Transcript Interactions, Chronic Effects & Nonspecific Factors

Interactions,
Chronic Effects, &
Nonspecific Factors
Lesson 7
Drug Interactions
Single drug
 Cumulative
 2 different drugs
 Additive
 physiological antagonism
 potentiation ~
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Drug Interactions
Cumulative
 single drug
 Additive
 2 different drugs
 as if adding individual drug effects
 Potentiation
 2 different drugs
 combined effect greatly enhanced
 as if multiplying individual effects ~
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Single Drug
Cumulative
 repeated administration
 before drug completely eliminated
  blood concentration
 Timing
 half-life important
 Time course different
 Subjective effects
 blood concentrtions ~
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Cumulative Effects
Hi
Response
Lo
Time
Multiple Drug Interactions
Physiological antagonism
 drugs have opposing effects
 Additive effects
 drugs have same effects
 Potentiation
 synergistic
 greater than expected by individual
drug effects ~
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Physiological Antagonism
Hi
A+B
A
Drug Effect
B
Lo
Additive Effects
A+B
A
Drug Effect
B
Potentiation
A+B
Drug Effect
A
B
Chronic Use: Tolerance
After repeated use
 Decreased response to the same dose
 Compensatory responses
 Not at a uniform rate
 different for each drug effect ~
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Tolerance
A
B
100
% population 50
0
0
DRUG DOSE
X
Types of Tolerance
Tachyphylaxis
 rapid & transient
st 2 doses
 usually between 1
 NT depletion, receptors occupied
 Drug Disposition Tolerance
 enzyme induction ~
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Types of Tolerance
Pharmacodynamic Tolerance
 decreased NT synthesis
 Down-regulation of receptors
 Behavioral Tolerance
 Volitional vs. Associative
 Cross Tolerance
 tolerance to 1 drug  also to a 2d
 e.g., alcohol & phenobarbitol ~
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Chronic Use: Tolerance
Repeated use:  response to same dose
 Compensatory responses
 Not at a uniform rate
 Tachyphylaxis
 Drug disposition
 Pharmacodynamic
 Behavioral
 Cross-tolerance~
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Chronic Use: Sensitization
Increased response to a repeated dose
 Reverse tolerance
 Cocaine & amphetamine
 motor activation
 Don’t know mechanism
 conditioning involved
 increased NT & receptor synthesis? ~
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Tolerance / Sensitization
Tolerance for CNS depressants?
 Sensitization for CNS stimulants?
 It depends!
 Alcohol: both
 Cocaine: both
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Chronic Cocaine in Chicks
Which curve shows sensitization?
A
B
100
% population 50
0
0
DRUG DOSE
X
Other Sources of Variability

Nonspecific factors
 Organism
 Psychological
 Environmental
 Task ~
Organism Variables
Weight
 Sex & Hormonal states
 Interspecies differences
 Intraspecies differences


codeine analgesia
Asian
men < European
metabolism
& clearance ~
Organism Variables
Age
 Disease
 Nutrition
 Biological rhythms ~
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Other Nonspecific Variables

Psychological
 Expectations
set
 Placebo effects

Environmental
 Setting
 Task
 Rate-dependent effects ~
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Rate Dependency
Interaction of drug...
& baseline rate of behavior
 ADHD & ritalin
 stimulant to treat hyperactivity? ~
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Different Effects, Same Dose
Why?
 initial activity of system
 Low activity in system
 drug increases effects
 High activity in system
 drug may decrease effects ~
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drug dose
max
drug dose
x
Behavior
x
x
x
min
lo
Drug amount (dose)
Difference in baseline activity.
hi
Should you take a drug?
Rational judgment process
 But often not
 Many factors involved
 Learning:
 Classical & Operant Conditioning ~
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