Copyright (c) Pearson Education 2010 Drugs, Behavior, and Modern Society SIXTH EDITION Charles F. Levinthal Chapter 3 How Drugs Work in the Body and on the Mind This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program any rental, lease, or lending of the program

Copyright (c) Pearson Education 2010 ROUTES OF DRUG ADMINISTRATION Injection (intravenous, intramuscular, or subcutaneous injection) Injection (intravenous, intramuscular, or subcutaneous injection) Inhalation (smoking)Inhalation (smoking) Oral administration (by mouth)Oral administration (by mouth) Absorption through the skin or membranes (intranasal sniffing, sublingual absorption, rectal suppository, transdermal patch)Absorption through the skin or membranes (intranasal sniffing, sublingual absorption, rectal suppository, transdermal patch)

Copyright (c) Pearson Education 2010 ELIMINATION HALF-LIFE A drug’s elimination half-life refers to the length of time it takes for the drug to be reduced to 50 percent of its equilibrium level in the bloodstream. A drug’s elimination half-life refers to the length of time it takes for the drug to be reduced to 50 percent of its equilibrium level in the bloodstream. Elimination half-life of Elimination half-life of nicotine --- a few hours nicotine --- a few hours cocaine --- a few hours marijuana --- much longer

Copyright (c) Pearson Education 2010 TIME-RELEASE DRUGS ARE FORMULATED TO STAY WITHIN THE THERAPEUTIC WINDOW FOR SEVERAL HOURS

Copyright (c) Pearson Education 2010 FORMS OF DRUG INTERACTION Additive interaction (additivity) Additive interaction (additivity) Hyperadditive (synergistic) interaction Hyperadditive (synergistic) interaction Potentiation (a special kind of synergism) Potentiation (a special kind of synergism) Antagonistic interaction Antagonistic interaction

Copyright (c) Pearson Education 2010 Additive effect: If the effect of one drug alone is equivalent to a 4 and the effect of another is a 6, then the combined additive effect is 10. Additive effect: If the effect of one drug alone is equivalent to a 4 and the effect of another is a 6, then the combined additive effect is 10. Hyperadditive/synergism: the combined effects exceed the sum of the individual drugs administered alone Hyperadditive/synergism: the combined effects exceed the sum of the individual drugs administered alone

Copyright (c) Pearson Education 2010 Potentiation: one drug combined with another drug produces an enhanced effect when one of the drugs alone would have no effect Potentiation: one drug combined with another drug produces an enhanced effect when one of the drugs alone would have no effect

Copyright (c) Pearson Education 2010 EXAMPLES OF HYPERADDITIVE DRUG INTERACTIONS Alcohol with sleep medications, insulin, painkillers Alcohol with sleep medications, insulin, painkillers Headache remedies with Coumadin Headache remedies with Coumadin Lanoxin with licorice Lanoxin with licorice Lanoxin with bran and oatmeal Lanoxin with bran and oatmeal Tagamet with Coumadin Tagamet with Coumadin

Copyright (c) Pearson Education 2010 EXAMPLES OF ANTAGONISTIC DRUG INTERACTIIONS Morphine with naloxone or naltrexone Morphine with naloxone or naltrexone Norpramin or related antidepressants with bran or oatmeal Norpramin or related antidepressants with bran or oatmeal Soy products with Coumadin Soy products with Coumadin Broccoli, cabbage and asparagus with Coumadin Broccoli, cabbage and asparagus with Coumadin

Copyright (c) Pearson Education 2010 CROSS-TOLERANCE Cross-tolerance results from the chronic use of one drug inducing a tolerance effect with regard to a second drug that has never been used before. Example: alcohol with barbiturates or other depressant drugs

Copyright (c) Pearson Education 2010 NAME ALL THE DRUGS THAT WOULD SHOW CROSS TOLERANCE TO EACH OTHER. WHICH ONES WOULD NOT?

Copyright (c) Pearson Education 2010 CROSS-DEPENDENCE Cross-dependence results from one drug substituting for whatever physiologicl effects have been produced by a second drug that has been discontinued.

Copyright (c) Pearson Education 2010 SOURCES OF INDIVIDUAL DIFFERENCES IN DRUG RESPONSES Body weightBody weight GenderGender Ethnic backgroundEthnic background Expectations of the drug userExpectations of the drug user

Copyright (c) Pearson Education 2010 THE ORGANIZATION OF THE NERVOUS SYSTEM

Copyright (c) Pearson Education 2010 SYMPATHETIC AND PARASYMPATHETIC BRANCHES OF THE AUTONOMIC NERVOUS SYSTEM

Copyright (c) Pearson Education 2010 THREE MAJOR DIVISIONS OF THE BRAIN Hindbrain --- medulla, pons, cerebellum Hindbrain --- medulla, pons, cerebellum Midbrain --- substantia nigra Midbrain --- substantia nigra Forebrain --- hypothalamus, limbic system, cerebral cortex Forebrain --- hypothalamus, limbic system, cerebral cortex

Copyright (c) Pearson Education 2010 STRUCTURES OF THE HUMAN BRAIN

Copyright (c) Pearson Education 2010 BASIC STRUCTURES OF A NEURON

Copyright (c) Pearson Education 2010 THE SEQUENCE OF EVENTS IN SYNAPTIC COMMUNICATION

Copyright (c) Pearson Education 2010 COMMUNICATION BETWEEN NEURONS DEPENDS ON A “MATCH” BETWEEN NEUROTRANSMITTER AND RECPETOR

Copyright (c) Pearson Education 2010 SEVEN MAJOR NEUROTRANSMITTERS Acetylcholine Acetylcholine Norepinephrine Norepinephrine Dopamine Dopamine Serotonin Serotonin Gamma aminobutyric acid (GABA) Gamma aminobutyric acid (GABA) Glutamate Glutamate Endorphins Endorphins

Copyright (c) Pearson Education 2010 Drug Effects and Synaptic Communication in the Nervous System

Copyright (c) Pearson Education 2010 TWO BIOCHEMICAL PROCESSES UNDERLYING DRUG TOLERANCE Cellular (pharmacodynamic) toleranceCellular (pharmacodynamic) tolerance --- through changes in synapses of neurons --- through changes in synapses of neurons Metabolic (dispositional) toleranceMetabolic (dispositional) tolerance --- through changes in biotransformation in the liver --- through changes in biotransformation in the liver

Copyright (c) Pearson Education 2010 PET SCANS SHOWING DOPAMINE ACTIVITY IN THE BRAINS OF A DRUG-FREE SUBJECT AND A COCAINE ABUSER AT TWO STAGES OF COCAINE USE

Copyright (c) Pearson Education 2010 A DRUG EFFECT AS A THREE-WAY INTERACTION

Copyright (c) Pearson Education 2010 DRUG RESEARCH PROCEDURES Testing the effectiveness of a drug against a no-treatment condition ---WRONG Testing the effectiveness of a drug against a no-treatment condition ---WRONG Testing the effectiveness of a drug against an active placebo --- RIGHT Testing the effectiveness of a drug against an active placebo --- RIGHT

Copyright (c) Pearson Education 2010 DOUBLE-BLIND PLACEBO CONTROL DESIGN Individuals administering the drug do not know whether the substance administered is actually the drug or a placebo. Individuals administering the drug do not know whether the substance administered is actually the drug or a placebo. Individuals receiving the drug do not know whether the substance received is actually the drug or a placebo. Individuals receiving the drug do not know whether the substance received is actually the drug or a placebo.