological effects. When
administered rapidly for emergency purposes, many drugs start to
work almost immediately and their effects can impact almost all body
systems. Assessing the patient’s clinical status and ensuring the
correct dose and route have been ordered, administering the drug
correctly (and sometimes very rapidly), and observing the patient for
the drug’s effects or for changes in clinical status are all major steps in
the process of giving drugs in the critical care setting.
Please take time to help NurseCe4Less.com course planners
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1. ________________ is a process that is sometimes given the
abbreviation ADME.
a.
b.
c.
d.
Pharmacodynamics
Biopharmaceutics
Pharmacokinetics
Pinocytosis
2. True or False: Studies that assess how drug act in the body
after administration, such as rates of absorption, volume
distribution, or rates of elimination, are often generated
from clinical research studies on healthy volunteers.
a. True
b. False
3. Which of the following processes describes the movement of
a drug from its point of administration to its target location,
i.e., the bloodstream?
a.
b.
c.
d.
Absorption
Pinocytosis
Diffusion
Transportation
4. Which of the following forms of drug administration
generally has the slower rate of absorption?
a.
b.
c.
d.
Intravenous administration
Intramuscular injection
Subcutaneous injection
All the above have similar absorption rates
5. ______________ occurs when a cell membrane surrounds
and encloses the particles of the drug.
a.
b.
c.
d.
Passive diffusion
Pinocytosis
Absorption
Active transport
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6. __________________ involves the movement of drug
particles across a membrane with the help of a carrier
molecule.
a.
b.
c.
d.
Passive diffusion
Pinocytosis
Facilitated passive diffusion
Active transport
7. True or False: Drugs that are given in aqueous solutions are
absorbed faster than those that contain oil-based solutions.
a. True
b. False
8. When an ointment is applied to the skin and covered by an
occlusive dressing, the medication may ________________
when compared to a layer of medication applied without an
occlusive dressing.
a.
b.
c.
d.
be absorbed more quickly
reduce swelling more
be less hydrating
decrease permeability
9. The process of drug absorption is one step of
pharmacokinetics that all drugs, except
___________________ drugs, must undergo to exert their
effects and to be therapeutically useful.
a.
b.
c.
d.
inhalation
intrathecally administered
subcutaneously injected
intravenously administered
10. __________________ refers to exactly how much of a
drug enters the circulation and the rate at which it is
absorbed and therefore available to be distributed.
a.
b.
c.
d.
Distribution
Diffusion
Absorption
Bioavailability
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11. Drugs that are ____________________ have greater
bioavailability because they do not need to undergo
absorption first.
a.
b.
c.
d.
inhaled
administered intravascularly
administered extravascularly
administered topically
12. When a drug is in the bloodstream, it moves from the
plasma into the tissues through the process of
a.
b.
c.
d.
absorption.
pinocytosis.
diffusion.
distribution.
13. The point at which a drug’s concentration in plasma and in
the tissues are in balance is known as
a.
b.
c.
d.
passive diffusion
the determinant phase.
the post-distribution phase.
the concentration phase.
14. True or False: A drug’s bioavailability in the bloodstream
and its distribution are the same regardless of the drug’s
composition or form, i.e., capsules or tablets.
a. True
b. False
15. Most drugs are metabolized and converted into an active
chemical substance in the
a.
b.
c.
d.
liver.
lungs.
plasma.
gastrointestinal tract.
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16. During the first phase or stage of metabolism, known as
Phase 1, a drug undergoes
a.
b.
c.
d.
absorption.
conjugation.
oxidation.
hydrolysis.
17. The process known as _______________, occurs during
Phase 2 of metabolism; in this phase a group of ions binds
to the metabolite within the cytoplasm of the hepatocyte.
a.
b.
c.
d.
hydrolysis
conjugation
oxidation
reduction
18. Elimination of a drug from the body begins
a.
b.
c.
d.
during excretion.
during metabolization.
after absorption.
as soon as it is administered.
19. One of the most common conjugation reactions of
metabolism is
a.
b.
c.
d.
glucuronidation.
acetylation.
sulfation.
methylation.
20. True or False: The process of conjugation contributes
toward the eventual excretion of the drug from the body’s
system, as the binding of an ionized group makes the
metabolite more water soluble.
a. True
b. False
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21. A drug referred to as a “prodrug” has which of the
following unique properties?
a. It builds up within the system without becoming toxic.
b. It metabolizes so it may be excreted from the body.
c. It remains pharmacologically active when undergoing
metabolism.
d. It can cross the blood-brain barrier.
22. The removal of a drug from the plasma is known as drug
________________, which is a factor used in
pharmacokinetic formulas to determine the half-life of a
drug and its steady state of concentration.
a.
b.
c.
d.
excretion
elimination
reduction
clearance
23. The ____________ of a drug describes how long the drug
is active in the body, which may be referred to as the
drug’s duration of action.
a.
b.
c.
d.
toxicity
bioavailability
half-life
metabolization
24. A patient is receiving a daily administration of digoxin to
treat a chronic atrial fibrillation. The administration and
dose is set based on the drug’s half-life with a goal
a.
b.
c.
d.
of
of
to
to
total drug clearance.
metabolizing the drug more quickly.
develop a steady state of the drug in the bloodstream.
assure that the initial drug administration is stronger.
25. True or False: As the process of metabolism continues, the
drug’s therapeutic effects are increased.
a. True
b. False
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26. A nurse is administering gentamicin as an antibiotic for a
patient and the nurse wants to measure the trough level of
the drug. The nurse should measure the trough level
a.
b.
c.
d.
just prior to giving the drug.
approximately 30 minutes after the drug has been given.
after administration of the drug.
at the mid-point of the drug’s half-life.
27. Elevated creatinine levels can indicate
a.
b.
c.
d.
that a drug is at its trough level.
liver dysfunction.
impaired kidney function.
that a drug’s concentration is at its highest level.
28. When estimating __________ function, a provider should
consider the patient’s estimated glomerular filtration rate
(GFR).
a.
b.
c.
d.
spleen
pancreatic
liver
kidney
29. Pharmacodynamics considers a drug’s
a.
b.
c.
d.
concentration at the site of action.
therapeutic effects.
adverse effects.
All of the above
30. True or False: For patients in the ICU, therapeutic drug
monitoring must be performed every day or with each
dose.
a. True
b. False
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31. A patient who receives anxiolysis
a.
b.
c.
d.
requires a ventilator to assist with breathing.
can respond to verbal commands.
has impaired motor skills and reflexes.
All of the above
32. Isoproterenol works by stimulating beta-receptors that are
normally stimulated by epinephrine, which makes this drug
an example of
a.
b.
c.
d.
an endogenous substance.
a receptor agonist.
a receptor antagonist.
a metabolite.
33. A patient with a Richmond Agitation-Sedation Scale (RASS)
score of -5 could be described as being
a.
b.
c.
d.
combative.
calm.
anxious.
unarousable.
34. An idiosyncratic drug reaction describes an adverse effect
a.
b.
c.
d.
that is an off-target event.
caused by drug tolerance.
that is rare and unpredictable.
that is life-threatening.
35. True or False: In contrast to pharmacokinetics, the concept
of pharmacodynamics describes a drug’s actions or what a
drug does in the body after it is administered.
a. True
b. False
36. In today’s healthcare, sedatives are often administered
a.
b.
c.
d.
to keep a ventilated patient restrained and confined.
to provide round-the-clock sedation for ventilated patients.
as adjuvant drugs to promote comfort alongside analgesics.
to keep a patient constantly subdued and controlled.
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37. Analgesic medications are primarily administered to
control
a.
b.
c.
d.
anxiety
delirium.
breathing.
pain.
38. Succinylcholine is a neuromuscular blocking agents,
classified as a depolarizing agent, used for deep muscle
relaxation, but it has the following limitation or side effect:
a.
b.
c.
d.
It cannot be administered with a sedative agent.
It cannot be used for short procedures.
It carries a risk of malignant hyperthermia.
Its effects as a neuromuscular blockade are slow.
39. One of the more disturbing or frightening complications for
a patient that may develop with the use of paralytic
medications is
a.
b.
c.
d.
amnesia of the hospital event.
drug tolerance.
hypertension.
anesthesia awareness.
40. True or False: For a patient in intensive care, antipsychotic
medications are often used as a first choice for calming,
even though the patient may have no history of mental
illness.
a. True
b. False
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CORRECT ANSWERS:
1. ________________ is a process that is sometimes given the
abbreviation ADME.
c. Pharmacokinetics
“When a drug is given for any type of illness or medical
condition, it is regulated in the body through pharmacokinetics,
which describes the processes of absorption, distribution,
metabolism, and excretion of a drug within the body. The
process is sometimes given the abbreviation ADME. The term
pharmacokinetics is also sometimes described as what the
body does to a drug when it is given.”
2. True or False: Studies that assess how drug act in the body
after administration, such as rates of absorption, volume
distribution, or rates of elimination, are often generated
from clinical research studies on healthy volunteers.
a. True
“When a drug is assessed by how it acts in the body after
administration, corresponding pharmacokinetic parameters can
be calculated to determine factors such as the rate of its
absorption, the volume of its distribution, or the rate of its
elimination. This information is often generated from clinical
research studies in which volunteers, who are often healthy,
take the drugs for specified periods and then scientists such as
biostatisticians and pharmacokineticists study the information,
apply the formulas, and determine the results of the drug’s
pharmacokinetics based on how it behaves after being
administered to study participants.”
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3. Which of the following processes describes the movement of
a drug from its point of administration to its target location,
i.e., the bloodstream?
a. Absorption
“Absorption is the process of moving the drug from its initial
location after it has been given (for instance, the stomach or
intestinal tract for oral drugs, or the skeletal muscle tissue for
an intramuscular injection) and transitioning its particles into
circulation.”
4. Which of the following forms of drug administration
generally has the slower rate of absorption?
c. Subcutaneous injection
“… medications that are given via the intravenous route are
administered directly into the bloodstream and do not require
the additional step of absorption…. Because there is less
vascular access to the subcutaneous tissue when compared to
skeletal muscle tissue used for an intramuscular injection, the
absorption rate of a subcutaneous injection is slower.”
5. ______________ occurs when a cell membrane surrounds
and encloses the particles of the drug.
b. Pinocytosis
“Drugs can be absorbed via passive diffusion using little to no
excess energy and a carrier molecule is not required. Passive
diffusion is the method of absorption by which most drugs are
transferred into systemic circulation…. Active transport
describes the active movement of molecules across a
membrane … Pinocytosis occurs when a cell membrane
surrounds and encloses the particles of the drug.”
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6. __________________ involves the movement of drug
particles across a membrane with the help of a carrier
molecule.
c. Facilitated passive diffusion
“Facilitated passive diffusion also does not require energy. It
involves the movement of drug particles across a membrane
with the help of a carrier molecule.”
7. True or False: Drugs that are given in aqueous solutions are
absorbed faster than those that contain oil-based solutions.
a. True
“Drugs that are given in aqueous solutions are absorbed faster
than those that contain oil-based solutions; medications with
high solubility also tend to be absorbed more slowly than those
with low solubility.”
8. When an ointment is applied to the skin and covered by an
occlusive dressing, the medication may ________________
when compared to a layer of medication applied without an
occlusive dressing.
a. be absorbed more quickly
“… when an ointment is applied to the skin and covered by an
occlusive dressing, the medication may be absorbed more
quickly than when a layer of the medication is applied without
any cover.”
9. The process of drug absorption is one step of
pharmacokinetics that all drugs, except ________________
drugs, must undergo to exert their effects and to be
therapeutically useful.
d. intravenously administered
“… the process of drug absorption is one step of
pharmacokinetics that all drugs, except intravenously
administered drugs, must undergo to exert their effects and to
be therapeutically useful.”
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10. __________________ refers to exactly how much of a
drug enters the circulation and the rate at which it is
absorbed and therefore available to be distributed.
d. Bioavailability
“Bioavailability refers to exactly how much of a drug enters the
circulation and the rate at which it is absorbed and therefore
available to be distributed…. Drugs that are administered
extravascularly are generally not completely absorbed. There
are usually traces of the medication that remain unabsorbed.
This reduces bioavailability since there is less of the drug
available for distribution from its original dose. By comparison,
drugs that are administered intravascularly have greater
bioavailability because they do not need to undergo absorption
first.”
11. Drugs that are ____________________ have greater
bioavailability because they do not need to undergo
absorption first.
b. administered intravascularly
“Drugs that are administered extravascularly are generally not
completely absorbed. There are usually traces of the
medication that remain unabsorbed. This reduces
bioavailability since there is less of the drug available for
distribution from its original dose. By comparison, drugs that
are administered intravascularly have greater bioavailability
because they do not need to undergo absorption first.”
12. When a drug is in the bloodstream, it moves from the
plasma into the tissues through the process of
c. diffusion.
“When a drug is in the bloodstream, it moves from the plasma
into the tissues through the process of diffusion.”
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13. The point at which a drug’s concentration in plasma and in
the tissues are in balance is known as
c. the post-distribution phase.
“Once more of the drug has entered the tissues, the process of
diffusion slows when the areas of concentration between the
plasma levels and tissue levels of the drug are more in
balance. This point is known as the post-distribution phase, in
which drug concentrations in plasma and in the tissues are in
balance.”
14. True or False: A drug’s bioavailability in the bloodstream
and its distribution are the same regardless of the drug’s
composition or form, i.e., capsules or tablets.
b. False
“… there are differences between drugs that are administered
as capsules and as tablets, even though they may be the same
drug at the same dose. Their composition as either capsules or
tablets can impact their qualities of absorption because of their
formulations. This, in turn, affects their bioavailability in the
bloodstream as well as the amount to be distributed.”
15. Most drugs are metabolized and converted into an active
chemical substance in the
a. liver.
“Once distributed, the drug is metabolized, which describes
how the chemical compound of the drug is converted into an
active chemical substance through the work of enzymes. Most
drugs are metabolized in the liver, but other body areas,
including the lungs, plasma, and the wall of the gastrointestinal
tract have the capacity to metabolize drugs as well.”
16. During the first phase or stage of metabolism, known as
Phase 1, a drug undergoes
c. oxidation.
“During the first phase, the most common change that takes
place is when the drug undergoes oxidation.”
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17. The process known as _______________, occurs during
Phase 2 of metabolism; in this phase a group of ions binds
to the metabolite within the cytoplasm of the hepatocyte.
b. conjugation
“Once the medication has passed through Phase 1, conjugation
occurs in the second phase of metabolism, in which a group of
ions binds to the metabolite. This process occurs within the
cytoplasm of the hepatocyte.”
18. Elimination of a drug from the body begins
d. as soon as it is administered.
“Technically, the elimination of a drug from the body begins as
soon as it is administered and it enters the body. When a drug
is first being absorbed, the body is also simultaneously
eliminating it, but the rate of absorption is greater than the
rate of elimination, so more of the drug is absorbed initially.
Over time, the processes balance out and eventually, more of
the drug is metabolized and excreted when there is less of the
initial drug to be absorbed.”
19. One of the most common conjugation reactions of
metabolism is
a. glucuronidation.
“While glucuronidation is one of the most common conjugation
reactions of metabolism, there are other forms that can occur
as well, in which a functional group is added to the molecule to
facilitate metabolism. Such examples include acetylation,
which is the addition of an acetyl group, and sulfation, which is
the conjugation of a sulfo group to the molecule.”
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20. True or False: The process of conjugation contributes
toward the eventual excretion of the drug from the body’s
system, as the binding of an ionized group makes the
metabolite more water soluble.
a. True
“The process of conjugation contributes toward the eventual
excretion of the drug from the body’s system, as the binding of
an ionized group makes the metabolite more water soluble and
therefore easier to excrete.”
21. A drug referred to as a “prodrug” has which of the
following unique properties?
c. It remains pharmacologically active when undergoing
metabolism.
“The overall outcome of metabolism is to take the parent
compound —which is the initial state of the drug after it has
been distributed — and break it down through metabolism so
that it becomes pharmacologically inactive for eventual
excretion. The body must metabolize drugs for excretion to
avoid the buildup of medication within the system that leads to
toxicity and potential organ damage. Most drugs become
pharmacologically inactive through the process of metabolism,
but note that some drugs, when undergoing metabolism,
remain pharmacologically active. This is sometimes called a
prodrug; the initial drug may actually have a weaker effect
until it is partially metabolized, and then its metabolite is more
active. An example of a prodrug is the antihypertensive drug
enalapril, a metabolite whose parent drug is enalaprilat, which
does not become pharmacologically active until it has
undergone metabolism.”
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22. The removal of a drug from the plasma is known as drug
________________, which is a factor used in
pharmacokinetic formulas to determine the half-life of a
drug and its steady state of concentration.
d. clearance
“The removal of a drug from the plasma is known as drug
clearance, which is a factor used in pharmacokinetic formulas
to determine the half-life of a drug and its steady state of
concentration.”
23. The ____________ of a drug describes how long the drug
is active in the body, which may be referred to as the
drug’s duration of action.
c. half-life
“The half-life therefore describes how long the drug is active in
the body, which may be referred to as the drug’s duration of
action.”
24. A patient is receiving a daily administration of digoxin to
treat a chronic atrial fibrillation. The administration and
dose is set based on the drug’s half-life with a goal
c. to develop a steady state of the drug in the bloodstream.
“… in cases where a drug is administered routinely, the goal is
to develop a steady state within the bloodstream, or a certain
amount of the drug that is constant within the plasma so that
it is therapeutically effective. An example of this is with the
administration of digoxin, which is given for the treatment of
heart failure or chronic atrial fibrillation. Digoxin is
administered routinely, typically on a daily basis. Because of
this, its concentration within the blood plasma is maintained
and it can exert its therapeutic effects. Clinicians can test for
digoxin levels in the bloodstream by assessing plasma values
because its chronic administration leads to a plasma steady
state.”
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25. True or False: As the process of metabolism continues, the
drug’s therapeutic effects are increased.
b. False
“As the process of metabolism continues, the drug’s
therapeutic effects are decreased.”
26. A nurse is administering gentamicin as an antibiotic for a
patient and the nurse wants to measure the trough level of
the drug. The nurse should measure the trough level
a. just prior to giving the drug.
“For example, when administering gentamicin as an antibiotic,
the patient requires peak and trough levels, which are
performed after dose administration and just prior to dose
administration, respectively. Measuring the peak involves
collecting a blood sample within approximately 30 minutes
after the drug has been given and has had a chance to be
distributed. Alternatively, the trough is measured just prior to
giving the drug, when the concentration of the drug in the
body from the last point of administration would be at its
lowest.”
27. Elevated creatinine levels can indicate
c. impaired kidney function.
“… elevated creatinine levels can indicate impaired kidney
function.”
28. When estimating __________ function, a provider should
consider the patient’s estimated glomerular filtration rate
(GFR).
d. kidney
“When estimating kidney function, a provider should consider
the patient’s estimated glomerular filtration rate (GFR).”
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29. Pharmacodynamics considers a drug’s
a.
b.
c.
d.
concentration at the site of action.
therapeutic effects.
adverse effects.
All of the above [correct answer]
“In essence, pharmacodynamics considers the drug
concentration at the site of action and its therapeutic effects,
including any adverse effects that may occur.”
30. True or False: For patients in the ICU, therapeutic drug
monitoring must be performed every day or with each
dose.
b. False
“There are several considerations to think through when using
therapeutic drug monitoring for patients in the ICU. First, this
type of monitoring is only appropriate for those drugs that
require therapeutic monitoring to check plasma levels, but it
does not need to be performed every day or with each dose.”
31. A patient who receives anxiolysis
b. can respond to verbal commands.
“Mild or minimal sedation, also referred to as anxiolysis,
provides some amount of sedation so that the patient is
calmed and comforted but not so much that it alters his level
of consciousness. A patient who receives anxiolysis can still
respond to verbal commands, has normal reflexes, and can
breathe spontaneously.”
32. Isoproterenol works by stimulating beta-receptors that are
normally stimulated by epinephrine, which makes this drug
an example of
b. a receptor agonist.
“An example of a receptor agonist is isoproterenol, which
works by stimulating beta-receptors that are normally
stimulated by epinephrine.”
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33. A patient with a Richmond Agitation-Sedation Scale (RASS)
score of -5 could be described as being
d. unarousable.
“One of the more common tools available for use in critical
care is the Richmond Agitation-Sedation Scale (RASS); this
scoring system can be used for any patient who is at risk of
delirium, agitation, or anxiety and who is receiving sedative
medications, but it is particularly useful for those who have
difficulty with communication, such as patients who have
mechanical ventilation. The RASS requires observation of the
patient’s behavior and responses to stimuli. The responses are
scored on a scale that ranges from -5 (unarousable) to +4
(combative, violent, dangerous to staff), with a score of ‘0’
described as being ‘alert and calm.’”
34. An idiosyncratic drug reaction describes an adverse effect
c. that is rare and unpredictable.
“Another type of adverse event that can occur with drug
administration is an idiosyncratic drug reaction. This describes
an adverse effect that is rare and unpredictable.”
35. True or False: In contrast to pharmacokinetics, the concept
of pharmacodynamics describes a drug’s actions or what a
drug does in the body after it is administered.
a. True
“In contrast to pharmacokinetics, the concept of
pharmacodynamics describes a drug’s actions or what a drug
does in the body after it is administered.”
36. In today’s healthcare, sedatives are often administered
c. as adjuvant drugs to promote comfort alongside analgesics.
“Sedatives should not be administered as a method of keeping
a patient constantly subdued and controlled. Historically,
sedatives were given around the clock to patients who required
mechanical ventilation in order to maintain such deep sedation
that the individual was relatively unaware of his condition until
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he was able to successfully breathe on his own. Today,
sedatives are still commonly administered, but are often given
as adjuvant drugs to promote comfort alongside analgesics;
they should be given as a method of controlling anxiety and
insomnia in the critical care environment, instead of just being
used to keep a ventilated patient restrained and confined.”
37. Analgesic medications are primarily administered to
control
d. pain.
“Analgesic medications are primarily administered to control
pain.”
38. Succinylcholine is a neuromuscular blocking agents,
classified as a depolarizing agent, used for deep muscle
relaxation, but it has the following limitation or side effect:
c. It carries a risk of malignant hyperthermia.
“Neuromuscular blocking agents are typically classified as one
of two types: depolarizing agents or non-depolarizing agents….
One of the only depolarizing drugs in current use is
succinylcholine, which works to cause significant muscle
relaxation by acting as an agonist at the nicotinic receptor
site…. Succinylcholine is administered as an intravenous
infusion and its effects of neuromuscular blockade are quite
rapid. When used, succinylcholine may be infused for very
short periods, such as during a brief treatment or procedure
that only lasts a few minutes. However, use of depolarizing
agents in critical care is becoming less common because of the
risk of certain complications, including malignant hyperthermia
as well as hypokalemia. Because it causes complete muscle
paralysis, succinylcholine should always be administered with a
sedative agent that will induce unconsciousness.”
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39. One of the more disturbing or frightening complications for
a patient that may develop with the use of paralytic
medications is
d. anesthesia awareness.
“One of the more disturbing complications that may develop
with the use of paralytic medications is anesthesia awareness,
in which a patient has not been given enough sedative or
anesthetic medications with the neuromuscular blocking agents
and is awake and aware of his surroundings.”
40. True or False: For a patient in intensive care, antipsychotic
medications are often used as a first choice for calming,
even though the patient may have no history of mental
illness.
b. False
“For a patient with no history of mental illness, antipsychotic
medications are often not used as a first choice for calming,
despite their ability to achieve sedation. However, for some
patients in the ICU who are already struggling with delirium
and agitation as a result of psychosis, neuroleptic agents can
control anxiety and can promote sleep.”
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