NR565 Week 1 Study Outline
Many questions are written to assess your clinical application of the material from the
textbook, in real-world scenarios.
Chapter 2: Review of Basic Principles of Pharmacology
How new drugs are developed :
the early part of the drug development process is called the preclinical stage. Identification
of promising drugs and their testing in animals occur during this stage. Pharmaceutical
companies will identify a drug target, starting sometimes with ingredients isolated from a
plant (or organism in the case of antibiotics) with desirable medicinal properties, sometimes
with a molecular target identified in the body to produce the desired response, and
sometimes with a disease in need of treatment.
Preclinical studies are performed on cells, isolated tissues and organs, and in laboratory animals to
identify promising compounds.
During the clinical stage of new drug development, pharmaceutical companies must
establish the safety and effectiveness of new products in humans. Phase I clinical trials
typically establish biological effects as well as safe dosages and pharmacokinetics in a small
number of healthy patients. During phase II clinical trials, new drugs are used to treat
disease in a small number of patients and to establish the potential of the drug to improve
patient outcomes. If the drug still looks promising, phase III clinical trials will compare the
new medication to standard therapy in a larger number of patients studied by at sites across
the country. New drugs must be at least as good as, and it is hoped better than, other
available therapies. Throughout the process, pharmaceutical companies work with the FDA.
During clinical trials, only several thousand patients receive a new drug. During the post-
marketing period, a larger population of patients receives the drug, and sometimes much is
learned about additional adverse effects that occur infrequently with use of the drug.
Drug responses :
There are two basic types of drug responses: quantal and graded. These responses differ in
how they are measured and dictate dosing decisions to achieve the desired effect.
Graded responses are biological effects that can be measured continually up to the
maximum responding capacity of the biological system (Box 2-2). Most drug responses are
graded. For example, changes in blood pressure are measured in millimeters of mercury
(mm Hg), and patients may experience small or large changes in blood pressure following
treatment with drugs. Graded responses are easier to manage clinically because we can see
how each patient responds to a particular dose of medication and, if appropriate, alter the
dosage to achieve a greater or lesser response. So if a patient's blood pressure is too low or
too high when a particular blood pressure medication is administered, we can adjust the
dosage based on the patient's individualized response to the medication. Other graded
resposnse are BP< heart rate, diuresis, bronchodilation, FEV1, pain (Scale ) Coma score
, Quantal resposnes:
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. If we designate
a response as either occurring or absent, it is a quantal response. Prediction of drug dosages
or blood levels that produce quantal effects is much more reliable for a population of
patients than for an individual patient. Data from a population of patients must be used to
establish appropriate doses or blood levels to predict quantal effects in a large number of
patients. For example, oral contraceptive doses are high enough to prevent pregnancy (a
quantal response!) in over 99% of women.
Convulsions, pregnancy, rash, sleep and death are quantal responses
Expressing Drug Responses Pharmacologists show the relationship between dose or concentration
and drug effect using graphs that show the dose-response relationship, or dose-response curve.
Potency is the expression of how much drug is needed to produce a biological response
(Fig. 2-1). Potency describes the difference in concentration or dosage of different drugs
required to produce a similar effect. Drugs that are more potent require a lower dosage or
concentration to produce the same response.
Efficacy expresses the ability of a drug to produce a maximum effect at any dosage.
Efficacy is the expression of the maximum effect a drug can produce.
Intrinsic activity is very similar to efficacy in that it represents the ability of a drug to
produce a large response. Intrinsic activity, however, is used to describe the ability of a drug
to produce a response once it has occupied specific receptors. Some drugs produce the
maximum receptor stimulation once they occupy receptors; their response is limited by how
many drug molecules occupy receptor sites. Other drugs with lower intrinsic activity can
occupy the same number of receptors but will produce a lesser response.
There are challenges to expressing drug selectivity. The most reasonable way to
express selectivity is as a ratio of the dose or concentration producing the undesired effect
to the dose or concentration producing the desired effect. This is the same as determining
how many times the therapeutic dosage needs to be increased to produce the undesired
effect.
The therapeutic index is a special ratio describing drug selectivity. The therapeutic index
is the ratio of the lethal dose of a drug to the therapeutic dose of a drug. There are some
limitations to the therapeutic index: it uses death, a really unacceptable adverse effect, and
it uses data from animal studies. But the therapeutic index provides a fixed comparison for
drug safety.
Receptors (understand how they function and examples): Receptors are the large
molecules, usually proteins, that interact with and mediate the action of drugs. Receptors
are important because they determine the relationship between dose and effect, the
selectivity of drugs, and the actions of pharmacological antagonists.
Receptors provide a theoretical framework for understanding and predicting drug actions
and the relationship between dose (or concentration) and effect.
Ion channel receptors,
Ion channel receptors transmit signals across the cell membrane by increasing the flow of
ions and altering the electrical potential or separation of charged ions across the
membrane. Ion channel receptors can produce responses with a rapid onset and short
duration. For example, activation of ion channels by nicotinic receptors is responsible for
Many questions are written to assess your clinical application of the material from the
textbook, in real-world scenarios.
Chapter 2: Review of Basic Principles of Pharmacology
How new drugs are developed :
the early part of the drug development process is called the preclinical stage. Identification
of promising drugs and their testing in animals occur during this stage. Pharmaceutical
companies will identify a drug target, starting sometimes with ingredients isolated from a
plant (or organism in the case of antibiotics) with desirable medicinal properties, sometimes
with a molecular target identified in the body to produce the desired response, and
sometimes with a disease in need of treatment.
Preclinical studies are performed on cells, isolated tissues and organs, and in laboratory animals to
identify promising compounds.
During the clinical stage of new drug development, pharmaceutical companies must
establish the safety and effectiveness of new products in humans. Phase I clinical trials
typically establish biological effects as well as safe dosages and pharmacokinetics in a small
number of healthy patients. During phase II clinical trials, new drugs are used to treat
disease in a small number of patients and to establish the potential of the drug to improve
patient outcomes. If the drug still looks promising, phase III clinical trials will compare the
new medication to standard therapy in a larger number of patients studied by at sites across
the country. New drugs must be at least as good as, and it is hoped better than, other
available therapies. Throughout the process, pharmaceutical companies work with the FDA.
During clinical trials, only several thousand patients receive a new drug. During the post-
marketing period, a larger population of patients receives the drug, and sometimes much is
learned about additional adverse effects that occur infrequently with use of the drug.
Drug responses :
There are two basic types of drug responses: quantal and graded. These responses differ in
how they are measured and dictate dosing decisions to achieve the desired effect.
Graded responses are biological effects that can be measured continually up to the
maximum responding capacity of the biological system (Box 2-2). Most drug responses are
graded. For example, changes in blood pressure are measured in millimeters of mercury
(mm Hg), and patients may experience small or large changes in blood pressure following
treatment with drugs. Graded responses are easier to manage clinically because we can see
how each patient responds to a particular dose of medication and, if appropriate, alter the
dosage to achieve a greater or lesser response. So if a patient's blood pressure is too low or
too high when a particular blood pressure medication is administered, we can adjust the
dosage based on the patient's individualized response to the medication. Other graded
resposnse are BP< heart rate, diuresis, bronchodilation, FEV1, pain (Scale ) Coma score
, Quantal resposnes:
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. If we designate
a response as either occurring or absent, it is a quantal response. Prediction of drug dosages
or blood levels that produce quantal effects is much more reliable for a population of
patients than for an individual patient. Data from a population of patients must be used to
establish appropriate doses or blood levels to predict quantal effects in a large number of
patients. For example, oral contraceptive doses are high enough to prevent pregnancy (a
quantal response!) in over 99% of women.
Convulsions, pregnancy, rash, sleep and death are quantal responses
Expressing Drug Responses Pharmacologists show the relationship between dose or concentration
and drug effect using graphs that show the dose-response relationship, or dose-response curve.
Potency is the expression of how much drug is needed to produce a biological response
(Fig. 2-1). Potency describes the difference in concentration or dosage of different drugs
required to produce a similar effect. Drugs that are more potent require a lower dosage or
concentration to produce the same response.
Efficacy expresses the ability of a drug to produce a maximum effect at any dosage.
Efficacy is the expression of the maximum effect a drug can produce.
Intrinsic activity is very similar to efficacy in that it represents the ability of a drug to
produce a large response. Intrinsic activity, however, is used to describe the ability of a drug
to produce a response once it has occupied specific receptors. Some drugs produce the
maximum receptor stimulation once they occupy receptors; their response is limited by how
many drug molecules occupy receptor sites. Other drugs with lower intrinsic activity can
occupy the same number of receptors but will produce a lesser response.
There are challenges to expressing drug selectivity. The most reasonable way to
express selectivity is as a ratio of the dose or concentration producing the undesired effect
to the dose or concentration producing the desired effect. This is the same as determining
how many times the therapeutic dosage needs to be increased to produce the undesired
effect.
The therapeutic index is a special ratio describing drug selectivity. The therapeutic index
is the ratio of the lethal dose of a drug to the therapeutic dose of a drug. There are some
limitations to the therapeutic index: it uses death, a really unacceptable adverse effect, and
it uses data from animal studies. But the therapeutic index provides a fixed comparison for
drug safety.
Receptors (understand how they function and examples): Receptors are the large
molecules, usually proteins, that interact with and mediate the action of drugs. Receptors
are important because they determine the relationship between dose and effect, the
selectivity of drugs, and the actions of pharmacological antagonists.
Receptors provide a theoretical framework for understanding and predicting drug actions
and the relationship between dose (or concentration) and effect.
Ion channel receptors,
Ion channel receptors transmit signals across the cell membrane by increasing the flow of
ions and altering the electrical potential or separation of charged ions across the
membrane. Ion channel receptors can produce responses with a rapid onset and short
duration. For example, activation of ion channels by nicotinic receptors is responsible for
