Interactions, Chronic Effects, &

Nonspecific Factors

Lesson 7

Single drug Cumulative

2 different drugs Additive physiological antagonism potentiation ~

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 ~

Drug Interactions

Single Drug Cumulative

repeated administration before drug completely eliminated blood concentration

Timing half-life important

Time course different Subjective effects blood concentrtions ~

Response

Hi

Lo

Time

Cumulative Effects

Multiple Drug Interactions

Physiological antagonism drugs have opposing effects

Additive effects drugs have same effects

Potentiation synergistic greater than expected by individual

drug effects ~

Drug Effect

Hi

Lo

Physiological Antagonism

A

B

A + B

Additive Effects

Drug Effect

A + B

B

A

Potentiation

Drug Effect

A + B

BA

Chronic Use: Tolerance

After repeated use Decreased response to the same dose

Compensatory responses Not at a uniform rate

different for each drug effect ~

100

50

0

DRUG DOSE0 X

A B

% population

Tolerance

Types of Tolerance

Tachyphylaxis rapid & transient usually between 1st 2 doses NT depletion, receptors occupied

Drug Disposition Tolerance enzyme induction ~

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 ~

Chronic Use: Tolerance

Repeated use: response to same dose Compensatory responses Not at a uniform rate Tachyphylaxis Drug disposition Pharmacodynamic Behavioral Cross-tolerance~

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? ~

Tolerance / Sensitization Tolerance for CNS depressants? Sensitization for CNS stimulants? It depends!

Alcohol: both Cocaine: both

Chronic Cocaine in Chicks

100

50

0

DRUG DOSE0 X

A B

% population

Which curve shows sensitization?

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 ~

Other Nonspecific Variables

Psychological Expectations

set Placebo effects

Environmental Setting

Task Rate-dependent effects ~

Rate Dependency

Interaction of drug...

& baseline rate of behavior ADHD & ritalin

stimulant to treat hyperactivity? ~

Different Effects, Same Dose

Why? initial activity of system

Low activity in system drug increases effects

High activity in system drug may decrease effects ~

Behavior

Drug amount (dose)

min

max

lo hi

x

x

drug dose

Difference in baseline activity.

x

x

drug dose

Should you take a drug?

Rational judgment process But often not

Many factors involved Learning:

Classical & Operant Conditioning ~