Class Notes (923,063)
CA (543,058)
UTSC (32,990)
Psychology (8,026)
PSYC62H3 (155)
Lecture

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13 Pages
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Department
Psychology
Course Code
PSYC62H3
Professor
Suzanne Erb

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Chapter 2
Basic Principles of Pharmacology
Drug (definition)
-A drug originally referred to any substance used in chemistry or medical practice.
-Any agent used in medicine or any ingredient in medicines.
-Synonym for a narcotic agent or illicit substance
None of this actually defines what a drug is.
-It is a chemical that affects one or more biological processes.
-However, not all chemicals that affect biological processes are considered drugs.
-Substances that are commonly used for nutritional purposes eg salt, vitamins and
minerals etc are generally considered drugs, because they are necessary for carrying out
the normal biological functions of the body.
-Chemicals originating or produced within an organism that are used to carry out the
normal bioligcal functions in the body are not usually thought of as drugs= endogenous
substances
-Drugs are exogenous substances
-Biochemists and neuroscientists have isolated a variety of substances found to be
important in the function of the body, have extracted or synthesized them, and have
administered them in purified form to reverse neurological deficits. The use of L-dopa, a
chemical necessary for the production of an important bran chemical, in the treatment of
Parkinson’s disease and L-dopa is a drug.
-Consider Aspirin, which is an effective treatment for several kinds of pain. It is believed
that most of its action is due to its ability to inhibit the activity of prostaglandins, a class
of chemicals found throughout the body that play a vital role in almost every life process,
including respiration, reproduction, and circulation.
-From a pharmacological perspective, it seems most appropriate to define a DRUG
as a non-food chemical that alters one of more normal biological processes in living
organism.
-The most important factors in determining a drug’s effect are the concentration of the
drug at its site(s) of action and the rate of accumulation there.
-These factors, in turn, can be affected by many other factors, most commonly the drug
dose- that is, the quantity of drug administered at one time.
-Dose of drug is expressed in terms of unit of drug per unit of body weight of the
organism, such as milligrams per kilogram.
Drug dosage refers to administrations of the drug per unit of time, such as 10mg/kg four
times a day for three days
-We will see that there is higher concentration in a rat than in a human and will exert a
much greater effect in that rat than in the human.
-There can be large differences in the rate and degree of drug’s absorption, distribution,
metabolization, and excretion across species and in different ages.
-Also, animal species differ with respect to the amounts of tissue for drug storage.
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-The fact that drugs are not generally dispersed evenly throughout the body and are
usually taken up in tissues other than the site of drug action can affect the drug’s action.
Drugs and Receptors
-Pharmacodynamics refers to the biochemical and physiological effects of drugs and
their mechanisms of action.
-The vast majority of durgs act very specific receptor sites.
-These are fairly large molecules usually proteins which comprise the sites wehre
biologically active chemicals of the body often called ligands, induce their effects.
-Eg. Insulin, testosterone, estrogen, adrenaline, neurotransmitter, neurohormones, and
neuromodulators.
-If the receptor then starts some biological activity, it is said to beactivated”
-In most cases, binding is temporary, or reversible, and when the chemical leaves the
receptor, it is said todissociate” from the receptor.
-Affinity refers to the relative capacity of the compound to maintain contact with or be
bound to a receptor.
-Efficacy refers to the degree of biological activity or relative capability of a compound
to activate the receptor after being bound to it.
-It should be noted that a compound’s efficacy and affinity are generally independent of
each other, although without receptor affinity, a compound is unlikely to exhibit efficacy.
-It should be noted that each neuroactive ligand in the nervous system generally had
several different types of receptors on which it acts, each with its own separate function.
-Drugs may mimic the actions of a particular ligand at one of more of its receptor types
and may have no actions or act in an opposing fashion at others.
-Agonist are compounds with both an affinity for and a capability of activating a
receptor=has efficacy.
-If the compound activating the receptor is endogenour (naturally occurring in the body,
it is typically called a ligand.
-If it is exogenous (produced outside the body), it is a drug and sometimes drugs can be
referred to as ligands.
-Both drugs and ligands can be agonists.
-In some cases, drugs do not combine directly with a receptor, but enhance the amount of
the endogenous ligands available for the receptor which is called an indirect agonists.
-Some drugs exert their effects by blocking the action of agonists and are thus called
antagonists.
-Partial agonists are drugs that display intermediate efficacy in receptor activation
between the efficacy of a full agonist and an antagonist. A partial agonist may actually
have a greater affinity for a particular receptor than a full agonist. It cannot achieve the
maximal response of the full agnonist at those receptors, it can reduce the effects of a full
agonist, because it reduces the full agonist’s accessibility to its receptors.
-Thus, partial agnosits may be therapeutically useful in conditions in which one wants to
reduce excessive receptor activity but without totally eliminating receptor activity.
www.notesolution.com
Eg. Aripiprazole prevents dopamine from binding to its receptors and eliminates the
excessive stimulation, this is a antipsychotic drugs to treat Schizophrenia.
-Drugs may produce complex patterns of response, which has led to the terms inverse
agonist and mixed agonist-antagonists eg. Opiates and benzodiazepines
-An inverse agonist is defined as a drug that appears to act through the same receptor as
an agonist but produces effects opposite to those of the agonists; thus, it can also be
viewed as a type of agonist.
-A mixed agonist-antagonists is evidenced when a drug acts as an agonist by itself, but
blocks the activity of another agonist in the same system.
-Functionally, mixed agonist-antagonists and partial agonists have similar properties; that
is, by themselves they exert agonist effects but are capable of reducing the effects of full
agonists in the same system.
-The basic difference appears to be that a partial agonist works on the same receptors as
full agonist, but because of its lower maximal effect and its ability to reduce the full
agonist’s access to those receptors, the maximal effect of the full agonists is reduced if
the two are given together.
-In contrast, a mixed agonist-antagonist may be a full agonist at one type of receptor and
a complete antagonist at another type of receptor: thus when combined with a full agonist
that activated both types of receptors, the mixed agonist-antagonist blocks some of the
effects that would normally occur with the full agonist alone.
-One view of the receptor is that it consists of one element comprising a “binding” site
and another element comprising an “effector” site.
-This model very easily handles cases in which a drug with a molecular structure
compatible with both sites is an agonist from binding and thus prevents its actions: that is,
the later drug acts as an antagonist.
-However, this model has difficulties in explaining some phenomena, most notably
inverse agonism and mixed agnonism-antagonism.
-Another model proposes that receptors exist in an active and in inactive configuration,
each of which is capable of combining with a drug molecule.
-Whether a drug acts as an antagonist or agonist will be determined b the ratio of the
drug’s affinity for the two configuration.
Eg. A drug may combine with the inactive configuration, preventing the receptor from
attaining its active configuration, so that the drug acts as an antagonist.
-These and other models of receptors are subject to changes as we find more information
-There are two classes of receptors
-The first class of receptors, which produce very rapid changes in neuronal activity, are
called ionotropic receptors
-Most are composed of five subunits made up of- ( , , , ) which are comprised of
strings of amino acids.
-These subunits form an internal pore or channel through which specific types of ions
(electrically charged ion eg. Na, K+ etc.) can flow to alter the excitability of the neuron.
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Description
Chapter 2 Basic Principles of Pharmacology Drug (definition) -A drug originally referred to any substance used in chemistry or medical practice. -Any agent used in medicine or any ingredient in medicines. -Synonym for a narcotic agent or illicit substance None of this actually defines what a drug is. -It is a chemical that affects one or more biological processes. -However, not all chemicals that affect biological processes are considered drugs. -Substances that are commonly used for nutritional purposes eg salt, vitamins and minerals etc are generally considered drugs, because they are necessary for carrying out the normal biological functions of the body. -Chemicals originating or produced within an organism that are used to carry out the normal bioligcal functions in the body are not usually thought of as drugs= endogenous substances -Drugs are exogenous substances -Biochemists and neuroscientists have isolated a variety of substances found to be important in the function of the body, have extracted or synthesized them, and have administered them in purified form to reverse neurological deficits. The use of L-dopa, a chemical necessary for the production of an important bran chemical, in the treatment of Parkinsons disease and L-dopa is a drug. -Consider Aspirin, which is an effective treatment for several kinds of pain. It is believed that most of its action is due to its ability to inhibit the activity of prostaglandins, a class of chemicals found throughout the body that play a vital role in almost every life process, including respiration, reproduction, and circulation. -From a pharmacological perspective, it seems most appropriate to define a DRUG as a non-food chemical that alters one of more normal biological processes in living organism. -The most important factors in determining a drugs effect are the concentration of the drug at its site(s) of action and the rate of accumulation there. -These factors, in turn, can be affected by many other factors, most commonly the drug dose- that is, the quantity of drug administered at one time. -Dose of drug is expressed in terms of unit of drug per unit of body weight of the organism, such as milligrams per kilogram. Drug dosage refers to administrations of the drug per unit of time, such as 10mgkg four times a day for three days -We will see that there is higher concentration in a rat than in a human and will exert a much greater effect in that rat than in the human. -There can be large differences in the rate and degree of drugs absorption, distribution, metabolization, and excretion across species and in different ages. -Also, animal species differ with respect to the amounts of tissue for drug storage. www.notesolution.com-The fact that drugs are not generally dispersed evenly throughout the body and are usually taken up in tissues other than the site of drug action can affect the drugs action. Drugs and Receptors -Pharmacodynamics refers to the biochemical and physiological effects of drugs and their mechanisms of action. -The vast majority of durgs act very specific receptor sites. -These are fairly large molecules usually proteins which comprise the sites wehre biologically active chemicals of the body often called ligands, induce their effects. -Eg. Insulin, testosterone, estrogen, adrenaline, neurotransmitter, neurohormones, and neuromodulators. -If the receptor then starts some biological activity, it is said to be activated -In most cases, binding is temporary, or reversible, and when the chemical leaves the receptor, it is said to dissociate from the receptor. -Affinity refers to the relative capacity of the compound to maintain contact with or be bound to a receptor. -Efficacy refers to the degree of biological activity or relative capability of a compound to activate the receptor after being bound to it. -It should be noted that a compounds efficacy and affinity are generally independent of each other, although without receptor affinity, a compound is unlikely to exhibit efficacy. -It should be noted that each neuroactive ligand in the nervous system generally had several different types of receptors on which it acts, each with its own separate function. -Drugs may mimic the actions of a particular ligand at one of more of its receptor types and may have no actions or act in an opposing fashion at others. -Agonist are compounds with both an affinity for and a capability of activating a receptor=has efficacy. -If the compound activating the receptor is endogenour (naturally occurring in the body, it is typically called a ligand. -If it is exogenous (produced outside the body), it is a drug and sometimes drugs can be referred to as ligands. -Both drugs and ligands can be agonists. -In some cases, drugs do not combine directly with a receptor, but enhance the amount of the endogenous ligands available for the receptor which is called an indirect agonists. -Some drugs exert their effects by blocking the action of agonists and are thus called antagonists. -Partial agonists are drugs that display intermediate efficacy in receptor activation between the efficacy of a full agonist and an antagonist. A partial agonist may actually have a greater affinity for a particular receptor than a full agonist. It cannot achieve the maximal response of the full agnonist at those receptors, it can reduce the effects of a full agonist, because it reduces the full agonists accessibility to its receptors. -Thus, partial agnosits may be therapeutically useful in conditions in which one wants to reduce excessive receptor activity but without totally eliminating receptor activity. www.notesolution.com
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