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Chapter 6

chapter6

9 Pages
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Department
Psychology
Course Code
PSYC62H3
Professor
Suzanne Erb

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Chapter 6
TORERANCE AND DEPENDENCE
What is tolerance?
-Drug tolerance occurs when there is decreased susceptibility (diminished
response) to the effects of a given amount of drug as a result of previous
exposure, typically caused by repeated exposure to the drug.
-Increasingly larger doses of drug are required to induce the same behavioural
effect.
-Tolerance due to drug exposure id different from so-called genetic or
dispositional tolerance, whereby an individual may not be effected by the drug as
much as other individuals are because of genetic or dispositional factors.
-Although tolerance generally requires several drug exposures before it is
evidenced, there is a special case of tolerance in which a noticeable decrease in
the organism’s sensitivity to the drug occurs over very short period of time—on
the order of few hours. = tachyhpylaxis or acute tolerance
-In this form of tolerance, the same amount of drug administered on two separate
occasions a couple of hours apart may induce greater effects with the first dose
than with the second doses.
-Tachyphylaxis is also evident when the behavioural or physiological effects of a
given dose of drug dissipate at a faster rate than the rate at which the drug is
eliminated from the brain.
-Cross-tolerance refers to the phenomenon in which the development of tolerance
to one type of drug results in decreased sensitivity to the effects of another type of
drug.
-Most psychoactive drugs we take in our culture are not especially harmful in and
of themselves when taken in reasonable quantities with sufficient time between
administrations.
-Once tolerance to a drug’s effects develops, larger and more frequent doses that
do become toxic are often administered.
-Second, tolerance to the effects ofdrugs does not develop uniformly; that is, some
effects may show profound toerelance whereas others may show little or no
tolerance.
-This is a distint problem with alcohol and many sedative-hypnotic drugs, where
the beneficial or recreastional effects of the drug may show considerable
tolerance, but little tolerance developed to the lethal effects of these drugs.
-In effect, with this type of tolerance, the therapeutic index for these drugs gets
smaller and smaller.
-With other drugs, tolerance to the desirable effects of a drug may occur while the
person actually becomes more sensitive to the side effects of the drug.
-Eg. The ability of amphetamine to induce euphoria decreases with regular use, but
the ability for amphetamine to induce psychotic-like effects may actually increase
with regular use of large doses.
www.notesolution.com
-Tolerance is of concern because many of the mechanism resulting in tolerance
contribute to a person’s compulsion to take a drug with loss of control over drug
intake—that is, drug addiction.
Tolerance Mechanisms
-There are three distinct types of drug tolerance: Pharmacokinetic tolerance,
pharmacodynamic tolerance (also called functional or non-associative
tolerance), and context-specific tolerance (also called behavioural, learned, or
associative tolerance)
-Pharmacokinetic and pharmacodynamic forms of tolerance are produced by
exposure to high concentrations of drug, generally with a certain minimum
amount of exposure times required, and are not affected by environmental or
behavioural manipulations of the organism.
-Context-specific tolerance is very sensitive to behavioural and environmental
manipulations and involves learning and memory.
Mechanism of Pharmacokinetic and Pharmacodynamic Tolerance
-Prominent mechanism- the ability of liver to synthesize more drug-metabolizing
enzymes than normal when exposed to drug.
-Once repeated exposure has taken place, the liver can metabolize the drug at a
faster rate than it could previously, thereby decreasing its duration of action.
-The peak intensity of the drug’s action may not be reduced very drug must first
pass through the liver before it can be metabolized.
-This mechanism is also responsible for some cross-tolerance between drugs, since
the actions of the drug=metabolizing enzymes are not specific to one particular
drug.
-One rather novel explanation for drug tolerance was that something akin to tan
immune reaction occurred.
-The drug molecules would be the antigen to which the organism would develop
antibodies.
-Presumably, the antibodies formed in mothers crossed over the placentas into the
fetus’s, so that when they were later grown and given morphine the antibodies
reduced the drug’ effectiveness.
-This mechanism would account for the persistence of some kinds of tolerance for
long periods of time and would account for some forms of cross-tolerance. – not
sure if this happens in normal circumstances
-By themselves, most drug molecules are too small to trigger antibody formation,
but it is theoretically possible for a drug molecule to bind to some types of tissue
and form a complex large enough to trigger an immune reaction to it.
-Tolerance to drug may also develop because the drug’s pharmocodynamic
properties lead to the depletion of neurotransmitters critical to the drug’s effects.
-Some drugs (amphetamine and cocaine) act by augmenting a specific type of NT
activity because they enhance the transmitter’ release or inhibit their reuptake and
increases the transmitter’s access to receptors.
www.notesolution.com
-The drug’s actions may lead to a depletion of the transmitter either because the
transmitter are used faster than they can be replenished or because the actual
synthesis of the tranismitters is decrease (excess activity of auto-receptor)
-With fewer tranimsitter molecules available, a larger drug dose must be
administered.
-If this cycle continues long enough,. This form of tolerance can lead to the drug\s
becoming completely ineffective, regardless of the dose administer.
-A drug\s ability to deplete neurotransmitter can also be a factor in some forms of
cross-tolerance.
-Eg. One drug may act bye enhancing the transmitter’s release, and another may
act by reducing the transmitter reuptake.
-With either drug, depletion of the transmitter will reduce the effect of the drug.
-Finally, depletion of neurotransmitters can lead to the person experiencing
symptoms that are the opposite of those he or she experienced with the drug this
where the drug initially induces its effects by amplifying a neurotransmitters
activity on its target neurons, absence of the drug results in a reduction in the
neurotransmitter’s activity on its target neurons
-Another possible tolerance mechanism involves the drug’s occupation and
saturation of receptor sites, whereby the drug molecules exert their action at the
time of occupation of receptor sites.
-One binding occurs, the drug no longer exerts and effect other than preventing the
initiation of a new response by other drug molecules combining with the receptor.
-Eg. Nicotine dissociates from the Ach receptor rather slowly, the cell remains
depolarized, and a new action potential cannot be initiated until the nicotine is
removed from the receptor.
-Large doses of nicotine may actually exert an antagonistic action at Ach receptors
(after initial agonistic action)
-There appear to be several mechanisms for tolerance involving cellular adaptation
related to homeostasis
-One of the more common homeostatic adaptation observed involving drug-
induced alteration in the receptors in neuronal membranes.
-The alterations may reflect either qualitative changes in the NTs receptors
configuration or changes in the actual number of receptors, which in turn affect
the transmitter binding or efficacy.
-In most cases, a continuous exposure to drugs that mimic or amplify the action of
neurotransmitters at their receptors tends to decrease receptor activity through
processes referred to as down-regulation and desensitization.
-Down-regulation refers to a decrease in the number of functional receptors
available for activation
-This can occur because the receptors dissociate from the neuronal membrane and
becomes sequestered inside the cytoplasm of the neuron, thus making them
inaccessible for activation by agonists, or it can occur because the receptors are
actually degraded.
www.notesolution.com

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Description
Chapter 6 TORERANCE AND DEPENDENCE What is tolerance? - Drug tolerance occurs when there is decreased susceptibility (diminished response) to the effects of a given amount of drug as a result of previous exposure, typically caused by repeated exposure to the drug. - Increasingly larger doses of drug are required to induce the same behavioural effect. - Tolerance due to drug exposure id different from so-called genetic or dispositional tolerance, whereby an individual may not be effected by the drug as much as other individuals are because of genetic or dispositional factors. - Although tolerance generally requires several drug exposures before it is evidenced, there is a special case of tolerance in which a noticeable decrease in the organisms sensitivity to the drug occurs over very short period of timeon the order of few hours. = tachyhpylaxis or acute tolerance - In this form of tolerance, the same amount of drug administered on two separate occasions a couple of hours apart may induce greater effects with the first dose than with the second doses. - Tachyphylaxis is also evident when the behavioural or physiological effects of a given dose of drug dissipate at a faster rate than the rate at which the drug is eliminated from the brain. - Cross-tolerance refers to the phenomenon in which the development of tolerance to one type of drug results in decreased sensitivity to the effects of another type of drug. - Most psychoactive drugs we take in our culture are not especially harmful in and of themselves when taken in reasonable quantities with sufficient time between administrations. - Once tolerance to a drugs effects develops, larger and more frequent doses that do become toxic are often administered. - Second, tolerance to the effects ofdrugs does not develop uniformly; that is, some effects may show profound toerelance whereas others may show little or no tolerance. - This is a distint problem with alcohol and many sedative-hypnotic drugs, where the beneficial or recreastional effects of the drug may show considerable tolerance, but little tolerance developed to the lethal effects of these drugs. - In effect, with this type of tolerance, the therapeutic index for these drugs gets smaller and smaller. - With other drugs, tolerance to the desirable effects of a drug may occur while the person actually becomes more sensitive to the side effects of the drug. - Eg. The ability of amphetamine to induce euphoria decreases with regular use, but the ability for amphetamine to induce psychotic-like effects may actually increase with regular use of large doses. www.notesolution.com
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