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Textbook Notes from Ch. 2-5

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Department
Psychology
Course Code
PSYC62H3
Professor
Suzanne Erb

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Chapter 2- Basic Principles of Pharmacology
In general, the definition of a drug is a chemical that affects one or more biological
processes.
Endogenous substances are chemicals that originate or are produced within an
organism for the use of normal biological processes. Exogenous substances are
drugs.
The most important determinants of a drugs effects are its concentration at the site
of action as well as the rate of accumulation at that point.
Drug dose is expressed in terms of unit of drug per unit of body weight of the
organism. Drug dosage refers to the administrations of the drug per unit of time.
DRUGS AND RECEPTORS:
Pharmacodynamics refers to the biochemical and physiological effects of drugs
and their mechanisms of action.
Receptors, which are fairly large molecules, comprise of sites at which biologically
active chemicals (ligands) induce their effects.
Affinity refers to the relative capacity of a compound to maintain contact with or be
bound to a receptor.
Efficacy refers to the degree of biological activity or relative a capability of a
compound to activate the receptor after being bound to it.
Agonists are compounds with both an affinity for and capability if activating a
receptor (efficacy). There are 4 types of agonists:
Indirect- a drug that doesnt bind to the receptor itself but enhances the
amount of the endogenous ligand to bind to a receptor.
Partial- drugs that display intermediate efficacy in receptor activation between
the efficacy of a full agonist and an antagonist. E.g. when these types of drugs bind
to a receptor they hinder the full agonists ability to bind completely to the receptor.
Hence, reducing the effect of that full agonist but not eliminating it; can be useful in
schizophrenia where there is too much receptor activity. However, there is a
disadvantage to these types of agonists; since they block the full activity of the full
agonist they may induce prolonged inactivity of the receptor which can cause some
side effects. Recently though, a drug known as aripiprazole (abilify) partially
blocks dopamine from binding to its receptors but still stimulates the receptors to a
certain degree do that the side effects of prolonged inactivity dont occur.
Inverse- a drug that appears to act through the same receptor as an agonist but
produces effects opposite to those of the agonist.
Mixed agonist-antagonist- when a drug acts as an agonist by itself, but blocks
the activity of another agonist in the same system.
There are two broad classes of receptors: ionotropic and metabotropic
receptors.
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Ionotropic- produce rapid changes in neuronal activity via a pore that allows for
the flow of certain ions that alter the excitability of the neuron. Most are composed
of five subunits (, , , ) which contain binding sites that change the conformation
of the receptor to increase of decrease the passage of ions through the channel.
Metabotropic- produce relatively slow-developing and long-lasting effects on
neurons. They are composed of a long string of amino acids that weave in and out of
the neuronal membrane and are attached to a G-protein. Neuronal transmission
occurs in these receptors via the G-protein and production of second messengers.
There are two main factors that effect ligand binding: the ligands molecular shape
and the location of positive and negative electrical charges.
Varied responsiveness to drugs in the human race is due to polymorphisms within
multiple genes and those in the discipline of pharmacogenetics attempt to
discover differential effects of drugs in variations of genes.
Those in the discipline of pharmacogenomics attempt to discover differential
effects of compounds on gene expression among all genes that expressed in humans.
DOSE-RESPONSE RELATIONSHIPS:
Dose-response function- expresses the relationship between the dose
administered and the response observed.
Active placebo- a substance that mimics some of the noticeable physiological
characteristics of the drug being evaluated but without the effects on the brain that
the researcher is interested in.
Biphasic functions are those that display that substantial concentrations of a drug
may cause even less stimulation in the subject than if no drug was administered at
all.
Therapeutic window- a specific range of drug concentration at which the optimal
therapeutic effect in patients can be obtained.
The plasma half-life of drugs can be an important factor in determining the
desirable drug doses and the time interval in which they should be administered to
maintain the optimal therapeutic concentration level.
In summary several observations can be made regarding dose-response
relationships:
One cannot say what effect a drug will have unless one specifies what the dose of
the drug is(and in what species).
There may be many different dose-response functions for any particular drug,
depending on the type of response monitored.
There is no typical dose-response function.
Larger doses of a drug do not necessarily mean a greater magnitude of response.
www.notesolution.com
There are two general types of dose-response functions: one that describes the
degree of a specified response and one that describes the percentage of organisms
displaying the specified response.
Median effective dose- dose of the drug that produces the desired, and generally
therapeutic effect in 50% of the individuals tested (ED50).
Median lethal dose- dose that causes death in 50% of the population(LD50).
Therapeutic index- the relative margin of safety between the ED50 and the LD50.
You generally want the LD50 to be considerably larger than that of the ED50. Drugs
that have a therapeutic index around 100 are usually considered safe and the ones
with a therapeutic index of 10 or below are considered hazardous.
Hyperreactors- individuals who over-respond to the ED50 of a drug
Hyporeactors- those who under-respond to the ED50 of a drug.
Idiosyncrasy- used to describe and unusual response or unexpected effect of the
drug.
PROPERTIES OF DRUGS:
Efficacy- refers to the degree to which as drug is able to induce a given effect
relative to the maximal response attainable in the system measured.
Potency- refers to the relative pharmacological activity of a compound or the
relative ability of a drug to produce a particular effect.
Sensitization- an enhanced response to a drug due to previous exposure; but the
drug is given at intervals far enough apart so that the response cannot be attributed
to drug accumulation.
Tolerance- where the effects noted with initials drug exposures are not evidenced
or are greatly reduced after chronic use.
DRUG INTERACTIONS:
Antagonism- the situation in which the response to one drug is decreased in
response to the presence of another drug.
Synergism- doses of two drugs taken together produce a greater effect than either
drug dose produces alone.
Competitive antagonist- where a drug has affinity of a receptor but has little to
no efficacy, thereby preventing a full agonist from producing its effects. Once a
competitive antagonist dissociates from the receptor the binding site becomes
available again for binding.
Non-competitive antagonist- a situation in which an antagonist binds so tightly
to a receptor that it is unable to dissociate from the binding site.
Physiological antagonism- a form of drug interaction in which two drugs (may
either be pharmacological antagonists or pharmacological agonists) act at two
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Description
Chapter 2- Basic Principles of Pharmacology In general, the definition of a drug is a chemical that affects one or more biological processes. Endogenous substances are chemicals that originate or are produced within an organism for the use of normal biological processes. Exogenous substances are drugs. The most important determinants of a drugs effects are its concentration at the site of action as well as the rate of accumulation at that point. Drug dose is expressed in terms of unit of drug per unit of body weight of the organism. Drug dosage refers to the administrations of the drug per unit of time. DRUGS AND RECEPTORS: Pharmacodynamics refers to the biochemical and physiological effects of drugs and their mechanisms of action. Receptors, which are fairly large molecules, comprise of sites at which biologically active chemicals (ligands) induce their effects. Affinity refers to the relative capacity of a compound to maintain contact with or be bound to a receptor. Efficacy refers to the degree of biological activity or relative a capability of a compound to activate the receptor after being bound to it. Agonists are compounds with both an affinity for and capability if activating a receptor (efficacy). There are 4 types of agonists: Indirect- a drug that doesnt bind to the receptor itself but enhances the amount of the endogenous ligand to bind to a receptor. Partial- drugs that display intermediate efficacy in receptor activation between the efficacy of a full agonist and an antagonist. E.g. when these types of drugs bind to a receptor they hinder the full agonists ability to bind completely to the receptor. Hence, reducing the effect of that full agonist but not eliminating it; can be useful in schizophrenia where there is too much receptor activity. However, there is a disadvantage to these types of agonists; since they block the full activity of the full agonist they may induce prolonged inactivity of the receptor which can cause some side effects. Recently though, a drug known as aripiprazole (abilify) partially blocks dopamine from binding to its receptors but still stimulates the receptors to a certain degree do that the side effects of prolonged inactivity dont occur. Inverse- a drug that appears to act through the same receptor as an agonist but produces effects opposite to those of the agonist. Mixed agonist-antagonist- when a drug acts as an agonist by itself, but blocks the activity of another agonist in the same system. There are two broad classes of receptors: ionotropic and metabotropic receptors. www.notesolution.com
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