Interactions, Chronic Effects,

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Interactions, Chronic Effects, Nonspecific
Factors

• Lecture 6

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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
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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
Response
Lo
Time
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Additive Effects
Hi
Response
Lo
Time
9
Potentiation
Hi
Response
Lo
Time
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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
X
DRUG DOSE
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Types of Tolerance

• Tachyphylaxis
• rapid transient
• usually between 1st 2 doses
• 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 Sensitization

• Increased response to a repeated dose
• Reverse tolerance
• Cocaine amphetamine
• motor activation
• Dont know mechanism
• conditioning involved
• increased NT receptor synthesis?

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Other Sources of Variability

• Nonspecific factors
• Organism
• Psychological
• Environmental
• Task

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Organism Variables

• Weight
• Sex Hormonal states
• Interspecies differences

• Intraspecies differences
• codeine analgesia
• Asian men lt European
• metabolism clearance

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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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max
x
Behavior
x
min
lo
hi
Drug amount (dose)
Difference in baseline activity.
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Should you take a drug?

• Rational judgment process
• But often not
• Many factors involved
• Learning
• Classical Operant Conditioning