PHARM NR 508 MIDTERM STUDY GUIDE
Midterm Outline
1. Chapter 1: The Role of the Advanced Practice Nurse as Prescriber
Roles and responsibilities of APRN prescribers
Prescriptive authority is different in all states. Responsibility of final decision and which
drug to use is the PRESCRIBER’s. Nurse Practitioner Journal releases legislative
updates every January. IOM called for removing all practice barriers and allowing NPs
to practice to their full scope of practice based upon education and training.
Clinical judgement in Prescribing
Prescribing a drug results from clinical judgment based on a thorough assessment of
the patient and the patient's environment, the determination of medical and nursing
diagnoses, a review of potential alternative therapies, and specific knowledge about the
drug chosen and the disease process it is designed to treat. In general, the best therapy
is the least invasive, least expensive, and least likely to cause adverse reactions.
Frequently, the best choice is to have lifestyle, nonpharmacological, and
pharmacological therapies working together. When the choice of treatment options is a
drug, several questions arise.
Collaboration with other providers-
No one member of the health-care team can provide high-quality care without
collaborating with other team members. They most often collaborate with physicians,
pharmacists, podiatrists, mental health specialists, therapists, and other providers,
including APRNs who are not NPs, physician assistants, and other nurses
Autonomy and Prescriptive authority
Long hard battle to obtain rights, with a long road ahead. Call to professionalism and
excellence.
2. Chapter 2: Review of Basic Principles of Pharmacology
Metabolism: Metabolism & Half Life
Pharmacogenomics is the study of how individual variations in drug targets or
metabolism affect drug therapy. Pharmacogenomic studies can identify factors that are
responsible for beneficial or adverse effects in individual patients.
Metabolism is the process of changing one chemical into another, and the process
usually either creates or uses energy. Metabolism of drugs can occur in every biological
tissue, but it occurs mostly in the smooth endoplasmic reticulum of cells in the liver. The
liver is a major organ for drug metabolism because it contains high amounts of drug-
metabolizing enzymes and because it is the first organ encountered by drugs once they
are absorbed from the gastrointestinal tract. Metabolism by the liver following oral
,administration is called first-pass metabolism and is important in determining whether a
drug can be orally administered.
The rate of drug metabolism depends on the blood levels of drug in relation to the
affinity of the drug for its metabolism enzymes. Most drugs are present at
concentrations below their Km for metabolism (the concentration at which metabolism is
half of maximum). Under these conditions, metabolism is related to drug concentration
so that a fixed fraction of drug is metabolized per hour. This is called first-order
metabolism and is characterized by a half-life, the time period over which the drug
concentration will decrease by half. So, blood levels decrease 50% in one half-life, 75%
in two half-lives, and 87.5% in three half-lives. As a general rule, drugs tend to be
administered at dosing intervals that are close to their half-life.
Drug Responses
Before a medication can produce a response, it often must overcome homeostatic
mechanisms. Drug effects depend on the amount of drug that is administered. If the
dose is below that needed to produce a measurable biological effect, then no response
is observed; any effects of the drug are not sufficient to overcome homeostatic
capabilities. If an adequate dose is administered, there will be a measurable biological
response. With an even higher dose, we may see a greater response. At some point,
however, we will be unwilling to increase the dosage further, either because we have
already achieved a desired or maximum response or because we are concerned about
producing additional responses that might harm the patient. Because pharmacology is
the study of substances that produce biological responses, measurement of what
happens when we administer medications is important. We will need ways to express
and compare drug activity so that we can describe the action or effect of drugs,
compare the effects of different drugs, and predict their pharmacological effects.
It is simplest to think that drug responses are directly related to the fraction of receptors
that are occupied, or bound, by a drug, so that 50% of the maximum response occurs at
a blood level or concentration at which a drug occupies 50% of its receptors. But
depending on the number of receptors in a tissue and the ability of drug binding to
produce a change in the receptor conformation, far fewer receptors (less than 10%)
may be needed to produce a maximum effect.
2 types:
1. Quantal-Quantal effects are responses that may or may not occur (Box 2-3). For
example, seizures either occur or they do not. The same is true for pregnancy, sleep,
and death.
2. Graded- biological effects that can be measured continually up to the maximum
responding capacity of the biological system. Most drug responses are graded.
• Blood pressure
• Heart rate
• Diuresis
, • Bronchodilation
• FEV1
• Pain (scale 1–10)
• Coma score
Receptors: agonists, antagonists
Antagonists are drugs that occupy receptors without stimulating them. Antagonists
occupy a receptor site and prevent other molecules, such as agonists, from occupying
the same site and producing a response. Antagonists produce no direct response. The
response we see following administration of antagonists results from their inhibiting
receptor stimulation by agonists. For example, beta blockers such as propranolol and
atenolol act as antagonists at the beta-adrenoceptor. Adrenergic nerve activity can raise
heart rate, and patients with high heart rates experience a significant drop in heart rate
following administration of beta blockers. The same administration may have little effect
on patients who lack adrenergic nerve activity and already have a lower heart rate. The
effect of antagonists is dependent on the background receptor activity that it can block.
Antagonists produce a shift in the concentration-effect relationship for agonists acting at
that same specific receptor as the antagonist; they make agonists for the same receptor
appear less potent. The effect of an antagonist is dependent on its blood levels and its
affinity for the receptor. Most antagonists in clinical use are competitive reversible
antagonists, and it is possible to overcome the antagonist effects with higher
concentrations of the competing agonist. A very small number of antagonist drugs (e.g.,
echothiophate, phenoxybenzamine) act by irreversibly binding to the receptor; their
antagonism remains until new receptors can be produced by the cell.
Partial agonists are drugs that have properties in between those of full agonists and
antagonists. Partial agonists bind to receptors but when they occupy the receptor sites,
they stimulate only some of the receptors. This is sometimes called intrinsic activity. So
they can act as part agonist and part antagonist. Partial agonists would require all of the
available receptors to produce their full response, and the maximum response for a
partial agonist is less than that for a full agonist. The beta blockers acebutolol,
penbutolol, and pindolol are partial agonists. Administration can block the effects of
adrenergic nerves on heart rate, but partial agonist activity keeps heart rate from falling
too low, as might occur following administration of a pure beta-adrenoceptor antagonist.
So beta blockers with intrinsic sympathomimetic activity control heart rate within a range
that is higher than the response to an antagonist and lower than the response to an
agonist.
Pharmacokinetics:
Absorption- determined by the route of administration> IV is best and most absorbed.
Oral is most common. If oral, then the medication must pass through the stomach,
intestines, then to the Liver. This is called the first-pass metabolism. Because not all of
the administered dosage may be dissolved or absorbed or survive liver passage, only a
fraction of an administered dosage makes it to the bloodstream. This percentage of the
, administered dose that does enter the bloodstream is called the bioavailability of the
dosage form. Bioavailability can range from less than 10% to more than 90% for oral
dosing. When the bioavailability of an oral preparation is low, a higher dose will be given
so that the amounts reaching the bloodstream are similar. For example, an oral dose of
500 mg of ciprofloxacin can be substituted for a 400 mg IV dose; ciprofloxacin has
about 80% oral bioavailability.
Distribution-After a drug is absorbed, it still must reach its site of action to produce an
effect. The process of drugs moving throughout the body is called distribution.
Distribution of drugs can occur by transfer through the bloodstream and passive
diffusion, or their distribution can be promoted or limited by the presence of transport
systems that may selectively transport or exclude drugs based on size, charge, or
chemical structure. Diffusion can influence the action of drugs; drugs can be effective
only if they reach their site of action in adequate concentrations before they are
metabolized.
Protein Binding-Drugs passively diffuse and distribute when they are unbound and
uncharged. Drugs can bind to a variety of proteins that are present in the bloodstream.
These are often called plasma proteins. Many plasma proteins are produced in the liver,
and their presence in the blood reflects liver function, nutritional status, and the effect of
aging and disease. Albumin is a major protein in the blood and is measured as part of a
typical blood analysis. Albumin has a molecular weight of 66,500 and is too large to be
excreted by the kidneys in healthy patients, although in renal disease albumin is lost in
the urine. Other plasma proteins include alpha-1-acid glycoprotein, cortisol-binding
globulin, sex hormone–binding globulin, and lipoproteins.
Binding to plasma proteins serves several important functions. Drugs bound to plasma
proteins can freely circulate in the bloodstream rather than be distributed by passive
diffusion from their site of absorption, so plasma protein binding helps normalize
concentrations throughout the body. Drugs that are bound to plasma protein can be
protected from metabolism in the liver and from excretion by the kidneys, so plasma
protein binding can extend the period of time that drugs remain in the body.
Plasma proteins can be altered by disease states. Patients with poor nutrition may not
have the protein building blocks to produce adequate amounts of plasma proteins.
Patients with cancer can be undernourished as the cancer cells feed off the body.
Patients with liver disease may lack the cellular function to produce one or more of the
plasma proteins. Plasma proteins can be affected by myocardial infarction, stress, and
infection as well.
Plasma protein binding has advantages and disadvantages. As mentioned above,
binding to plasma proteins can protect drugs from metabolism and excretion, extending
the time the drugs remain in the body. But remember the general principle that drug
action occurs through free, unbound drug. Protein binding, which may include binding to
proteins that are not in the plasma, also prevents the interaction of drug molecules with
their site of action. Plasma protein binding creates a reservoir of bound drug molecules
that can unbind at any time to interact with drug receptors and produce responses.
Midterm Outline
1. Chapter 1: The Role of the Advanced Practice Nurse as Prescriber
Roles and responsibilities of APRN prescribers
Prescriptive authority is different in all states. Responsibility of final decision and which
drug to use is the PRESCRIBER’s. Nurse Practitioner Journal releases legislative
updates every January. IOM called for removing all practice barriers and allowing NPs
to practice to their full scope of practice based upon education and training.
Clinical judgement in Prescribing
Prescribing a drug results from clinical judgment based on a thorough assessment of
the patient and the patient's environment, the determination of medical and nursing
diagnoses, a review of potential alternative therapies, and specific knowledge about the
drug chosen and the disease process it is designed to treat. In general, the best therapy
is the least invasive, least expensive, and least likely to cause adverse reactions.
Frequently, the best choice is to have lifestyle, nonpharmacological, and
pharmacological therapies working together. When the choice of treatment options is a
drug, several questions arise.
Collaboration with other providers-
No one member of the health-care team can provide high-quality care without
collaborating with other team members. They most often collaborate with physicians,
pharmacists, podiatrists, mental health specialists, therapists, and other providers,
including APRNs who are not NPs, physician assistants, and other nurses
Autonomy and Prescriptive authority
Long hard battle to obtain rights, with a long road ahead. Call to professionalism and
excellence.
2. Chapter 2: Review of Basic Principles of Pharmacology
Metabolism: Metabolism & Half Life
Pharmacogenomics is the study of how individual variations in drug targets or
metabolism affect drug therapy. Pharmacogenomic studies can identify factors that are
responsible for beneficial or adverse effects in individual patients.
Metabolism is the process of changing one chemical into another, and the process
usually either creates or uses energy. Metabolism of drugs can occur in every biological
tissue, but it occurs mostly in the smooth endoplasmic reticulum of cells in the liver. The
liver is a major organ for drug metabolism because it contains high amounts of drug-
metabolizing enzymes and because it is the first organ encountered by drugs once they
are absorbed from the gastrointestinal tract. Metabolism by the liver following oral
,administration is called first-pass metabolism and is important in determining whether a
drug can be orally administered.
The rate of drug metabolism depends on the blood levels of drug in relation to the
affinity of the drug for its metabolism enzymes. Most drugs are present at
concentrations below their Km for metabolism (the concentration at which metabolism is
half of maximum). Under these conditions, metabolism is related to drug concentration
so that a fixed fraction of drug is metabolized per hour. This is called first-order
metabolism and is characterized by a half-life, the time period over which the drug
concentration will decrease by half. So, blood levels decrease 50% in one half-life, 75%
in two half-lives, and 87.5% in three half-lives. As a general rule, drugs tend to be
administered at dosing intervals that are close to their half-life.
Drug Responses
Before a medication can produce a response, it often must overcome homeostatic
mechanisms. Drug effects depend on the amount of drug that is administered. If the
dose is below that needed to produce a measurable biological effect, then no response
is observed; any effects of the drug are not sufficient to overcome homeostatic
capabilities. If an adequate dose is administered, there will be a measurable biological
response. With an even higher dose, we may see a greater response. At some point,
however, we will be unwilling to increase the dosage further, either because we have
already achieved a desired or maximum response or because we are concerned about
producing additional responses that might harm the patient. Because pharmacology is
the study of substances that produce biological responses, measurement of what
happens when we administer medications is important. We will need ways to express
and compare drug activity so that we can describe the action or effect of drugs,
compare the effects of different drugs, and predict their pharmacological effects.
It is simplest to think that drug responses are directly related to the fraction of receptors
that are occupied, or bound, by a drug, so that 50% of the maximum response occurs at
a blood level or concentration at which a drug occupies 50% of its receptors. But
depending on the number of receptors in a tissue and the ability of drug binding to
produce a change in the receptor conformation, far fewer receptors (less than 10%)
may be needed to produce a maximum effect.
2 types:
1. Quantal-Quantal effects are responses that may or may not occur (Box 2-3). For
example, seizures either occur or they do not. The same is true for pregnancy, sleep,
and death.
2. Graded- biological effects that can be measured continually up to the maximum
responding capacity of the biological system. Most drug responses are graded.
• Blood pressure
• Heart rate
• Diuresis
, • Bronchodilation
• FEV1
• Pain (scale 1–10)
• Coma score
Receptors: agonists, antagonists
Antagonists are drugs that occupy receptors without stimulating them. Antagonists
occupy a receptor site and prevent other molecules, such as agonists, from occupying
the same site and producing a response. Antagonists produce no direct response. The
response we see following administration of antagonists results from their inhibiting
receptor stimulation by agonists. For example, beta blockers such as propranolol and
atenolol act as antagonists at the beta-adrenoceptor. Adrenergic nerve activity can raise
heart rate, and patients with high heart rates experience a significant drop in heart rate
following administration of beta blockers. The same administration may have little effect
on patients who lack adrenergic nerve activity and already have a lower heart rate. The
effect of antagonists is dependent on the background receptor activity that it can block.
Antagonists produce a shift in the concentration-effect relationship for agonists acting at
that same specific receptor as the antagonist; they make agonists for the same receptor
appear less potent. The effect of an antagonist is dependent on its blood levels and its
affinity for the receptor. Most antagonists in clinical use are competitive reversible
antagonists, and it is possible to overcome the antagonist effects with higher
concentrations of the competing agonist. A very small number of antagonist drugs (e.g.,
echothiophate, phenoxybenzamine) act by irreversibly binding to the receptor; their
antagonism remains until new receptors can be produced by the cell.
Partial agonists are drugs that have properties in between those of full agonists and
antagonists. Partial agonists bind to receptors but when they occupy the receptor sites,
they stimulate only some of the receptors. This is sometimes called intrinsic activity. So
they can act as part agonist and part antagonist. Partial agonists would require all of the
available receptors to produce their full response, and the maximum response for a
partial agonist is less than that for a full agonist. The beta blockers acebutolol,
penbutolol, and pindolol are partial agonists. Administration can block the effects of
adrenergic nerves on heart rate, but partial agonist activity keeps heart rate from falling
too low, as might occur following administration of a pure beta-adrenoceptor antagonist.
So beta blockers with intrinsic sympathomimetic activity control heart rate within a range
that is higher than the response to an antagonist and lower than the response to an
agonist.
Pharmacokinetics:
Absorption- determined by the route of administration> IV is best and most absorbed.
Oral is most common. If oral, then the medication must pass through the stomach,
intestines, then to the Liver. This is called the first-pass metabolism. Because not all of
the administered dosage may be dissolved or absorbed or survive liver passage, only a
fraction of an administered dosage makes it to the bloodstream. This percentage of the
, administered dose that does enter the bloodstream is called the bioavailability of the
dosage form. Bioavailability can range from less than 10% to more than 90% for oral
dosing. When the bioavailability of an oral preparation is low, a higher dose will be given
so that the amounts reaching the bloodstream are similar. For example, an oral dose of
500 mg of ciprofloxacin can be substituted for a 400 mg IV dose; ciprofloxacin has
about 80% oral bioavailability.
Distribution-After a drug is absorbed, it still must reach its site of action to produce an
effect. The process of drugs moving throughout the body is called distribution.
Distribution of drugs can occur by transfer through the bloodstream and passive
diffusion, or their distribution can be promoted or limited by the presence of transport
systems that may selectively transport or exclude drugs based on size, charge, or
chemical structure. Diffusion can influence the action of drugs; drugs can be effective
only if they reach their site of action in adequate concentrations before they are
metabolized.
Protein Binding-Drugs passively diffuse and distribute when they are unbound and
uncharged. Drugs can bind to a variety of proteins that are present in the bloodstream.
These are often called plasma proteins. Many plasma proteins are produced in the liver,
and their presence in the blood reflects liver function, nutritional status, and the effect of
aging and disease. Albumin is a major protein in the blood and is measured as part of a
typical blood analysis. Albumin has a molecular weight of 66,500 and is too large to be
excreted by the kidneys in healthy patients, although in renal disease albumin is lost in
the urine. Other plasma proteins include alpha-1-acid glycoprotein, cortisol-binding
globulin, sex hormone–binding globulin, and lipoproteins.
Binding to plasma proteins serves several important functions. Drugs bound to plasma
proteins can freely circulate in the bloodstream rather than be distributed by passive
diffusion from their site of absorption, so plasma protein binding helps normalize
concentrations throughout the body. Drugs that are bound to plasma protein can be
protected from metabolism in the liver and from excretion by the kidneys, so plasma
protein binding can extend the period of time that drugs remain in the body.
Plasma proteins can be altered by disease states. Patients with poor nutrition may not
have the protein building blocks to produce adequate amounts of plasma proteins.
Patients with cancer can be undernourished as the cancer cells feed off the body.
Patients with liver disease may lack the cellular function to produce one or more of the
plasma proteins. Plasma proteins can be affected by myocardial infarction, stress, and
infection as well.
Plasma protein binding has advantages and disadvantages. As mentioned above,
binding to plasma proteins can protect drugs from metabolism and excretion, extending
the time the drugs remain in the body. But remember the general principle that drug
action occurs through free, unbound drug. Protein binding, which may include binding to
proteins that are not in the plasma, also prevents the interaction of drug molecules with
their site of action. Plasma protein binding creates a reservoir of bound drug molecules
that can unbind at any time to interact with drug receptors and produce responses.
