Interactions, Chronic Effects, & Nonspecific Factors Lesson 7

n Single drug l Cumulative n 2 different drugs l Additive l physiological antagonism l potentiation ~ Drug Interactions

n Cumulative l single drug n Additive l 2 different drugs l as if adding individual drug effects n Potentiation l 2 different drugs l combined effect greatly enhanced l as if multiplying individual effects ~ Drug Interactions

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

Response Hi Lo Time Cumulative Effects

Multiple Drug Interactions n Physiological antagonism l drugs have opposing effects n Additive effects l drugs have same effects n Potentiation l synergistic l 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 B A

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

DRUG DOSE 0X AB % population Tolerance

Types of Tolerance n Tachyphylaxis l rapid & transient l usually between 1 st 2 doses l NT depletion, receptors occupied n Drug Disposition Tolerance l enzyme induction ~

Types of Tolerance n Pharmacodynamic Tolerance l decreased NT synthesis l Down-regulation of receptors n Behavioral Tolerance l Volitional vs. Associative n Cross Tolerance l tolerance to 1 drug  also to a 2d l e.g., alcohol & phenobarbitol ~

Chronic Use: Tolerance n Repeated use:  response to same dose l Compensatory responses l Not at a uniform rate n Tachyphylaxis n Drug disposition n Pharmacodynamic n Behavioral n Cross-tolerance~

Chronic Use: Sensitization n Increased response to a repeated dose l Reverse tolerance n Cocaine & amphetamine l motor activation n Don’t know mechanism l conditioning involved l increased NT & receptor synthesis? ~

Tolerance / Sensitization n Tolerance for CNS depressants? n Sensitization for CNS stimulants? n It depends! l Alcohol: both l Cocaine: both

Chronic Cocaine in Chicks

DRUG DOSE 0X AB % population Which curve shows sensitization?

Other Sources of Variability n Nonspecific factors l Organism l Psychological l Environmental l Task ~

Organism Variables n Weight n Sex & Hormonal states n Interspecies differences n Intraspecies differences l codeine analgesia u Asian men < European u metabolism & clearance ~

Organism Variables n Age n Disease n Nutrition n Biological rhythms ~

Other Nonspecific Variables n Psychological l Expectations u set u Placebo effects n Environmental l Setting n Task l Rate-dependent effects ~

Rate Dependency n Interaction of drug... & baseline rate of behavior n ADHD & ritalin l stimulant to treat hyperactivity? ~

Different Effects, Same Dose n Why? l initial activity of system n Low activity in system l drug increases effects n High activity in system l drug may decrease effects ~

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

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