Interactions, Chronic Effects, & Nonspecific Factors

Interactions, Chronic Effects, & Nonspecific Factors Lesson 7

Drug Interactions • 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 ~

Single Drug • Cumulative • repeated administration • before drug completely eliminated •  blood concentration • Timing • half-life important • Time course different • Subjective effects • blood concentrtions ~

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 ~

Physiological Antagonism A A + B Hi Drug Effect B Lo

Additive Effects A + B B A Drug Effect

Potentiation A + B B Drug Effect A

Chronic Use: Tolerance • After repeated use • Decreased response to the same dose • Compensatory responses • Not at a uniform rate • different for each drug effect ~

Tolerance A B 100 % population 50 0 0 X DRUG DOSE

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

Which curve shows sensitization? A B 100 % population 50 0 0 X DRUG DOSE

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 ~

drug dose drug dose x x max x Behavior x min lo hi Drug amount (dose) Difference in baseline activity.

Should you take a drug? • Rational judgment process • But often not • Many factors involved • Learning: • Classical & Operant Conditioning ~

Interactions, Chronic Effects, & Nonspecific Factors