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Copyright (c) Pearson Education 20Copyright (c) Pearson Education 201010
Drugs, Behavior, and Modern Society Drugs, Behavior, and Modern Society SIXTH EDITIONSIXTH EDITION
Charles F. LevinthalCharles F. Levinthal
Chapter 3Chapter 3How Drugs Work in the Body How Drugs Work in the Body
and on the Mindand on the Mind
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ROUTES OF DRUG ROUTES OF DRUG ADMINISTRATIONADMINISTRATION
• Injection (intravenous, intramuscular, Injection (intravenous, intramuscular, or or subcutaneous injection)subcutaneous injection)
• Inhalation (smoking)Inhalation (smoking)• Oral administration (by mouth)Oral administration (by mouth)• Absorption through the skin or Absorption through the skin or
membranes (intranasal sniffing, membranes (intranasal sniffing, sublingual absorption, rectal sublingual absorption, rectal suppository, transdermal patch)suppository, transdermal patch)
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ELIMINATION HALF-LIFEELIMINATION HALF-LIFE
• A drug’s elimination half-life refers to A drug’s elimination half-life refers to the length of time it takes for the drug the length of time it takes for the drug to be reduced to 50 percent of its to be reduced to 50 percent of its equilibrium level in the bloodstream.equilibrium level in the bloodstream.
• Elimination half-life ofElimination half-life of nicotine --- a few hoursnicotine --- a few hours
cocaine --- a few hourscocaine --- a few hoursmarijuana --- much longermarijuana --- much longer
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TIME-RELEASE DRUGS ARE TIME-RELEASE DRUGS ARE FORMULATED TO STAY WITHIN THE FORMULATED TO STAY WITHIN THE
THERAPEUTIC WINDOW FOR SEVERAL THERAPEUTIC WINDOW FOR SEVERAL HOURSHOURS
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FORMS OF DRUG INTERACTIONFORMS OF DRUG INTERACTION
• Additive interaction (additivity)Additive interaction (additivity)
• Hyperadditive (synergistic) interactionHyperadditive (synergistic) interaction
• Potentiation (a special kind of Potentiation (a special kind of synergism)synergism)
• Antagonistic interactionAntagonistic interaction
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Additive effect: If the effect of one Additive effect: If the effect of one drug alone is equivalent to a 4 and drug alone is equivalent to a 4 and the effect of another is a 6, then the the effect of another is a 6, then the combined additive effect is 10.combined additive effect is 10.
Hyperadditive/synergism: the Hyperadditive/synergism: the combined effects exceed the sum of combined effects exceed the sum of the individual drugs administered the individual drugs administered alonealone
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Potentiation: one drug combined with Potentiation: one drug combined with another drug produces an enhanced another drug produces an enhanced effect when one of the drugs alone effect when one of the drugs alone would have no effectwould have no effect
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EXAMPLES OF HYPERADDITIVE DRUG EXAMPLES OF HYPERADDITIVE DRUG INTERACTIONSINTERACTIONS
• Alcohol with sleep medications, Alcohol with sleep medications, insulin, painkillersinsulin, painkillers
• Headache remedies with CoumadinHeadache remedies with Coumadin• Lanoxin with licoriceLanoxin with licorice• Lanoxin with bran and oatmealLanoxin with bran and oatmeal• Tagamet with CoumadinTagamet with Coumadin
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EXAMPLES OF ANTAGONISTIC DRUG EXAMPLES OF ANTAGONISTIC DRUG INTERACTIIONSINTERACTIIONS
• Morphine with naloxone or Morphine with naloxone or naltrexonenaltrexone
• Norpramin or related antidepressants Norpramin or related antidepressants with bran or oatmealwith bran or oatmeal
• Soy products with CoumadinSoy products with Coumadin• Broccoli, cabbage and asparagus Broccoli, cabbage and asparagus
with Coumadinwith Coumadin
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CROSS-TOLERANCECROSS-TOLERANCE
Cross-tolerance results from the chronic Cross-tolerance results from the chronic use of one drug inducing a tolerance use of one drug inducing a tolerance effect with regard to a second drug effect with regard to a second drug that has never been used before.that has never been used before.
Example: alcohol with barbiturates or Example: alcohol with barbiturates or other depressant drugsother depressant drugs
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NAME ALL THE DRUGS THAT WOULD NAME ALL THE DRUGS THAT WOULD SHOW CROSS TOLERANCE SHOW CROSS TOLERANCE
TO EACH OTHER. TO EACH OTHER. WHICH ONES WOULD NOT?WHICH ONES WOULD NOT?
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CROSS-DEPENDENCECROSS-DEPENDENCE
Cross-dependence results from one Cross-dependence results from one drug substituting for whatever drug substituting for whatever physiologicl effects have been physiologicl effects have been produced by a second drug that has produced by a second drug that has been discontinued.been discontinued.
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SOURCES OF INDIVIDUAL SOURCES OF INDIVIDUAL DIFFERENCES IN DRUG DIFFERENCES IN DRUG
RESPONSESRESPONSES
•Body weightBody weight
•GenderGender
•Ethnic backgroundEthnic background
•Expectations of the drug userExpectations of the drug user
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THE ORGANIZATION OF THE THE ORGANIZATION OF THE NERVOUS SYSTEMNERVOUS SYSTEM
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SYMPATHETIC AND PARASYMPATHETIC SYMPATHETIC AND PARASYMPATHETIC BRANCHES OF THE BRANCHES OF THE
AUTONOMIC NERVOUS SYSTEMAUTONOMIC NERVOUS SYSTEM
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THREE MAJOR DIVISIONS OF THE THREE MAJOR DIVISIONS OF THE BRAINBRAIN
• Hindbrain --- medulla, pons, Hindbrain --- medulla, pons, cerebellumcerebellum
• Midbrain --- substantia nigraMidbrain --- substantia nigra
• Forebrain --- hypothalamus, limbic Forebrain --- hypothalamus, limbic system, cerebral cortexsystem, cerebral cortex
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STRUCTURES OF THE HUMAN STRUCTURES OF THE HUMAN BRAINBRAIN
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BASIC STRUCTURES OF A NEURONBASIC STRUCTURES OF A NEURON
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THE SEQUENCE OF EVENTS THE SEQUENCE OF EVENTS IN SYNAPTIC COMMUNICATIONIN SYNAPTIC COMMUNICATION
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COMMUNICATION BETWEEN NEURONS COMMUNICATION BETWEEN NEURONS DEPENDS ON A “MATCH” BETWEEN DEPENDS ON A “MATCH” BETWEEN
NEUROTRANSMITTER AND RECPETORNEUROTRANSMITTER AND RECPETOR
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SEVEN MAJOR SEVEN MAJOR NEUROTRANSMITTERSNEUROTRANSMITTERS
• AcetylcholineAcetylcholine• NorepinephrineNorepinephrine• DopamineDopamine• SerotoninSerotonin• Gamma aminobutyric acid (GABA)Gamma aminobutyric acid (GABA)• GlutamateGlutamate• EndorphinsEndorphins
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Drug Effects and Synaptic Drug Effects and Synaptic Communication in the Nervous SystemCommunication in the Nervous System
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TWO BIOCHEMICAL PROCESSES TWO BIOCHEMICAL PROCESSES UNDERLYING DRUG TOLERANCE UNDERLYING DRUG TOLERANCE
• Cellular (pharmacodynamic) tolerance Cellular (pharmacodynamic) tolerance
--- through changes in synapses of --- through changes in synapses of neuronsneurons
• Metabolic (dispositional) tolerance Metabolic (dispositional) tolerance
--- through changes in --- through changes in biotransformation in biotransformation in the the liverliver
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normal subject
cocaine abuser (1 month post)
cocaine abuser (4 months post)
Effect of Cocaine Abuse on Dopamine D2 Receptors
PET SCANS SHOWING DOPAMINE PET SCANS SHOWING DOPAMINE ACTIVITY IN THE BRAINS OF A DRUG-ACTIVITY IN THE BRAINS OF A DRUG-
FREE SUBJECT AND A COCAINE FREE SUBJECT AND A COCAINE ABUSER AT TWO STAGES OF COCAINE ABUSER AT TWO STAGES OF COCAINE
USEUSE
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A DRUG EFFECT A DRUG EFFECT AS A THREE-WAY INTERACTIONAS A THREE-WAY INTERACTION
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DRUG RESEARCH PROCEDURESDRUG RESEARCH PROCEDURES
• Testing the effectiveness of a drug Testing the effectiveness of a drug against a no-treatment condition ---against a no-treatment condition ---WRONGWRONG
• Testing the effectiveness of a drug Testing the effectiveness of a drug against an active placebo --- RIGHTagainst an active placebo --- RIGHT
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DOUBLE-BLIND PLACEBO DOUBLE-BLIND PLACEBO CONTROL DESIGNCONTROL DESIGN
• Individuals administering the drug do Individuals administering the drug do not know whether the substance not know whether the substance administered is actually the drug or a administered is actually the drug or a placebo.placebo.
• Individuals receiving the drug do not Individuals receiving the drug do not know whether the substance received is know whether the substance received is actually the drug or a placebo.actually the drug or a placebo.